BJP8 v. 170

S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2013/14: Transporters.
British Journal of Pharmacology (2013) 170, 17061796
THE CONCISE GUIDE TO PHARMACOLOGY 2013/14:

TRANSPORTERS
Stephen P.H. Alexander*1, Helen E. Benson2, Elena Faccenda2, Adam J. Pawson2,
2
Joanna L. Sharman , Michael Spedding3, John A. Peters4, Anthony J. Harmar2 and
CGTP Collaborators
IUPHAR
International Union of Basic
and Clinical Pharmacology
*Author for correspondence; [email protected]

1
School of Life Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, UK
2
The University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK
3
Spedding Research Solutions SARL, Le Vsinet 78110, France
4
Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee Dundee DD1 9SY, UK
L
N
Abstract
The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase
of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/
doi/10.1111/bph.12444/full.
Transporters are one of the seven major pharmacological targets into which the Guide is divided, with the others being G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic
receptors, nuclear hormone receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and
suggestions for further reading. A new landscape format has easy to use tables comparing related targets.
It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented
in previous Guides to Receptors and Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate.
It consolidates information previously curated and displayed separately in IUPHAR-DB and the Guide to Receptors and Channels, providing a permanent, citable, point-in-time record that will survive
database updates.
An Introduction to Transporters
The majority of biological solutes are charged organic or inorganic molecules. Cellular membranes are hydrophobic and,
therefore, effective barriers to separate them allowing the formation of gradients, which can be exploited, for example, in the
generation of energy. Membrane transporters carry solutes across
cell membranes, which would otherwise be impermeable to
them. The energy required for active transport processes is
obtained from ATP turnover or by exploiting ion gradients.
ATP-driven transporters can be divided into three major classes:
P-type ATPases; F-type or V-type ATPases and ATP-binding
cassette transporters. The first of these, P-type ATPases, are multimeric proteins, which transport (primarily) inorganic cations.
The second, F-type or V-type ATPases, are proton-coupled

motors, which can function either as transporters or as
motors. Last, are ATP-binding cassette transporters, heavily
involved in drug disposition as well as transporting endogenous
solutes.
The second largest family of membrane proteins in the human
genome, after the G protein-coupled receptors, are the SLC solute
carrier family. Within the solute carrier family, there are not only
a great variety of solutes transported, from simple inorganic ions
to amino acids and sugars to relatively complex organic molecules like haem. The solute carrier family includes 52 families of
almost 400 members. Many of these overlap in terms of the
Searchable database: http://www.guidetopharmacology.org/index.jsp

Full Contents of Concise Guide: http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full
solutes that they carry. For example, amino acid accumulation is

mediated by members of the SLC1, SLC3/7, SLC6, SLC15, SLC16,
SLC17, SLC32, SLC36, SLC38 and SLC43. Further members of the
SLC superfamily regulate ion fluxes at the plasma membrane, or
solute transport into and out of cellular organelles. Some SLC
family members remain orphan transporters, in as much as a
physiological function has yet to be determined. Within the SLC
superfamily, there is an abundance in diversity of structure. Two
families (SLC3 and SLC7) only generate functional transporters
as heteromeric partners, where one partner is a single TM domain
protein. Membrane topology predictions for other families
suggest 3, 4, 6, 7, 8, 9, 10, 11, 12, 13, or 14 TM domains. The SLC
transporters include members which function as antiports,
Transporters 1706
S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2013/14: Transporters. British Journal of Pharmacology (2013) 170, 17061796
where solute movement in one direction is balanced by a solute

moving in the reverse direction. Symports allow concentration
gradients of one solute to allow movement of a second solute
across a membrane. A third, relatively small group are equilibrative transporters, which allow solutes to travel across membranes
down their concentration gradients. A more complex family of
transporters, the SLC27 fatty acid transporters also express enzymatic function. Many of the transporters also express electrogenic properties of ion channels.
Acknowledgements
We wish to acknowledge the tremendous help provided by the Consultants to the Guides past and present (see list in the Overview, p. 1452). We are also extremely grateful for the financial contributions
from the British Pharmacological Society, the International Union of Basic and Clinical Pharmacology, the Wellcome Trust (099156/Z/12/Z]), which support the website and the University of Edinburgh,
who host the guidetopharmacology.org website.
Conflict of interest
The authors state that there is no conflict of interest to disclose.
List of records presented

1708
1712
1714
1717
1719
1721
1723
1724
1728
1732
1733
1734
1736
1737
1739
1740
1741
1742
1744
1746
1748
1749
1750
1753
1754
1755
1760
ATP-binding cassette transporter family

F-type and V-type ATPases
P-type ATPases
SLC1 family of amino acid transporters
SLC2 family of hexose and sugar alcohol transporters
SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)
SLC4 family of bicarbonate transporters
SLC5 family of sodium-dependent glucose transporters
SLC6 neurotransmitter transporter family
SLC8 family of sodium/calcium exchangers
SLC9 family of sodium/hydrogen exchangers
SLC10 family of sodium-bile acid co-transporters
SLC11 family of proton-coupled metal ion transporters
SLC12 family of cation-coupled chloride transporters
SLC13 family of sodium-dependent sulphate/carboxylate transporters
SLC14 family of facilitative urea transporters
SLC15 family of peptide transporters
SLC16 family of monocarboxylate transporters
SLC17 phosphate and organic anion transporter family
SLC18 family of vesicular amine transporters
SLC19 family of vitamin transporters
SLC20 family of sodium-dependent phosphate transporters
SLC22 family of organic cation and anion transporters
SLC23 family of ascorbic acid transporters
SLC24 family of sodium/potassium/calcium exchangers
SLC25 family of mitochondrial transporters
SLC26 family of anion exchangers

1762
1763
1765
1766
1767
1768
1769
1770
1772
1773
1774
1776
1777
1778
1779
1780
1781
1782
1783
1784
1785
1786
1787
1788
1789
1790
SLC27 family of fatty acid transporters

SLC28 and SLC29 families of nucleoside transporters
SLC30 zinc transporter family
SLC31 family of copper transporters
SLC32 vesicular inhibitory amino acid transporter
SLC33 acetylCoA transporter
SLC34 family of sodium phosphate co-transporters
SLC35 family of nucleotide sugar transporters
SLC36 family of proton-coupled amino acid transporters
SLC37 family of phosphosugar/phosphate exchangers
SLC38 family of sodium-dependent neutral amino acid transporters
SLC39 family of metal ion transporters
SLC40 iron transporter
SLC41 family of divalent cation transporters
SLC42 family of Rhesus glycoprotein ammonium transporters
SLC43 family of large neutral amino acid transporters
SLC44 choline transporter-like family
SLC45 family of putative sugar transporters
SLC46 family of folate transporters
SLC47 family of multidrug and toxin extrusion transporters
SLC48 heme transporter
SLC49 family of FLVCR-related heme transporters
SLC50 sugar transporter
SLC51 family of steroid-derived molecule transporters
SLC52 family of riboflavin transporters
SLCO family of organic anion transporting polypeptides
Transporters 1707
ATP-binding cassette transporter family

Overview: ATP-binding cassette transporters are ubiquitous
membrane proteins characterized by active ATP-dependent
movement of a range of substrates, including ions, lipids, peptides, steroids. Individual subunits are typically made up of two
groups of 6TM-spanning domains, with two nucleotide-binding
domains (NBD). The majority of eukaryotic ABC transporters are

full transporters incorporating both TM and NBD entities. Some
ABCs, notably the ABCD and ABCG families are half-transporters
with only a single membrane spanning domain and one NBD,
and are only functional as homo- or heterodimers. Eukaryotic
ABC transporters convey substrates from the cytoplasm, either

out of the cell or into intracellular organelles. Their role in the
efflux of exogenous compounds, notably chemotherapeutic
agents, has led to considerable interest.
ABCA subfamily
Systematic
nomenclature
Common
abbreviation
HGNC, UniProt
Comment
ABCA1
ABC1, CERP
ABCA1, O95477
Loss-of-function mutations are associated with Tangier disease, in which plasma HDL cholesterol
levels are greatly reduced
ABCA2
ABC2
ABCA2, Q9BZC7
ABCA3
ABC3, ABCC
ABCA3, Q99758
Loss-of-function mutations are associated with pulmonary surfactant deficiency
ABCA4
ABCR
ABCA4, P78363
Retinal-specific transporter of N-retinylPE; loss-of-function mutations are associated with Stargardt

disease, a juvenile onset macular degenerative disease
ABCA5
ABCA5, Q8WWZ7
ABCA6
ABCA6, Q8N139
ABCA7
ABCA7, Q8IZY2
Genome wide association studies identify ABCA7 variants as associated with Alzheimers Disease [6]
ABCA8
ABCA8, O94911
ABCA9
ABCA9, Q8IUA7
ABCA10
ABCA10, Q8WWZ4
ABCA12
ABCA12, Q86UK0
Reported to play a role in skin ceramide formation [23]
ABCA13
ABCA13, Q86UQ4
Comments: A number of structural analogues are not found in man: ABCA14 (ENSMUSG00000062017); ABCA15 (ENSMUSG00000054746); ABCA16 (ENSMUSG00000051900) and ABCA17
(ENSMUSG00000035435).

ATP-binding cassette transporter family 1708
ABCB subfamily
Systematic
nomenclature
Common
abbreviation
HGNC, UniProt
Comment
ABCB1
MDR1, PGP1
ABCB1, P08183
Responsible for the cellular export of many therapeutic drugs. The mouse and rat have two Mdr1 genes (gene
names; Mdr1a and Mdr1b) while the human has only the one gene, MDR1
ABCB2
TAP1
TAP1, Q03518
Endoplasmic reticulum peptide transporter, possibly requires heterodimerization with TAP2
ABCB3
TAP2
TAP2, Q03519
Endoplasmic reticulum peptide transporter, possibly requires heterodimerization with TAP1
ABCB4
PGY3
ABCB4, P21439
Transports phosphatidylcholine from intracellular to extracellular face of the hepatocyte canalicular membrane [13]
ABCB5
ABCB5, Q2M3G0
Multidrug resistance protein in, and marker of, melanoma cells [17]
ABCB6
MTABC3
ABCB6, Q9NP58
Putative mitochondrial porphyrin transporter [11]; other subcellular localizations are possible, such as the plasma
membrane, as a specific determinant of the Langereis blood group system [5]
ABCB7
ABC7
ABCB7, O75027
Mitochondrial; reportedly essential for haematopoiesis [15]
ABCB8
MABC1
ABCB8, Q9NUT2
Mitochondrial; suggested to play a role in chemoresistance of melanoma [4]
ABCB9
TAPL
ABCB9, Q9NP78
Reported to be lysosomal [7]
ABCB10
MTABC2
ABCB10, Q9NRK6
Mitochondrial location; the first human ABC transporter to have a crystal structure reported [18]
ABCB11
ABC16
ABCB11, O95342
Loss-of-function mutations are associated with progressive familial intrahepatic cholestasis type 2 [19]
ABCC subfamily
Systematic nomenclature
Common abbreviation
HGNC, UniProt
Comment
ABCC1
MRP1
ABCC1, P33527
Exhibits a broad substrate specificity [1], including LTC4 (Km 97 nM [12]) and estradiol-17-glucuronide [20]
ABCC2
MRP2, cMOAT
ABCC2, Q92887
Loss-of-function mutations are associated with Dubin-Johnson syndrome, in which plasma levels of
conjugated bilirubin are elevated (OMIM: 237500)
ABCC3
MRP3
ABCC3, O15438
Transports conjugates of glutathione, sulfate or glucuronide [2]
ABCC4
MRP4
ABCC4, O15439
Although reported to facilitate cellular cyclic nucleotide export, this role has been questioned [2]; reported
to export prostaglandins in a manner sensitive to NSAIDS [16]
ABCC5
MRP5
ABCC5, O15440
Although reported to facilitate cellular cyclic nucleotide export, this role has been questioned [2]
ABCC6
MRP6
ABCC6, O95255
Loss-of-function mutations in ABCC6 are associated with pseudoxanthoma elasticum (OMIM: 264800)
ABCC10
MRP7
ABCC10, Q5T3U5
ABCC11
MRP8
ABCC11, Q96J66
Single nucleotide polymorphisms distinguish wet vs. dry earwax (OMIM: 117800); an association between
earwax allele and breast cancer risk is reported in Japanese but not European populations
ABCC12
MRP9
ABCC12, Q96J65

Comments: ABCC7 (also known as CFTR), a 12TM ABC

transporter-type protein, is a cAMP-regulated epithelial cell
membrane Cl- channel involved in normal fluid transport
across various epithelia and can be viewed in the Chloride
channels section of the Guide ABCC8 (ENSG00000006071,

also known as SUR1, sulfonylurea receptor 1) and ABCC9
(ENSG00000069431, also known as SUR2, sulfonylurea receptor
2) are unusual in that they lack transport capacity but regulate
the activity of particular K+ channels (Kir6.16.2), conferring

nucleotide sensitivity to these channels to generate the canonical
KATP channels. ABCC13 (ENSG00000155288) is a possible
pseudogene.
ABCD subfamily of peroxisomal ABC transporters

Overview: This family of half-transporters act as homo- or heterodimers to accumulate fatty acid-CoA esters into peroxisomes for oxidative metabolism [9].
Systematic
nomenclature
Common
abbreviation
HGNC, UniProt
Comment
ABCD1
ALDP
ABCD1, P33897
Transports coenzyme A esters of very long chain fatty acids [2122]; loss-of-function mutations in ABCD1
are associated with adrenoleukodystrophy (OMIM: 3001002)
ABCD2
ALDR
ABCD2, Q9UBJ2
Coenzyme A esters of very long chain unsaturated fatty acids [22]
ABCD3
PMP70
ABCD3, P28288
Comments: ABCD4 (ENSG00000119688, also known as PMP69, PXMP1-L or P70R) appears to be located on the endoplasmic reticulum [8], with an unclear function. Loss-of-function mutations in the
gene encoding ALDP underlie the metabolic storage disorder X-linked adrenoleukodystrophy.
ABCG subfamily
Overview: This family of half-transporters act as homo- or heterodimers; particularly ABCG5 and ABCG8 are thought to be obligate heterodimers. They are associated with cellular export of sterols
and phospholipids, as well as exogenous drugs (ABCG2).
Systematic
nomenclature
Common
abbreviation
HGNC, UniProt
Comment
ABCG1
ABC8
ABCG1, P45844
Transports sterols and choline phospholipids [10]
ABCG2
ABCP
ABCG2, Q9UNQ0
Exhibits a broad substrate specificity, including urate and haem, as well as multiple synthetic compounds [10]. The
functional transporter is likely to be a homodimer, although higher oligomeric states have also been proposed
ABCG4
ABCG4, Q9H172
Putative functional dependence on ABCG1
ABCG5
ABCG5, Q9H222
Transports phytosterols and cholesterol; forms an obligate heterodimer with ABCG8. Loss-of-function mutations in
ABCG5 are associated with sitosterolemia (OMIM: 210250)
ABCG8
ABCG8, Q9H221
Transports phytosterols and cholesterol; forms an obligate heterodimer with ABCG5. Loss-of-function mutations in
ABCG8 are associated with sitosterolemia (OMIM: 210250)
Comments: A further group of ABC transporter-like proteins have been identified to lack membrane spanning regions and are not believed to be functional transporters, but appear to have a role in
protein translation [3,14]: ABCE1 (P61221, also known as OABP or 2-5 oligoadenylate-binding protein); ABCF1 (Q8NE71, also known as ABC50 or TNF--stimulated ABC protein); ABCF2 (Q9UG63, also
known as iron-inhibited ABC transporter 2) and ABCF3 (Q9NUQ8).

Further reading
Aye IL, Singh AT, Keelan JA. (2009) Transport of lipids by ABC proteins: interactions and implications for cellular toxicity, viability and function. Chem Biol Interact 180: 327339.
[PMID:19426719]
Gutmann DA, Ward A, Urbatsch IL, Chang G, van Veen HW. (2010) Understanding polyspecificity
of multidrug ABC transporters: closing in on the gaps in ABCB1. Trends Biochem Sci 35: 3642.
[PMID:19819701]
Hinz A, Tamp R. (2012) ABC transporters and immunity: mechanism of self-defense. Biochemistry
51: 49814989. [PMID:22668350]
Kemp S, Theodoulou FL, Wanders RJ. (2011) Mammalian peroxisomal ABC transporters: from
endogenous substrates to pathology and clinical significance. Br J Pharmacol 164: 17531766.
[PMID:21488864]
Kerr ID, Haider AJ, Gelissen IC. (2011) The ABCG family of membrane-associated transporters: you
dont have to be big to be mighty. Br J Pharmacol 164: 17671779. [PMID:21175590]

Miller DS. (2010) Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain
barrier. Trends Pharmacol Sci 31: 246254. [PMID:20417575]
Procko E, OMara ML, Bennett WF, Tieleman DP, Gaudet R. (2009) The mechanism of ABC
transporters: general lessons from structural and functional studies of an antigenic peptide
transporter. FASEB J 23: 12871302. [PMID:19174475]
Ravna AW, Sager G. (2009) Molecular modeling studies of ABC transporters involved in multidrug
resistance. Mini Rev Med Chem 9: 186193. [PMID:19200023]
Rees DC, Johnson E, Lewinson O. (2009) ABC transporters: the power to change. Nat Rev Mol Cell
Biol 10: 218227. [PMID:19234479]
Seeger MA, van Veen HW. (2009) Molecular basis of multidrug transport by ABC transporters.
Biochim Biophys Acta 1794: 725737. [PMID:19135557]
F-type and V-type ATPases

Overview: The F-type (ATP synthase) and the V-type (vacuolar
or vesicular proton pump) ATPases, although having distinct
subcellular locations and roles, exhibit marked similarities in
subunit structure and mechanism. They are both composed
of a soluble complex (termed F1 or V1) and a membrane

complex (Fo or Vo). Within each ATPase complex, the two
individual sectors appear to function as connected opposing
rotary motors, coupling catalysis of ATP synthesis or
hydrolysis to proton transport. Both the F-type and V-type

ATPases have been assigned enzyme commission number E.C.
3.6.3.14
protein, OSCP, (P48047)), acts as a connector between F1 and F0

motors.
subunits in the membrane, together with D, E, F2, F6, G2 and 8

subunits. Multiple pseudogenes for the F0 motor proteins have
been defined in the human genome.
F-type ATPase
Overview: The F-type ATPase, also known as ATP synthase
or ATP phosphohydrolase (H+-transporting), is a mitochondrial
membrane-associated multimeric complex consisting of two
domains, an F0 channel domain in the membrane and an F1
domain extending into the lumen. Proton transport across the
inner mitochondrial membrane is used to drive the synthesis of
ATP, although it is also possible for the enzyme to function as an
ATPase. The ATP5O subunit (oligomycin sensitivity-conferring
The F1 motor, responsible for ATP turnover, has the subunit

composition 33.
The F0 motor, responsible for ion translocation, is complex in
mammals, with probably nine subunits centring on A, B, and C
Nomenclature
subunit
subunit
subunit
subunit
subunit
HGNC, UniProt
ATP5A1, P25705
ATP5B, P06576
ATP5C1, P36542
ATP5D, P30049
ATP5E, P56381
Nomenclature
A subunit
B subunit
C subunit
D subunit
E subunit
F2 subunit
F6 subunit
G2 subunit
8 subunit
HGNC, UniProt
MT-ATP6, P00846
ATP5F1, P24539
ATP5G1, P05496; ATP5G2,

P48201; ATP5G3, Q06055
ATP5H, O75947
ATP5I, P56385
ATP5J2, P56134
ATP5J, P18859
ATP5L2, Q7Z4Y8
MT-ATP8, P03928
V-type ATPase
Overview: The V-type ATPase is most prominently associated with lysosomes in mammals, but also appears to be expressed on the plasma membrane and neuronal synaptic vesicles.
The V1 motor, responsible for ATP turnover, has eight subunits with a composition of A-H.
The Vo motor, responsible for ion translocation, has six subunits (a-e).
Nomenclature
A subunit
B1 subunit
B2 subunit
C1 subunit
C2 subunit
D subunit
E1 subunit
E2 subunit
F subunit
G1 subunit
G2 subunit
G3 subunit
H subunit
HGNC,
UniProt
ATP6V1A,
P38606
ATP6V1B1,
P15313
ATP6V1B2,
P21281
ATP6V1C1,
P21283
ATP6V1C2,
Q8NEY4
ATP6V1D,
Q9Y5K8
ATP6V1E1,
P36543
ATP6V1E2,
Q96A05
ATP6V1F,
Q16864
ATP6V1G1,
O75348
ATP6V1G2,
O95670
ATP6V1G3,
Q96LB4
ATP6V1H,
Q9UI12

F-type and V-type ATPases 1712
Nomenclature
a1 subunit
a2 subunit
a3 subunit
a4 subunit
b subunit
c subunit
d1 subunit
d2 subunit
e1 subunit
e2 subunit
HGNC,
UniProt
ATP6V0A1,
Q93050
ATP6V0A2,
Q9Y487
TCIRG1,
Q13488
ATP6V0A4,
Q9HBG4
ATP6V0B,
Q99437
ATP6V0C,
P27449
ATP6V0D1,
P61421
ATP6V0D2,
Q8N8Y2
ATP6V0E1,
O15342
ATP6V0E2,
Q8NHE4
Further reading
El Far O, Seagar M. (2011) A role for V-ATPase subunits in synaptic vesicle fusion?. J Neurochem 117:
603612. [PMID:21375531]
Junge W, Sielaff H, Engelbrecht S. (2009) Torque generation and elastic power transmission in the
rotary F(O)F(1)-ATPase. Nature 459: 364370. [PMID:19458712]
Mindell JA. (2012) Lysosomal acidification mechanisms. Annu Rev Physiol 74: 6986.
[PMID:22335796]
Nakamoto RK, Baylis Scanlon JA, Al-Shawi MK. (2008) The rotary mechanism of the ATP synthase.
Arch Biochem Biophys 476: 4350. [PMID:18515057]

Nakanishi-Matsui M, Sekiya M, Nakamoto RK, Futai M. (2010) The mechanism of rotating proton
pumping ATPases. Biochim Biophys Acta 1797: 13431352. [PMID:20170625]
Okuno D, Iino R, Noji H. (2011) Rotation and structure of FoF1-ATP synthase. J Biochem 149:
655664. [PMID:21524994]
von Ballmoos C, Cook GM, Dimroth P. (2008) Unique rotary ATP synthase and its biological
diversity. Annu Rev Biophys 37: 4364. [PMID:18573072]
von Ballmoos C, Wiedenmann A, Dimroth P. (2009) Essentials for ATP synthesis by F1F0 ATP
synthases. Annu Rev Biochem 78: 649672. [PMID:19489730]
F-type and V-type ATPases 1713
P-type ATPases
Overview: Phosphorylation-type ATPases (EC 3.6.3.-) are associated with membranes and the transport of ions or phospholipids.
Characteristics of the family are the transient phosphorylation of
the transporters at an aspartate residue and the interconversion
between E1 and E2 conformations in the activity cycle of
the transporters, taken to represent half-channels facing the
cytoplasm and extracellular/luminal side of the membrane,

respectively.
includes calcium, sodium/potassium and proton/potassium

pumps. The P4 and P5 subfamilies include putative phospholipid flippases.
Sequence analysis across multiple species allows the definition

of five subfamilies, P1-P5. The P1 subfamily includes heavy
metal pumps, such as the copper ATPases. The P2 subfamily
Na+/K+-ATPases (EC 3.6.3.9)

Overview: The cell-surface Na+/K+-ATPase is an integral membrane protein which regulates the membrane potential of the
cell by maintaining gradients of Na+ and K+ ions across the
plasma membrane, also making a small, direct contribution to
membrane potential, particularly in cardiac cells. For every mol-
ecule of ATP hydrolysed, the Na+/K+-ATPase extrudes three Na+

ions and imports two K+ ions. The active transporter is a heteromultimer with incompletely defined stoichiometry, possibly as
tetramers of heterodimers, each consisting of one of four large,
ten TM domain catalytic subunits and one of three smaller,
single TM domain glycoprotein -subunits (see table). Additional protein partners known as FXYD proteins (e.g. FXYD2,
P54710) appear to associate with and regulate the activity of the
pump.
Nomenclature
1 subunit
2 subunit
3 subunit
4 subunit
1 subunit
2 subunit
3 subunit
HGNC, UniProt
ATP1A1, P05023
ATP1A2, P50993
ATP1A3, P13637
ATP1A4, Q13733
ATP1B1, P05026
ATP1B2, P14415
ATP1B3, P54709
Comments: Na+/K+-ATPases are inhibited by ouabain and cardiac glycosides, such as digoxin, as well as potentially endogenous cardiotonic steroids [24].
Ca2+-ATPases (EC 3.6.3.8)

Overview: The sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) is an intracellular membrane-associated pump for sequestering calcium from the cytosol into intracellular
organelles, usually associated with the recovery phase following excitation of muscle and nerves.
The plasma membrane Ca2+-ATPase (PMCA) is a cell-surface pump for extruding calcium from the cytosol, usually associated with the recovery phase following excitation of cells. The active pump is a
homodimer, each subunit of which is made up of ten TM segments, with cytosolic C- and N-termini and two large intracellular loops.
Secretory pathway Ca2+-ATPases (SPCA) allow accumulation of calcium and manganese in the Golgi apparatus.
Nomenclature
SERCA1
SERCA2
SERCA3
HGNC, UniProt
ATP2A1, O14983
ATP2A2, P16615
ATP2A3, Q93084
Comments: The fungal toxin ochratoxin A has been described to activate SERCA in kidney microsomes [25]. cyclopiazonic acid [29], thapsigargin [27] and BHQ are widely employed to block SERCA.
Thapsigargin has also been described to block the TRPV1 vanilloid receptor [30].

P-type ATPases 1714
Nomenclature
PMCA1
PMCA2
PMCA3
PMCA4
HGNC, UniProt
ATP2B1, P20020
ATP2B2, Q01814
ATP2B3, Q16720
ATP2B4, P23634
Comments: The stoichiometry of flux through the PMCA differs from SERCA, with the PMCA transporting 1 Ca2+ while SERCA transports 2 Ca2+.
Nomenclature
SPCA1
SPCA2
HGNC, UniProt
ATP2C1, P98194
ATP2C2, O75185
Comments: Loss-of-function mutations in SPCA1 appear to underlie Hailey-Hailey disease [26].

