ACVRL1

Activin A receptor type II-like 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2LCR, 3MY0, 4FAO
Identifiers
Symbols	ACVRL1; ACVRLK1; ALK-1; ALK1; HHT; HHT2; ORW2; SKR3; TSR-I
External IDs	OMIM: 601284 MGI: 1338946 HomoloGene: 20058 ChEMBL: 5311 GeneCards: ACVRL1 Gene
EC number	2.7.11.30
Gene Ontology Molecular function • protein serine/threonine kinase activity • transmembrane receptor protein serine/threonine kinase activity • receptor signaling protein serine/threonine kinase activity • transforming growth factor beta-activated receptor activity • transforming growth factor beta receptor activity, type I • protein binding • ATP binding • activin receptor activity, type I • protein kinase binding • SMAD binding • metal ion binding • activin binding • transforming growth factor beta binding Cellular component • integral to plasma membrane • cell surface • dendrite • neuronal cell body Biological process • angiogenesis • in utero embryonic development • regulation of endothelial cell proliferation • negative regulation of endothelial cell proliferation • positive regulation of endothelial cell proliferation • lymphangiogenesis • blood vessel maturation • blood vessel remodeling • blood vessel endothelial cell proliferation involved in sprouting angiogenesis • regulation of DNA replication • regulation of transcription, DNA-dependent • protein phosphorylation • negative regulation of cell adhesion • signal transduction • transforming growth factor beta receptor signaling pathway • blood circulation • regulation of blood pressure • negative regulation of cell proliferation • negative regulation of endothelial cell migration • positive regulation of pathway-restricted SMAD protein phosphorylation • negative regulation of cell growth • negative regulation of cell migration • BMP signaling pathway • positive regulation of BMP signaling pathway • positive regulation of chondrocyte differentiation • wound healing, spreading of epidermal cells • regulation of blood vessel endothelial cell migration • negative regulation of blood vessel endothelial cell migration • negative regulation of endothelial cell differentiation • positive regulation of endothelial cell differentiation • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • protein heterooligomerization • negative regulation of focal adhesion assembly • lymphatic endothelial cell differentiation • artery development • venous blood vessel development • endothelial tube morphogenesis • retina vasculature development in camera-type eye • cellular response to transforming growth factor beta stimulus • cellular response to BMP stimulus • negative regulation of DNA biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	94	11482
Ensembl	ENSG00000139567	ENSMUSG00000000530
UniProt	P37023	Q61288
RefSeq (mRNA)	NM_000020	NM_001277255
RefSeq (protein)	NP_000011	NP_001264184
Location (UCSC)	Chr 12: 52.3 – 52.32 Mb	Chr 15: 101.13 – 101.15 Mb
PubMed search	[1]	[2]

Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.

ACVRL1 is a receptor in the TGF beta signaling pathway. It is also known as activin receptor-like kinase 1, or ALK1.

This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2.

Pathology

It is associated with hereditary hemorrhagic telangiectasia.

Further reading

• Attisano L, Cárcamo J, Ventura F, et al. (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. 
• Johnson DW, Berg JN, Gallione CJ, et al. (1996). "A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12.". Genome Res. 5 (1): 21–8. doi:10.1101/gr.5.1.21. PMID 8717052. 
• Panchenko MP, Williams MC, Brody JS, Yu Q (1996). "Type I receptor serine-threonine kinase preferentially expressed in pulmonary blood vessels.". Am. J. Physiol. 270 (4 Pt 1): L547–58. PMID 8928814. 
• Berg JN, Gallione CJ, Stenzel TT, et al. (1997). "The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2". Am. J. Hum. Genet. 61 (1): 60–7. doi:10.1086/513903. PMC 1715857. PMID 9245985. 
• Stockwell BR, Schreiber SL (1998). "Probing the role of homomeric and heteromeric receptor interactions in TGF-beta signaling using small molecule dimerizers". Curr. Biol. 8 (13): 761–70. doi:10.1016/S0960-9822(98)70299-4. PMID 9651680. 
• Lux A, Attisano L, Marchuk DA (1999). "Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1". J. Biol. Chem. 274 (15): 9984–92. doi:10.1074/jbc.274.15.9984. PMID 10187774. 
• Klaus DJ, Gallione CJ, Anthony K, et al. (2000). "Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online". Hum. Mutat. 12 (2): 137. 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, et al. (2000). "Activin receptor-like kinase 1 modulates transforming growth factor-β1 signaling in the regulation of angiogenesis". Proc. Natl. Acad. Sci. U.S.A. 97 (6): 2626–31. doi:10.1073/pnas.97.6.2626. PMC 15979. PMID 10716993. 
• Abdalla SA, Pece-Barbara N, Vera S, et al. (2000). "Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2". Hum. Mol. Genet. 9 (8): 1227–37. doi:10.1093/hmg/9.8.1227. PMID 10767348. 
• Kjeldsen AD, Brusgaard K, Poulsen L, et al. (2001). "Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families". Am. J. Med. Genet. 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, et al. (2001). "Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone". J. Biol. Chem. 276 (22): 19495–502. doi:10.1074/jbc.M006473200. PMID 11278302. 
• Parks WT, Frank DB, Huff C, et al. (2001). "Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases". J. Biol. Chem. 276 (22): 19332–9. doi:10.1074/jbc.M100606200. PMID 11279102. 
• Birkey Reffey S, Wurthner JU, Parks WT, et al. (2001). "X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling". J. Biol. Chem. 276 (28): 26542–9. doi:10.1074/jbc.M100331200. PMID 11356828. 
• Trembath RC, Thomson JR, Machado RD, et al. (2001). "Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia". N. Engl. J. Med. 345 (5): 325–34. doi:10.1056/NEJM200108023450503. PMID 11484689. 
• Inman GJ, Nicolás FJ, Callahan JF, et al. (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". Mol. Pharmacol. 62 (1): 65–74. doi:10.1124/mol.62.1.65. PMID 12065756. 
• Olivieri C, Mira E, Delù G, et al. (2002). "Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia". J. Med. Genet. 39 (7): E39. doi:10.1136/jmg.39.7.e39. PMC 1735165. PMID 12114496. 
• Mo J, Fang SJ, Chen W, Blobe GC (2003). "Regulation of ALK-1 signaling by the nuclear receptor LXRbeta". J. Biol. Chem. 277 (52): 50788–94. doi:10.1074/jbc.M210376200. PMID 12393874. 
• Lamouille S, Mallet C, Feige JJ, Bailly S (2003). "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, et al. (2010). "ALK1-Fc inhibits multiple mediators of angiogenesis and suppresses tumor growth.". Mol Cancer Ther 9 (2): 379–88. doi:10.1158/1535-7163.MCT-09-0650. PMID 20124460. 

External links

• GeneReviews/NCBI/NIH/UW entry on Hereditary Hemorrhagic Telangiectasia

This article incorporates text from the United States National Library of Medicine, which is in the public domain.