ACVRL1

ACVRL1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2LCR, 3MY0, 4FAO
Identifikatori
Aliasi	ACVRL1
Vanjski ID-jevi	OMIM: 601284 MGI: 1338946 HomoloGene: 20058 GeneCards: ACVRL1
Lokacija gena (čovjek)
Hrom.	Hromosom 12 (čovjek)
Kraj	51,923,361 bp
Lokacija gena (miš)
Hrom.	Hromosom 15 (miš)
Kraj	101,043,217 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • nucleotide binding; • protein kinase activity; • activin binding; • transforming growth factor beta-activated receptor activity; • vezivanje iona metala; • kinase activity; • protein serine/threonine kinase activity; • transmembrane receptor protein serine/threonine kinase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • BMP receptor activity; • ATP binding; • protein kinase binding; • transforming growth factor beta binding; • transforming growth factor beta receptor activity, type I; • activin receptor activity, type I; • SMAD binding; • growth factor binding;
Ćelijska komponenta	• integral component of membrane; • membrana; • integral component of plasma membrane; • soma; • dendrit; • ćelijska membrana; • cell surface; • receptor complex; • activin receptor complex;
Biološki proces	• cellular response to transforming growth factor beta stimulus; • negative regulation of cell adhesion; • GO:0009373 regulation of transcription, DNA-templated; • positive regulation of endothelial cell differentiation; • positive regulation of endothelial cell proliferation; • blood vessel morphogenesis; • negative regulation of blood vessel endothelial cell migration; • lymphangiogenesis; • regulation of DNA replication; • Fosforilacija; • endothelial tube morphogenesis; • retina vasculature development in camera-type eye; • wound healing, spreading of epidermal cells; • lymphatic endothelial cell differentiation; • positive regulation of pathway-restricted SMAD protein phosphorylation; • cellular response to BMP stimulus; • negative regulation of endothelial cell differentiation; • in utero embryonic development; • blood vessel endothelial cell proliferation involved in sprouting angiogenesis; • Krvotok; • positive regulation of angiogenesis; • venous blood vessel development; • negative regulation of endothelial cell migration; • negative regulation of endothelial cell proliferation; • regulation of blood vessel endothelial cell migration; • regulation of blood pressure; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • protein phosphorylation; • blood vessel remodeling; • negative regulation of cell migration; • transmembrane receptor protein serine/threonine kinase signaling pathway; • negative regulation of cell growth; • positive regulation of chondrocyte differentiation; • Angiogeneza; • artery development; • regulation of endothelial cell proliferation; • positive regulation of BMP signaling pathway; • transforming growth factor beta receptor signaling pathway; • negative regulation of focal adhesion assembly; • negative regulation of DNA biosynthetic process; • GO:0072468 Transdukcija signala; • negative regulation of cell population proliferation; • blood vessel maturation; • activin receptor signaling pathway; • response to hypoxia; • endocardial cushion to mesenchymal transition; • endocardial cushion morphogenesis; • negative regulation of gene expression; • dorsal aorta morphogenesis; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • BMP signaling pathway; • pattern specification process;
	Izvori:Amigo / QuickGO
Ortolozi
	94
	11482
	ENSG00000139567
	ENSMUSG00000000530
	P37023
	Q61288
	NM_000020; NM_001077401
	NM_001277255; NM_001277257; NM_001277258; NM_001277259; NM_009612
	NP_000011; NP_001070869
	NP_001264184; NP_001264186; NP_001264187; NP_001264188; NP_033742
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Receptor R3 serin/treonin-protein kinaze je enzim koji je kod ljudi kodiran genom ACVRL1.^[5]^[6]^[7]

ACVRL1 je receptor u signalnom putu TGF-beta. Poznat je i kao aktivinska receptoolika kinaza 1 ili ALK1.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 503 aminokiseline, a molekulska težina 56.124 Da.^[8].

10	20	30	40	50
MTLGSPRKGL	LMLLMALVTQ	GDPVKPSRGP	LVTCTCESPH	CKGPTCRGAW
CTVVLVREEG	RHPQEHRGCG	NLHRELCRGR	PTEFVNHYCC	DSHLCNHNVS
LVLEATQPPS	EQPGTDGQLA	LILGPVLALL	ALVALGVLGL	WHVRRRQEKQ
RGLHSELGES	SLILKASEQG	DSMLGDLLDS	DCTTGSGSGL	PFLVQRTVAR
QVALVECVGK	GRYGEVWRGL	WHGESVAVKI	FSSRDEQSWF	RETEIYNTVL
LRHDNILGFI	ASDMTSRNSS	TQLWLITHYH	EHGSLYDFLQ	RQTLEPHLAL
RLAVSAACGL	AHLHVEIFGT	QGKPAIAHRD	FKSRNVLVKS	NLQCCIADLG
LAVMHSQGSD	YLDIGNNPRV	GTKRYMAPEV	LDEQIRTDCF	ESYKWTDIWA
FGLVLWEIAR	RTIVNGIVED	YRPPFYDVVP	NDPSFEDMKK	VVCVDQQTPT
IPNRLAADPV	LSGLAQMMRE	CWYPNPSARL	TALRIKKTLQ	KISNSPEKPK
VIQ