H+/K+-ATPases (EC 3.6.3.10)
Overview: The H+/K+ ATPase is a heterodimeric protein, made up of and subunits. The subunit has 10 TM domains and exhibits catalytic and pore functions, while the subunit has a single TM
domain, which appears to be required for intracellular trafficking and stabilising the subunit. The ATP4A and ATP4B subunits are expressed together, while the ATP12A subunit is suggested to be expressed
with the 1 (ATP1B1) subunit of the Na+/K+-ATPase [28].
Nomenclature
ATP4A
ATP12A
ATP4B
HGNC, UniProt
ATP4A, P20648
ATP12A, P54707
ATP4B, P51164
Comments: The gastric H+/K+-ATPase is inhibited by proton pump inhibitors used for treating excessive gastric acid secretion, including (R)-lansoprazole and a metabolite of esomeprazole.
Cu+-ATPases (EC 3.6.3.4)
Overview: Copper-transporting ATPases convey copper ions across cell-surface and intracellular membranes. They consist of eight TM domains and associate with multiple copper chaperone proteins
(e.g. ATOX1, O00244).
Nomenclature
ATP7A
ATP7B
HGNC, UniProt
ATP7A, Q04656
ATP7B, P35670

P-type ATPases 1715
Phospholipid-transporting ATPases (EC 3.6.3.1)

Overview: These transporters are thought to translocate the aminophospholipids phosphatidylserine and phosphatidylethanolamine from one side of the phospholipid bilayer to the other to generate
asymmetric membranes. They are also proposed to be involved in the generation of vesicles from intracellular and cell-surface membranes.
Nomenclature
ATP8A1
ATP8A2
ATP8B1
ATP8B2
ATP8B3
ATP8B4
ATP9A
ATP9B
ATP10A
ATP10B
ATP10D
ATP11A
ATP11B
ATP11C
HGNC,
UniProt
ATP8A1,
Q9Y2Q0
ATP8A2,
Q9NTI2
ATP8B1,
O43520
ATP8B2,
P98198
ATP8B3,
O60423
ATP8B4,
Q8TF62
ATP9A,
O75110
ATP9B,
O43861
ATP10A,
O60312
ATP10B,
O94823
ATP10D,
Q9P241
ATP11A,
P98196
ATP11B,
Q9Y2G3
ATP11C,
Q8NB49
Comments: Loss-of-function mutations in ATP8B1 are associated with type I familial intrahepatic cholestasis.
A further series of structurally-related proteins have been identified in the human genome, with as yet undefined function, including ATP13A1 (Q9HD20), ATP13A2 (Q9NQ11), ATP13A3 (Q9H7F0),
ATP13A4 (Q4VNC1) and ATP13A5 (Q4VNC0).
Further reading
Argello JM, Raimunda D, Gonzlez-Guerrero M. (2012) Metal transport across biomembranes:
emerging models for a distinct chemistry. J Biol Chem 287: 1351013517. [PMID:22389499]
Benarroch EE. (2011) Na+, K+-ATPase: functions in the nervous system and involvement in neurologic disease. Neurology 76: 287293. [PMID:21242497]
Brini M, Carafoli E. (2009) Calcium pumps in health and disease. Physiol Rev 89: 13411378.
[PMID:19789383]
Bublitz M, Musgaard M, Poulsen H, Thgersen L, Olesen C, Schitt B, Morth JP, Mller JV, Nissen
P. (2013) Ion pathways in the sarcoplasmic reticulum Ca2+-ATPase. J Biol Chem 288:
1075910765. [PMID:23400778]
Cereijido M, Contreras RG, Shoshani L, Larre I. (2012) The Na+-K+-ATPase as self-adhesion molecule
and hormone receptor. Am J Physiol, Cell Physiol 302: C473C481. [PMID:22049208]
Galougahi KK, Liu CC, Bundgaard H, Rasmussen HH. (2012) -Adrenergic regulation of the
cardiac Na+-K+ ATPase mediated by oxidative signaling. Trends Cardiovasc Med 22: 8387.
[PMID:23040838]
Gupta SP. (2012) Quantitative structure-activity relationship studies on Na+,K(+)-ATPase inhibitors.
Chem Rev 112: 31713192. [PMID:22360614]
Kaler SG. (2011) ATP7A-related copper transport diseases-emerging concepts and future trends. Nat
Rev Neurol 7: 1529. [PMID:21221114]
Lpez-Marqus RL, Holthuis JC, Pomorski TG. (2011) Pumping lipids with P4-ATPases. Biol Chem
392: 6776. [PMID:21194369]

Mattle D, Sitsel O, Autzen HE, Meloni G, Gourdon P, Nissen P. (2013) On allosteric modulation of
P-type Cu(+)-ATPases. J Mol Biol 425: 22992308. [PMID:23500486]
Michelangeli F, East JM. (2011) A diversity of SERCA Ca2+ pump inhibitors. Biochem Soc Trans 39:
789797. [PMID:21599650]
Morth JP, Pedersen BP, Buch-Pedersen MJ, Andersen JP, Vilsen B, Palmgren MG, Nissen P. (2011) A
structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps. Nat Rev
Mol Cell Biol 12: 6070. [PMID:21179061]
Palmgren MG, Nissen P. (2011) P-type ATPases. Annu Rev Biophys 40: 243266. [PMID:
21351879]
Pittman JK. (2011) Vacuolar Ca(2+) uptake. Cell Calcium 50: 139146. [PMID:21310481]
Pizzo P, Lissandron V, Capitanio P, Pozzan T. (2011) Ca(2+) signalling in the Golgi apparatus. Cell
Calcium 50: 184192. [PMID:21316101]
Reinhard L, Tidow H, Clausen MJ, Nissen P. (2013) Na(+),K (+)-ATPase as a docking station:
protein-protein complexes of the Na(+),K (+)-ATPase. Cell Mol Life Sci 70: 205222.
[PMID:22695678]
Sebastian TT, Baldridge RD, Xu P, Graham TR. (2012) Phospholipid flippases: building asymmetric
membranes and transport vesicles. Biochim Biophys Acta 1821: 10681077. [PMID:22234261]
P-type ATPases 1716
SLC1 family of amino acid transporters

Overview: The SLC1 family of sodium dependent transporters includes the plasma membrane located glutamate transporters and the neutral amino acid transporters ASCT1 and ASCT2 [31,37,6465,76].
Glutamate transporter subfamily

Overview: Glutamate transporters present the unusual structural motif of 8TM segments and 2 re-entrant loops [60]. The
crystal structure of a glutamate transporter homologue (GltPh)
from Pyrococcus horikoshii supports this topology and indicates
that the transporter assembles as a trimer, where each monomer
is a functional unit capable of substrate permeation [38,78,93]
reviewed by [63]). This structural data is in agreement with the
proposed quaternary structure for EAAT2 [55] and several functional studies that propose the monomer is the functional unit
[57,67,69,83]. Recent evidence suggests that EAAT3 and EAAT4
may assemble as heterotrimers [74]. The activity of glutamate
transporters located upon both neurones (predominantly EAAT3,
4 and 5) and glia (predominantly EAAT 1 and 2) serves, dependent upon their location, to regulate excitatory neurotransmis-
sion, maintain low ambient extracellular concentrations of

glutamate (protecting against excitotoxicity) and provide glutamate for metabolism including the glutamate-glutamine cycle.
The Na+/K+-ATPase that maintains the ion gradients that drive
transport has been demonstrated to co-assemble with EAAT1 and
EAAT2 [80]. Recent evidence supports altered glutamate transport and novel roles in brain for splice variants of EAAT1 and
EAAT2 [54,70]. Three patients with dicarboxylic aminoaciduria
(DA) were recently found to have loss-of-function mutations in
EAAT3 [36]. DA is characterized by excessive excretion of the
acidic amino acids glutamate and aspartate and EAAT3 is the
predominant glutamate/aspartate transporter in the kidney.
Enhanced expression of EAAT2 resulting from administration
of -lactam antibiotics (e.g. ceftriaxone) is neuroprotective and
occurs through NF-B-mediated EAAT2 promoter activation

[53,71,81] reviewed by [66]). PPAR activation (e.g. by rosiglitazone) also leads to enhanced expression of EAAT though promoter activation [79]. In addition, several translational activators
of EAAT2 have recently been described [42] along with treatments that increase the surface expression of EAAT2 (e.g. [68];
[98]), or prevent its down-regulation (e.g. [56]). A thermodynamically uncoupled Cl- flux, activated by Na+ and glutamate
[59,64,73] (Na+ and aspartate in the case of GltPh [82]), is sufficiently large, in the instances of EAAT4 and EAAT5, to influence
neuronal excitability [88,92]. Indeed, it has recently been suggested that the primary function of EAAT5 is as a slow anion
channel gated by glutamate, rather than a glutamate transporter
[52].
Nomenclature
Excitatory amino acid

transporter 1

transporter 2

transporter 3

transporter 4

transporter 5
SLC1A3
SLC1A2
SLC1A1
SLC1A6
SLC1A7
Common abbreviation
EAAT1
EAAT2
EAAT3
EAAT4
EAAT5
HGNC, UniProt
SLC1A3, P43003
SLC1A2, P43004
SLC1A1, P43005
SLC1A6, P48664
SLC1A7, O00341
Endogenous substrates
L-glutamic acid, L-aspartic acid
L-glutamic acid, L-aspartic acid,

L-cysteine [94]
Substrates
DL-threo--hydroxyaspartate,
L-trans-2,4-pyrolidine
dicarboxylate, D-aspartic acid
Inhibitors (pIC50)
DL-TBOA (pKB 5.0) [85],

UCPH-101 (membrane
potential assay) (6.9) [62]
DL-TBOA (pKB 6.9) [85], SYM2081

(pKB 5.5) [91], dihydrokainate (pKB
5.0), threo-3-methylglutamate (pKB
4.7) [91], WAY-213613 (6.9)
NBI-59159 (7.6), L--BA

([3H]D-aspartate uptake assay)
(6.1), DL-TBOA (5.1)
DL-TBOA (pKi 5.4) [84],

threo-3-methylglutamate (pKi
4.3) [47]
DL-TBOA (pKi 5.5) [84]
Radioligands (Kd)
[3H](2S,4R)-4-methylglutamate,
[3H]D-aspartic acid,
[3H]L-aspartic acid,
[3H]ETB-TBOA (1.55x108 M)
[3H](2S,4R)-4-methylglutamate,
[3H]D-aspartic acid, [3H]L-aspartic
acid, [3H]ETB-TBOA (1.62x108 M)
Stoichiometry
Probably 3 Na+: 1 H+ : 1
glutamate (in): 1 K+ (out)
3 Na+: 1 H+ : 1 glutamate (in): 1 K+

(out) [72]
3 Na+: 1 H+ : 1 glutamate (in):

1 K+ (out) [95]
glutamate (in): 1 K+(out)
glutamate (in): 1 K+ (out)

SLC1 family of amino acid transporters 1717
Comments: The KB (or Ki) values reported, unless indicated otherwise, are derived from transporter currents mediated by EAATs
expressed in voltage-clamped Xenopus laevis oocytes [47,84
85,91]. KB (or Ki) values derived in uptake assays are generally
higher (e.g. [85]). In addition to acting as a poorly transportable
inhibitor of EAAT2, (2S,4R)-4-methylglutamate, also known as
SYM2081, is a competitive substrate for EAAT1 (KM = 54M;
[61,91]) and additionally is a potent kainate receptor agonist [97]
which renders the compound unsuitable for autoradiographic
localisation of EAATs [33]. Similarly, at concentrations that
inhibit EAAT2, dihydrokainate binds to kainate receptors [85].
WAY-855 and WAY-213613 are both non-substrate inhibitors
with a preference for EAAT2 over EAAT3 and EAAT1 [4546].

NBI-59159 is a non-substrate inhibitor with modest selectivity
for EAAT3 over EAAT1 (>10-fold) and EAAT2 (5-fold) [4344].
Analogously, L--threo-benzyl-aspartate (L--BA) is a competitive
non-substrate inhibitor that preferentially blocks EAAT3 versus
EAAT1, or EAAT2 [48]. [3H](2S,4R)-4-methylglutamate demonstrates low affinity binding (KD 6.0 M) to EAAT1 and EAAT2 in
rat brain homogenates [34] and EAAT1 in murine astrocyte membranes [32], whereas [3H]ETB-TBOA binds with high affinity to all
EAATs other than EAAT3 [86]. The novel isoxazole derivative
()-HIP-A may interact at the same site as TBOA and preferentially inhibit reverse transport of glutamate [41]. threo-3-
methylglutamate induces substrate-like currents at EAAT4, but

does not elicit heteroexchange of [3H]-aspartate in synaptosome
preparations, inconsistent with the behaviour of a substrate
inhibitor [47]. parawixin 1, a compound isolated from the
venom from the spider Parawixia bistriata is a selective enhancer
of the glutamate uptake through EAAT2 but not through EAAT1
or EAAT3 [5051]. In addition to the agents listed in the table,
DL-threo--hydroxyaspartate and L-trans-2,4-pyrolidine dicarboxylate act as non-selective competitive substrate inhibitors of all
EAATs. Zn2+ and arachidonic acid are putative endogenous modulators of EAATs with actions that differ across transporter subtypes (reviewed by [90]).
Alanine/serine/cysteine transporter subfamily

Overview: ASC transporters mediate Na+-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr and their structure is predicted to be similar to that of the glutamate transporters
[35,89]. ASCT1 and ASCT2 also exhibit thermodynamically uncoupled chloride channel activity associated with substrate transport [40,96]. Whereas EAATs counter-transport K+ (see above) ASCTs do not
and their function is independent of the intracellular concentration of K+ [96].
Nomenclature
Alanine/serine/cysteine transporter 1
Alanine/serine/cysteine transporter 2
SLC1A4
SLC1A5
Common abbreviation
ASCT1
ASCT2
HGNC, UniProt
SLC1A4, P43007
SLC1A5, Q15758
L-cysteine > L-alanine = L-serine > L-threonine
L-alanine = L-serine = L-cysteine (low Vmax) = L-threonine = L-glutamine = L-asparagine >> L-methionine
glycine L-leucine > L-valine > L-glutamic acid (enhanced at low pH)
Inhibitors (pIC50)
benzylcysteine [58], benzylserine [58], p-nitrophenyl glutamyl anilide [49]
Stoichiometry
1 Na+: 1 amino acid (in): 1 Na+: 1 amino acid (out);

(homo-, or hetero-exchange; [95])
1 Na+: 1 amino acid (in): 1 Na+: 1 amino acid (out); (homo-, or hetero-exchange; [39])
Comments: The substrate specificity of ASCT1 may extend to L-proline and L-hydroxyproline [77]. At low pH (5.5) both ASCT1 and ASCT2 are able to exchange acidic amino acids such as L-cysteate
and glutamate [87,89]. In addition to the inhibitors tabulated above, HgCl2, methylmercury, mersalyl, at low micromolar concentrations, non-competitively inhibit ASCT2 by covalent modificiation of
cysteine residues [75].
Further reading
Brer S, Palacn M. (2011) The role of amino acid transporters in inherited and acquired diseases.
Biochem J 436: 193211. [PMID:21568940]
Chao XD, Fei F, Fei Z. (2010) The role of excitatory amino acid transporters in cerebral ischemia.
Neurochem Res 35: 12241230. [PMID:20440555]
Jiang J, Amara SG. (2011) New views of glutamate transporter structure and function: advances and
challenges. Neuropharmacology 60: 172181. [PMID:20708631]

Kanai Y, Clmenon B, Simonin A, Leuenberger M, Lochner M, Weisstanner M, Hediger MA. (2013)

The SLC1 high-affinity glutamate and neutral amino acid transporter family. Mol Aspects Med 34:
108120. [PMID:23506861]
Kim K, Lee SG, Kegelman TP, Su ZZ, Das SK, Dash R, Dasgupta S, Barral PM, Hedvat M, Diaz P et al. (2011)
Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J Cell Physiol 226: 24842493. [PMID:21792905]
SLC1 family of amino acid transporters 1718
SLC2 family of hexose and sugar alcohol transporters

Overview: The SLC2 family transports D-glucose, D-fructose, inositol (e.g. myo-inositol) and related hexoses. Three classes of glucose transporter can be identified, separating GLUT1-4 and 14, GLUT6,
8, 10 and 12; and GLUT5, 7, 9 and 11. Modelling suggests a 12 TM membrane topology, with intracellular termini, with functional transporters acting as homodimers or homotetramers.
Class I transporters
Overview: Class I transporters are able to transport D-glucose, but not D-fructose, in the direction of the concentration gradient and may be inhibited non-selectively by phloretin and cytochalasin B.
GLUT1 is the major glucose transporter in brain, placenta and erythrocytes, GLUT2 is found in the pancreas, liver and kidneys, GLUT3 is neuronal and placental, while GLUT4 is the insulin-responsive
transporter found in skeletal muscle, heart and adipose tissue. GLUT14 appears to result from gene duplication of GLUT3 and is expressed in the testes [105].
Nomenclature
Glucose transporter 1
SLC2A1
SLC2A2
SLC2A3
SLC2A4
SLC2A14
Common abbreviation
GLUT1
GLUT2
GLUT3
GLUT4
GLUT14
HGNC, UniProt
SLC2A1, P11166
SLC2A2, P11168
SLC2A3, P11169
SLC2A4, P14672
SLC2A14, Q8TDB8
Substrates
D-glucose = D-glucosamine
[104], dehydroascorbic acid
[99]
D-glucosamine > D-glucose

[104]
D-glucose
D-glucosamine D-glucose
[104]
Radioligands (Kd)
[3H]2-deoxyglucose
[3H]2-deoxyglucose
[3H]2-deoxyglucose
[3H]2-deoxyglucose
Class II transporters
Overview: Class II transporters transport D-fructose and appear to be insensitive to cytochalasin B. Class II transporters appear to be predominantly intracellularly located.
Nomenclature
SLC2A6
SLC2A8
SLC2A10
SLC2A12
Common abbreviation
GLUT6
GLUT8
GLUT10
GLUT12
HGNC, UniProt
SLC2A6, Q9UGQ3
SLC2A8, Q9NY64
SLC2A10, O95528
SLC2A12, Q8TD20
Substrates
D-glucose [101]
D-glucose [102], dehydroascorbic acid [102]
D-glucose [103]

SLC2 family of hexose and sugar alcohol transporters 1719
Proton-coupled inositol transporter

Overview: Proton-coupled inositol transporters are expressed predominantly in the brain and can be inhibited by phloretin and cytochalasin B [104].
Nomenclature
Proton myo-inositol cotransporter
SLC2A13
Common abbreviation
HMIT
HGNC, UniProt
SLC2A13, Q96QE2
Substrates
myo-inositol [104], D-chiro-inositol [104], muco-inositol [104], scyllo-inositol [104]
Stoichiometry
1 H+ : 1 inositol (in) [100]
Further reading
Augustin R. (2010) The protein family of glucose transport facilitators: Its not only about glucose
after all. IUBMB Life 62: 315333. [PMID:20209635]
Leney SE, Tavar JM. (2009) The molecular basis of insulin-stimulated glucose uptake: signalling,
trafficking and potential drug targets. J Endocrinol 203: 118. [PMID:19389739]

Mueckler M, Thorens B. (2013) The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med
34: 121138. [PMID:23506862]
Uldry M, Thorens B. (2004) The SLC2 family of facilitated hexose and polyol transporters. Pflugers
Arch 447: 480489. [PMID:12750891]
SLC2 family of hexose and sugar alcohol transporters 1720
SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)

Overview: The SLC3 and SLC7 families combine to generate functional transporters, where the subunit composition is a disulphide-linked combination of a heavy chain (SLC3 family) with a light chain
(SLC7 family).
SLC3 family
Overview: SLC3 family members are single TM proteins with extensive glycosylation of the exterior C-terminus, which heterodimerize with SLC7 family members in the endoplasmic reticulum and assist
in the plasma membrane localization of the transporter.
Nomenclature
rBAT
4F2hc
SLC3A1
SLC3A2
Common abbreviation
rBAT
4F2hc
HGNC, UniProt
SLC3A1, Q07837
SLC3A2, P08195
SLC7 family
Overview: SLC7 family members may be divided into two major groups: cationic amino acid transporters (CATs) and glycoprotein-associated amino acid transporters (gpaATs).
Cationic amino acid transporters are 14 TM proteins, which mediate pH- and sodium-independent transport of cationic amino acids (system y+), apparently as an exchange mechanism. These transporters
are sensitive to inhibition by N-ethylmaleimide.
Nomenclature
High affinity cationic amino acid

transporter 1
Low affinity cationic amino acid

transporter 2
Cationic amino acid

transporter 3
Cationic amino acid

transporter 4
Probable cationic amino

acid transporter
SLC7A1
SLC7A2
SLC7A3
SLC7A4
SLC7A14
Common abbreviation
CAT1
CAT2
CAT3
CAT4
HGNC, UniProt
SLC7A1, P30825
SLC7A2, P52569
SLC7A3, Q8WY07
SLC7A4, O43246
SLC7A14, Q8TBB6
Substrates
L-arginine, L-lysine, L-ornithine, L-histidine
L-arginine, L-lysine, L-ornithine, L-histidine
L-arginine, L-lysine, L-ornithine
Glycoprotein-associated amino acid transporters are 12 TM proteins, which heterodimerize with members of the SLC3 family to act as cell-surface amino acid exchangers.
L-type amino acid

transporter 1
L-type amino acid

transporter 2
y+L amino acid

transporter 1
y+L amino acid

transporter 2
b0,+-type amino acid

transporter 1
Asc-type amino acid

transporter 1
Cystine/glutamate
transporter
SLC7A5
SLC7A8
SLC7A7
SLC7A6
SLC7A9
SLC7A10
SLC7A11
Common abbreviation
LAT1
LAT2
y+LAT1
y+LAT2
b0,+AT
Asc-1
xCT
HGNC, UniProt
SLC7A5, Q01650
SLC7A8, Q9UHI5
SLC7A7, Q9UM01
SLC7A6, Q92536
SLC7A9, P82251
SLC7A10, Q9NS82
SLC7A11, Q9UPY5
Nomenclature

SLC3 and SLC7 families of heteromeric amino acid transporters (HATs) 1721
Heterodimers between 4F2hc and LAT1 or LAT2 generate

sodium-independent system L transporters. LAT1 transports
large neutral amino acids including branched-chain and aromatic amino acids as well as miglustat, whereas LAT2 transports
most of the neutral amino acids.
(L-arginine, L-lysine, L-ornithine) amino acids independent of

sodium and neutral (L-leucine, L-isoleucine, L-methionine,
L-glutamine) amino acids in a partially sodium-dependent
manner. These transporters are N-ethylmaleimide-insensitive.
Heterodimers between rBAT and b0,+AT appear to mediate sodiumindependent system b0,+ transport of most of the neutral amino
acids and cationic amino acids (L-arginine, L-lysine and
L-ornithine).
Heterodimers between 4F2hc and y+LAT1 or y+LAT2 generate

transporters similar to the system y+L , which transport cationic
Asc-1 appears to heterodimerize with 4F2hc to allow the transport of small neutral amino acids (such as L-alanine, L-serine,
Comments: CAT4 appears to be non-functional in heterologous

expression [106], while SLC7A14 has yet to be characterized.
L-threonine, L-glutamine and glycine), as well as D-serine, in a

sodium-independent manner.
xCT generates a heterodimer with 4F2hc for a system x-e-c transporter that mediates the sodium-independent exchange of
L-cystine and L-glutamic acid.
AGT has been conjugated with SLC3 members as fusion proteins
to generate functional transporters, but the identity of a native
heterodimer has yet to be ascertained.
Further reading
Closs EI, Boissel JP, Habermeier A, Rotmann A. (2006) Structure and function of cationic amino acid
transporters (CATs). J Membr Biol 213: 6777. [PMID:17417706]
Fotiadis D, Kanai Y, Palacn M. (2013) The SLC3 and SLC7 families of amino acid transporters. Mol
Aspects Med 34: 139158. [PMID:23506863]
Palacn M, Kanai Y. (2004) The ancillary proteins of HATs: SLC3 family of amino acid transporters.
Pflugers Arch 447: 490494. [PMID:14770309]

Palacn M, Nunes V, Font-Llitjs M, Jimnez-Vidal M, Fort J, Gasol E, Pineda M, Feliubadal L,

Chillarn J, Zorzano A. (2005) The genetics of heteromeric amino acid transporters. Physiology
(Bethesda) 20: 112124. [PMID:15772300]
Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y. (2004) CATs and HATs: the SLC7 family
of amino acid transporters. Pflugers Arch 447: 532542. [PMID:14770310]
SLC3 and SLC7 families of heteromeric amino acid transporters (HATs) 1722
SLC4 family of bicarbonate transporters

Overview: Together with the SLC26 family, the SLC4 family of
transporters subserve anion exchange, principally of chloride
and bicarbonate (HCO3-), but also carbonate and hydrogen sulphate (HSO4-). SLC4 family members regulate bicarbonate fluxes
as part of carbon dioxide movement, chyme neutralization and
reabsorption in the kidney.
Within the family, subgroups of transporters are identifiable: the

electroneutral sodium-independent Cl-/HCO3- transporters (AE1,
AE2 and AE3), the electrogenic sodium-dependent HCO3- transporters (NBCe1 and NBCe2) and the electroneutral HCO3- transporters (NBCn1 and NBCn2). Topographical information derives
mainly from study of AE1, abundant in erythrocytes, which
suggests a dimeric or tetrameric arrangement, with subunits

made up of 13 TM domains and re-entrant loops at TM9/10 and
TM11/12. The N terminus exhibits sites for interaction with
multiple proteins, including glycolytic enzymes, haemoglobin
and cytoskeletal elements.
Anion exchangers
Nomenclature
Anion exchange protein 1
SLC4A1
SLC4A2
SLC4A3
SLC4A9
Common abbreviation
AE1
AE2
AE3
AE4
HGNC, UniProt
SLC4A1, P02730
SLC4A2, P04920
SLC4A3, P48751
SLC4A9, Q96Q91
Cl-, HCO3-
Cl-, HCO3-
Cl-, HCO3-
Stoichiometry
1 Cl- (in) : 1 HCO3- (out)
1 Cl- (in) : 1 HCO3- (out)
1 Cl- (in) : 1 HCO3- (out)
Sodium-dependent HCO3- transporters
Nomenclature
Electrogenic sodium
bicarbonate cotransporter 1
Electrogenic sodium
Electroneutral sodium
Electroneutral sodium
NBCBE
NaBC1
SLC4A4
SLC4A5
SLC4A7
SLC4A10
SLC4A8
SLC4A11
Common abbreviation
NBCe1
NBCe2
NBCn1
NBCn2
NDCBE
BTR1
HGNC, UniProt
SLC4A4, Q9Y6R1
SLC4A5, Q9BY07
SLC4A7, Q9Y6M7
SLC4A10, Q6U841
SLC4A8, Q2Y0W8
SLC4A11, Q8NBS3
NaHCO3-
NaHCO3-
NaHCO3-
NaHCO3-
Cl-, NaHCO3-
Cl-, NaHCO3-
Stoichiometry
1 Na+ : 2/3 HCO3- (out) or

1 Na+ : CO32*
1 Na+ : 2/3 HCO3- (out) or

1 Na+ : CO32*
1 Na+ : 1 HCO3- (out) or 1

Na+ : CO32*
1 Na+ : 1 HCO3- (out) or 1

Na : CO32*
1 Na+ : 2HCO3- (in) : 1 Cl(out)
Further reading
Alper SL. (2009) Molecular physiology and genetics of Na+-independent SLC4 anion exchangers. J
Exp Biol 212 (Pt 11): 16721683. [PMID:19448077]
Boron WF, Chen L, Parker MD. (2009) Modular structure of sodium-coupled bicarbonate transporters. J Exp Biol 212 (Pt 11): 16971706. [PMID:19448079]
Liu Y, Wang DK, Chen LM. (2012) The physiology of bicarbonate transporters in mammalian
reproduction. Biol Reprod 86: 99. [PMID:22262691]
Majumdar D, Bevensee MO. (2010) Na-coupled bicarbonate transporters of the solute carrier 4
family in the nervous system: function, localization, and relevance to neurologic function.
Neuroscience 171: 951972. [PMID:20884330]

