PTPLAD1

PTPLAD1
Identifikatori
Aliasi	HACD3
Vanjski ID-jevi	OMIM: 615940 MGI: 1889341 HomoloGene: 9494 GeneCards: HACD3
Lokacija gena (čovjek)
Hrom.	Hromosom 15 (čovjek)
Kraj	65,578,349 bp
Lokacija gena (miš)
Hrom.	Hromosom 9 (miš)
Kraj	64,928,975 bp
Ontologija gena
Molekularna funkcija	• GO:0005097, GO:0005099, GO:0005100 GTPase activator activity; • GO:0001948, GO:0016582 vezivanje za proteine; • lyase activity; • vezivanje enzima; • 3-hydroxyacyl-CoA dehydratase activity; • 3-hydroxy-lignoceroyl-CoA dehydratase activity; • 3-hydroxy-behenoyl-CoA dehydratase activity; • 3-hydroxy-arachidoyl-CoA dehydratase activity; • very-long-chain 3-hydroxyacyl-CoA dehydratase activity;
Ćelijska komponenta	• integral component of membrane; • Jedarna membrana; • endoplasmic reticulum membrane; • membrana; • focal adhesion; • Endoplazmatski retikulum; • mitohondrija; • citosol; • integral component of endoplasmic reticulum membrane;
Biološki proces	• positive regulation by virus of viral protein levels in host cell; • lipid metabolism; • small GTPase mediated signal transduction; • fatty acid metabolic process; • JNK cascade; • fatty acid biosynthetic process; • very long-chain fatty acid biosynthetic process; • Rho protein signal transduction; • fatty acid elongation; • positive regulation of viral genome replication; • Rac protein signal transduction; • I-kappaB kinase/NF-kappaB signaling; • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity; • sphingolipid biosynthetic process;
	Izvori:Amigo / QuickGO
Ortolozi
	51495
	57874
	ENSG00000074696
	ENSMUSG00000033629
	Q9P035
	Q8K2C9
	NM_016395
	NM_021345
	NP_057479
	NP_067320
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Tirozinski fosfatazoliki protein PTPLAD1 je enzim koji je kod ljudi kodiran genom PTPLAD1.^[5]^[6]^[7] Sabbah et al. (2006) utvrdili su da promotorska regija PTPLAD1 sadrži proksimalne CG kutije i nekoliko mjesta vezivanja za faktore transkripcije.^[8] Patficia Hartz (2014) mapiraka je gen PTPLAD1 na [[hromosom 15|hromosomu 15, sekvenca 15q22.31. na osnovu poravnanja PTPLAD1 sekvence (GenBank AF161470) sa genomskom sekvencom (GRCh38).^[9] Dugolančane masne kiseline (LCFA) mogu se pretvoriti u vrlo dugolančane masne kiseline (VLCFA) pomoću enzima vezanih za endoplazmatski retikulum (ER) u četverostepenom ciklusu kondenzacije, redukcije, dehidracije i dalje redukcije, uz dodavanje 2 ugljika po ciklusu. PTPLAD1 pripada porodici enzima koji kataliziraju korak dehidracije sinteze VLCFA (sažetak Ikeda et al., 2008).

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 362 aminokiseline, a molekulska težina 43.160 Da.^[10]

10	20	30	40	50
MENQVLTPHV	YWAQRHRELY	LRVELSDVQN	PAISITENVL	HFKAQGHGAK
GDNVYEFHLE	FLDLVKPEPV	YKLTQRQVNI	TVQKKVSQWW	ERLTKQEKRP
LFLAPDFDRW	LDESDAEMEL	RAKEEERLNK	LRLESEGSPE	TLTNLRKGYL
FMYNLVQFLG	FSWIFVNLTV	RFCILGKESF	YDTFHTVADM	MYFCQMLAVV
ETINAAIGVT	TSPVLPSLIQ	LLGRNFILFI	IFGTMEEMQN	KAVVFFVFYL
WSAIEIFRYS	FYMLTCIDMD	WKVLTWLRYT	LWIPLYPLGC	LAEAVSVIQS
IPIFNETGRF	SFTLPYPVKI	KVRFSFFLQI	YLIMIFLGLY	INFRHLYKQR
RRRYGQKKKK	IH

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Kloniranje i ekspresija

Korištenje mišjeg Bind1 za ispitivanje cDNK biblioteke ljudskog mozga, Courilleau et al. (2000) klonirali PTPLAD1, koji su označili BIND1. Izvedeni protein od 370 aminokiselina ima značajnu sličnost sa PTPLA i p23 (PTGES3). Northern blot analiza otkrila je varijabilnu ekspresiju Bind1 u svim ispitivanim tkivima miša, s najvećom ekspresijom u sjemenicima, bubrezima, mozgu i jetri, a znatno nižom u skeletnim mišićima, slezeni i srcu. Ortolozi PTPLAD1 otkriveni su u C. elegans' (obla glista) i S. cerevisiae (kvasac) PCR-om biblioteke cDNK u ćelijama HEK293, Ikeda et al. (2008) klonirali su PTPLAD1, kojeg su označili kao HACD3. Izvedeni protein od 362 aminokiseline ima šest transmembranskih domena i PTP-sličan motiv između transmembranskih domena 2 i 3. Northern blot analizom otkrivena je varijabilna ekspresija prevladavajućeg transkripta HACD3 od 3,2 kb u svim ispitivanim ljudskim tkivima, osim u leukocitima. Najjača ekspresija bila je u mozgu, bubrezima, jetri i posteljici. Epitop-označen kao HACD3 eksprimiran je u ER-u transficiranih HeLa ćelija.