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

Funkcija

Ovaj gen kodira receptor ćelijske površine tipa I za superporodicu liganada TGF-beta. S drugim receptorima tipa I dijeli visok stupanj sličnosti u poddomenima serin-treonin kinaza, regiji bogatoj glicinom i serinom (zvanoim GS-domen) koji prethodi domenu kinaze i kratkom repu C-terminala. Kodirani protein, koji se ponekad naziva i ALK1, dijeli slične domenske strukture sa drugim blisko povezanim proteinima ALK ili proteinima kinaze sličnim aktivinu koji tvore potporodicu receptorskih serin/treonin kinaza. Mutacije u ovom genu povezane su s hemoragičnom telangiektazijom tipa 2, poznatom i kao Rendu-Osler-Weberov sindrom 2.^[7]

Patologija

Mutacija germinativne linije ACVRL1 su povezane sa:

nasljednom hemoragijskom telangiektazijom tip 2 (Rendu-Osler-Weberov sindrom 2)^[9]
Plućne arteriovenske malformacije^[10]

Somatski mozaicizam u ACVRL1 povezan je s teškom plućnom arterijskom hipertenzijom.^[11]

ACVRL1 direktno stupa u interakciju s lipoproteinom niske gustoće (LDL), što implicira da bi mogao inicirati rane faze ateroskleroze.^[12]

Utvrđeno je da je abnormalna aktivnost ACVRL1 usko povezana s idiopatskom plućnom arterijskom hipertenzijom.

Kao cilj lijekova

Dalantercept je eksperimentalni inhibitor ALK1.^[13]

Bliske/porodično-srodne kinaze

(Ne miješati s anaplazijska limfomska kinaza (ALK))
ALK4 je ACVR1B, ALK7 je ACVR1C, a ALK5 je [dio] receptor TGF-β tip I.^[14]

Također pogledajte

Signalni put TG-beta, pogledajte sažetu tabelu za ALK*

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000139567 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000000530 - 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.
^ ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K (oktobar 1993). "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene. 8 (10): 2879–87. PMID 8397373.
^ Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA (juni 1996). "Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2". Nature Genetics. 13 (2): 189–95. doi:10.1038/ng0696-189. PMID 8640225. S2CID 21379604.
^ ^a ^b "Entrez Gene: ACVRL1 activin A receptor type II-like 1".
^ "UniProt, P37023". Pristupljeno 6. 8. 2021.
^ Olivieri C, Mira E, Delù G, Pagella F, Zambelli A, Malvezzi L, Buscarini E, Danesino C (juli 2002). "Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia". Journal of Medical Genetics. 39 (7): 39e–39. doi:10.1136/jmg.39.7.e39. PMC 1735165. PMID 12114496.
^ Vandenbriele C, Peerlinck K, de Ravel T, Verhamme P, Vanassche T (april 2014). "Pulmonary arterio-venous malformations in a patient with a novel mutation in exon 10 of the ACVRL1 gene". Acta Clinica Belgica. 69 (2): 139–41. doi:10.1179/0001551213Z.00000000012. PMID 24724759. S2CID 35264961.
^ Jones G, Robertson L, Harrison R, Ridout C, Vasudevan P (august 2014). "Somatic mosaicism in ACVRL1 with transmission to several offspring affected with severe pulmonary arterial hypertension". American Journal of Medical Genetics. Part A. 164A (8): 2121–3. doi:10.1002/ajmg.a.36568. PMID 24753439. S2CID 5417225.
^ Kraehling JR, Chidlow JH, Rajagopal C, Sugiyama MG, Fowler JW, Lee MY, Zhang X, Ramírez CM, Park EJ, Tao B, Chen K, Kuruvilla L, Larriveé B, Folta-Stogniew E, Ola R, Rotllan N, Zhou W, Nagle MW, Herz J, Williams KJ, Eichmann A, Lee WL, Fernández-Hernando C, Sessa WC (novembar 2016). "Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells". Nature Communications. 7: 13516. Bibcode:2016NatCo...713516K. doi:10.1038/ncomms13516. PMC 5121336. PMID 27869117.
^ Gupta S, Gill D, Pal SK, Agarwal N (2015). "Activin receptor inhibitors--dalantercept". Current Oncology Reports. 17 (4): 14. doi:10.1007/s11912-015-0441-5. PMID 25708802. S2CID 22676858.
^ Laping NJ, Grygielko E, Mathur A, Butter S, Bomberger J, Tweed C, Martin W, Fornwald J, Lehr R, Harling J, Gaster L, Callahan JF, Olson BA (juli 2002). "Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542". Molecular Pharmacology. 62 (1): 58–64. doi:10.1124/mol.62.1.58. PMID 12065755.