Parker MD, Boron WF. (2013) The divergence, actions, roles, and relatives of sodium-coupled
bicarbonate transporters. Physiol Rev 93: 803959. [PMID:23589833]
Romero MF, Chen AP, Parker MD, Boron WF. (2013) The SLC4 family of bicarbonate (HCO3)
transporters. Mol Aspects Med 34: 159182. [PMID:23506864]
SLC4 family of bicarbonate transporters 1723
SLC5 family of sodium-dependent glucose transporters

Overview: The SLC5 family of sodium-dependent glucose transporters includes, in mammals, the Na+/substrate co-transporters for glucose (e.g. choline), D-glucose, monocarboxylates, myo-inositol and
I- [121-122,142-143]. Members of the SLC5 and SLC6 families, along with other unrelated Na+ cotransporters (i.e. Mhp1 and BetP), share a common structural core that contains an inverted repeat of 5TM
-helical domains [107].
Hexose transporter family

Overview: Detailed characterisation of members of the hexose transporter family is limited to SGLT1, 2 and 3, which are all inhibited in a competitive manner by phlorizin, a natural dihydrocholine
glucoside, that exhibits modest selectivity towards SGLT2 (see [142] for an extensive review). SGLT1 is predominantly expressed in the small intestine, mediating the absorption of glucose (e.g. D-glucose),
but also occurs in the brain, heart and in the late proximal straight tubule of the kidney. The expression of SGLT2 is almost exclusively restricted to the early proximal convoluted tubule of the kidney,
where it is largely responsible for the renal reabsorption of glucose. SGLT3 is not a transporter but instead acts as a glucosensor generating an inwardly directed flux of Na+ that causes membrane
depolarization [117].
Nomenclature
SGLT1
SGLT2
SGLT3
SGLT4
SGLT5
SLC5A1
SLC5A2
SLC5A4
SLC5A9
SLC5A10
Common abbreviation
SGLT1
SGLT2
SGLT3
SGLT4
SGLT5
HGNC, UniProt
SLC5A1, P13866
SLC5A2, P31639
SLC5A4, Q9NY91
SLC5A9, Q2M3M2
SLC5A10, A0PJK1
Substrates
D-glucose, -MDG, D-galactose
D-glucose, -MDG
D-glucose, N-ethyl-1-deoxynojirimycin,
1-deoxynojirimycin, 1-deoxynojirimycin-1sulfonic acid, miglustat, miglitol
D-glucose, -MDG,
D-mannose
D-glucose,
D-galactose
Inhibitors (pIC50)
remogliflozin (pKi 5.4), sergliflozin (pKi 5.1),

canagliflozin (6.4), dapagliflozin (5.9),
empagliflozin (5.1)
remogliflozin (pKi 7.9), sergliflozin (pKi 6.8),

dapagliflozin (9.0), canagliflozin (8.7),
empagliflozin (8.5)
Stoichiometry
2 Na+ : 1 glucose [129]
1 Na+ : 1 glucose [127]
Comments: Recognition and transport of substrate by SGLTs requires that the sugar is a pyranose. De-oxyglucose derivatives have reduced affinity for SGLT1, but the replacement of the
sugar equatorial hydroxyl group by fluorine at some positions, excepting C2 and C3, is tolerated (see [142] for a detailed quantification). Although SGLT1 and SGLT2 have been described as high- and
low-affinity sodium glucose co-transporters, respectively, recent work suggests that they have a similar affinity for glucose under physiological conditions [127]. Selective blockers of SGLT2, and thus
blocking 50% of renal glucose reabsorption, are in use and in further development for the treatment of diabetes (e.g. [113]).
Choline transporter
Overview: The high affinity, hemicholinium-3-sensitive, choline transporter (CHT) is expressed mainly in cholinergic neurones on nerve cell terminals and synaptic vesicles (keratinocytes being an
additional location). In autonomic neurones, expression of CHT requires an activity-dependent retrograde signal from postsynaptic neurones [130]. Through recapture of choline generated by the
hydrolysis of ACh by acetylcholinesterase, CHT serves to maintain acetylcholine synthesis within the presynaptic terminal [121]. Homozygous mice engineered to lack CHT die within one hour of birth
as a result of hypoxia arising from failure of transmission at the neuromuscular junction of the skeletal muscles that support respiration [120]. A low affinity choline uptake mechanism that remains to
be identified at the molecular level may involve multiple transporters. In addition, a family of choline transporter-like (CTL) proteins, (which are members of the SLC44 family) with weak Na+ dependence
have been described [140].

SLC5 family of sodium-dependent glucose transporters 1724
Nomenclature
CHT
SLC5A7
Common abbreviation
CHT
HGNC, UniProt
SLC5A7, Q9GZV3
choline
Substrates
triethylcholine
Selective inhibitors (pIC50)
hemicholinium-3 (pKi 8.3 9.0)
Radioligands (Kd)
[3H]hemicholinium-3 (4x10-9 6x10-9 M)
Stoichiometry
Na+ : choline (variable stoichimetry); modulated by extracellular Cl- [128]
Comments: Ki and KD values for hemicholinium-3 listed in the table are for human CHT expressed in Xenopus laevis oocytes [133], or COS-7 cells [109]. hemicholinium mustard is a substrate for CHT
that causes covalent modification and irreversible inactivation of the transporter. Several exogenous substances (e.g. triethylcholine) that are substrates for CHT act as precursors to cholinergic false
transmitters.
Sodium iodide symporter, sodium-dependent multivitamin transporter and sodium-coupled monocarboxylate transporters
Overview: The sodium-iodide symporter (NIS) is an iodide
transporter found principally in the thyroid gland where it mediates the accumulation of I- within thyrocytes. Transport of I- by
NIS from the blood across the basolateral membrane followed by
apical efflux into the colloidal lumen, mediated at least in part
by pendrin (SLC22A4), and most likely not SMCT1 (SLC5A8) as
once thought, provides the I- required for the synthesis of the
thyroid hormones triiodothyronine (T3) and thyroxine (T4) [111].
NIS is also expressed in the salivary glands, gastric mucosa, intestinal enterocytes and lactating breast. NIS mediates I- absorption
in the intestine and I- secretion into the milk. SMVT is expressed
on the apical membrane of intestinal enterocytes and colonocytes and is the main system responsible for biotin (vitamin H)
and pantothenic acid (vitamin B5) uptake in humans [135].
SMVT located in kidney proximal tubule epithelial cells mediates
the reabsorption of biotin and pantothenic acid. SMCT1
(SLC5A8), which transports a wide range of monocarboxylates, is

expressed in the apical membrane of epithelia of the small intestine, colon, kidney, brain neurones and the retinal pigment epithelium [122]. SMCT2 (SLC5A12) also localises to the apical
membrane of kidney, intestine, and colon, but in the brain and
retina is restricted to astrocytes and Mller cells, respectively
[122]. SMCT1 is a high-affinity transporter whereas SMCT2 is a
low-affinity transporter. The physiological substrates for SMCT1
and SMCT2 are lactate (L-lactic acid and D-lactic acid), pyruvic
acid, propanoic acid, and nicotinic acid in non-colonic tissues
such as the kidney. SMCT1 is also likely to be the principal
transporter for the absorption of nicotinic acid (vitamin B3) in
the intestine and kidney [124]. In the small intestine and colon,
the physiological substrates for these transporters are nicotinic
acid and the short-chain fatty acids acetic acid, propanoic acid,
and butyric acid that are produced by bacterial fermentation of

dietary fiber [132]. In the kidney, SMCT2 is responsible for the

bulk absorption of lactate because of its low-affinity/highcapacity nature. Absence of both transporters in the kidney leads
to massive excretion of lactate in urine and consequently drastic
decrease in the circulating levels of lactate in blood [138]. SMCT1
also functions as a tumour suppressor in the colon as well as in
various other non-colonic tissues [123]. The tumour-suppressive
function of SMCT1 is based on its ability to transport pyruvic
acid, an inhibitor of histone deacetylases, into cells in noncolonic tissues [139]; in the colon, the ability of SMCT1 to transport butyric acid and propanoic acid, also inhibitors of histone
deacetylases, underlies the tumour-suppressive function of this
transporter [122-123,125]. The ability of SMCT1 to promote
histone acetylase inhibition through accumulation of butyric
acid and propanoic acid in immune cells is also responsible for
suppression of dendritic cell development in the colon [137].
Nomenclature
NIS
SMVT
SMCT1
SMCT2
SLC5A5
SLC5A6
SLC5A8
SLC5A12
Common abbreviation
NIS
SMVT
SMCT1
SMCT2
HGNC, UniProt
SLC5A5, Q92911
SLC5A6, Q9Y289
SLC5A8, Q8N695
SLC5A12, Q1EHB4
Substrates
NO3-, pertechnetate,
perchlorate, thiocyanate, I-
pantothenic acid [116], I[116], biotin [116], lipoic

acid [116]
acetic acid, butyric acid, propanoic acid, nicotinic acid, -D-hydroxybutyric acid,
L-lactic acid, D-lactic acid, salicylic acid, 3-bromopyruvate, dichloroacetate,
2-oxothiazolidine-4-carboxylate, acetoacetic acid, benzoate, 5-aminosalicylate,
-ketoisocaproate, -L-hydroxybutyric acid, pyroglutamic acid, -hydroxybutyric
acid, pyruvic acid
nicotinic acid, L-lactic acid,

pyruvic acid
Inhibitors (pIC50)
fenoprofen, ketoprofen, ibuprofen (4.2)
Stoichiometry
2Na+ : 1 I- [119]; 1Na+ : 1

ClO4- [118]
2Na+ : 1 biotin (or

pantothenic acid) [134]
2Na+ : 1 monocarboxylate [114]
Comments: I-, perchlorate, thiocyanate and NO3- are competitive substrate inhibitors of NIS [118]. lipoic acid appears to act as a competitive substrate inhibitor of SMVT [141] and the anticonvulsant
drugs primidone and carbamazepine competitively block the transport of biotin by brush border vesicles prepared from human intestine [136].
Sodium myo-inositol cotransporter transporters

Overview: Three different mammalian myo-inositol cotransporters are currently known; two are the Na+-coupled SMIT1 and SMIT2 tabulated below and the third is proton-coupled HMIT (SLC2A13).
SMIT1 and SMIT2 have a widespread and overlapping tissue location but in polarized cells, such as the Madin-Darby canine kidney cell line, they segregate to the basolateral and apical membranes,
respectively [110]. In the nephron, SMIT1 mediates myo-inositol uptake as a compatible osmolyte when inner medullary tubules are exposed to increases in extracellular osmolality, whilst SMIT2 mediates
the reabsorption of myo-inositol from the filtrate. In some species (e.g. rat, but not rabbit) apically located SMIT2 is responsible for the uptake of myo-inositol from the intestinal lumen [108].
Nomenclature
SMIT
SGLT6
SLC5A3
SLC5A11
Common abbreviation
SMIT1
SMIT2
HGNC, UniProt
SLC5A3, P53794
SLC5A11, Q8WWX8
Substrates
myo-inositol, scyllo-inositol > L-fucose > L-xylose > L-glucose, D-glucose, -methyl-D-glucopyranoside >
D-galactose, D-fucose > D-xylose [126]
myo-inositol = D-chiro-inositol> D-glucose > D-xylose > L-xylose [115]
Inhibitors (pIC50)
phlorizin
phlorizin
Stoichiometry
2 Na+ :1 myo-inositol [126]
2 Na+ :1 myo-inositol [112]
Comments: The data tabulated are those for dog SMIT1 and rabbit SMIT2. SMIT2 transports D-chiro-inositol, but SMIT1 does not. In addition, whereas SMIT1 transports both D-xylose and L-xylose and
D-fucose and L-fucose , SMIT2 transports only the D-isomers of these sugars [115,126]. Thus the substrate specificities of SMIT1 (for L-fucose ) and SMIT2 (for D-chiro-inositol) allow discrimination between
the two SMITs. Human SMIT2 appears not to transport glucose [131].

Further reading
Bailey CJ. (2011) Renal glucose reabsorption inhibitors to treat diabetes. Trends Pharmacol Sci 32:
6371. [PMID:21211857]
Chao EC, Henry RR. (2010) SGLT2 inhibitiona novel strategy for diabetes treatment. Nat Rev Drug
Discov 9: 551559. [PMID:20508640]
Kinne RK, Castaneda F. (2011) SGLT inhibitors as new therapeutic tools in the treatment of diabetes.
Handb Exp Pharmacol (203): 105126. [PMID:21484569]

Wright EM. (2013) Glucose transport families SLC5 and SLC50. Mol Aspects Med 34: 183196.
[PMID:23506865]
Wright EM, Loo DD, Hirayama BA. (2011) Biology of human sodium glucose transporters. Physiol
Rev 91: 733794. [PMID:21527736]
SLC6 neurotransmitter transporter family

Overview: Members of the solute carrier family 6 (SLC6) of sodium- and (sometimes chloride-) dependent neurotransmitter transporters [152,156,179] are primarily plasma membrane located and may
be divided into four subfamilies that transport monoamines, GABA, glycine and neutral amino acids, plus the related bacterial NSS transporters [189]. The members of this superfamily share a structural
motif of 10 TM segments that has been observed in crystal structures of the NSS bacterial homolog LeuTAa, a Na+-dependent amino acid transporter from Aquiflex aeolicus [206] and in several other
transporter families structurally related to LeuT [164].
Monoamine transporter subfamily

Overview: Monoamine neurotransmission is limited by perisynaptic transporters. Presynaptic monoamine transporters allow recycling of synaptically released noradrenaline, dopamine and
5-hydroxytryptamine (5-HT).
Nomenclature
Noradrenaline transporter
Dopamine transporter
5HT transporter
SLC6A2
SLC6A3
SLC6A4
Common abbreviation
NET
DAT
SERT
HGNC, UniProt
SLC6A2, P23975
SLC6A3, Q01959
SLC6A4, P31645
(-)-adrenaline, (-)-noradrenaline, dopamine
(-)-adrenaline, (-)-noradrenaline, dopamine
5-HT
Substrates
MPP+, methamphetamine, amphetamine
MPP+, methamphetamine, amphetamine
MDMA, p-chloroamphetamine
mazindol (pKi 8.9), nisoxetine (pKi 8.4), nomifensine

(pKi 8.1), reboxetine (pKi 8.0) [205]
mazindol (pKi 8.0), WIN35428 (pKi 7.9), GBR12935

(pKi 7.6)
paroxetine (pKi 9.6) [198], sertraline (pKi 9.1),

fluoxetine (pKi 8.5) [198]
Radioligands (Kd)
[3H]mazindol (5x10-10 M), [3H]nisoxetine (4x10-9 M)
[3H]GBR12935 (3x10-9 M) [186], [3H]WIN35428

(1x10-8 M) [186]
[3H]paroxetine (2x10-10 M), [3H]citalopram

(5x10-9 M)
Stoichiometry
1 noradrenaline: 1 Na+:1 Cl- [171]
1 dopamine: 12 Na+: 1 Cl- [170]
1 5-HT:1 Na+:1 Cl- (in), + 1 K+ (out) [197]
Comments: [125I]RTI55 labels all three monoamine transporters (NET, DAT and SERT) with affinities between 0.5 and 5 nM. cocaine is an inhibitor of all three transporters with pKi values between 6.5
and 7.2. Potential alternative splicing sites in non-coding regions of SERT and NET have been identified. A bacterial homologue of SERT shows allosteric modulation by selected anti-depressants [194].

SLC6 neurotransmitter transporter family 1728
GABA transporter subfamily

Overview: The activity of GABA-transporters located predominantly upon neurones (GAT-1), glia (GAT-3) or both (GAT-2,
BGT-1) serves to terminate phasic GABA-ergic transmission,
maintain low ambient extracellular concentrations of GABA, and
recycle GABA for reuse by neurones. Nonetheless, ambient concentrations of GABA are sufficient to sustain tonic inhibition
mediated by high affinity GABAA receptors in certain neuronal
populations [192]. GAT1 is the predominant GABA transporter in

the brain and occurs primarily upon the terminals of presynaptic
neurones and to a much lesser extent upon distal astocytic processes that are in proximity to axons terminals. GAT3 resides
predominantly on distal astrocytic terminals that are close to the
GABAergic synapse. By contrast, BGT1 occupies an extrasynaptic
location possibly along with GAT2 which has limited expression
in the brain [181]. TauT is a high affinity taurine transporter

involved in osmotic balance that occurs in the brain and nonneuronal tissues, such as the kidney, brush border membrane
of the intestine and blood brain barrier [156,172]. CT1, which
transports creatine, has a ubiquitous expression pattern, often
co-localizing with creatine kinase [156].
Nomenclature
GAT1
GAT2
GAT3
BGT1
TauT
CT1
SLC6A1
SLC6A13
SLC6A11
SLC6A12
SLC6A6
SLC6A8
HGNC, UniProt
SLC6A1, P30531
SLC6A13, Q9NSD5
SLC6A11, P48066
SLC6A12, P48065
SLC6A6, P31641
SLC6A8, P48029
GABA
GABA, -alanine
GABA, -alanine
GABA, betaine
GABA [145], -alanine,

taurine
creatine
Substrates
nipecotic acid, guvacine
nipecotic acid, guvacine
nipecotic acid,
guvacine
Selective inhibitors
(pIC50)
SKF89976A (6.9), CI-966 (6.6), NNC-711

(5.9 6.9), tiagabine (5.6 7.0),
LU32-176B (5.4), (R/S) EF-1500 (4.9
5.7), (R)-EF-1520 (5.05 5.4), (S)-EF-1520
(3.6 3.92)
SNAP-5114 (5.2),
SNAP-5114 (4.7)
NNC052090 (5.6), (R/S)

EF-1500 (4.9), (R)-EF-1520
(3.74 4.66), (S)-EF-1520
(3.6 4.47), LU32-176B
(4.0)
Radioligands (Kd)
[3H]tiagabine
Stoichiometry
2Na+: 1Cl-: 1GABA
2Na+: 1Cl-:1GABA
2Na+: 2 Cl-: 1GABA
3Na+: 1 (or 2) Cl-: 1GABA
2Na+: 1Cl-: 1 taurine
Probably 2Na+: 1Cl-: 1

creatine
Comments: The IC50 values for GAT1-4 reported in the table

reflect the range reported in the literature from studies of both
human and mouse transporters. There is a tendency towards
lower IC50 values for the human orthologue [180]. SNAP-5114 is
only weakly selective for GAT 2 and GAT3, with IC50 values in the
range 22 to >30 M at GAT1 and BGT1, whereas NNC052090 has
at least an order of magnitude selectivity for BGT1 [see [157,191]
for reviews]. (R)-(1-{2-[tris(4-methoxyphenyl)methoxy]ethyl}
pyrrolidin-2-yl)acetic acid is a recently described compound that
displays 20-fold selectivity for GAT3 over GAT1 [165]. In addition

to the inhibitors listed, EGYT3886 is a moderately potent,
though non-selective, inhibitor of all cloned GABA transporters
(IC50 = 26-46 M; [160]). Diaryloxime and diarylvinyl ether
derivatives of nipecotic acid and guvacine that potently inhibit
the uptake of [3H]GABA into rat synaptosomes have been
described [178]. Several derivatives of exo-THPO (e.g. N-methylexo-THPO and N-acetyloxyethyl-exo-THPO) demonstrate selectivity as blockers of astroglial, versus neuronal, uptake of GABA
[see [157,190] for reviews]. GAT3 is inhibited by physiologically

relevant concentrations of Zn2+ [158]. TauT transports GABA, but
with low affinity, but CT1 does not, although it can be engineered to do so by mutagenesis guided by LeuT as a structural
template [161]. Although inhibitors of creatine transport by CT1
(e.g. -guanidinopropionic acid, cyclocreatine, guanidinoethane
sulfonic acid) are known (e.g. [159]) they insufficiently characterized to be included in the table.
promoter usage and splicing, and three splice variants of GlyT2

(a,b & c) have also been identified (see [148,163,167,196] for
reviews). GlyT1 transporter isoforms expressed in glia surrounding glutamatergic synapses regulate synaptic glycine concentra-
tions influencing NMDA receptor-mediated neurotransmission

[147,166], but also are important, in early neonatal life, for regulating glycine concentrations at inhibitory glycinergic synapses
[168]. Homozygous mice engineered to totally lack GlyT1 exhibit
Glycine transporter subfamily

Overview: Two gene products, GlyT1 and GlyT2, are known
that give rise to transporters that are predominantly located on
glia and neurones, respectively. Five variants of GlyT1 (a,b,c,d &
e) differing in their N- and C-termini are generated by alternative

severe respiratory and motor deficiencies due to hyperactive

glycinergic signalling and die within the first postnatal day
[168,199]. Disruption of GlyT1 restricted to forebrain neurones is
associated with enhancement of EPSCs mediated by NMDA
receptors and behaviours that are suggestive of a promnesic
action [207]. GlyT2 transporters localised on the axons and
boutons of glycinergic neurones appear crucial for efficient trans-
mitter loading of synaptic vesicles but may not be essential for

the termination of inhibitory neurotransmission [169,188]. Mice
in which GlyT2 has been deleted develop a fatal hyperekplexia
phenotype during the second postnatal week [169] and mutations in the human gene encoding GlyT2 (SLC6A5) have been
identified in patients with hyperekplexia (reviewed by [173]).
ATB0+ (SLCA14) is a transporter for numerous dipolar and cati-
onic amino acids and thus has a much broader substrate specificity than the glycine transporters alongside which it is grouped
on the basis of structural similarity [156]. ATB0+ is expressed in
various peripheral tissues [156]. By contrast PROT (SLC6A7),
which is expressed only in brain in association with a subset of
excitatory nerve terminals, shows specificity for the transport of
L-proline.
Nomenclature
Glycine transporter 1
Glycine transporter 2
ATB0,+
Proline transporter
SLC6A9
SLC6A5
SLC6A14
SLC6A7
Common abbreviation
GlyT1
GlyT2
ATB0,+
PROT
HGNC, UniProt
SLC6A9, P48067
SLC6A5, Q9Y345
SLC6A14, Q9UN76
SLC6A7, Q99884
glycine, sarcosine
glycine
L-isoleucine > L-leucine, L-methionine >

L-phenylalanine > L-tryptophan > L-valine >
L-serine [195], -alanine [144-145]
L-proline
Substrates
1-methyltryptophan [177], BCH , valganciclovir

[200], zwitterionic or cationic NOS inhibitors [174]
(R)-NFPS (8.5 9.1), SSR-103800 (8.7),

N-methyl-SSR504734 (8.6), LY2365109 (7.8),
GSK931145 (7.6)
ALX 1393, ALX 1405, Org 25543 (7.7)
-methyl-D,L-tryptophan (3.6) [177]
LP-403812 (7.0)
[208]
Radioligands (Kd)
[3H](R)-NPTS (1x10-9 M), [3H]GSK931145

(1.7x10-9 M), [35S]ACPPB (2x10-9 M),
[3H]SB-733993 (2.2x10-9 M),
[3H]N-methyl-SSR504734 (3.3x10-9 8.1x10-9 M),
[3H]NFPS (7x10-9 2.1x10-8 M)
Stoichiometry
2 Na+: 1 Cl-: 1 glycine
3 Na+: 1 Cl-: 1 glycine
2-3 Na+: 1 Cl-: 1 amino acid [195]
Probably 2 Na+: 1
Cl-: 1 L-proline
Comment
N-Oleoyl-L-carnitine (0.3M, [155]) and and

N-arachidonoylglycine (IC50 5-8 M, [204])
have been described as potential endogenous
selective GlyT2 inhibitors
Comments: sarcosine is a selective transportable inhibitor of

GlyT1 and also a weak agonist at the glycine binding site of the
NMDA receptor [210], but has no effect on GlyT2. This difference
has been attributed to a single glycine residue in TM6 (serine
residue in GlyT2) [202]. Inhibition of GLYT1 by the sarcosine
derivatives NFPS, NPTS and Org 24598 is non-competitive [182183]. IC50 values for Org 24598 reported in the literature vary,
most likely due to differences in assay conditions [149,182]. The
tricyclic antidepressant amoxapine weakly inhibits GlyT2 (IC50

92 M) with approximately 10-fold selectivity over GlyT1 [184].
The endogenous lipids arachidonic acid and anandamide exert
opposing effects upon GlyT1a, inhibiting (IC50 2 M) and
potentiating (EC50 13 M) transport currents, respectively
[185]. N-arachidonyl-glycine, N-arachidonyl--aminobutyric acid
and N-arachidonyl-D-alanine have been described as endogenous non-competitive inhibitors of GlyT2a, but not GlyT1b

[162,175,204]. Protons [146] and Zn2+ [176] act as noncompetitive inhibitors of GlyT1b, with IC50 values of 100 nM
and 10 M respectively, but neither ion affects GlyT2 (reviewed
by [201]). Glycine transport by GLYT1 is inhibited by lithium,
whereas GLYT2 transport is stimulated (both in the presence of
Na+) [187].
Neutral amino acid transporter subfamily

Overview: Certain members of neutral amino acid transport family are expressed upon the apical surface of epithelial cells and are important for the absorption of amino acids from the duodenum,
jejunum and ileum and their reabsorption within the proximal tubule of the nephron (i.e. B0AT1 (SLC6A19), SLC6A17, SLC6A18, SLC6A20). Others may function as transporters for neurotransmitters
or their precursors (i.e. B0AT2, SLC6A17) [153].
Nomenclature
B0AT1
B0AT2
B0AT3
NTT5
NTT4
SIT1
SLC6A19
SLC6A15
SLC6A18
SLC6A16
SLC6A17
SLC6A20
HGNC, UniProt
SLC6A19, Q695T7
SLC6A15, Q9H2J7
SLC6A18, Q96N87
SLC6A16, Q9GZN6
SLC6A17, Q9H1V8
SLC6A20, Q9NP91
L-leucine, L-methionine,
L-isoleucine, L-valine >
L-asparagine,
L-phenylalanine, L-alanine,
L-serine > L-threonine,
glycine, L-proline [152]
L-proline > L-alanine,

L-valine, L-methionine,
L-leucine > L-isoleucine,
L-threonine, L-asparagine,
L-serine, L-phenylalanine >
glycine [152]
L-alanine, glycine >

L-methionine,
L-phenylalanine, L-leucine,
L-histidine, L-glutamine
[203]
L-leucine, L-methionine,
L-proline > L-cysteine,
L-alanine, L-glutamine,
L-serine > L-histidine,
glycine [209]
L-proline
Stoichiometry
1 Na+: 1 amino acid [154]
1 Na+: 1 amino acid [151]
Na+- and Cl- -dependent

transport [193]
Na+-dependent,
Cl--independent transport
[209]
2 Na+: 1 Cl-: 1 imino acid

[150]
Comment
Mutations in B0AT1 are

associated with Hartnup
disorder
Further reading
Brer S, Gether U. (2012) The solute carrier 6 family of transporters. Br J Pharmacol 167: 256278.
[PMID:22519513]
Pramod AB, Foster J, Carvelli L, Henry LK. (2013) SLC6 transporters: structure, function, regulation,
disease association and therapeutics. Mol Aspects Med 34: 197219. [PMID:23506866]
Ramamoorthy S, Shippenberg TS, Jayanthi LD. (2011) Regulation of monoamine transporters: Role
of transporter phosphorylation. Pharmacol Ther 129: 220238. [PMID:20951731]