Funkcija gena

Natrij-butirat je reverzibilni inhibitor histon-deacetilaze, što rezultira hiperacetilacijom histona i promjenama u ekspresiji gena da inducira diferencijaciju i inhibira proliferaciju ćelija. Korištenjem PCR analize diferencijalnog prikaza, Courilleau et al. (2000) otkrili su da natrij-butirat inducira ekspresiju mišjeg Bind1. Ljudski BIND1 je direktno stupio u interakciju s RAC1 u transficiranim ćelijama i potencirao RAC1-induciranu aktivaciju NFKB i JNK.^[11]

Koristeći analizu delecija, Sabbah et al. (2006) identificirali su elemente u ljudskom BIND1 promotoru koji su posredovali njegovu aktivaciju inhibitorima HDAC. Ikeda et al. (2008) otkrili su da je afinitet HACD3 pročišćen iz transficiranih HeLa ćelija pretvorio 3-hidroksipalmitoil-CoA u 2,3-trans heksadecenoil-CoA. Ostali članovi porodice enzima HACD, uključujući HACD1 (PTPLA), HACD2 (PTPLB) i HACD4 (PTPLAD2), pokazali su istu aktivnost, ali svaki je imao različit afinitet i brzinu reakcije. Analiza koimunoprecipitacije transficiranih ćelija HEK293T otkrila je da HACD3 preferira interakciju s nekoliko enzima kondenzacije FA , vjerovatno u kompleksu FA elongaze.^[12]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000074696 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000033629 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Courilleau D, Chastre E, Sabbah M, Redeuilh G, Atfi A, Mester J (Jul 2000). "B-ind1, a novel mediator of Rac1 signaling cloned from sodium butyrate-treated fibroblasts". J Biol Chem. 275 (23): 17344–8. doi:10.1074/jbc.M000887200. PMID 10747961.
^ Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (Nov 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
^ "Entrez Gene: PTPLAD1 protein tyrosine phosphatase-like A domain containing 1".
^ Sabbah, M., Saucier, C., Redeuilh, G. Human B-ind1 gene promoter: cloning and regulation by histone deacetylase inhibitors. Gene 374: 128-133, 2006. PubMed: 16516406
^ Hartz, P. A. Personal Communication. Baltimore, Md. 8/12/2014.
^ "UniProt, Q9P035". Pristupljeno 17. 7. 2021.
^ Courilleau, D., Chastre, E., Sabbah, M., Redeuilh, G., Atfi, A., Mester, J. B-ind1, a novel mediator of Rac1 signaling cloned from sodium butyrate-treated fibroblasts. J. Biol. Chem. 275: 17344-17348, 2000. PubMed: 10747961
^ Ikeda, M., Kanao, Y., Yamanaka, M., Sakuraba, H., Mizutani, Y., Igarashi, Y., Kihara, A. Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis. FEBS Lett. 582: 2435-2440, 2008. PubMed: 18554506

Dopunska literatura

Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Ballif BA, Villén J, Beausoleil SA, et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell. Proteomics. 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
Sabbah M, Saucier C, Redeuilh G (2006). "Human B-ind1 gene promoter: cloning and regulation by histone deacetylase inhibitors". Gene. 374: 128–33. doi:10.1016/j.gene.2006.01.022. PMID 16516406.
Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000074696 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000033629 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10747961-5] Courilleau D, Chastre E, Sabbah M, Redeuilh G, Atfi A, Mester J (Jul 2000). "B-ind1, a novel mediator of Rac1 signaling cloned from sodium butyrate-treated fibroblasts". J Biol Chem. 275 (23): 17344–8. doi:10.1074/jbc.M000887200. PMID 10747961.

[pmid11042152-6] Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (Nov 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.

[entrez-7] "Entrez Gene: PTPLAD1 protein tyrosine phosphatase-like A domain containing 1".

[8] Sabbah, M., Saucier, C., Redeuilh, G. Human B-ind1 gene promoter: cloning and regulation by histone deacetylase inhibitors. Gene 374: 128-133, 2006. PubMed: 16516406

[9] Hartz, P. A. Personal Communication. Baltimore, Md. 8/12/2014.

[UniProt-10] "UniProt, Q9P035". Pristupljeno 17. 7. 2021.

[11] Courilleau, D., Chastre, E., Sabbah, M., Redeuilh, G., Atfi, A., Mester, J. B-ind1, a novel mediator of Rac1 signaling cloned from sodium butyrate-treated fibroblasts. J. Biol. Chem. 275: 17344-17348, 2000. PubMed: 10747961

[12] Ikeda, M., Kanao, Y., Yamanaka, M., Sakuraba, H., Mizutani, Y., Igarashi, Y., Kihara, A. Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis. FEBS Lett. 582: 2435-2440, 2008. PubMed: 18554506

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