Dopunska literatura

Attisano L, Cárcamo J, Ventura F, Weis FM, Massagué J, Wrana JL (novembar 1993). "Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors". Cell. 75 (4): 671–80. doi:10.1016/0092-8674(93)90488-C. PMID 8242742. S2CID 25408172.
Johnson DW, Berg JN, Gallione CJ, McAllister KA, Warner JP, Helmbold EA, Markel DS, Jackson CE, Porteous ME, Marchuk DA (august 1995). "A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12". Genome Research. 5 (1): 21–8. doi:10.1101/gr.5.1.21. PMID 8717052.
Panchenko MP, Williams MC, Brody JS, Yu Q (april 1996). "Type I receptor serine-threonine kinase preferentially expressed in pulmonary blood vessels". The American Journal of Physiology. 270 (4 Pt 1): L547-58. doi:10.1152/ajplung.1996.270.4.L547. PMID 8928814.
Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA (juli 1997). "The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2". American Journal of Human Genetics. 61 (1): 60–7. doi:10.1086/513903. PMC 1715857. PMID 9245985.
Stockwell BR, Schreiber SL (juni 1998). "Probing the role of homomeric and heteromeric receptor interactions in TGF-beta signaling using small molecule dimerizers". Current Biology. 8 (13): 761–70. doi:10.1016/S0960-9822(98)70299-4. PMID 9651680. S2CID 93779.
Lux A, Attisano L, Marchuk DA (april 1999). "Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1". The Journal of Biological Chemistry. 274 (15): 9984–92. doi:10.1074/jbc.274.15.9984. PMID 10187774.
Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA (2000). "Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online". Human Mutation. 12 (2): 137–138. doi:10.1002/(SICI)1098-1004(1998)12:2<137::AID-HUMU16>3.0.CO;2-J. PMID 10694922.
Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (mart 2000). "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proceedings of the National Academy of Sciences of the United States of America. 97 (6): 2626–31. Bibcode:2000PNAS...97.2626O. doi:10.1073/pnas.97.6.2626. PMC 15979. PMID 10716993.
Abdalla SA, Pece-Barbara N, Vera S, Tapia E, Paez E, Bernabeu C, Letarte M (maj 2000). "Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2". Human Molecular Genetics. 9 (8): 1227–37. doi:10.1093/hmg/9.8.1227. PMID 10767348.
Kjeldsen AD, Brusgaard K, Poulsen L, Kruse T, Rasmussen K, Green A, Vase P (februar 2001). "Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families". American Journal of Medical Genetics. 98 (4): 298–302. doi:10.1002/1096-8628(20010201)98:4<298::AID-AJMG1093>3.0.CO;2-K. PMID 11170071.
Wurthner JU, Frank DB, Felici A, Green HM, Cao Z, Schneider MD, McNally JG, Lechleider RJ, Roberts AB (juni 2001). "Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone". The Journal of Biological Chemistry. 276 (22): 19495–502. doi:10.1074/jbc.M006473200. PMID 11278302.
Parks WT, Frank DB, Huff C, Renfrew Haft C, Martin J, Meng X, de Caestecker MP, McNally JG, Reddi A, Taylor SI, Roberts AB, Wang T, Lechleider RJ (juni 2001). "Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases". The Journal of Biological Chemistry. 276 (22): 19332–9. doi:10.1074/jbc.M100606200. PMID 11279102.
Birkey Reffey S, Wurthner JU, Parks WT, Roberts AB, Duckett CS (juli 2001). "X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling". The Journal of Biological Chemistry. 276 (28): 26542–9. doi:10.1074/jbc.M100331200. PMID 11356828.
Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L (august 2001). "Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia" (PDF). The New England Journal of Medicine. 345 (5): 325–34. doi:10.1056/NEJM200108023450503. hdl:2381/35988. PMID 11484689.
Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS (juli 2002). "SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7". Molecular Pharmacology. 62 (1): 65–74. doi:10.1124/mol.62.1.65. PMID 12065756.
Olivieri C, Mira E, Delù G, Pagella F, Zambelli A, Malvezzi L, Buscarini E, Danesino C (juli 2002). "Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia". Journal of Medical Genetics. 39 (7): 39e–39. doi:10.1136/jmg.39.7.e39. PMC 1735165. PMID 12114496.
Mo J, Fang SJ, Chen W, Blobe GC (decembar 2002). "Regulation of ALK-1 signaling by the nuclear receptor LXRbeta". The Journal of Biological Chemistry. 277 (52): 50788–94. doi:10.1074/jbc.M210376200. PMID 12393874.
Lamouille S, Mallet C, Feige JJ, Bailly S (decembar 2002). "Activin receptor-like kinase 1 is implicated in the maturation phase of angiogenesis". Blood. 100 (13): 4495–501. doi:10.1182/blood.V100.13.4495. PMID 12453878.
Mitchell D, Pobre EG, Mulivor AW, Grinberg AV, Castonguay R, Monnell TE, Solban N, Ucran JA, Pearsall RS, Underwood KW, Seehra J, Kumar R (februar 2010). "ALK1-Fc inhibits multiple mediators of angiogenesis and suppresses tumor growth". Molecular Cancer Therapeutics. 9 (2): 379–88. doi:10.1158/1535-7163.MCT-09-0650. PMID 20124460.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Hereditary Hemorrhagic Telangiectasia
Lokacija ljudskog genoma ACVRL1 i stranica sa detaljima o genu ACVRL1 u UCSC Genome Browseru.