Rudnick G. (2011) Cytoplasmic permeation pathway of neurotransmitter transporters. Biochemistry

50: 74627475. [PMID:21774491]
Zhong H, Snchez C, Caron MG. (2012) Consideration of allosterism and interacting proteins in
the physiological functions of the serotonin transporter. Biochem Pharmacol 83: 435442.
[PMID:21983034]
SLC8 family of sodium/calcium exchangers

Overview: The sodium/calcium exchangers (NCX) use the
extracellular sodium concentration to facilitate the extrusion
of calcium out of the cell. Alongside the plasma membrane
Ca2+-ATPase (PMCA) and sarcoplasmic/endoplasmic reticulum
Ca2+-ATPase (SERCA), as well as the sodium/potassium/calcium
exchangers (NKCX, SLC24 family), NCX allow recovery of intracellular calcium back to basal levels after cellular stimulation.
When intracellular sodium ion levels rise, for example, following
depolarisation, these transporters can operate in the reverse
direction to allow calcium influx and sodium efflux, as an
electrogenic mechanism. Structural modelling suggests the presence of 9 TM segments, with a large intracellular loop between
the fifth and sixth TM segments.
Nomenclature
Sodium/calcium exchanger 1
SLC8A1
SLC8A2
SLC8A3
Common abbreviation
NCX1
NCX2
NCX3
HGNC, UniProt
SLC8A1, P32418
SLC8A2, Q9UPR5
SLC8A3, P57103
Stoichiometry
3 Na+ (in) : 1 Ca2+ (out) or 4 Na+ (in) : 1 Ca2+ (out) [211]; Reverse mode 1 Ca2+ (in): 1 Na+ (out)
Comments: Although subtype-selective inhibitors of NCX function are not widely available, 3,4dichlorobenzamil and CBDMB act as non-selective NCX inhibitors, while SEA0400, KB-R7943, SN6 and
ORM-10103 [212] act to inhibit NCX function selectively.
Further reading
Annunziato L, Pignataro G, Di Renzo GF. (2004) Pharmacology of brain Na+/Ca2+ exchanger:
from molecular biology to therapeutic perspectives. Pharmacol Rev 56: 633654.
[PMID:15602012]
Gabellini N. (2004) Transcriptional regulation by cAMP and Ca2+ links the Na+/Ca2+ exchanger 3
to memory and sensory pathways. Mol Neurobiol 30: 91116. [PMID:15247490]
Lytton J. (2007) Na+/Ca2+ exchangers: three mammalian gene families control Ca2+ transport.
Biochem J 406: 365382. [PMID:17716241]

Quednau BD, Nicoll DA, Philipson KD. (2004) The sodium/calcium exchanger family-SLC8. Pflugers
Arch 447: 543548. [PMID:12734757]
Watanabe Y, Koide Y, Kimura J. (2006) Topics on the Na+/Ca2+ exchanger: pharmacological
characterization of Na+/Ca2+ exchanger inhibitors. J Pharmacol Sci 102: 716. [PMID:16990699]
Zhang YH, Hancox JC. (2009) Regulation of cardiac Na+-Ca2+ exchanger activity by protein kinase
phosphorylationstill a paradox?. Cell Calcium 45: 110. [PMID:18614228]
SLC8 family of sodium/calcium exchangers 1732
SLC9 family of sodium/hydrogen exchangers

Overview: Sodium/hydrogen exchangers or sodium/proton
antiports are a family of transporters that maintain cellular pH by
utilising the sodium gradient across the plasma membrane to
extrude protons produced by metabolism, in a stoichiometry of
1 Na+ (in) : 1 H+ (out). Several isoforms, NHE6, NHE7, NHE8 and
NHE9 appear to locate on intracellular membranes [215217]. Li+

and NH4+, but not K+, ions may also be transported by some
isoforms. Modelling of the topology of these transporters indicates 12 TM regions with an extended intracellular C-terminus
containing multiple regulatory sites.
NHE1 is considered to be a ubiquitously-expressed housekeeping transporter. NHE3 is highly expressed in the intestine and
kidneys and regulate sodium movements in those tissues. NHE10
is present in sperm [220] and osteoclasts [214]; gene disruption
results in infertile male mice [220].
Nomenclature
Common abbreviation
HGNC, UniProt
Sodium/hydrogen exchanger 1
SLC9A1
NHE1
SLC9A1, P19634
SLC9A2
NHE2
SLC9A2, Q9UBY0
SLC9A3
NHE3
SLC9A3, P48764
SLC9A4
NHE4
SLC9A4, Q6AI14
SLC9A5
NHE5
SLC9A5, Q14940
SLC9A6
NHE6
SLC9A6, Q92581
SLC9A7
NHE7
SLC9A7, Q96T83
SLC9A8
NHE8
SLC9A8, Q9Y2E8
SLC9A9
NHE9
SLC9A9, Q8IVB4
solute carrier family 9, subfamily B (NHA1, cation proton antiporter 1), member 1
SLC9B1
NHA1
SLC9B1, Q4ZJI4
solute carrier family 9, subfamily B (NHA2, cation proton antiporter 2), member 2
SLC9B2
NHA2
SLC9B2, Q86UD5
SLC9C1
Sperm-NHE
SLC9C1, Q4G0N8
SLC9C2
NHE11
SLC9C2, Q5TAH2
Comments: Analogues of the non-selective cation transport inhibitor amiloride appear to inhibit NHE function through competitive inhibition of the extracellular Na+ binding site. The more selective
amiloride analogues MPA and EIPA exhibit a rank order of affinity of inhibition of NHE1 > NHE2 > NHE3 [213,218219].
Further reading
Bobulescu IA, Moe OW. (2009) Luminal Na(+)/H (+) exchange in the proximal tubule. Pflugers Arch
458: 521. [PMID:18853182]
Casey JR, Grinstein S, Orlowski J. (2010) Sensors and regulators of intracellular pH. Nat Rev Mol Cell
Biol 11: 5061. [PMID:19997129]
Donowitz M, Ming Tse C, Fuster D. (2013) SLC9/NHE gene family, a plasma membrane and
organellar family of Na+/H+ exchangers. Mol Aspects Med 34: 236251. [PMID:23506868]
Kato A, Romero MF. (2011) Regulation of electroneutral NaCl absorption by the small intestine.
Annu Rev Physiol 73: 261281. [PMID:21054167]

Kemp G, Young H, Fliegel L. (2008) Structure and function of the human Na+/H+ exchanger isoform
1. Channels (Austin) 2: 329336. [PMID:19001864]
Ohgaki R, van IJzendoorn SC, Matsushita M, Hoekstra D, Kanazawa H. (2011) Organellar Na+/H+
exchangers: novel players in organelle pH regulation and their emerging functions. Biochemistry
50: 443450. [PMID:21171650]
SLC9 family of sodium/hydrogen exchangers 1733
SLC10 family of sodium-bile acid co-transporters

Overview: The SLC10 family transport bile acids, sulphated
solutes, and other xenobiotics in a sodium-dependent manner.
The founding members, SLC10A1 (NTCP) and SLC10A2 (ASBT)
function, along with members of the ABC transporter family
(MDR1/ABCB1, BSEP/ABCB11 and MRP2/ABCC2) and the
organic solute transporter obligate heterodimer OST:OST
(SLC51), to maintain the enterohepatic circulation of bile acids

[225,234]. SLC10A6 (SOAT) functions as a sodium-dependent
transporter of sulphated solutes included sulfphated steroids and
bile acids [228,230]. Transport function has not yet been demonstrated for the 4 remaining members of the SLC10 family,
SLC10A3 (P3), SLC10A4 (P4), SLC10A5 (P5), and SLC10A7 (P7),
and the identity of their endogenous substrates remain unknown

[227,230231,237]. Members of the SLC10 family are predicted
to have seven transmembrane domains with an extracellular
N-terminus and cytoplasmic C-terminus [221,232].
Nomenclature
Sodium/bile acid and sulphated solute cotransporter 1
SLC10A1
SLC10A2
SLC10A6
Common abbreviation
NTCP
ASBT
SOAT
HGNC, UniProt
SLC10A1, Q14973
SLC10A2, Q12908
SLC10A6, Q3KNW5
Substrates
tauroursodeoxycholic acid, taurocholic acid,

taurochenodeoxycholic acid > GCA > cholic acid [235]
GDCA > GUDCA, GCDA > taurocholic acid > cholic acid
[224]
pregnenolone sulphate [228], dehydroepiandrosterone

sulphate [230], taurolithocholic acid-3-sulphate,
estrone-3-sulphate
T3, dehydroepiandrosterone sulphate [224,227,235],

estrone-3-sulphate, iodothyronine sulphates
Radioligands (Kd)
[3H]taurocholic acid [224]
Stoichiometry
2 Na : 1 bile acid [221,228]
>1 Na+: 1 bile acid [224,238]
Comment
chenodeoxycholyl-N-nitrobenzoxadiazol-lysine is a
fluorescent bile acid analogue used as a probe [229].
Inhibitors (pIC50)
cyclosporin A [226,233], irbesartan [226], propranolol

[224]
SC-435 (8.82) [222], 264W94 (7.32) [236,239]
Nomenclature
Sodium/bile acid and sulphated

solute cotransporter 3



SLC10A3
SLC10A4
SLC10A5
SLC10A7
Common abbreviation
P3
P4
P5
P7
HGNC, UniProt
SLC10A3, P09131
SLC10A4, Q96EP9
SLC10A5, Q5PT55
SLC10A7, Q0GE19
Comments: Heterologously expressed SLC10A4 [229] or SLC10A7 [231] failed to exhibit significant transport of taurocholic acid, pregnenolone sulphate, DHEAS or choline. SLC10A4 has recently been
suggested to associate with neuronal vesicles [223].

SLC10 family of sodium-bile acid co-transporters 1734
Further reading
Borges K. (2013) Slc10A4 - what do we know about the function of this secret ligand carrier
protein?. Exp Neurol 248C: 258261 [Epub ahead of print]. [PMID:23810836]
Claro da Silva T, Polli JE, Swaan PW. (2013) The solute carrier family 10 (SLC10): beyond bile acid
transport. Mol Aspects Med 34: 252269. [PMID:23506869]
Dawson PA, Lan T, Rao A. (2009) Bile acid transporters. J Lipid Res 50: 23402357. [PMID:19498215]

Dring B, Ltteke T, Geyer J, Petzinger E. (2012) The SLC10 carrier family: transport functions and
molecular structure. Curr Top Membr 70: 105168. [PMID:23177985]
Zwicker BL, Agellon LB. (2013) Transport and biological activities of bile acids. Int J Biochem Cell Biol
45: 13891398. [PMID:23603607]
SLC10 family of sodium-bile acid co-transporters 1735
SLC11 family of proton-coupled metal ion transporters

Overview: The family of proton-coupled metal ion transporters
are responsible for movements of divalent cations, particularly
ferrous and manganese ions, across the cell membrane
(SLC11A2/DMT1) and across endosomal (SLC11A2/DMT1)
or lysosomal/phagosomal membranes (SLC11A1/NRAMP1),
dependent on proton transport. Both proteins appear to have 12

TM regions and cytoplasmic N- and C- termini. NRAMP1 is
involved in antimicrobial action in macrophages, although its
precise mechanism is undefined. Facilitated diffusion of divalent
cations into phagosomes may increase intravesicular free radicals
to damage the pathogen. Alternatively, export of divalent cations

from the phagosome may deprive the pathogen of essential
enzyme cofactors. SLC11A1/DMT1 is more widely expressed and
appears to assist in divalent cation assimilation from the diet, as
well as in phagocytotic cells.
Nomenclature
NRAMP1
DMT1
SLC11A1
SLC11A2
HGNC, UniProt
SLC11A1, P49279
SLC11A2, P49281
Fe2+, Mn2+
Cd2+, Co2+, Cu2+, Fe2+, Mn2+
Stoichiometry
1 H+ : 1 Fe2+ (out) or 1 Fe2+ (in) : 1 H+ (out)
1 H+ : 1 Fe2+ (out) [240]
Comments: Loss-of-function mutations in NRAMP1 are associated with increased susceptibility to microbial infection (OMIM: 607948). Loss-of-function mutations in DMT1 are associated with
microcytic anemia (OMIM: 206100).
Further reading
Li X, Yang Y, Zhou F, Zhang Y, Lu H, Jin Q, Gao L. (2011) SLC11A1 (NRAMP1) polymorphisms and
tuberculosis susceptibility: updated systematic review and meta-analysis. PLoS ONE 6: e15831.
[PMID:21283567]
Mackenzie B, Hediger MA. (2004) SLC11 family of H+-coupled metal-ion transporters NRAMP1 and
DMT1. Pflugers Arch 447: 571579. [PMID:14530973]
Montalbetti N, Simonin A, Kovacs G, Hediger MA. (2013) Mammalian iron transporters: families
SLC11 and SLC40. Mol Aspects Med 34: 270287. [PMID:23506870]

Nevo Y, Nelson N. (2006) The NRAMP family of metal-ion transporters. Biochim Biophys Acta 1763:
609620. [PMID:16908340]
Zheng W, Monnot AD. (2012) Regulation of brain iron and copper homeostasis by brain barrier
systems: implication in neurodegenerative diseases. Pharmacol Ther 133: 177188.
[PMID:22115751]
SLC11 family of proton-coupled metal ion transporters 1736
SLC12 family of cation-coupled chloride transporters

Overview: The SLC12 family of chloride transporters contribute to ion fluxes across a variety of tissues, particularly in the
kidney and choroid plexus of the brain. Within this family,
further subfamilies are identifiable: NKCC1, NKCC2 and NCC
constitute a group of therapeutically-relevant transporters,
targets for loop and thiazide diuretics. These 12 TM proteins

exhibit cytoplasmic termini and an extended extracellular loop
at TM7/8 and are kidney-specific (NKCC2 and NCC) or show a
more widespread distribution (NKCC1). A second family, the
K-Cl co-transporters are also 12 TM domain proteins with cyto-
plasmic termini, but with an extended extracellular loop at TM

5/6. CCC6 exhibits structural similarities with the K-Cl
co-transporters, while CCC9 is divergent, with 11 TM domains
and a cytoplasmic N-terminus and extracellular C-terminus.
Nomenclature
Kidney-specific Na-K-Cl symporter
Basolateral Na-K-Cl symporter
Na-Cl symporter
SLC12A1
SLC12A2
SLC12A3
Common abbreviation
NKCC2
NKCC1
NCC
HGNC, UniProt
SLC12A1, Q13621
SLC12A2, P55011
SLC12A3, P55017
Inhibitors (pIC50)
bumetanide [242], furosemide [242], piretanide [242]
bumetanide [242], furosemide [242], piretanide [242]
chlorothiazide, hydrochlorothiazide, metolazone
Stoichiometry
1 Na+ : 1 K+ : 2 Cl- (in)
1 Na+ : 1 K+ : 2 Cl- (in)
1 Na+ : 1 Cl- (in)
Nomenclature
K-Cl cotransporter 1
SLC12A4
SLC12A5
SLC12A6
SLC12A7
Common abbreviation
KCC1
KCC2
KCC3
KCC4
HGNC, UniProt
SLC12A4, Q9UP95
SLC12A5, Q9H2X9
SLC12A6, Q9UHW9
SLC12A7, Q9Y666
Inhibitors (pIC50)
DIOA
DIOA, VU0240551 [241]
DIOA
DIOA
Stoichiometry
1 K+ : 1 Cl- (out)
1 K+ : 1 Cl- (out)
1 K+ : 1 Cl- (out)
1 K+ : 1 Cl- (out)
Nomenclature
Cation-chloride cotransporter 9
Cation-chloride cotransporter 6
SLC12A8
SLC12A9
Common abbreviation
CCC9
CCC6
HGNC, UniProt
SLC12A8, A0AV02
SLC12A9, Q9BXP2
Substrates
spermine, L-glutamic acid, spermidine, L-aspartic acid
Stoichiometry
Unknown
Comment
CCC6 is regarded as an orphan transporter
Comments: DIOA is able to differentiate KCC isoforms from NKCC and NCC transporters, but also inhibits CFTR [243].

SLC12 family of cation-coupled chloride transporters 1737
Further reading
Arroyo JP, Kahle KT, Gamba G. (2013) The SLC12 family of electroneutral cation-coupled chloride
cotransporters. Mol Aspects Med 34: 288298. [PMID:23506871]
Gagnon KB, Delpire E. (2013) Physiology of SLC12 transporters: lessons from inherited human
genetic mutations and genetically engineered mouse knockouts. Am J Physiol, Cell Physiol 304:
C693C714. [PMID:23325410]
Gamba G, Friedman PA. (2009) Thick ascending limb: the Na(+):K (+):2Cl (-) co-transporter, NKCC2,
and the calcium-sensing receptor, CaSR. Pflugers Arch 458: 6176. [PMID:18982348]

Hebert SC, Mount DB, Gamba G. (2004) Molecular physiology of cation-coupled Cl- cotransport:
the SLC12 family. Pflugers Arch 447: 580593. [PMID:12739168]
Kahle KT, Rinehart J, Lifton RP. (2010) Phosphoregulation of the Na-K-2Cl and K-Cl cotransporters
by the WNK kinases. Biochim Biophys Acta 1802: 11501158. [PMID:20637866]
Lang F, Vallon V, Knipper M, Wangemann P. (2007) Functional significance of channels and
transporters expressed in the inner ear and kidney. Am J Physiol, Cell Physiol 293: C1187C1208.
[PMID:17670895]
SLC12 family of cation-coupled chloride transporters 1738
SLC13 family of sodium-dependent sulphate/carboxylate transporters

Overview: Within the SLC13 family, two groups of transporters may be differentiated on the basis of the substrates transported: NaS1 and NaS2 convey sulphate, while NaC1-3 transport carboxylates.
NaS1 and NaS2 transporters are made up of 13 TM domains, with an intracellular N terminus and are electrogenic with physiological roles in the intestine, kidney and placenta. NaC1, NaC2 and NaC3
are made up of 11 TM domains with an intracellular N terminus and are electrogenic, with physiological roles in the kidney and liver.
Nomenclature
Na+/sulfate cotransporter
Na+/dicarboxylate cotransporter 1
Na+/dicarboxylate cotransporter 3
Na+/sulfate cotransporter
Na+/citrate cotransporter
SLC13A1
SLC13A2
SLC13A3
SLC13A4
SLC13A5
Common abbreviation
NaS1
NaC1
NaC3
NaS2
NaC2
HGNC, UniProt
SLC13A1, Q9BZW2
SLC13A2, Q13183
SLC13A3, Q8WWT9
SLC13A4, Q9UKG4
SLC13A5, Q86YT5
SeO42-, S2O32-, SO42-
citric acid, succinic acid
citric acid, succinic acid
SO42-
citric acid, pyruvic acid
Stoichiometry
3 Na+ : 1 SO42- (in)
3 Na+ : 1 dicarboxylate2- (in)
Unknown
3 Na+ : SO42- (in)
Unknown
Further reading
Lee A, Dawson PA, Markovich D. (2005) NaSi-1 and Sat-1: structure, function and transcriptional
regulation of two genes encoding renal proximal tubular sulfate transporters. Int J Biochem Cell
Biol 37: 13501356. [PMID:15833267]
Markovich D. (2011) Physiological roles of renal anion transporters NaS1 and Sat1. Am J Physiol
Renal Physiol 300: F1267F1270. [PMID:21490138]

Markovich D, Aronson PS. (2007) Specificity and regulation of renal sulfate transporters. Annu Rev
Physiol 69: 361375. [PMID:17002596]
Markovich D, Murer H. (2004) The SLC13 gene family of sodium sulphate/carboxylate cotransporters. Pflugers Arch 447: 594602. [PMID:12915942]
SLC13 family of sodium-dependent sulphate/carboxylate transporters 1739
SLC14 family of facilitative urea transporters

Overview: As a product of protein catabolism, urea is moved
around the body and through the kidneys for excretion.
Although there is experimental evidence for concentrative urea
transporters, these have not been defined at the molecular level.
The SLC14 family are facilitative transporters, allowing urea
movement down its concentration gradient. Multiple splice variants of these transporters have been identified; for UT-A transporters, in particular, there is evidence for cell-specific expression
of these variants with functional impact [245]. Topographical
modelling suggests that the majority of the variants of SLC14
transporters have 10 TM domains, with a glycosylated extracellular loop at TM5/6, and intracellular C- and N-termini. The
UT-A1 splice variant, exceptionally, has 20 TM domains, equivalent to a combination of the UT-A2 and UT-A3 splice variants.
Nomenclature
Erythrocyte urea transporter
Kidney urea transporter
SLC14A1
SLC14A2
Common abbreviation
UT-B
UT-A
HGNC, UniProt
SLC14A1, Q13336
SLC14A2, Q15849
ammonium carbonate [246], urea [246], formamide [246]
urea [244]
Substrates
acrylamide [246], acetamide [246], methylurea [246]
Stoichiometry
Equilibrative
Equilibrative
Further reading
Pannabecker TL. (2013) Comparative physiology and architecture associated with the mammalian
urine concentrating mechanism: role of inner medullary water and urea transport pathways in
the rodent medulla. Am J Physiol Regul Integr Comp Physiol 304: R488R503. [PMID:23364530]
Shayakul C, Clmenon B, Hediger MA. (2013) The urea transporter family (SLC14): physiological,
pathological and structural aspects. Mol Aspects Med 34: 313322. [PMID:23506873]

Shayakul C, Hediger MA. (2004) The SLC14 gene family of urea transporters. Pflugers Arch 447:
603609. [PMID:12856182]
Smith CP. (2009) Mammalian urea transporters. Exp Physiol 94: 180185. [PMID:19028811]
Stewart G. (2011) The emerging physiological roles of the SLC14A family of urea transporters. Br J
Pharmacol 164: 17801792. [PMID:21449978]
SLC14 family of facilitative urea transporters 1740
SLC15 family of peptide transporters

Overview: The SLC15 family of peptide transporters may be
divided on the basis of structural and functional differences into
two subfamilies: SLC15A1 (PepT1) and SLC15A2 (PepT2) transport di- and tripeptides, but not amino acids, whereas SLC15A3
(PHT2) and SLC15A4 (PHT1) transport L-histidine and some diand tripeptides [251]. The transporters are 12 TM proteins with
intracellular termini and an extended extracellular loop at TM
9/10. The crystal structure of PepTSo (a prokaryote homologue of

PepT1 and PepT2 from Shewanella oneidensis) confirms many of
the predicted structural features of mammalian PepT1 and PepT2
[261].
PHT1 has been suggested to be intracellular [262], while PHT2
protein is located on lysosomes in transfected cells
[250,257,264]. PHT1 is hypothesised to mediate efflux of

bacterial-derived peptides into the cytosol perhaps in the colon
where SLC15A4 mRNA expression is increased in inflammatory
bowel disease [259]. Transport via PHT1 may be important in
immune responses as both Toll-like receptor- and NOD1mediated responses are reduced in PHT1 knockout mice or
mouse strains expressing mutations in PHT1 [249,265].
Nomenclature
Peptide transporter 1
SLC15A1
SLC15A2
SLC15A3
SLC15A4
Common abbreviation
PepT1
PepT2
PHT2
PHT1
HGNC, UniProt
SLC15A1, P46059
SLC15A2, Q16348
SLC15A3, Q8IY34
SLC15A4, Q8N697
5-aminolevulinic acid [253], dipeptides [253],

tripeptides [253]
5-aminolevulinic acid, dipeptides, tripeptides
L-histidine, carnosine,
dipeptides, tripeptides
L-histidine, carnosine,
dipeptides, tripeptides
Substrates
fMet-Leu-Phe [260], cyclacillin [254], valacyclovir

[255], cefadroxil [254], muramyl dipeptide [268]
cyclacillin [254], cefadroxil [254]
valacyclovir [247]
Inhibitors (pIC50)
4-AMBA [252], Lys[Z(NO2)]-Pro [258]
Lys[Z(NO2)]-Lys[Z(NO2)] [248,267], Lys[Z(NO2)]-Pro
Radioligands (Kd)
[11C]GlySar, [14C]GlySar, [3H]GlySar
[11C]GlySar, [14C]GlySar, [3H]GlySar
[14C]histidine, [3H]histidine
Stoichiometry
1 H+ : 1 zwitterionic peptide (in)
2 H+ : 1 zwitterionic peptide (in)
Unknown
Unknown
Comments: The PepT1 and PepT2 transporters are particularly promiscuous in the transport of dipeptides and tripeptides from the endogenous amino acids, as well as some D-amino acid containing
peptides. PepT1 has also been exploited to allow delivery of therapeutic pro-drugs, such as those for zidovudine [256], sulpiride [269] and cytarabine [266].
D-Ala-Lys-AMCA has been used as a fluorescent probe to identify transport via both PepT1 and PepT2 [263].
Further reading
Anderson CM, Thwaites DT. (2010) Hijacking solute carriers for proton-coupled drug transport.
Physiol (Bethesda) 25: 364377. [PMID:21186281]
Biegel A, Kntter I, Hartrodt B, Gebauer S, Theis S, Luckner P, Kottra G, Rastetter M, Zebisch K,
Thondorf I et al. (2006) The renal type H+/peptide symporter PEPT2: structure-affinity relationships. Amino Acids 31: 137156. [PMID:16868651]
Brandsch M. (2009) Transport of drugs by proton-coupled peptide transporters: pearls and pitfalls.
Expert Opin Drug Metab Toxicol 5: 887905. [PMID:19519280]
Ingersoll SA, Ayyadurai S, Charania MA, Laroui H, Yan Y, Merlin D. (2012) The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and

inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 302: G484G492.

[PMID:22194420]
Smith DE, Clmenon B, Hediger MA. (2013) Proton-coupled oligopeptide transporter family
SLC15: physiological, pharmacological and pathological implications. Mol Aspects Med 34:
323336. [PMID:23506874]
Thwaites DT, Anderson CM. (2007) H+-coupled nutrient, micronutrient and drug transporters in
the mammalian small intestine. Exp Physiol 92: 603619. [PMID:17468205]
SLC15 family of peptide transporters 1741
SLC16 family of monocarboxylate transporters

Overview: Members of the SLC16 family may be divided into subfamilies on the basis of substrate selectivities, particularly lactate (e.g. L-lactic acid), pyruvic acid and ketone bodies, as well as aromatic
amino acids. Topology modelling suggests 12 TM domains, with intracellular termini and an extended loop at TM 6/7.
The proton-coupled monocarboxylate transporters (monocarboxylate transporters 1, 4, 2 and 3) allow transport of the products of cellular metabolism, principally lactate (e.g. L-lactic acid) and pyruvic
acid.
Nomenclature
Monocarboxylate transporter 1
SLC16A1
SLC16A3
SLC16A7
SLC16A8
Common abbreviation
MCT1
MCT4
MCT2
MCT3
HGNC, UniProt
SLC16A1, P53985
SLC16A3, O15427
SLC16A7, O60669
SLC16A8, O95907
-D-hydroxybutyric acid, L-lactic acid, pyruvic acid
L-lactic acid, pyruvic acid
L-lactic acid, pyruvic acid
L-lactic acid
Substrates
-hydroxybutyric acid [272]
Stoichiometry
1 H+: 1 monocarboxylate- (out)
Nomenclature
SLC16A2
SLC16A10
Common abbreviation
MCT8
TAT1
HGNC, UniProt
SLC16A2, P36021
SLC16A10, Q8TF71
T3 [270], T4 [270]
L-tryptophan, L-phenylalanine, L-DOPA, L-tyrosine
Stoichiometry
Unknown
Unknown
Nomenclature
Monocarboxylate
transporter 5
Monocarboxylate
transporter 6
Monocarboxylate
transporter 7
Monocarboxylate
transporter 9
Monocarboxylate
transporter 11
Monocarboxylate
transporter 12
Monocarboxylate
transporter 13
Monocarboxylate
transporter 14
SLC16A4
SLC16A5
SLC16A6
SLC16A9
SLC16A11
SLC16A12
SLC16A13
SLC16A14
Common abbreviation
MCT5
MCT6
MCT7
MCT9
MCT11
MCT12
MCT13
MCT14
HGNC, UniProt
SLC16A4, O15374
SLC16A5, O15375
SLC16A6, O15403
SLC16A9, Q7RTY1
SLC16A11, Q8NCK7
SLC16A12, Q6ZSM3
SLC16A13, Q7RTY0
SLC16A14, Q7RTX9
Stoichiometry
Unknown
Unknown
Unknown
Unknown
Unknown
Unknown
Unknown
Unknown
Comment
MCT6 has been

reported to transport
bumetanide, but not
short chain fatty acids
[271]

SLC16 family of monocarboxylate transporters 1742
Comments: MCT1 and MCT2, but not MCT3 and MCT4, are inhibited by CHC, which also inhibits members of the mitochondrial transporter family, SLC25.
MCT5-MCT7, MCT9 and MCT11-14 are regarded as orphan transporters.
Further reading
Physiology (Bethesda) 25: 364377. [PMID:21186281]
Braun D, Wirth EK, Schweizer U. (2010) Thyroid hormone transporters in the brain. Rev Neurosci 21:
173186. [PMID:20879691]
Friesema EC, Visser WE, Visser TJ. (2010) Genetics and phenomics of thyroid hormone transport by
MCT8. Mol Cell Endocrinol 322: 107113. [PMID:20083155]
Halestrap AP, Meredith D. (2004) The SLC16 gene family-from monocarboxylate transporters
(MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447: 619628.
[PMID:12739169]
Heuer H, Visser TJ. (2009) Minireview: Pathophysiological importance of thyroid hormone transporters. Endocrinology 150: 10781083. [PMID:19179441]
Jansen J, Friesema EC, Milici C, Visser TJ. (2005) Thyroid hormone transporters in health and
disease. Thyroid 15: 757768. [PMID:16131319]

Meredith D, Christian HC. (2008) The SLC16 monocaboxylate transporter family. Xenobiotica 38:
10721106. [PMID:18668440]
Morris ME, Felmlee MA. (2008) Overview of the proton-coupled MCT (SLC16A) family of transporters: characterization, function and role in the transport of the drug of abuse gammahydroxybutyric acid. AAPS J 10: 311321. [PMID:18523892]
van der Deure WM, Peeters RP, Visser TJ. (2010) Molecular aspects of thyroid hormone transporters,
including MCT8, MCT10, and OATPs, and the effects of genetic variation in these transporters.
J Mol Endocrinol 44: 111. [PMID:19541799]
Visser TJ. (2007) Thyroid hormone transporters. Horm Res 68 Suppl 5: 2830. [PMID:18174701]
Visser WE, Friesema EC, Jansen J, Visser TJ. (2008) Thyroid hormone transport in and out of cells.
Trends Endocrinol Metab 19: 5056. [PMID:18291666]
SLC16 family of monocarboxylate transporters 1743
SLC17 phosphate and organic anion transporter family

Overview: The SLC17 family are sometimes referred to as Type I sodium-phosphate co-transporters, alongside Type II (SLC34 family) and Type III (SLC20 family) transporters. Within the SLC17 family,
however, further subgroups of organic anion transporters may be defined, allowing the accumulation of sialic acid in the endoplasmic reticulum and glutamate (e.g. L-glutamic acid) or nucleotides in
synaptic and secretory vesicles. Topology modelling suggests 12 TM domains.
Type I sodium-phosphate co-transporters

Overview: Type I sodium-phosphate co-transporters are expressed in the kidney and intestine.
Nomenclature
Sodium/phosphate cotransporter 1
Sodium/phosphate
cotransporter 3
Sodium/phosphate
cotransporter 4
Sodium/phosphate
cotransporter homolog
SLC17A1
SLC17A2
SLC17A3
SLC17A4
Common abbreviation
NPT1
NPT3
NPT4
HGNC, UniProt
SLC17A1, Q14916
SLC17A2, O00624
SLC17A3, O00476
SLC17A4, Q9Y2C5
Substrates
Cl- [275], probenecid [274], PO34- [275], uric acid [275],

penicillin G [274], organic acids [275]
Stoichiometry
Unknown
Unknown
Unknown
Unknown
Sialic acid transporter

Overview: The sialic acid transporter is expressed on both lysosomes and synaptic vesicles, where it appears to allow export of sialic acid and accumulation of acidic amino acids, respectively [277], driven
by proton gradients. In lysosomes, degradation of glycoproteins generates amino acids and sugar residues, which are metabolized further following export from the lysosome.
Nomenclature
Sialin
SLC17A5
Common abbreviation
AST
HGNC, UniProt
SLC17A5, Q9NRA2
L-glutamic acid (in) [277], L-lactic acid, L-aspartic acid [277], gluconate (out), sialic acid, glucuronic acid
Stoichiometry
1 H+: 1 sialic acid (out)
Comments: Loss-of-function mutations in sialin are associated with Salla disease (OMIM: 604369), an autosomal recessive neurodegenerative disorder associated with sialic acid storage disease [279].

SLC17 phosphate and organic anion transporter family 1744
Vesicular glutamate transporters (VGLUTs)

Overview: Vesicular glutamate transporters (VGLUTs) allow accumulation of glutamate into synaptic vesicles, as well as secretory vesicles in endocrine tissues. The roles of VGLUTs in kidney and liver
are unclear. These transporters appear to utilize the proton gradient and also express a chloride conductance [273].
Nomenclature
Vesicular glutamate transporter 1
SLC17A7
SLC17A6
SLC17A8
Common abbreviation
VGLUT1
VGLUT2
VGLUT3
HGNC, UniProt
SLC17A7, Q9P2U7
SLC17A6, Q9P2U8
SLC17A8, Q8NDX2
L-glutamic acid > D-glutamic acid
Stoichiometry
Unknown
Unknown
Unknown
Comments: Endogenous ketoacids produced during fasting have been proposed to regulate VGLUT function through blocking chloride ion-mediated allosteric enhancement of transporter function [276].
Vesicular nucleotide transporter
Overview: The vesicular nucleotide transporter is the most recent member of the SLC17 family to have an assigned function. Uptake of ATP was independent of pH, but dependent on chloride ions and
membrane potential [278].
Nomenclature
Vesicular nucleotide transporter
SLC17A9
Common abbreviation
VNUT
HGNC, UniProt
SLC17A9, Q9BYT1
ATP [278], GTP [278], GDP [278]
Stoichiometry
Unknown
Comments: VGLUTs and VNUT can be inhibited by DIDS and evans blue dye.
Further reading
Biber J, Hernando N, Forster I. (2013) Phosphate transporters and their function. Annu Rev Physiol
75: 535550. [PMID:23398154]
El Mestikawy S, Walln-Mackenzie A, Fortin GM, Descarries L, Trudeau LE. (2011) From glutamate
co-release to vesicular synergy: vesicular glutamate transporters. Nat Rev Neurosci 12: 204216.
[PMID:21415847]
Marks J, Debnam ES, Unwin RJ. (2010) Phosphate homeostasis and the renal-gastrointestinal axis.
Am J Physiol Renal Physiol 299: F285F296. [PMID:20534868]
Miyamoto K, Haito-Sugino S, Kuwahara S, Ohi A, Nomura K, Ito M, Kuwahata M, Kido S, Tatsumi
S, Kaneko I et al. (2011) Sodium-dependent phosphate cotransporters: lessons from gene knockout and mutation studies. J Pharm Sci 100: 37193730. [PMID:21567407]

Omote H, Miyaji T, Juge N, Moriyama Y. (2011) Vesicular neurotransmitter transporter: bioenergetics and regulation of glutamate transport. Biochemistry 50: 55585565. [PMID:21612282]
Reimer RJ. (2013) SLC17: a functionally diverse family of organic anion transporters. Mol Aspects
Med 34: 350359. [PMID:23506876]
Shobeiri N, Adams MA, Holden RM. (2013) Phosphate: an old bone molecule but new cardiovascular risk factor. Br J Clin Pharmacol [Epub ahead of print]. [PMID:23506202]
SLC17 phosphate and organic anion transporter family 1745
SLC18 family of vesicular amine transporters

Overview: The vesicular amine transporters (VATs) are putative
12 TM domain proteins that function to transport singly positively charged amine neurotransmitters and hormones from the
cytoplasm and concentrate them within secretory vesicles. They
function as amine/proton antiporters driven by secondary active
transport utilizing the proton gradient established by a multisubunit vacuolar ATPase that acidifies secretory vesicles
(reviewed by [283]). The vesicular acetylcholine transporter
(VAChT; [287]) localizes to cholinergic neurons, but nonneuronal expression has also been claimed [290]. Vesicular
monoamine transporter 1 (VMAT1, [285]) is mainly expressed in

peripheral neuroendocrine cells, but most likely not in the CNS,
whereas VMAT2 [286] distributes between both central and
peripheral sympathetic monoaminergic neurones [284].
Nomenclature
Vesicular monoamine transporter 1
Vesicular monoamine transporter 2
Vesicular acetylcholine transporter
solute carrier family 18,

subfamily B, member 1
SLC18A1
SLC18A2
SLC18A3
SLC18B1
Common abbreviation
VMAT1
VMAT2
VAChT
HGNC, UniProt
SLC18A1, P54219
SLC18A2, Q05940
SLC18A3, Q16572
SLC18B1, Q6NT16
5-HT (Ki 1.4x10-6 M) [286], (-)-adrenaline

(Ki 5.5x10-6 M) [286], (-)-noradrenaline
(Ki 1.37x10-5 M) [286], dopamine (Ki
3.8x10-6 M) [286], histamine (Ki
4.696x10-3 M) [286]
5-HT (Ki 9x10-7 M) [286], (-)-adrenaline

(Ki 1.9x10-6 M) [286], (-)-noradrenaline (Ki
3.4x10-6 M) [286], dopamine (Ki 1.4x10-6
M) [286], histamine (Ki 1.43x10-4 M)
[286]
acetylcholine (Ki 7.94x10-4 M) [280,288],

choline (Ki 5x10-4 M) [280,288]
Substrates
-phenylethylamine (Ki 3.4x10-5 M) [286],

dextroamphetamine (Ki 4.7x10-5 M) [286],
MPP+ (Ki 6.9x10-5 M) [286], MDMA (Ki
1.9x10-5 M) [286], fenfluramine (Ki
3.1x10-6 M) [286]
-phenylethylamine (Ki 3.7x10-6 M) [286],

dextroamphetamine (Ki 2.1x10-6 M) [286],
MPP+ (Ki 8.9x10-6 M) [286], MDMA (Ki
6.9x10-6 M) [286], fenfluramine (Ki
5.1x10-6 M) [286]
TPP+ [281], ethidium [281],

N-methyl-pyridinium-2-aldoxime [281],
N-(4-pentanonyl)-4-(4-dimethylaminostyryl)pyridinium [281]
Inhibitors (pIC50)
reserpine (pKi 7.45) [286], ketanserin (pKi

5.8) [286], tetrabenazine (pKi 4.7) [286]
reserpine (pKi 7.9) [286], tetrabenazine

(pKi 7.0) [286], ketanserin (pKi 6.3) [286]
aminobenzovesamicol (pKi 10.9) [282],

vesamicol (pKi 8.7) [282]
Radioligands (Kd)
[11C]DTBZ, [125I]8-azido-3-iodoketanserine,
[3H]TBZOH (6.6x10-9 M) [291],
[125I]iodovinyl-TBZ (8.2x10-9 M) [289]
[123I]iodobenzovesamicol, [3H]vesamicol
(4.1x10-9 M) [291]
Stoichiometry
1 amine (in): 2H+ (out)
Comments: pKi values for endogenous and synthetic substrate inhibitors of human VMAT1 and VMAT2 are for inhibition of [3H]5-HT uptake in transfected and permeabilised CV-1 cells as detailed by
[286]. In addition to the monoamines listed in the table, the trace amines tyramine and -phenylethylamine are probable substrates for VMAT2 [284]. Probes listed in the table are those currently
employed; additional agents have been synthesized (e.g. [292]).
Further reading
Chaudhry FA, Edwards RH, Fonnum F. (2008) Vesicular neurotransmitter transporters as targets for
endogenous and exogenous toxic substances. Annu Rev Pharmacol Toxicol 48: 277301.
[PMID:17883368]
Eiden LE, Weihe E. (2011) VMAT2: a dynamic regulator of brain monoaminergic neuronal function
interacting with drugs of abuse. Ann N Y Acad Sci 1216: 8698. [PMID:21272013]

Giboureau N, Som IM, Boucher-Arnold A, Guilloteau D, Kassiou M. (2010) PET radioligands for
the vesicular acetylcholine transporter (VAChT). Curr Top Med Chem 10: 15691583.
[PMID:20583990]
Khare P, White AR, Mulakaluri A, Parsons SM. (2010) Equilibrium binding and transport by
vesicular acetylcholine transporter. Methods Mol Biol 637: 181219. [PMID:20419436]
SLC18 family of vesicular amine transporters 1746
Lawal HO, Krantz DE. (2013) SLC18: Vesicular neurotransmitter transporters for monoamines and
acetylcholine. Mol Aspects Med 34: 360372. [PMID:23506877]
Prado VF, Roy A, Kolisnyk B, Gros R, Prado MA. (2013) Regulation of cholinergic activity by the
vesicular acetylcholine transporter. Biochem J 450: 265274. [PMID:23410039]

Ramamoorthy S, Shippenberg TS, Jayanthi LD. (2011) Regulation of monoamine transporters: Role
of transporter phosphorylation. Pharmacol Ther 129: 220238. [PMID:20951731]
Wimalasena K. (2011) Vesicular monoamine transporters: structure-function, pharmacology, and
medicinal chemistry. Med Res Rev 31: 483519. [PMID:20135628]
SLC18 family of vesicular amine transporters 1747
SLC19 family of vitamin transporters

Overview: The B vitamins folic acid and thiamine are transported across the cell membrane, particularly in the intestine, kidneys and placenta, using pH differences as driving forces. Topological
modelling suggests the transporters have 12 TM domains.
Nomenclature
Reduced folate transporter 1
Thiamine transporter 1
SLC19A1
SLC19A2
Thiamine transporter 2
SLC19A3
Common abbreviation
FOLT
ThTr1
ThTr2
HGNC, UniProt
SLC19A1, P41440
SLC19A2, O60779
SLC19A3, Q9BZV2
thiamine monophosphate [298], tetrahydrofolic acid [296],

N5-methylfolate [296], Organic phosphates; in particular, adenine
nucleotides, Other tetrahydrofolate-cofactors
thiamine
thiamine
Substrates
folic acid [296], methotrexate, folinic acid, N5-formyltetrahydrofolate
Radioligands (Kd)
[3H]folic acid [293], [3H]methotrexate [293]
[3H]thiamine [295]
[3H]thiamine [297]
Stoichiometry
Folate (in) : organic phosphate (out), precise stoichiometry unknown
A facilitative carrier not known to be coupled

to an inorganic or organic ion gradient
A facilitative carrier not known to be coupled

to an inorganic or organic ion gradient
Comments: Loss-of-function mutations in ThTr1 underlie thiamine-responsive megaloblastic anemia syndrome [294].
Further reading
Ganapathy V, Smith SB, Prasad PD. (2004) SLC19: the folate/thiamine transporter family. Pflugers
Arch 447: 641646. [PMID:14770311]
Goldman ID, Chattopadhyay S, Zhao R, Moran R. (2010) The antifolates: evolution, new agents in
the clinic, and how targeting delivery via specific membrane transporters is driving the development of a next generation of folate analogs. Curr Opin Investig Drugs 11: 14091423.
[PMID:21154123]
Matherly LH, Hou Z. (2008) Structure and function of the reduced folate carrier a paradigm of a
major facilitator superfamily mammalian nutrient transporter. Vitam Horm 79: 145184.
[PMID:18804694]

Yuasa H, Inoue K, Hayashi Y. (2009) Molecular and functional characteristics of proton-coupled

folate transporter. J Pharm Sci 98: 16081616. [PMID:18823045]
Zhao R, Diop-Bove N, Visentin M, Goldman ID. (2011) Mechanisms of membrane transport of
folates into cells and across epithelia. Annu Rev Nutr 31: 177201. [PMID:21568705]
Zhao R, Goldman ID. (2013) Folate and thiamine transporters mediated by facilitative carriers
(SLC19A1-3 and SLC46A1) and folate receptors. Mol Aspects Med 34: 373385. [PMID:23506878]
SLC19 family of vitamin transporters 1748
SLC20 family of sodium-dependent phosphate transporters

Overview: The SLC20 family is looked upon not only as ion transporters, but also as retroviral receptors. As ion transporters, they are sometimes referred to as Type III sodium-phosphate co-transporters,
alongside Type I (SLC17 family) and Type II (SLC34 family). PiTs are cell-surface transporters, composed of ten TM domains with extracellular C- and N-termini. PiT1 is a focus for dietary PO34- and vitamin
D regulation of parathyroid hormone secretion from the parathyroid gland. PiT2 appears to be involved in intestinal absorption of dietary PO34-.
Nomenclature
Sodium-dependent phosphate transporter 1
Sodium-dependent phosphate transporter 2
SLC20A1
SLC20A2
Common abbreviation
PiT1
PiT2
HGNC, UniProt
SLC20A1, Q8WUM9
SLC20A2, Q08357
Substrates
AsO43 [299], PO34- [299]
PO34- [299]
Stoichiometry
>1 Na : 1 HPO4 (in)
>1 Na+ : 1 HPO42- (in)
2-
Further reading
75: 535550. [PMID:23398154]
Forster IC, Hernando N, Biber J, Murer H. (2013) Phosphate transporters of the SLC20 and SLC34
families. Mol Aspects Med 34: 386395. [PMID:23506879]
Am J Physiol Renal Physiol 299: F285-F296. [PMID:20534868]


SLC20 family of sodium-dependent phosphate transporters 1749
SLC22 family of organic cation and anion transporters

Overview: The SLC22 family of transporters is mostly composed of non-selective transporters, which are expressed highly in liver, kidney and intestine, playing a major role in drug disposition. The family
may be divided into three subfamilies based on the nature of the substrate transported: organic cations (OCTs), organic anions (OATs) and organic zwiterrion/cations (OCTN). Membrane topology is
predicted to contain 12 TM domains with intracellular termini, and an extended extracellular loop at TM 1/2.
Organic cation transporters (OCT)

Overview: Organic cation transporters (OCT) are electrogenic, Na+-independent and reversible.
Nomenclature
Organic cation transporter 1
SLC22A1
SLC22A2
SLC22A3
Common abbreviation
OCT1
OCT2
OCT3
HGNC, UniProt
SLC22A1, O15245
SLC22A2, O15244
SLC22A3, O75751
5-HT, PGE2, PGF2, choline
dopamine [303], histamine [303], PGE2 [304]
5-HT [307], (-)-noradrenaline [307], dopamine [307]
Substrates
tetraethylammonium, desipramine, MPP+, metformin,

acyclovir
(+)-tubocurarine [302], tetraethylammonium [302],

pancuronium [302], MPP+ [302]
quinidine, tetraethylammonium, MPP+
Stoichiometry
Unknown
Unknown
Unknown
Comments: corticosterone and quinine are able to inhibit all three organic cation transporters.
Organic zwitterions/cation transporters (OCTN)
Overview: Organic zwitterions/cation transporters (OCTN) function as organic cation uniporters, organic cation/proton exchangers or sodium/L-carnitine co-transporters.
Nomenclature
Organic cation/carnitine transporter 1
Organic cation/carnitine transporter 2
Carnitine transporter 2
SLC22A4
SLC22A5
SLC22A16
Common abbreviation
OCTN1
OCTN2
CT2
HGNC, UniProt
SLC22A4, Q9H015
SLC22A5, O76082
SLC22A16, Q86VW1
L-carnitine
acetyl-L-carnitine, L-carnitine
L-carnitine
Substrates
pyrilamine, tetraethylammonium, verapamil, MPP+
pyrilamine, tetraethylammonium, verapamil, MPP+
Stoichiometry
Unknown
Unknown
Unknown

SLC22 family of organic cation and anion transporters 1750
Organic anion transporters (OATs)

Overview: Organic anion transporters (OATs) are non-selective transporters prominent in the kidney and intestine.
Nomenclature
Organic anion
transporter 1
Organic anion
transporter 2
Organic anion transporter 3
Organic anion
transporter 7
Organic anion
transporter 5
Organic anion transporter 4
SLC22A6
SLC22A7
SLC22A8
SLC22A9
SLC22A10
SLC22A11
Common abbreviation
OAT1
OAT2
OAT3
OAT4
OAT5
HGNC, UniProt
SLC22A6, Q4U2R8
SLC22A7, Q9Y694
SLC22A8, Q8TCC7
SLC22A9, Q8IVM8
SLC22A10, Q63ZE4
SLC22A11, Q9NSA0
Substrates
aminohippuric acid,
non-steroidal
anti-inflammatory drugs
PGE2, aminohippuric acid,

non-steroidal
anti-inflammatory drugs
cimetidine [305], ochratoxin A

[305], estrone-3-sulphate [305],
aminohippuric acid [305]
ochratoxin A [306]
dehydroepiandrosterone
sulphate [300], ochratoxin A
[300], estrone-3-sulphate [300]
Stoichiometry
Unknown
Unknown
Unknown
Unknown
Unknown
Unknown
Urate transporter
Nomenclature
Urate anion exchanger 1
SLC22A12
Common abbreviation
URAT1
HGNC, UniProt
SLC22A12, Q96S37
orotic acid [301], uric acid [301]
Stoichiometry
Unknown

Orphan or poorly characterized SLC22 family members
Nomenclature
Common abbreviation
HGNC, UniProt
Organic cation transporter-like 3
SLC22A13
ORCTL3
SLC22A13, Q9Y226
SLC22A14
ORCTL4
SLC22A14, Q9Y267
Fly-like putative transporter 1
SLC22A15
FLIPT1
SLC22A15, Q8IZD6
Brain-type organic cation transporter
SLC22A17
BOIT
SLC22A17, Q8WUG5
SLC22A18
ORCTL2
SLC22A18, Q96BI1
OAT6
SLC22A20
SLC22A20, A6NK97
SLC22A23
SLC22A23, A1A5C7
SLC22A24
SLC22A24, Q8N4F4
UST6
SLC22A25
SLC22A25, Q6T423
solute carrier family 22, member 31
SLC22A31
SLC22A31, A6NKX4
Further reading
Burckhardt G. (2012) Drug transport by Organic Anion Transporters (OATs). Pharmacol Ther 136:
106130. [PMID:22841915]
Koepsell H. (2013) The SLC22 family with transporters of organic cations, anions and zwitterions.
Mol Aspects Med 34: 413435. [PMID:23506881]

Knig J, Mller F, Fromm MF. (2013) Transporters and drug-drug interactions: important determinants of drug disposition and effects. Pharmacol Rev 65: 944966. [PMID:23686349]
Motohashi H, Inui K. (2013) Organic cation transporter OCTs (SLC22) and MATEs (SLC47) in the
human kidney. AAPS J 15: 581588. [PMID:23435786]
SLC23 family of ascorbic acid transporters

Overview: Predicted to be 12 TM segment proteins, members of this family transport the reduced form of ascorbic acid (while the oxidized form may be handled by members of the SLC2 family
(GLUT1/SLC2A1, GLUT3/SLC2A3 and GLUT4/SLC2A4). phloretin is considered a non-selective inhibitor of these transporters, with an affinity in the micromolar range.
Nomenclature
Sodium-dependent vitamin C
transporter 1
transporter 2
transporter 3
Sodium-dependent nucleobase
transporter
SLC23A1
SLC23A2
SLC23A3
SLC23A4
Common abbreviation
SVCT1
SVCT2
SVCT3
SNBT1
HGNC, UniProt
SLC23A1, Q9UHI7
SLC23A2, Q9UGH3
SLC23A3, Q6PIS1
SLC23A4P,
L-ascorbic acid > D-ascorbic acid >

dehydroascorbic acid [308]
L-ascorbic acid > D-ascorbic acid >

dehydroascorbic acid [308]
uracil > thymine > guanine, hypoxanthine

> xanthine, uridine [309]
Substrates
Inhibitors (pIC50)
phloretin [308]
5-fluorouracil [309]
Radioligands (Kd)
[14C]ascorbic acid
[14C]ascorbic acid
Stoichiometry
2 Na+: 1 ascorbic acid (in) [308]
2 Na+: 1 ascorbic acid (in) [308]
1 Na+ : 1 uracil (in) [309]
Comment
SLC23A3 does not transport ascorbic acid

and remains an orphan transporter.
SLC23A4/SNBT1 is found in rodents and

non-human primates, but the sequence is
truncated in the human genome and
named as a pseudogene, SLC23A4P
Further reading
Brzle M, Suzuki Y, Ackermann D, Miyazaki H, Maeda N, Clmenon B, Burrier R, Hediger MA.
(2013) The sodium-dependent ascorbic acid transporter family SLC23. Mol Aspects Med 34:
436454. [PMID:23506882]
May JM. (2011) The SLC23 family of ascorbate transporters: ensuring that you get and keep your
daily dose of vitamin C. Br J Pharmacol 164: 17931801. [PMID:21418192]

Rivas CI, Ziga FA, Salas-Burgos A, Mardones L, Ormazabal V, Vera JC. (2008) Vitamin C transporters. J Physiol Biochem 64: 357375. [PMID:19391462]
Savini I, Rossi A, Pierro C, Avigliano L, Catani MV. (2008) SVCT1 and SVCT2: key proteins for
vitamin C uptake. Amino Acids 34: 347355. [PMID:17541511]
SLC23 family of ascorbic acid transporters 1753
SLC24 family of sodium/potassium/calcium exchangers

Overview: The sodium/potassium/calcium exchange family of transporters utilize the extracellular sodium gradient to drive calcium and potassium co-transport out of the cell. As is the case for NCX
transporters (SLC8A family), NKCX transporters are thought to be bidirectional, with the possibility of calcium influx following depolarization of the plasma membrane. Topological modeling suggests
the presence of 10 TM domains, with a large intracellular loop between the fifth and sixth TM regions.
Nomenclature
Sodium/potassium/calcium
exchanger 1
exchanger 2
exchanger 3
exchanger 4
exchanger 5
exchanger 6
SLC24A1
SLC24A2
SLC24A3
SLC24A4
SLC24A5
SLC24A6
Common abbreviation
NKCX1
NKCX2
NKCX3
NKCX4
NKCX5
NKCX6
HGNC, UniProt
SLC24A1, O60721
SLC24A2, Q9UI40
SLC24A3, Q9HC58
SLC24A4, Q8NFF2
SLC24A5, Q71RS6
SLC8B1, Q6J4K2
Stoichiometry
4Na+:(1Ca2+ + 1K+)
Comments: NKCX6 exhibits sufficient structural diversity for its function as a NKCX to be questioned [310].
To date, there are no agents selective for this family of transporters.
Further reading
Altimimi HF, Schnetkamp PP. (2007) Na+/Ca2+-K+ exchangers (NCKX): functional properties and
physiological roles. Channels (Austin) 1: 6269. [PMID:18690016]