Šablon:Signalizacija TGF-beta

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000139567 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000000530 - 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.

[pmid8397373-5] ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K (oktobar 1993). "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene. 8 (10): 2879–87. PMID 8397373.

[pmid8640225-6] Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA (juni 1996). "Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2". Nature Genetics. 13 (2): 189–95. doi:10.1038/ng0696-189. PMID 8640225. S2CID 21379604.

[entrez-7] "Entrez Gene: ACVRL1 activin A receptor type II-like 1".

[UniProt-8] "UniProt, P37023". Pristupljeno 6. 8. 2021.

[pmid12114496-9] Olivieri C, Mira E, Delù G, Pagella F, Zambelli A, Malvezzi L, Buscarini E, Danesino C (juli 2002). "Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia". Journal of Medical Genetics. 39 (7): 39e–39. doi:10.1136/jmg.39.7.e39. PMC 1735165. PMID 12114496.

[pmid24724759-10] Vandenbriele C, Peerlinck K, de Ravel T, Verhamme P, Vanassche T (april 2014). "Pulmonary arterio-venous malformations in a patient with a novel mutation in exon 10 of the ACVRL1 gene". Acta Clinica Belgica. 69 (2): 139–41. doi:10.1179/0001551213Z.00000000012. PMID 24724759. S2CID 35264961.

[Jones_2014-11] Jones G, Robertson L, Harrison R, Ridout C, Vasudevan P (august 2014). "Somatic mosaicism in ACVRL1 with transmission to several offspring affected with severe pulmonary arterial hypertension". American Journal of Medical Genetics. Part A. 164A (8): 2121–3. doi:10.1002/ajmg.a.36568. PMID 24753439. S2CID 5417225.

[12] Kraehling JR, Chidlow JH, Rajagopal C, Sugiyama MG, Fowler JW, Lee MY, Zhang X, Ramírez CM, Park EJ, Tao B, Chen K, Kuruvilla L, Larriveé B, Folta-Stogniew E, Ola R, Rotllan N, Zhou W, Nagle MW, Herz J, Williams KJ, Eichmann A, Lee WL, Fernández-Hernando C, Sessa WC (novembar 2016). "Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells". Nature Communications. 7: 13516. Bibcode:2016NatCo...713516K. doi:10.1038/ncomms13516. PMC 5121336. PMID 27869117.

[pmid25708802-13] Gupta S, Gill D, Pal SK, Agarwal N (2015). "Activin receptor inhibitors--dalantercept". Current Oncology Reports. 17 (4): 14. doi:10.1007/s11912-015-0441-5. PMID 25708802. S2CID 22676858.

[Grygielko2002-14] Laping NJ, Grygielko E, Mathur A, Butter S, Bomberger J, Tweed C, Martin W, Fornwald J, Lehr R, Harling J, Gaster L, Callahan JF, Olson BA (juli 2002). "Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542". Molecular Pharmacology. 62 (1): 58–64. doi:10.1124/mol.62.1.58. PMID 12065755.

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