Schnetkamp PP. (2013) The SLC24 gene family of Na+/Ca2+-K+ exchangers: from sight and smell to
memory consolidation and skin pigmentation. Mol Aspects Med 34: 455464. [PMID:23506883]
SLC24 family of sodium/potassium/calcium exchangers 1754
SLC25 family of mitochondrial transporters

Overview: Mitochondrial transporters are nuclear-encoded proteins, which convey solutes across the inner mitochondrial membrane. Topological modelling suggests homodimeric transporters, each
with six TM segments and termini in the cytosol.
Mitochondrial di- and tri-carboxylic acid transporter subfamily

Overview: Mitochondrial di- and tri-carboxylic acid transporters are grouped on the basis of commonality of substrates and include the citrate transporter which facilitates citric acid export from the
mitochondria to allow the generation of oxalacetic acid and acetyl CoA through the action of ATP:citrate lyase.
Nomenclature
Mitochondrial citrate
transporter
Mitochondrial dicarboxylate
transporter
Mitochondrial oxoglutarate
carrier
Mitochondrial
oxodicarboxylate carrier
SLC25A1
SLC25A10
SLC25A11
SLC25A21
SLC25A34
SLC25A35
Common abbreviation
CIC
DIC
OGC
ODC
HGNC, UniProt
SLC25A1, P53007
SLC25A10, Q9UBX3
SLC25A11, Q02978
SLC25A21, Q9BQT8
SLC25A34, Q6PIV7
SLC25A35, Q3KQZ1
Substrates
citric acid, malic acid, PEP
malic acid, succinic acid,

PO34-, S2O32-, SO42-
malic acid, -ketoglutaric acid
-ketoglutaric acid,
-oxoadipic acid
Inhibitors (pIC50)
1,2,3-benzenetricarboxylic acid
Stoichiometry
Malate2- (in) : H-citrate2- (out)
PO34- (in) : malate2- (out)
Malate2- (in) : oxoglutarate2- (out)
Oxoadipate (in) :
oxoglutarate (out)
Mitochondrial amino acid transporter subfamily

Overview: Mitochondrial amino acid transporters can be subdivided on the basis of their substrates. Mitochondrial ornithine transporters play a role in the urea cycle by exchanging cytosolic ornithine
(L-ornithine and D-ornithine) for mitochondrial citrulline (L-citrulline and D-citrulline) in equimolar amounts. Further members of the family include transporters of S-adenosylmethionine and carnitine.
Nomenclature
Mitochondrial glutamate carrier 1
Mitochondrial glutamate carrier 2
AGC1
AGC2
SLC25A22
SLC25A18
SLC25A12
SLC25A13
Common abbreviation
GC1
GC2
AGC1
AGC2
HGNC, UniProt
SLC25A22, Q9H936
SLC25A18, Q9H1K4
SLC25A12, O75746
SLC25A13, Q9UJS0
Substrates
L-glutamic acid
L-glutamic acid

2-amino-3-sulfinopropanoic acid

2-amino-3-sulfinopropanoic acid
Stoichiometry
Glutamate : H+ (bidirectional)
Glutamate : H+ (bidirectional)
Aspartate : glutamate H+ (bidirectional)
Aspartate : glutamate H+ (bidirectional)

SLC25 family of mitochondrial transporters 1755
Nomenclature
Mitochondrial ornithine transporter 1
Mitochondrial ornithine transporter 2
Carnitine/acylcarnitine carrier
SLC25A15
SLC25A2
SLC25A20
Common abbreviation
ORC1
ORC2
CAC
HGNC, UniProt
SLC25A15, Q9Y619
SLC25A2, Q9BXI2
SLC25A20, O43772
Substrates
L-arginine [311], L-citrulline [311], L-lysine [311],

L-ornithine [311]
L-arginine [311], L-citrulline [311], L-lysine [311], L-ornithine

[311], L-histidine [311], D-histidine [311], D-arginine [311],
D-lysine [311], D-ornithine [311], D-citrulline [311]
Stoichiometry
1 Ornithine (in) :1 citrulline : 1 H+ (out)
1 Ornithine (in) :1 citrulline : 1 H+ (out)
Comment
Exchanges cytosolic acylcarnitine for

mitochondrial carnitine
Nomenclature

member 47

member 48
ORNT3
CGI-69
MCFP
SLC25A47
SLC25A48
SLC25A29
SLC25A38
SLC25A39
SLC25A40
SLC25A44
SLC25A45
Common abbreviation
ORNT3
HGNC, UniProt
SLC25A47,
Q6Q0C1
SLC25A48,
Q6ZT89
SLC25A29,
Q8N8R3
SLC25A38,
Q96DW6
SLC25A39,
Q9BZJ4
SLC25A40,
Q8TBP6
SLC25A44,
Q96H78
SLC25A45,
Q8N413
Comments: Both ornithine transporters are inhibited by the polyamine spermine [312]. Loss-of-function mutations in these genes are associated with hyperornithinemia-hyperammonemiahomocitrullinuria.
Mitochondrial phosphate transporters

Overview: Mitochondrial phosphate transporters allow the import of inorganic PO34- for ATP production.
Nomenclature
Mitochondrial phosphate carrier
SLC25A3
Common abbreviation
PHC
HGNC, UniProt
SLC25A3, Q00325
Stoichiometry
PO34- (in) : OH- (out) or PO34- : H+ (in)

Mitochondrial nucleotide transporter subfamily

Overview: Mitochondrial nucleotide transporters, defined by structural similarlities, include the adenine nucleotide translocator family (SLC25A4, SLC25A5, SLC25A6 and SLC25A31), which under
conditions of aerobic metabolism, allow coupling between mitochondrial oxidative phosphorylation and cytosolic energy consumption by exchanging cytosolic ADP for mitochondrial ATP. Further
members of the mitochondrial nucleotide transporter subfamily convey diverse substrates including CoA, although not all members have had substrates identified.
Nomenclature
Mitochondrial adenine
nucleotide translocator 1
SLC25A4
SLC25A5
SLC25A6
SLC25A31
SLC25A42
Common abbreviation
ANT1
ANT2
ANT3
ANT4
HGNC, UniProt
SLC25A4, P12235
SLC25A5, P05141
SLC25A6, P12236
SLC25A31, Q9H0C2
SLC25A42, Q86VD7
Inhibitors (pIC50)
BKA, CATR
Stoichiometry
ADP3- (in) : ATP4- (out)
Substrates
ADP
Nomenclature
Graves disease carrier
Peroxisomal membrane protein
Deoxynucleotide carrier 1
S-Adenosylmethionine carrier
SLC25A16
SLC25A17
SLC25A19
SLC25A26
Common abbreviation
GDC
PMP34
DNC
SAMC1
HGNC, UniProt
SLC25A16, P16260
SLC25A17, O43808
SLC25A19, Q9HC21
SLC25A26, Q70HW3
Substrates
CoA and congeners
ADP, ATP, AMP
Deoxynucleotide Diphosphates (dNDPs), Deoxynucleotide

Triphosphates (dNTPs), Dideoxynucleotide Triphosphates (ddNTPs),
Nucleotide Diphosphates (NDPs)
S-adenosyl methionine
Stoichiometry
CoA (in)
ATP (in)
dNDP (in) : ATP (out)
Nomenclature
Mitochondrial phosphate
carrier 1
carrier 2
carrier 3
MFT
PNC1
SCaMC-3L
SLC25A24
SLC25A23
SLC25A25
SLC25A32
SLC25A33
SLC25A36
SLC25A41
SLC25A43
Common abbreviation
APC1
APC2
APC3
MFTC
PNC2
HGNC, UniProt
SLC25A24,
Q6NUK1
SLC25A23,
Q9BV35
SLC25A25,
Q6KCM7
SLC25A32,
Q9H2D1
SLC25A33,
Q9BSK2
SLC25A36,
Q96CQ1
SLC25A41,
Q8N5S1
SLC25A43,
Q8WUT9

Mitochondrial uncoupling proteins

Overview: Mitochondrial uncoupling proteins allow dissipation of the mitochondrial proton gradient associated with thermogenesis and regulation of radical formation.
Nomenclature
Uncoupling protein 1
SLC25A7
SLC25A8
SLC25A9
Common abbreviation
UCP1
UCP2
UCP3
HGNC, UniProt
UCP1, P25874
UCP2, P55851
UCP3, P55916
Stoichiometry
H+ (in)
H+ (in)
H+ (in)
Nomenclature
KMCP1
SLC25A27
SLC25A14
SLC25A30
Common abbreviation
UCP4
UCP5
HGNC, UniProt
SLC25A27, O95847
SLC25A14, O95258
SLC25A30, Q5SVS4
Stoichiometry
H+ (in)
H+ (in)
Miscellaneous SLC25 mitochondrial transporters

Overview: Many of the transporters identified below have yet to be assigned functions and are currently regarded as orphans.
Nomenclature
mitochondrial carrier 1
mitochondrial carrier 2
Mitoferrin1
Mitoferrin2
SLC25A49
SLC25A50
SLC25A37
SLC25A28
HGNC, UniProt
MTCH1, Q9NZJ7
MTCH2, Q9Y6C9
SLC25A37, Q9NYZ2
SLC25A28, Q96A46
Nomenclature
SLC25A51
SLC25A52
SLC25A53
SLC25A46
HGNC, UniProt
SLC25A51, Q9H1U9
SLC25A52, Q3SY17
SLC25A53, Q5H9E4
SLC25A46, Q96AG3

Further reading
Cioffi F, Senese R, de Lange P, Goglia F, Lanni A, Lombardi A. (2009) Uncoupling proteins: a
complex journey to function discovery. Biofactors 35: 417428. [PMID:19626697]
Clmenon B, Babot M, Trzguet V. (2013) The mitochondrial ADP/ATP carrier (SLC25 family):
pathological implications of its dysfunction. Mol Aspects Med 34: 485493. [PMID:23506884]
Gnoni GV, Priore P, Geelen MJ, Siculella L. (2009) The mitochondrial citrate carrier: metabolic role
and regulation of its activity and expression. IUBMB Life 61: 987994. [PMID:19787704]

Gutirrez-Aguilar M, Baines CP. (2013) Physiological and pathological roles of mitochondrial SLC25
carriers. Biochem J 454: 371386. [PMID:23988125]
Palmieri F. (2004) The mitochondrial transporter family (SLC25): physiological and pathological
implications. Pflugers Arch 447: 689709. [PMID:14598172]
Palmieri F. (2013) The mitochondrial transporter family SLC25: identification, properties and
physiopathology. Mol Aspects Med 34: 465484. [PMID:23266187]
SLC26 family of anion exchangers

Overview: Along with the SLC4 family, the SLC26 family acts to allow movement of monovalent and divalent anions across cell membranes. The predicted topology is of 1014 TM domains with
intracellular C- and N-termini, probably existing as dimers. Within the family, subgroups may be identified on the basis of functional differences, which appear to function as anion exchangers and anion
channels (SLC26A7 and SLC26A9).
Selective sulphate transporters
Nomenclature
Sat-1
DTDST
SLC26A1
SLC26A2
HGNC, UniProt
SLC26A1, Q9H2B4
SLC26A2, P50443
Substrates
SO42-, oxalate
SO42-
Stoichiometry
SO42- (in) : anion (out)
1 SO42- (in) : 2 Cl- (out)
Chloride/bicarbonate exchangers
Nomenclature
DRA
Pendrin
PAT-1
SLC26A3
SLC26A4
SLC26A6
HGNC, UniProt
SLC26A3, P40879
SLC26A4, O43511
SLC26A6, Q9BXS9
Substrates
Cl-
Cl-, HCO3-, formate, I-, OH-
Cl-, HCO3-, SO42-, oxalate, formate, I-, OH-
Stoichiometry
2 Cl- (in) : 1 HCO3- (out) or 2 Cl- (in) : 1 OH- (out)
Unknown
1 SO42- (in) : 2 HCO3- (out) or 1 Cl- (in) : 2 HCO3- (out)
Anion channels
SLC26A7
HGNC, UniProt
SLC26A7, Q8TE54
SLC26A9, Q7LBE3
Substrates
NO3- >> Cl- = Br- = I- > SO42- = L-glutamic acid
I- > Br- > NO3- > Cl- > L-glutamic acid
Functional characteristics
Voltage- and time-independent current, linear I-V relationship [315]
Voltage- and time-independent current, linear I-V relationship [314]
Comment
SLC26A9 has been suggested to operate in two additional modes as a Cl--HCO3- exchanger and as a
Na+-anion cotransporter [313]

SLC26A9
SLC26 family of anion exchangers 1760
Other SLC26 anion exchangers
Nomenclature
Prestin
Tat1
KBAT
SLC26A5
SLC26A8
SLC26A10
SLC26A11
Common abbreviation
KBAT
HGNC, UniProt
SLC26A5, P58743
SLC26A8, Q96RN1
SLC26A10, Q8NG04
SLC26A11, Q86WA9
Substrates
Cl-, HCO3-
Cl-, SO42-, oxalate
HSO4-
Stoichiometry
Unknown
Unknown
Unknown
Unknown
Comment
Prestin has been suggested to function as a molecular motor, rather than a transporter
SLC26A10 is a possible pseudogene
Further reading
Alper SL, Sharma AK. (2013) The SLC26 gene family of anion transporters and channels. Mol Aspects
Med 34: 494515. [PMID:23506885]
Dorwart MR, Shcheynikov N, Yang D, Muallem S. (2008) The solute carrier 26 family of proteins in
epithelial ion transport. Physiology (Bethesda) 23: 104114. [PMID:18400693]
Kato A, Romero MF. (2011) Regulation of electroneutral NaCl absorption by the small intestine.
Annu Rev Physiol 73: 261281. [PMID:21054167]
Mount DB, Romero MF. (2004) The SLC26 gene family of multifunctional anion exchangers.
Pflugers Arch 447: 710721. [PMID:12759755]

Nofziger C, Dossena S, Suzuki S, Izuhara K, Paulmichl M. (2011) Pendrin function in airway

epithelia. Cell Physiol Biochem 28: 571578. [PMID:22116372]
Ohana E, Yang D, Shcheynikov N, Muallem S. (2009) Diverse transport modes by the solute carrier
26 family of anion transporters. J Physiol (Lond) 587 (Pt 10): 21792185. [PMID:19015189]
Soleimani M. (2013) SLC26 Cl(-)/HCO3(-) exchangers in the kidney: roles in health and disease.
Kidney Int [Epub ahead of print]. [PMID:23636174]
SLC26 family of anion exchangers 1761
SLC27 family of fatty acid transporters

Overview: Fatty acid transporter proteins (FATPs) are a family
(SLC27) of six transporters (FATP1-6). They have at least one, and
possibly six [319,325], transmembrane segments, and are predicted on the basis of structural similarities to form dimers.
SLC27 members have several structural domains: integral
membrane associated domain, peripheral membrane associated

domain, FATP signature, intracellular AMP binding motif,
dimerization domain, lipocalin motif, and an ER localization
domain (identified in FATP4 only) [317,322323]. These transporters are unusual in that they appear to express intrinsic very
long-chain acyl-CoA synthetase (EC 6.2.1.- , EC 6.2.1.7) enzyme

activity. Within the cell, these transporters may associate with
plasma and peroxisomal membranes. FATP1-4 and -6 transport
long- and very long-chain fatty acids, while FATP5 transports
long-chain fatty acids as well as bile acids [321,325].
Nomenclature
Fatty acid transport

protein 1

protein 2

protein 3

protein 4

protein 5

protein 6
SLC27A1
SLC27A2
SLC27A3
SLC27A4
SLC27A5
SLC27A6
Common abbreviation
FATP1
FATP2
FATP3
FATP4
FATP5
FATP6
HGNC, UniProt
SLC27A1, Q6PCB7
SLC27A2, O14975
SLC27A3, Q5K4L6
SLC27A4, Q6P1M0
SLC27A5, Q9Y2P5
SLC27A6, Q9Y2P4
arachidonic acid > palmitic

acid > oleic acid > butyric
acid [325], palmitic acid >
oleic acid > -linolenic acid
> octanoic acid [318]
palmitic acid > oleic acid >

butyric acid, -linolenic acid
> arachidonic acid [326],
palmitic acid, oleic acid >
-linolenic acid > octanoic
acid [318]
palmitic acid > oleic acid >

-linolenic acid > octanoic
acid [318]
Comment
FATP4 is genetically linked

to restrictive dermopathy
Comments: Although the stoichiometry of fatty acid transport

is unclear, it has been proposed to be facilitated by the coupling of fatty acid transport to conjugation with coenzyme A to
form fatty acyl CoA esters. Small molecule inhibitors of FATP2
[320,324] and FATP4 [316,327], as well as bile acid inhibitors of
FATP5 [327], have been described; analysis of the mechanism of
action of some of these inhibitors suggests that transport may be

selectively inhibited without altering enzymatic activity of the
FATP.
C1-BODIPY-C12 accumulation has been used as a non-selective
index of fatty acid transporter activity.
FATP2 has two variants: Variant 1 encodes the full-length

protein, while Variant 2 encodes a shorter isoform missing an
internal protein segment. FATP6 also has two variants: Variant 2
encodes the same protein as Variant 1 but has an additional
segment in the 5 UTR.
Further reading
Anderson CM, Stahl A. (2013) SLC27 fatty acid transport proteins. Mol Aspects Med 34: 516528.
[PMID:23506886]

Schwenk RW, Holloway GP, Luiken JJ, Bonen A, Glatz JF. (2010) Fatty acid transport across the cell
membrane: regulation by fatty acid transporters. Prostaglandins Leukot Essent Fatty Acids 82:
149154. [PMID:20206486]
SLC27 family of fatty acid transporters 1762
SLC28 and SLC29 families of nucleoside transporters

Overview: Nucleoside transporters are divided into two families, the sodium-dependent, solute carrier family 28 (SLC28) and the equilibrative, solute carrier family 29 (SLC29), where the endogenous
substrates are nucleosides.
SLC28 family
Overview: SLC28 family members have 13 TM segments with cytoplasmic N-termini and extracellular C-termini.
Nomenclature
CNT1
CNT2
CNT3
SLC28A1
SLC28A2
SLC28A3
Common abbreviation
CNT1
CNT2
CNT3
HGNC, UniProt
SLC28A1, O00337
SLC28A2, O43868
SLC28A3, Q9HAS3
adenosine, uridine, thymidine, cytidine
adenosine, inosine, guanosine, thymidine
adenosine, inosine, uridine, guanosine, thymidine, cytidine
Substrates
gemcitabine, zidovudine, zalcitabine
formycin B, cladribine, fludarabine, vidarabine, didanosine
5-fluorouridine, zebularine, formycin B, gemcitabine,

cladribine, floxuridine, zidovudine, zalcitabine, didanosine
Stoichiometry
1 Na+ : 1 nucleoside (in)
Comments: A further two Na+-dependent (stoichiometry 1 Na+ : 1 nucleoside (in)) nucleoside transporters have been defined on the basis of substrate and inhibitor selectivity: CNT4 (N4/cit, which
transports uridine, thymidine and guanosine) and CNT5 (N5/csg, which transports guanosine and adenosine, and may be inhibited by NBTI).
SLC29 family
Overview: SLC29 family members appear to be composed of 11 TM segments with cytoplasmic N-termini and extracellular C-termini. ENT1 and ENT2 are cell-surface transporters, while ENT3 is
intracellular, possibly lysosomal [328]. ENT1-3 are described as broad-spectrum nucleoside transporters.
Nomenclature
Equilibrative nucleoside transporter 1
Plasma membrane monoamine transporter
SLC29A1
SLC29A2
SLC29A3
SLC29A4
Common abbreviation
ENT1
ENT2
ENT3
PMAT
HGNC, UniProt
SLC29A1, Q99808
SLC29A2, Q14542
SLC29A3, Q9BZD2
SLC29A4, Q7RTT9
adenosine [335], inosine [335],

hypoxanthine [335], uridine [335],
guanosine [335], thymine [335],
thymidine [335], cytidine [335], adenine
[335]
adenosine, inosine, hypoxanthine, uridine,

guanosine, thymidine
adenosine [328], inosine [328], uridine

[328], guanosine [328], thymidine [328],
adenine [328]
5-HT [329], dopamine [329], histamine

[329], tyramine [329]

SLC28 and SLC29 families of nucleoside transporters 1763
Nomenclature
Plasma membrane monoamine transporter
Substrates
2-chloroadenosine, formycin B, tubercidin,

gemcitabine, cladribine, floxuridine,
pentostatin, vidarabine, cytarabine,
zalcitabine, didanosine
2-chloroadenosine, formycin B, tubercidin,

gemcitabine, cladribine, vidarabine,
zidovudine, cytarabine
cordycepin [328], zebularine [328],

tubercidin [328], cladribine [328],
floxuridine [328], fludarabine [328],
zidovudine [328], zalcitabine [328],
didanosine [328]
tetraethylammonium [329], MPP+ [329]
Inhibitors (pIC50)
NBTI (pKi 9.7), draflazine (pKi 9.5),

KF24345 (pKi 9.4) [330], NBTGR (pKi 9.3),
dilazep (pKi 9.0), dipyridamole (pKi 8.5)
cimetidine [329], quinidine [329], quinine

[329], rhodamine123 [329], verapamil
[329]
Radioligands (Kd)
[3H]NBTI (5x10-10 M)
Stoichiometry
Equilibrative
Equilibrative
Equilibrative
Equilibrative
Comment
ENT1 has 100-1000-fold lower affinity for

nucleobases as compared with nucleosides
[335]., The affinities of draflazine, dilazep,
KF24345 and dipyridamole at ENT1
transporters are species dependent,
exhibiting lower affinity at rat transporters
than at human transporters [330,333].,
The loss of ENT1 activity in ENT1-null
mice has been associated with a
hypermineralization disorder similar to
human diffuse idiopathic skeletal
hyperostosis [334]
Defects in SLC29A3 have been implicated

in Histiocytosis-lymphadenopathy plus
syndrome (OMIM:602782) and lysosomal
storage diseases [331332]
Further reading
Baldwin SA, McConkey GA, Cass CE, Young JD. (2007) Nucleoside transport as a potential target for
chemotherapy in malaria. Curr Pharm Des 13: 569580. [PMID:17346175]
Cano-Soldado P, Pastor-Anglada M. (2012) Transporters that translocate nucleosides and structural
similar drugs: structural requirements for substrate recognition. Med Res Rev 32: 428457.
[PMID:21287570]
King AE, Ackley MA, Cass CE, Young JD, Baldwin SA. (2006) Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol Sci 27: 416425. [PMID:16820221]

Pastor-Anglada M, Cano-Soldado P, Errasti-Murugarren E, Casado FJ. (2008) SLC28 genes and

concentrative nucleoside transporter (CNT) proteins. Xenobiotica 38: 972994. [PMID:18668436]
Young JD, Yao SY, Baldwin JM, Cass CE, Baldwin SA. (2013) The human concentrative and
equilibrative nucleoside transporter families, SLC28 and SLC29. Mol Aspects Med 34: 529547.
[PMID:23506887]
SLC28 and SLC29 families of nucleoside transporters 1764
SLC30 zinc transporter family

Overview: Along with the SLC39 family, SLC30 transporters
regulate the movement of zinc ions around the cell. In particular,
these transporters remove zinc ions from the cytosol, allowing
accumulation into intracellular compartments or efflux through
the plasma membrane. ZnT1 is thought to be placed on the
Nomenclature
plasma membrane extruding zinc, while ZnT3 is associated with

synaptic vesicles and ZnT4 and ZnT5 are linked with secretory
granules. Membrane topology predictions suggest a multimeric
assembly, potentially heteromultimeric [337], with subunits
having six TM domains, and both termini being cytoplasmic.
Dityrosine covalent linking has been suggested as a mechanism

for dimerisation, particularly for ZnT3 [336]. The mechanism for
zinc transport is unknown.
Common abbreviation
HGNC, UniProt
Zinc transporter 1
SLC30A1
ZnT1
SLC30A1, Q9Y6M5
Zinc transporter 2
SLC30A2
ZnT2
SLC30A2, Q9BRI3
Zinc transporter 3
SLC30A3
ZnT3
SLC30A3, Q99726
Zinc transporter 4
SLC30A4
ZnT4
SLC30A4, O14863
Zinc transporter 5
SLC30A5
ZnT5
SLC30A5, Q8TAD4
Zinc transporter 6
SLC30A6
ZnT6
SLC30A6, Q6NXT4
Zinc transporter 7
SLC30A7
ZnT7
SLC30A7, Q8NEW0
Zinc transporter 8
SLC30A8
ZnT8
SLC30A8, Q8IWU4
Zinc transporter 9
SLC30A9
ZnT9
SLC30A9, Q6PML9
Zinc transporter 10
SLC30A10
ZnT10
SLC30A10, Q6XR72
Comments: ZnT8/SLC30A8 is described as a type 1 diabetes susceptibility gene.

Zinc fluxes may be monitored through the use of radioisotopic Zn-65 or the fluorescent dye FluoZin 3.
Further reading
Bouron A, Oberwinkler J. (2013) Contribution of calcium-conducting channels to the transport of
zinc ions. Pflugers Arch [Epub ahead of print]. [PMID:23719866]
Huang L, Tepaamorndech S. (2013) The SLC30 family of zinc transporters - a review of current
understanding of their biological and pathophysiological roles. Mol Aspects Med 34: 548560.
[PMID:23506888]
Kawasaki E. (2012) ZnT8 and type 1 diabetes. Endocr J 59: 531537. [PMID:22447136]

Palmiter RD, Huang L. (2004) Efflux and compartmentalization of zinc by members of the SLC30
family of solute carriers. Pflugers Arch 447: 744751. [PMID:12748859]
Rungby J. (2010) Zinc, zinc transporters and diabetes. Diabetologia 53: 15491551. [PMID:20490449]
Wang X, Zhou B. (2010) Dietary zinc absorption: A play of Zips and ZnTs in the gut. IUBMB Life 62:
176182. [PMID:20120011]
SLC30 zinc transporter family 1765
SLC31 family of copper transporters

Overview: SLC31 family members, alongside the Cu-ATPases are involved in the regulation of cellular copper levels. The CTR1 transporter is a cell-surface transporter to allow monovalent copper
accumulation into cells, while CTR2 appears to be a vacuolar/vesicular transporter [341]. Functional copper transporters appear to be trimeric with each subunit having three TM regions and an
extracellular N-terminus. CTR1 is considered to be a higher affinity copper transporter compared to CTR2. The stoichiometry of copper accumulation is unclear, but appears to be energy-independent
[340].
Nomenclature
Copper transporter 1
Copper transporter 2
SLC31A1
SLC31A2
Common abbreviation
CTR1
CTR2
HGNC, UniProt
SLC31A1, O15431
SLC31A2, O15432
copper [340]
copper
Substrates
cisplatin [339]
cisplatin [338]
Stoichiometry
Unknown
Unknown
Comments: Copper accumulation through CTR1 is sensitive to silver ions, but not divalent cations [340].
Further reading
Howell SB, Safaei R, Larson CA, Sailor MJ. (2010) Copper transporters and the cellular pharmacology
of the platinum-containing cancer drugs. Mol Pharmacol 77: 887894. [PMID:20159940]
Kim H, Wu X, Lee J. (2013) SLC31 (CTR) family of copper transporters in health and disease. Mol
Aspects Med 34: 561570. [PMID:23506889]
Nose Y, Rees EM, Thiele DJ. (2006) Structure of the Ctr1 copper transPOREter reveals novel
architecture. Trends Biochem Sci 31: 604607. [PMID:16982196]

Petris MJ. (2004) The SLC31 (Ctr) copper transporter family. Pflugers Arch 447: 752755.
[PMID:12827356]
Zheng W, Monnot AD. (2012) Regulation of brain iron and copper homeostasis by brain barrier
systems: implication in neurodegenerative diseases. Pharmacol Ther 133: 177188.
[PMID:22115751]
SLC31 family of copper transporters 1766
SLC32 vesicular inhibitory amino acid transporter

Overview: The vesicular inhibitory amino acid transporter,
VIAAT (also termed the vesicular GABA transporter VGAT),
which is the sole representative of the SLC32 family, transports
GABA, or glycine, into synaptic vesicles [343344], and is a
member of the structurally-defined amino acid-polyamineorganocation/APC clan composed of SLC32, SLC36 and SLC38
transporter families (see [349]). VIAAT was originally suggested to
be composed of 10 TM segments with cytoplasmic N- and
C-termini [347]. However, an alternative 9TM structure with the
N terminus facing the cytoplasm and the C terminus residing in

the synaptic vesicle lumen has subsequently been reported [346].
VIAAT acts as an antiporter for inhibitory amino acids and
protons. The accumulation of GABA and glycine within vesicles
is driven by both the chemical (pH) and electrical () components of the proton electrochemical gradient (H+) established
by a vacuolar H+-ATPase [347]. However, one study, [345], presented evidence that VIAAT is instead a Cl-/GABA co-transporter.
VIAAT co-exists with VGLUT1 (SLC17A7), or VGLUT2
(SLC17A6), in the synaptic vesicles of selected nerve terminals

[342,351]. VIAAT knock out mice die between embryonic day
18.5 and birth [350]. In cultures of spinal cord neurones established from earlier embryos, the co-release of of GABA and
glycine from synaptic vesicles is drastically reduced, providing
direct evidence for the role of VIAAT in the sequestration of both
transmitters [348,350].
Nomenclature
Vesicular inhibitory amino acid transporter
SLC32A1
Common abbreviation
VIAAT
HGNC, UniProt
SLC32A1, Q9H598
glycine, -alanine, -hydroxybutyric acid, GABA (Km 5x10-3 M) [347]
Inhibitors (pIC50)
vigabatrin (2.1) [347]
Stoichiometry
1 amino acid (in): 1 H+ (out) [344] or 1 amino acid: 2Cl- (in) [345]
Further reading
Erickson JD, De Gois S, Varoqui H, Schafer MK, Weihe E. (2006) Activity-dependent regulation of
vesicular glutamate and GABA transporters: a means to scale quantal size. Neurochem Int 48:
643649. [PMID:16546297]
Gasnier B. (2000) The loading of neurotransmitters into synaptic vesicles. Biochimie 82: 327337.
[PMID:10865121]

Gasnier B. (2004) The SLC32 transporter, a key protein for the synaptic release of inhibitory amino
acids. Pflugers Arch 447: 756759. [PMID:12750892]
Schith HB, Roshanbin S, Hgglund MG, Fredriksson R. (2013) Evolutionary origin of amino acid
transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic
aspects. Mol Aspects Med 34: 571585. [PMID:23506890]
SLC32 vesicular inhibitory amino acid transporter 1767
SLC33 acetylCoA transporter

Overview: Acetylation of proteins is a post-translational modification mediated by specific acetyltransferases, using the donor acetyl CoA. SLC33A1/AT1 is a putative 11 TM transporter present on the
endoplasmic reticulum, expressed in all tissues, but particularly abundant in the pancreas [353], which imports cytosolic acetyl CoA into these intracellular organelles.
Nomenclature
AcetylCoA transporter
SLC33A1
Common abbreviation
ACATN1
HGNC, UniProt
SLC33A1, O00400
acetyl CoA
Radioligands (Kd)
[14C]acetylCoA
Stoichiometry
Unknown
Comments: In heterologous expression studies, acetyl CoA transport through AT1 was inhibited by coenzyme A, but not acetic acid, ATP or UDP-galactose [352]. A loss-of-function mutation in
ACATN1/SLC33A1 has been associated with spastic paraplegia (SPG42, [354]), although this observation could not be replicated in a subsequent study [355].
Further reading
Hirabayashi Y, Kanamori A, Nomura KH, Nomura K. (2004) The acetyl-CoA transporter family
SLC33. Pflugers Arch 447: 760762. [PMID:12739170]

Hirabayashi Y, Nomura KH, Nomura K. (2013) The acetyl-CoA transporter family SLC33. Mol Aspects
Med 34: 586589. [PMID:23506891]
SLC33 acetylCoA transporter 1768
SLC34 family of sodium phosphate co-transporters

Overview: The SLC34 family are sometimes referred to as Type II sodium-phosphate co-transporters, alongside Type I (SLC17 family) and Type III (SLC20 family) transporters. Topological modelling
suggests eight TM domains with C- and N- termini in the cytoplasm, and a re-entrant loop at TM7/8. SLC34 family members are expressed on the apical surfaces of epithelia in the intestine and kidneys
to regulate body phosphate levels, principally NaPi-IIa and NaPi-IIb, respectively. NaPi-IIa and NaPi-IIb are electrogenic, while NaPiIIc is electroneutral [356].
Nomenclature
Sodium phosphate 1
Sodium phosphate 2
Sodium phosphate 3
SLC34A1
SLC34A2
SLC34A3
Common abbreviation
NaPi-IIa
NaPi-IIb
NaPi-IIc
HGNC, UniProt
SLC34A1, Q06495
SLC34A2, O95436
SLC34A3, Q8N130
Stoichiometry
3 Na+ : 1 HPO42- (in) [357]
3 Na+ : 1 HPO42- (in) [356]
2 Na+ : 1 HPO42- (in) [356]
Comments: These transporters can be inhibited by PFA, in contrast to type III sodium-phosphate cotransporters, the SLC20 family.
Further reading
75: 535550. [PMID:23398154]
Forster IC, Hernando N, Biber J, Murer H. (2013) Phosphate transporters of the SLC20 and SLC34
families. Mol Aspects Med 34: 386395. [PMID:23506879]

Murer H, Forster I, Biber J. (2004) The sodium phosphate cotransporter family SLC34. Pflugers Arch
447: 763767. [PMID:12750889]
SLC34 family of sodium phosphate co-transporters 1769
SLC35 family of nucleotide sugar transporters

Overview: Glycoprotein formation in the Golgi and endoplasmic reticulum relies on the accumulation of nucleotideconjugated sugars via the SLC35 family of transporters. These
transporters have a predicted topology of 10 TM domains, with
cytoplasmic termini, and function as exchangers, swopping

nucleoside monophosphates for the corresponding nucleoside
diphosphate conjugated sugar. Five subfamilies of transporters
have been identified on the basis of sequence similarity, namely
SLC35A1, SLC35A2, SLC35A3, SLC35A4 and SLC35A5; SLC35B1,

SLC35B2, SLC35B3 and SLC35B4; SLC35C1 and SLC35C2;
SLC35D1, SL35D1, SLC35D2 and SLC35D3, and the subfamily of
orphan SLC35 transporters, SLC35E1-4 and SLC35F1-5.
Nomenclature
CMP-sialic acid transporter
UDP-galactose transporter
UDP-N-acetylglucosamine
transporter
MGC2541
FLJ11130
SLC35A1
SLC35A2
SLC35A3
SLC35A4
SLC35A5
HGNC, UniProt
SLC35A1, P78382
SLC35A2, P78381
SLC35A3, Q9Y2D2
SLC35A4, Q96G79
SLC35A5, Q9BS91
Substrates
CMP-sialic acid [359]
UDP N-acetyl-glucosamine [361,366],

UDP-galactose [361,366]
UDP N-acetyl-glucosamine
[362]
Nomenclature
UGTREL1
PAPS transporter 1
PAPS transporter 2
YEA
SLC35B1
SLC35B2
SLC35B3
SLC35B4
HGNC, UniProt
SLC35B1, P78383
SLC35B2, Q8TB61
SLC35B3, Q9H1N7
SLC35B4, Q969S0
Substrates
A3P5PS [364]
A3P5PS [363]
UDP N-acetyl-glucosamine
[358], UDP-xylose [358]
Nomenclature
GDP-Fucose transporter
OVCOV1
UDP-glucuronic acid/UDP-Nacetylgalactosamine dual transporter
HFRC1
FRCL1
SLC35C1
SLC35C2
SLC35D1
SLC35D2
SLC35D3
HGNC, UniProt
SLC35C1, Q96A29
SLC35C2, Q9NQQ7
SLC35D1, Q9NTN3
SLC35D2, Q76EJ3
SLC35D3, Q5M8T2
Substrates
GDP-fucose [365]
UDP-glucuronic acid [367],

UDP-N-acetylgalactosamine [367]
UDP-N-acetylgalactosamine
[360]
Nomenclature

member E2B
SLC35E1
SLC35E2
SLC35E2B
SLC35E3
SLC35E4
HGNC, UniProt
SLC35E1, Q96K37
SLC35E2, P0CK97
SLC35E2B, P0CK96
SLC35E3, Q7Z769
SLC35E4, Q6ICL7
Comment
Orphan transporter
Orphan transporter
Orphan transporter
Orphan transporter

SLC35 family of nucleotide sugar transporters 1770
Nomenclature

member F6
SLC35F1
SLC35F2
SLC35F3
SLC35F4
SLC35F5
SLC35F6
HGNC, UniProt
SLC35F1, Q5T1Q4
SLC35F2, Q8IXU6
SLC35F3, Q8IY50
SLC35F4, A4IF30
SLC35F5, Q8WV83
SLC35F6, Q8N357
Comment
Orphan transporter
Orphan transporter
Orphan transporter
Orphan transporter
Orphan transporter
Nomenclature

member G1

member G3

member G4

member G5

member G6
SLC35G1
SLC35G3
SLC35G4
SLC35G5
SLC35G6
HGNC, UniProt
SLC35G1, Q2M3R5
SLC35G3, Q8N808
SLC35G4, P0C7Q5
SLC35G5, Q96KT7
SLC35G6, P0C7Q6
Further reading
Ishida N, Kawakita M. (2004) Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35). Pflugers Arch 447: 768775. [PMID:12759756]

Song Z. (2013) Roles of the nucleotide sugar transporters (SLC35 family) in health and disease. Mol
Aspects Med 34: 590600. [PMID:23506892]
SLC35 family of nucleotide sugar transporters 1771
SLC36 family of proton-coupled amino acid transporters

Overview: The SLC36 family of proton-coupled amino acid transporters (or PAT) is highly expressed in the intestine and kidney, having roles in the disposition of amino acids [383]. PAT1 is found on
the gut epithelia luminal surface accumulating dietary amino acids, and additionally in lysosomal membranes where it likely functions as an efflux mechanism for amino acids produced during
intralysosomal proteolysis [369,382]. PAT2 is found at the apical membrane of the kidney proximal tubule [372]. PAT1 and PAT2 are predicted to have 11 TM domains with intracellular N-termini
[370,382].
Nomenclature
Proton-coupled Amino acid Transporter 1
Proton-coupled Amino acid Transporter 2
Proton-coupled Amino
acid Transporter 3
Proton-coupled Amino acid

Transporter 4
SLC36A1
SLC36A2
SLC36A3
SLC36A4
Common abbreviation
PAT1
PAT2
PAT3
PAT4
HGNC, UniProt
SLC36A1, Q7Z2H8
SLC36A2, Q495M3
SLC36A3, Q495N2
SLC36A4, Q6YBV0
L-alanine, glycine, GABA, -alanine, taurine,

L-proline, D-serine, D-cysteine, D-proline, D-alanine,
trans-4-hydroxy-proline, sarcosine
L-alanine, glycine, -alanine, L-proline,

trans-4-hydroxy-proline, sarcosine
L-tryptophan [381], L-proline [381]
Substrates
THIP [378], betaine, L-azetidine-2-carboxylate [377],

MeAIB [373], -guanidinopropionic acid, THPO
[379], 5-aminolevulinic acid, vigabatrin [368]
L-azetidine-2-carboxylate [377], MeAIB [374]
Inhibitors (pIC50)
5-hydroxy-L-tryptophan (pKi 3.0) [380], indole-3propionic acid (pKi 2.3) [380], L-tryptophan (pKi 2.3)
[380], 5-HT (pKi 2.2) [380]
5-hydroxy-L-tryptophan (2.8) [375],

-methyl-D,L-tryptophan (2.5) [375]
Stoichiometry
1 H+ : 1 amino acid (in)
1 H+ : 1 amino acid (in)
Unknown
Unknown
[3H] or [14C] labelled substrates as listed above are

used as probes
Comment
14
[ H] or [ C] labelled substrates as listed above are

used as probes
Comments: Both PAT1 and PAT2 can also function as an electroneutral transport system for H+ and fatty acids including acetic acid, propanoic acid and butyric acid [376].
Loss-of-function mutations in PAT2 lead to iminoglycinuria and hyperglycinuria in man [371].
Further reading
Boll M, Daniel H, Gasnier B. (2004) The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis. Pflugers Arch 447:
776779. [PMID:12748860]

Thwaites DT, Anderson CM. (2007) Deciphering the mechanisms of intestinal imino (and amino)
acid transport: the redemption of SLC36A1. Biochim Biophys Acta 1768: 179197.
[PMID:17123464]
Thwaites DT, Anderson CM. (2011) The SLC36 family of proton-coupled amino acid transporters
and their potential role in drug transport. Br J Pharmacol 164: 18021816. [PMID:21501141]
SLC36 family of proton-coupled amino acid transporters 1772
SLC37 family of phosphosugar/phosphate exchangers

Overview: The family of sugar-phosphate exchangers pass particular phosphorylated sugars across intracellular membranes, exchanging for inorganic phosphate. Of the family of sugar phosphate
transporters, most information is available on SPX4, the glucose-6-phosphate transporter. This is a 10 TM domain protein with cytoplasmic termini and is associated with the endoplasmic reticulum, with
tissue-specific splice variation.
Nomenclature
Glycerol-3-phosphate transporter
SPX2
SPX3
Glucose-6-phosphate transporter
SLC37A1
SLC37A2
SLC37A3
SLC37A4
Common abbreviation
SPX1
SPX4
HGNC, UniProt
SLC37A1, P57057
SLC37A2, Q8TED4
SLC37A3,
Q8NCC5
SLC37A4, O43826
glucose 6-phosphate, glycerol 3-phosphate
glucose 6-phosphate
glucose 6-phosphate
Stoichiometry
Glucose 6-phosphate (in): phosphate (out) [386]
Unknown
Comment
Multiple polymorphisms have been described for the

SLC37A4 gene, some of which associate with a
glycogen storage disease [384]
Further reading
Bartoloni L, Antonarakis SE. (2004) The human sugar-phosphate/phosphate exchanger family
SLC37. Pflugers Arch 447: 780783. [PMID:12811562]

Chou JY, Sik Jun H, Mansfield BC. (2013) The SLC37 family of phosphate-linked sugar phosphate
antiporters. Mol Aspects Med 34: 601611. [PMID:23506893]
SLC37 family of phosphosugar/phosphate exchangers 1773
SLC38 family of sodium-dependent neutral amino acid transporters

Overview: The SLC38 family of transporters appears to be responsible for the functionally-defined system A and system N mechanisms of amino acid transport and are mostly expressed in the CNS. Two
distinct subfamilies are identifiable within the SLC38 transporters. SNAT1, SNAT2 and SNAT4 appear to resemble system A transporters in accumulating neutral amino acids under the influence of the
sodium gradient. SNAT3 and SNAT5 appear to resemble system N transporters in utilizing proton co-transport to accumulate amino acids. The predicted membrane topology is of 11 TM domains with
an extracellular C-terminus and intracellular N-terminus [394].
System A-like transporters
Nomenclature
SNAT1
SNAT2
SNAT4
SLC38A1
SLC38A2
SLC38A4
Common abbreviation
SNAT1
SNAT2
SNAT4
HGNC, UniProt
SLC38A1, Q9H2H9
SLC38A2, Q96QD8
SLC38A4, Q969I6
L-alanine > L-serine, L-glutamine, L-asparagine,

L-histidine, L-cysteine, L-methionine > glycine,
L-threonine, L-proline, L-tyrosine, L-valine [387]
L-alanine, L-methionine > L-asparagine, L-glutamine,

L-serine, L-proline, glycine > L-threonine, L-leucine,
L-phenylalanine [391]
L-histidine > L-arginine, L-alanine, L-asparagine,

L-lysine > glycine, L-glutamine, L-serine, L-proline,
L-leucine, L-phenylalanine [390]
Substrates
MeAIB
MeAIB
MeAIB
Radioligands (Kd)
[14C]alanine, [3H]alanine
[14C]alanine, [3H]alanine
[14C]alanine, [14C]glycine, [3H]alanine, [3H]glycine
Stoichiometry
1 Na : 1 amino acid (in) [387]
1 Na : 1 amino acid (in) [391]
1 Na+ : 1 neutral amino acid (in) [390]
Comment
Transport of cationic amino acids by SNAT4 was

sodium-independent [390]
System N-like transporters
Nomenclature
SNAT3
SNAT5
SLC38A3
SLC38A5
Common abbreviation
SNAT3
SNAT5
HGNC, UniProt
SLC38A3, Q99624
SLC38A5, Q8WUX1
L-histidine , L-glutamine > L-asparagine, L-alanine > L-glutamic acid [389]
L-asparagine, L-serine, L-histidine, L-glutamine > glycine, L-alanine [393]
Substrates
MeAIB
MeAIB
Radioligands (Kd)
[14C]glutamine, [3H]glutamine
Stoichiometry
+
1 Na : 1 amino acid (in) : 1 H (out) [388]

1 Na+ : 1 amino acid (in) : 1 H+ (out) [393]
SLC38 family of sodium-dependent neutral amino acid transporters 1774
Orphan SLC38 transporters
Nomenclature
SNAT6
SNAT7
PP1744
AVT2
SLC38A6
SLC38A7
SLC38A8
SLC38A9
SLC38A10
SLC38A11
Common abbreviation
SNAT6
SNAT7
HGNC, UniProt
SLC38A6,
Q8IZM9
SLC38A7, Q9NVC3
SLC38A8,
A6NNN8
SLC38A9,
Q8NBW4
SLC38A10,
Q9HBR0
SLC38A11,
Q08AI6
Comment
SNAT7/SLC38A7 has been described to be a system N-like transporter allowing

preferential accumulation of L-glutamine, L-histidine and L-asparagine [392]
Further reading
Brer S, Palacn M. (2011) The role of amino acid transporters in inherited and acquired diseases.
Biochem J 436: 193211. [PMID:21568940]
Hgglund MG, Sreedharan S, Nilsson VC, Shaik JH, Almkvist IM, Bcklin S, Wrange O, Fredriksson
R. (2011) Identification of SLC38A7 (SNAT7) protein as a glutamine transporter expressed in
neurons. J Biol Chem 286: 2050020511. [PMID:21511949]
Mackenzie B, Erickson JD. (2004) Sodium-coupled neutral amino acid (System N/A) transporters of
the SLC38 gene family. Pflugers Arch 447: 784795. [PMID:12845534]

Sundberg BE, Wg E, Jacobsson JA, Stephansson O, Rumaks J, Svirskis S, Alsi J, Roman E, Ebendal
T, Klusa V et al. (2008) The evolutionary history and tissue mapping of amino acid transporters
belonging to solute carrier families SLC32, SLC36, and SLC38. J Mol Neurosci 35: 179193.
[PMID:18418736]
SLC38 family of sodium-dependent neutral amino acid transporters 1775
SLC39 family of metal ion transporters

Overview: Along with the SLC30 family, SLC39 family members regulate zinc movement in cells. SLC39 metal ion transporters accumulate zinc into the cytosol. Membrane topology modelling suggests
the presence of eight TM regions with both termini extracellular or in the lumen of intracellular organelles. The mechanism for zinc transport for many members is unknown but appears to involve
co-transport of bicarbonate ions [396397].
Nomenclature
Zinc transporter 1
Zinc transporter 2
Zinc transporter 3
Zinc transporter 4
metal ion transporter 5
Zinc transporter 6
Zinc transporter 7
SLC39A1
SLC39A2
SLC39A3
SLC39A4
SLC39A5
SLC39A6
SLC39A7
Common abbreviation
ZIP1
ZIP2
ZIP3
ZIP4
ZIP5
ZIP6
ZIP7
HGNC, UniProt
SLC39A1, Q9NY26
SLC39A2, Q9NP94
SLC39A3, Q9BRY0
SLC39A4, Q6P5W5
SLC39A5, Q6ZMH5
SLC39A6, Q13433
SLC39A7, Q92504
Nomenclature
Zinc transporter 8
Zinc transporter 9
Zinc transporter 10
Zinc transporter 11
Zinc transporter 12
Zinc transporter 13
Zinc transporter 14
SLC39A8
SLC39A9
SLC39A10
SLC39A11
SLC39A12
SLC39A13
SLC39A14
Common abbreviation
ZIP8
ZIP9
ZIP10
ZIP11
ZIP12
ZIP13
ZIP14
HGNC, UniProt
SLC39A8, Q9C0K1
SLC39A9, Q9NUM3
SLC39A10, Q9ULF5
SLC39A11, Q8N1S5
SLC39A12, Q504Y0
SLC39A13, Q96H72
SLC39A14, Q15043
Substrates
Cd2+ [395,397]
Cd2+ [396], Fe2+ [398],

Mn2+ [396]
Stoichiometry
1 Zn2+ (in) : 2 HCO3- (in) [397]
Comments: Zinc fluxes may be monitored through the use of radioisotopic Zn-65 or the fluorescent dye FluoZin 3.
The bicarbonate transport inhibitor DIDS has been reported to inhibit cation accumulation through ZIP14 [396].
Further reading
Eide DJ. (2004) The SLC39 family of metal ion transporters. Pflugers Arch 447: 796800.
[PMID:12748861]
Franz MC, Anderle P, Brzle M, Suzuki Y, Freeman MR, Hediger MA, Kovacs G. (2013) Zinc
transporters in prostate cancer. Mol Aspects Med 34: 735741. [PMID:23506906]
Himeno S, Yanagiya T, Fujishiro H. (2009) The role of zinc transporters in cadmium and manganese
transport in mammalian cells. Biochimie 91: 12181222. [PMID:19375483]

Jeong J, Eide DJ. (2013) The SLC39 family of zinc transporters. Mol Aspects Med 34: 612619.
[PMID:23506894]
Rungby J. (2010) Zinc, zinc transporters and diabetes. Diabetologia 53: 15491551. [PMID:20490449]
Thvenod F. (2010) Catch me if you can! Novel aspects of cadmium transport in mammalian cells.
Biometals 23: 857875. [PMID:20204475]
SLC39 family of metal ion transporters 1776
SLC40 iron transporter

Overview: Alongside the SLC11 family of proton-coupled metal transporters, ferroportin allows the accumulation of iron from the diet. Whilst SLC11A2 functions on the apical membrane, ferroportin
acts on the basolateral side of the enterocyte, as well as regulating macrophage and placental iron levels. The predicted topology is of 12 TM domains, with intracellular termini [403], with the functional
transporter potentially a dimeric arrangement [399400].
Nomenclature
Ferroportin
SLC40A1
Common abbreviation
IREG1
HGNC, UniProt
SLC40A1, Q9NP59
Fe2+
Stoichiometry
Unknown
Comments: Hepcidin (HAMP, P81172), cleaved into hepcidin-25 (HAMP, P81172) and hepcidin-20 (HAMP, P81173), is a small protein that increases upon inflammation, binds to ferroportin to regulate
its cellular distribution and degradation. Gene disruption in mice results in embryonic lethality [402], while loss-of-function mutations in man are associated with haemochromatosis [401].
Further reading
McKie AT, Barlow DJ. (2004) The SLC40 basolateral iron transporter family (IREG1/ferroportin/
MTP1). Pflugers Arch 447: 801806. [PMID:12836025]

Montalbetti N, Simonin A, Kovacs G, Hediger MA. (2013) Mammalian iron transporters: families
SLC11 and SLC40. Mol Aspects Med 34: 270287. [PMID:23506870]
SLC40 iron transporter 1777
SLC41 family of divalent cation transporters

Overview: By analogy with bacterial orthologues, this family is probably magnesium transporters. The prokaryote orthologue, MgtE, is responsible for uptake of divalent cations, while the heterologous
expression studies of mammalian proteins suggest Mg2+ efflux [406], possibly as a result of co-expression of particular protein partners (see [407]). Topological modelling suggests 10 TM domains with
cytoplasmic C- and N- termini.
SLC41A1
SLC41A2
Common abbreviation
MgtE
SLC41A3
HGNC, UniProt
SLC41A1, Q8IVJ1
SLC41A2, Q96JW4
SLC41A3, Q96GZ6
Substrates
Zn2+ [404], Mg2+ [404], Ba2+ [404], Cd2+ [404], Co2+ [404], Cu2+ [404],
Fe2+ [404], Sr2+ [404]
Mg2+ [405], Ba2+ [405], Ni2+ [405], Co2+ [405], Fe2+ [405], Mn2+ [405]
Stoichiometry
Unknown
Unknown
Unknown
Further reading
Moomaw AS, Maguire ME. (2008) The unique nature of mg2+ channels. Physiology (Bethesda) 23:
275285. [PMID:18927203]
Payandeh J, Pfoh R, Pai EF. (2013) The structure and regulation of magnesium selective ion
channels. Biochim Biophys Acta [Epub ahead of print]. [PMID:23954807]

Quamme GA. (2010) Molecular identification of ancient and modern mammalian magnesium
transporters. Am J Physiol, Cell Physiol 298: C407C429. [PMID:19940067]
Sahni J, Scharenberg AM. (2013) The SLC41 family of MgtE-like magnesium transporters. Mol
Aspects Med 34: 620628. [PMID:23506895]
SLC41 family of divalent cation transporters 1778
SLC42 family of Rhesus glycoprotein ammonium transporters

Overview: Rhesus is commonly defined as a factor that determines, in part, blood type, and whether neonates suffer from
haemolytic disease of the newborn. These glycoprotein antigens
derive from two genes, RHCE (P18577) and RHD (Q02161),
expressed on the surface of erythrocytes. On erythrocytes, RhAG
associates with these antigens and functions as an ammonium

transporter. RhBG and RhBG are non-erythroid related sequences
associated with epithelia. Topological modelling suggests the
presence of 12TM with cytoplasmic N- and C- termini. The
majority of information on these transporters derives from
orthologues in yeast, plants and bacteria. More recent evidence

points to family members being permeable to carbon dioxide,
leading to the term gas channels.
Nomenclature
RhAG
RhBG
RhCG
SLC42A1
SLC42A2
SLC42A3
Common abbreviation
RhAG
RhBG
RhCG
HGNC, UniProt
RHAG, Q02094
RHBG, Q9H310
RHCG, Q9UBD6
Substrates
NH3 [409], NH4+ [410], CO2 [408]
NH3 [411]
Radioligands (Kd)
[14C]methylamine
[14C]methylamine
Stoichiometry
Unknown
Unknown
Unknown
Further reading
Huang CH, Ye M. (2010) The Rh protein family: gene evolution, membrane biology, and disease
association. Cell Mol Life Sci 67: 12031218. [PMID:19953292]
Nakhoul NL, Hamm LL. (2004) Non-erythroid Rh glycoproteins: a putative new family
of mammalian ammonium transporters. Pflugers Arch 447: 807812. [PMID:
12920597]

Nakhoul NL, Lee Hamm L. (2013) Characteristics of mammalian Rh glycoproteins (SLC42 transporters) and their role in acid-base transport. Mol Aspects Med 34: 629637. [PMID:23506896]
Weiner ID, Verlander JW. (2011) Role of NH3 and NH4+ transporters in renal acid-base transport.
SLC42 family of Rhesus glycoprotein ammonium transporters 1779
SLC43 family of large neutral amino acid transporters

Overview: LAT3 (SLC43A1) and LAT4 (SLC43A2) are transporters with system L amino acid transporter activity, along with the
structurally and functionally distinct transporters LAT1 and LAT2
that are members of the SLC7 family. LAT3 and LAT4 contain
12 putative TM domains with both N and C termini located
intracellularly. They transport neutral amino acids in a manner

independent of Na+ and Cl- and with two kinetic components
[412413]. LAT3/SLC43A1 is expressed in human tissues at high
levels in the pancreas, liver, skeletal muscle and fetal liver [412]
whereas LAT4/SLC43A2 is primarily expressed in the placenta,
kidney and peripheral blood leukocytes [413]. SLC43A3 is

expressed in vascular endothelial cells [414] but remains to be
characterised.
Nomenclature
L-type amino acid transporter 3
L-type amino acid transporter 4
EEG1
SLC43A1
SLC43A2
SLC43A3
Common abbreviation
LAT3
LAT4
HGNC, UniProt
SLC43A1, O75387
SLC43A2, Q8N370
SLC43A3, Q8NBI5
Substrates
L-isoleucine, L-leucine, L-phenylalanine, L-valinol, L-leucinol,

L-phenylalaninol, L-valine, L-methionine
L-isoleucine, L-leucine, L-phenylalanine, L-valinol, L-leucinol, L-valine,

L-methionine
Stoichiometry
Operates by facilitative diffusion
Operates by facilitative diffusion
Comments: Covalent modification of LAT3 by N-ethylmaleimide inhibits its function [412] and at LAT4 inhibits the low-, but not high-affinity component of transport [413].
Further reading
Bodoy S, Fotiadis D, Stoeger C, Kanai Y, Palacn M. (2013) The small SLC43 family: facilitator
system l amino acid transporters and the orphan EEG1. Mol Aspects Med 34: 638645.
[PMID:23268354]

SLC43 family of large neutral amino acid transporters 1780
SLC44 choline transporter-like family

Overview: Members of the choline transporter-like family are
encoded by five genes (CTL1-CTL5) with further diversity
occurring through alternative splicing of CTL1, 4 and 5 [423].
CTL family members are putative 10TM domain proteins with
extracellular termini that mediate Na+-independent transport
of choline with an affinity that is intermediate to that of the
high affinity choline transporter CHT1 (SLC5A7) and the low

affinity organic-cation transporters [OCT1 (SLC22A1) and OCT2
(SLC22A2)] [420]. CLT1 is expressed almost ubiquitously in
human tissues [425] and mediates choline transport across the
plasma and mitochondrial membranes [419]. Transport of
choline by CTL2, which in rodents is expressed as two isoforms
(CTL2P1 and CLTP2; [417]) in lung, colon, inner ear and spleen
and to a lesser extent in brain, tongue, liver, and kidney, has only
recently been demonstrated [417,422]. CTL3-5 remain to be
characterized functionally.
Nomenclature
Choline transporter-like 1
SLC44A1
SLC44A2
SLC44A3
SLC44A4
SLC44A5
Common abbreviation
CTL1
CTL2
CTL3
CTL4
CTL5
HGNC, UniProt
SLC44A1, Q8WWI5
SLC44A2, Q8IWA5
SLC44A3, Q8N4M1
SLC44A4, Q53GD3
SLC44A5, Q8NCS7
Substrates
choline
choline
Inhibitors (pIC50)
hemicholinium-3 (pKi 3.5 4.5)
Stoichiometry
Unknown: uptake enhanced in the absence of

extracellular Na+, reduced by membrane depolarization,
extracellular acidification and collapse of plasma
membrane H+ electrochemical gradient
Comments: Data tabulated are features observed for CLT1 endogenous to: rat astrocytes [416]; rat renal tubule epithelial cells [426]; human colon carcinoma cells [418]; human keratinocytes [424] and
human neuroblastoma cells [427]. Choline uptake by CLT1 is inhibited by numerous organic cations (e.g. [416,426427]). In the guinea-pig, CTL2 is a target for antibody-induced hearing loss [421] and
in man, a polymorphism in CTL2 constitutes the human neutrophil alloantigen-3a (HNA-3a; [415]).
Further reading
Lockman PR, Allen DD. (2002) The transport of choline. Drug Dev Ind Pharm 28: 749771.
[PMID:12236062]
Michel V, Yuan Z, Ramsubir S, Bakovic M. (2006) Choline transport for phospholipid synthesis. Exp
Biol Med (Maywood) 231: 490504. [PMID:16636297]

Traiffort E, ORegan S, Ruat M. (2013) The choline transporter-like family SLC44: properties and
roles in human diseases. Mol Aspects Med 34: 646654. [PMID:23506897]
SLC44 choline transporter-like family 1781
SLC45 family of putative sugar transporters

Overview: Members of the SLC45 family remain to be fully characterised. SLC45A1 was initially identified in the rat brain, particularly predominant in the hindbrain, as a proton-associated sugar
transport, induced by hypercapnia [430]. The protein is predicted to have 12TM domains, with intracellular termini. The SLC45A2 gene is thought to encode a transporter protein that mediates melanin
synthesis. Mutations in SLC45A2 are a cause of oculocutaneous albinism type 4 (e.g. [429]), and polymorphisms in this gene are associated with variations in skin and hair color (e.g. [428]).
SLC45A1
SLC45A2
SLC45A3
HGNC, UniProt
SLC45A1, Q9Y2W3
SLC45A2, Q9UMX9
SLC45A3, Q96JT2
SLC45A4
SLC45A4, Q5BKX6
Substrates
L-glucose (Rat) [430], Galactose (Rat) [430]
Stoichiometry
Unknown; increased at acid pH [430].
Further reading
Vitavska O, Wieczorek H. (2013) The SLC45 gene family of putative sugar transporters. Mol Aspects
Med 34: 655660. [PMID:23506898]

SLC45 family of putative sugar transporters 1782
SLC46 family of folate transporters

Overview: Based on the proptypical member of this family, PCFT, this family includes proton-driven transporters with 11 TM segments. SLC46A1 has been described to act as an intestinal proton-coupled
high-affinity folic acid transporter [432], with lower affinity for heme. folic acid accumulation is independent of Na+ or K+ ion concentrations, but driven by extracellular protons with an as yet undefined
stoichiometry.
Nomenclature
Proton-coupled folate transporter
Thymic stromal co-transporter
SLC46A1
SLC46A2
SLC46A3
Common abbreviation
PCFT
TSCOT
HGNC, UniProt
SLC46A1, Q96NT5
SLC46A2, Q9BY10
SLC46A3, Q7Z3Q1
Substrates
folic acid (1.3M) > heme (>100 M) [431]
N5-methyltetrafolate [432]
Substrates
methotrexate [432], N-formyltetrahydrofolate, pemetrexed
Radioligands (Kd)
[3H]folic acid, [3H]folinic acid, [3H]methotrexate, [3H]N5-methylfolate, [3H]pemetrexed
Comment
Loss-of-function mutations in PCFT (SLC46A1) are the molecular basis for hereditary
folate maladsorption [433]
Function as-yet unknown
Function as-yet unknown
Further reading
Physiology (Bethesda) 25: 364377. [PMID:21186281]
Desmoulin SK, Hou Z, Gangjee A, Matherly LH. (2012) The human proton-coupled folate transporter: Biology and therapeutic applications to cancer. Cancer Biol Ther 13: 13551373.
[PMID:22954694]
Thwaites DT, Anderson CM. (2007) H+-coupled nutrient, micronutrient and drug transporters in
the mammalian small intestine. Exp Physiol 92: 603619. [PMID:17468205]

Zhao R, Diop-Bove N, Visentin M, Goldman ID. (2011) Mechanisms of membrane transport of

folates into cells and across epithelia. Annu Rev Nutr 31: 177201. [PMID:21568705]
Zhao R, Goldman ID. (2013) Folate and thiamine transporters mediated by facilitative carriers
(SLC19A1-3 and SLC46A1) and folate receptors. Mol Aspects Med 34: 373385. [PMID:23506878]
SLC46 family of folate transporters 1783
SLC47 family of multidrug and toxin extrusion transporters

Overview: These proton:organic cation exchangers are predicted to have 13 TM segments [443] and are suggested to be responsible for excretion of many drugs in the liver and kidneys.
Nomenclature
Multi antimicrobial extrusion protein
MATE2
SLC47A1
SLC47A2
Common abbreviation
MATE1
MATE2-K
HGNC, UniProt
SLC47A1, Q96FL8
SLC47A2, Q86VL8
creatine [439], thiamine [439]
creatine [439], thiamine [439]
Substrates
cimetidine [437], quinidine [439], paraquat [434], cephradine [439],

cephalexin [439]
cimetidine [436], MPP+ [436], N1-methylnicotinamide [436],

metformin [436], guanidine [439], procainamide [436], acyclovir [439]
(Sub)family-selective inhibitors (pIC50)
pyrimethamine (pKi 6.8), cimetidine (pKi 6.0) [441]
pyrimethamine (pKi 6.3 - Mouse) [435], cimetidine (pKi 5.1) [441]
Radioligands (Kd)
[14C]metformin [439440], [14C]TEA [438,440]
[14C]TEA [439]
Comments: DAPI has been used to allow quantification of MATE1 and MATE2-mediated transport activity [442]. MATE2 and MATE2-B are inactive splice variants of MATE2-K [436].
Further reading
Damme K, Nies AT, Schaeffeler E, Schwab M. (2011) Mammalian MATE (SLC47A) transport proteins:
impact on efflux of endogenous substrates and xenobiotics. Drug Metab Rev 43: 499523.
[PMID:21923552]
Motohashi H, Inui K. (2013) Multidrug and toxin extrusion family SLC47: physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2-K. Mol Aspects Med 34: 661668.
[PMID:23506899]

Terada T, Inui K. (2008) Physiological and pharmacokinetic roles of H+/organic cation antiporters
(MATE/SLC47A). Biochem Pharmacol 75: 16891696. [PMID:18262170]
Yonezawa A, Inui K. (2011) Importance of the multidrug and toxin extrusion MATE/SLC47A
family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics. Br J
Pharmacol 164: 18171825. [PMID:21457222]
SLC47 family of multidrug and toxin extrusion transporters 1784
SLC48 heme transporter

Overview: HRG1 has been identified as a cell surface and lysosomal heme transporter [445]. In addition, evidence suggests this 4TM-containing protein associates with the V-ATPase in lysosomes [444].
Recent studies confirm its lysosomal location and demonstrate that it has an important physiological function in macrophages ingesting senescent red blood cells (erythrophagocytosis), recycling heme
(released from the red cell hemoglobin) from the phagolysosome into the cytosol, where the heme is subsequently catabolized to recycle the iron [446].
Nomenclature
Heme transporter
SLC48A1
Common abbreviation
HRG1
HGNC, UniProt
SLC48A1, Q6P1K1
Further reading
Khan AA, Quigley JG. (2013) Heme and FLVCR-related transporter families SLC48 and SLC49. Mol
Aspects Med 34: 669682. [PMID:23506900]

SLC48 heme transporter 1785
SLC49 family of FLVCR-related heme transporters

Overview: FLVCR1 was initially identified as a cell-surface
attachment site for feline leukemia virus subgroup C [455], and
later identified as a cell surface accumulation which exports
heme from the cytosol [452]. A recent study indicates that an
isoform of FLVCR1 is located in the mitochondria, the site of the
final steps of heme synthesis, and appears to transport heme into
the cytosol [448]. FLVCR-mediated heme transport is essential for
erythropoiesis. Flvcr1 gene mutations have been identified as the

cause of PCARP (posterior column ataxia with retinitis pigmentosa (PCARP) [453].There are three paralogs of FLVCR1 in the
human genome.
FLVCR2, most similar to FLVCR1 [450], has been reported to
function as a heme importer [449]. In addition, a congenital
syndrome of proliferative vasculopathy and hydranencephaly,

also known as Fowlers syndrome, is associated with a loss-offunction mutation in FLVCR2 [451].
The functions of the other two members of the SLC49 family,
MFSD7 and DIRC2, are unknown, although DIRC2 has been
implicated in hereditary renal carcinomas [447].
Nomenclature
Feline leukemia virus subgroup C cellular

receptor family, member 1
Feline leukemia virus subgroup C cellular

receptor family, member 2
Major facilitator superfamily domain

containing 7
Disrupted in renal carcinoma 2
SLC49A1
SLC49A2
SLC49A3
SLC49A4
Common abbreviation
FLVCR1
FLVCR2
MFSD7
DIRC2
HGNC, UniProt
FLVCR1, Q9Y5Y0
FLVCR2, Q9UPI3
MFSD7, Q6UXD7
DIRC2, Q96SL1
Substrates
heme [452]
heme [449]
Stoichiometry
Unknown
Unknown
Unknown
Unknown
Comments: Non-functional splice alternatives of FLVCR1 have been implicated as a cause of a congenital red cell aplasia, Diamond Blackfan anemia [454].
Further reading
Khan AA, Quigley JG. (2011) Control of intracellular heme levels: heme transporters and heme
oxygenases. Biochim Biophys Acta 1813: 668682. [PMID:21238504]
Khan AA, Quigley JG. (2013) Heme and FLVCR-related transporter families SLC48 and SLC49. Mol
Aspects Med 34: 669682. [PMID:23506900]

Krishnamurthy P, Xie T, Schuetz JD. (2007) The role of transporters in cellular heme and porphyrin
homeostasis. Pharmacol Ther 114: 345358. [PMID:17368550]
Latunde-Dada GO, Simpson RJ, McKie AT. (2006) Recent advances in mammalian haem transport.
Trends Biochem Sci 31: 182188. [PMID:16487711]
SLC49 family of FLVCR-related heme transporters 1786
SLC50 sugar transporter

Overview: A mouse stromal cell cDNA library was used to clone C2.3 [457], later termed Rag1-activating protein 1, with a sequence homology predictive of a 4TM topology. The plant orthologues,
termed SWEETs, appear to be 7 TM proteins, with extracellular N-termini, and the capacity for bidirectional flux of D-glucose [456]. Expression of mouse SWEET in the mammary gland was suggestive
of a role in Golgi lactose synthesis [456].
Nomenclature
SLC50 sugar exporter
SLC50A1
Common abbreviation
RAG1AP1
HGNC, UniProt
SLC50A1, Q9BRV3
Further reading
Wright EM. (2013) Glucose transport families SLC5 and SLC50. Mol Aspects Med 34: 183196.
[PMID:23506865]

Wright EM, Loo DD, Hirayama BA. (2011) Biology of human sodium glucose transporters. Physiol
Rev 91: 733794. [PMID:21527736]
SLC50 sugar transporter 1787
SLC51 family of steroid-derived molecule transporters

Overview: The SLC51 organic solute transporter family of transporters is a pair of heterodimeric proteins which regulate bile
salt movements in the bile duct, small intestine and kidney, and
elsewhere, as part of the enterohepatic circulation [458,460].
OST/OST is also expressed in steroidogenic cells of the brain
and adrenal gland, where it may contribute to steroid movement
[461]. Bile acid transport is suggested to be facilitative and

independent of sodium, potassium, chloride ions or protons
[458,460]. OST/OST heterodimers have been shown to transport [3H]taurocholic acid, [3H]DHEAS, [3H]estrone-3-sulphate,
[3H]-pregnenolone sulphate and [3H]DHEAS [458,460461].
OST is suggested to be a seven TM protein, while OST is a
single TM ancillary protein, both of which are thought to

have intracellular C-termini [462]. Bimolecular fluorescence
complementation studies suggest the possibility of OST homooligomers, as well as OST/OST hetero-oligomers [459,462].
Nomenclature
OST
SLC51A1
OST
SLC51A1BP
HGNC, UniProt
SLC51A, Q86UW1
SLC51B, Q86UW2
Further reading
Ballatori N. (2011) Pleiotropic functions of the organic solute transporter Ost-Ost. Dig Dis 29:
1317. [PMID:21691099]
Ballatori N, Christian WV, Wheeler SG, Hammond CL. (2013) The heteromeric organic solute
transporter, OST-OST/SLC51: a transporter for steroid-derived molecules. Mol Aspects Med 34:
683692. [PMID:23506901]

Dawson PA. (2011) Role of the intestinal bile acid transporters in bile acid and drug disposition.
SLC51 family of steroid-derived molecule transporters 1788
SLC52 family of riboflavin transporters

Overview: riboflavin, also known as vitamin B2, is a precursor of the enzyme cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Riboflavin transporters are predicted to possess
10 or 11 TM segments.
Nomenclature
solute carrier family 52 (riboflavin

transporter), member 1


Common abbreviation
SLC52A1
SLC52A2
SLC52A3
RFVT1
RFVT2
RFVT3
HGNC, UniProt
SLC52A1, Q9NWF4
SLC52A2, Q9HAB3
SLC52A3, Q9NQ40
riboflavin (Km 1.38x10-9 M) [463]
Stoichiometry
Unknown
Unknown
H+-dependent
Comments: Although expressed elsewhere, RFVT3 is found on the luminal surface of intestinal epithelium and is thought to mediate uptake of dietary riboflavin, while RFVT1 and RFVT2 are thought
to allow movement from the epithelium into the blood.
Further reading
Yamamoto S, Inoue K, Ohta KY, Fukatsu R, Maeda JY, Yoshida Y, Yuasa H. (2009) Identification
and functional characterization of rat riboflavin transporter 2. J Biochem 145: 437443.
[PMID:19122205]

Yonezawa A, Inui K. (2013) Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52. Mol Aspects Med 34:
693701. [PMID:23506902]
SLC52 family of riboflavin transporters 1789
SLCO family of organic anion transporting polypeptides

Overview: The SLCO superfamily is comprised of the organic
anion transporting polypeptides (OATPs). The 11 human OATPs
are divided into 6 families and ten subfamilies based on amino
acid identity. These proteins are located on the plasma mem-
brane of cells throughout the body. They have 12 TM domains

and intracellular termini, with multiple putative glycosylation
sites. OATPs mediate the sodium-independent uptake of a wide
range of amphiphilic substrates, including many drugs and
toxins. Due to the multispecificity of these proteins, this guide

lists classes of substrates and inhibitors for each family member.
More comprehensive lists of substrates, inhibitors, and their relative affinities may be found in the review articles listed below.
Nomenclature
OATP1A2
OATP1B1
OATP1B3
OATP1C1
SLCO1A2
SLCO1B1
SLCO1B3
SLCO1C1
HGNC, UniProt
SLCO1A2, P46721
SLCO1B1, Q9Y6L6
SLCO1B3, Q9NPD5
SLCO1C1, Q9NYB5
PGE2, bilirubin, bile acids, steroid

conjugates, thyroid hormones
bilirubin, bile acids, leukotrienes, steroid conjugates,

thyroid hormones
CCK-8, LTC4, bilirubin, bile acids, steroid

conjugates, thyroid hormones
steroid conjugates,
thyroid hormones
Substrates
deltorphin II, rosuvastatin, BSP,

talinolol, microcystin, fexofenadine,
ouabain, antibiotics, anticancer drugs,
beta blockers, fluoroquinolones, HIV
protease inhibitors
rifampicin, BSP, fexofenadine, ACE inhibitors,

anticancer drugs, antifungals, -lactam antibiotics,
bile acid derivatives and conjugates, endothelin
receptor antagonists, HIV protease inhibitors, opioids,
sartans, statins
erythromycin-A, rifampicin, BSP, amanitin,

digoxin, phalloidin, saquinavir, fexofenadine,
ouabain, anticancer drugs, -lactam antibiotics,
bile acid derivatives and conjugates, opioids,
sartans, statins
BSP, statins
Inhibitors (pIC50)
naringin, rifampicin, rifamycin SV
cyclosporin A, gemfibrozil, glycyrrhizin, indocyanine

Green, rifampicin, rifamycin SV, sildenafil
cyclosporin A, gemfibrozil, glycyrrhizin,

rifampicin, rifamycin SV, sildenafil
DPDPE, probenecid,
taurocholic acid
Radioligands (Kd)
[3H]BSP, [3H]DPDPE,
[3H]estrone-3-sulphate
[3H]estradiol-17-glucuronide, [3H]estrone-3-sulphate
[3H]BSP, [3H]CCK-8 (human, mouse, rat),

[3H]estradiol-17-glucuronide
[125I]thyroxine, [3H]BSP,
Comment
Other inhibitors include fibrates, flavonoids,

glitazones and macrolide antibiotics. pravastatin is
used as a probe
Other inhibitors include HIV protease inhibitors,

glitazones and macrolide antibiotics
Nomenclature
OATP2A1
OATP2B1
OATP3A1
SLCO2A1
SLCO2B1
SLCO3A1
HGNC, UniProt
SLCO2A1, Q92959
SLCO2B1, O94956
SLCO3A1, Q9UIG8
eicosanoids, prostaglandins
T4, dehydroepiandrosterone sulphate, estrone-3-sulphate
BQ123, vasopressin, prostaglandins, thyroid hormones
Substrates
synthetic prostaglandin derivatives
telmisartan, glibenclamide, amiodarone, bosentan, BSP, talinolol,

aliskiren, fexofenadine, statins
Inhibitors (pIC50)
bromocresol green, BSP
gemfibrozil, glibenclamide, rifamycin SV
Radioligands (Kd)
[3H]PGE2
[3H]BSP, [3H]estrone-3-sulphate
[3H]estrone-3-sulphate, [3H]PGE2
Comment
Other inhibitors include NSAIDs
Other inhibitors include glitazones and citrus juices

SLCO family of organic anion transporting polypeptides 1790
Nomenclature
OATP4A1
OATP4C1
OATP5A1
OATP6A1
SLCO4A1
SLCO4C1
SLCO5A1
SLCO6A1
HGNC, UniProt
SLCO4A1, Q96BD0
SLCO4C1, Q6ZQN7
SLCO5A1,
Q9H2Y9
SLCO6A1,
Q86UG4
bile acids, prostaglandins, steroid conjugates, thyroid hormones
cAMP, steroid conjugates, thyroid hormones
Substrates
penicillin G
anticancer drugs, cardiac glycosides, dipeptidyl peptidase-4 inhibitors
Radioligands (Kd)
[3H]digoxin
Further reading
Hagenbuch B. (2010) Drug uptake systems in liver and kidney: a historic perspective. Clin Pharmacol
Ther 87: 3947. [PMID:19924123]
Hagenbuch B, Meier PJ. (2004) Organic anion transporting polypeptides of the OATP/ SLC21 family:
phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/
functional properties. Pflugers Arch 447: 653665. [PMID:14579113]
Knig J. (2011) Uptake transporters of the human OATP family: molecular characteristics, substrates, their role in drug-drug interactions, and functional consequences of polymorphisms.

Niemi M, Pasanen MK, Neuvonen PJ. (2011) Organic anion transporting polypeptide 1B1: a
genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev
63: 157181. [PMID:21245207]
SLCO family of organic anion transporting polypeptides 1791
References
1.
2.
3.
4.
5.
6.
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S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2013/14: Transporters.

British Journal of Pharmacology (2013) 170, 17061796

THE CONCISE GUIDE TO PHARMACOLOGY 2013/14:

*Author for correspondence; [email protected]

The second, F-type or V-type ATPases, are proton-coupled

Searchable database: http://www.guidetopharmacology.org/index.jsp

solutes that they carry. For example, amino acid accumulation is

where solute movement in one direction is balanced by a solute

List of records presented

ATP-binding cassette transporter family

Searchable database: http://www.guidetopharmacology.org/index.jsp

SLC27 family of fatty acid transporters

ATP-binding cassette transporter family

domains (NBD). The majority of eukaryotic ABC transporters are

ABC transporters convey substrates from the cytoplasm, either

Loss-of-function mutations are associated with pulmonary surfactant deficiency

Retinal-specific transporter of N-retinylPE; loss-of-function mutations are associated with Stargardt

Reported to play a role in skin ceramide formation [23]

Searchable database: http://www.guidetopharmacology.org/index.jsp

ATP-binding cassette transporter family 1708

Endoplasmic reticulum peptide transporter, possibly requires heterodimerization with TAP2

Endoplasmic reticulum peptide transporter, possibly requires heterodimerization with TAP1

Mitochondrial; reportedly essential for haematopoiesis [15]

Mitochondrial; suggested to play a role in chemoresistance of melanoma [4]

Reported to be lysosomal [7]

Transports conjugates of glutathione, sulfate or glucuronide [2]

Searchable database: http://www.guidetopharmacology.org/index.jsp

ATP-binding cassette transporter family 1709

Comments: ABCC7 (also known as CFTR), a 12TM ABC

channels section of the Guide ABCC8 (ENSG00000006071,

the activity of particular K+ channels (Kir6.16.2), conferring

ABCD subfamily of peroxisomal ABC transporters

Coenzyme A esters of very long chain unsaturated fatty acids [22]

Transports sterols and choline phospholipids [10]

Putative functional dependence on ABCG1

Searchable database: http://www.guidetopharmacology.org/index.jsp

ATP-binding cassette transporter family 1710

Searchable database: http://www.guidetopharmacology.org/index.jsp

ATP-binding cassette transporter family 1711

F-type and V-type ATPases

of a soluble complex (termed F1 or V1) and a membrane

hydrolysis to proton transport. Both the F-type and V-type

protein, OSCP, (P48047)), acts as a connector between F1 and F0

subunits in the membrane, together with D, E, F2, F6, G2 and 8

The F1 motor, responsible for ATP turnover, has the subunit

ATP5G1, P05496; ATP5G2,

Searchable database: http://www.guidetopharmacology.org/index.jsp

F-type and V-type ATPases 1712

Searchable database: http://www.guidetopharmacology.org/index.jsp

F-type and V-type ATPases 1713

cytoplasm and extracellular/luminal side of the membrane,

includes calcium, sodium/potassium and proton/potassium

Sequence analysis across multiple species allows the definition

Na+/K+-ATPases (EC 3.6.3.9)

ecule of ATP hydrolysed, the Na+/K+-ATPase extrudes three Na+

Ca2+-ATPases (EC 3.6.3.8)

Searchable database: http://www.guidetopharmacology.org/index.jsp

P-type ATPases 1714

Comments: Loss-of-function mutations in SPCA1 appear to underlie Hailey-Hailey disease [26].