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 component of plasma membrane • cell surface 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-templated • 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 • signal transduction by 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 • activin receptor signaling pathway • 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 angiogenesis • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • 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: 51.91 – 51.92 Mb	Chr 15: 101.13 – 101.15 Mb
PubMed search

Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.^[1][2][3]

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.^[3]

Pathology

Germline mutations of ACVRL1 are associated with:

• hereditary hemorrhagic telangiectasia type 2 (Rendu-Osler-Weber syndrome 2)^[4]
• Pulmonary arteriovenous malformations^[5]

Somatic mosaicism in ACVRL1 are associated with severe pulmonary arterial hypertension.^[6]

Closely/family related kinases

(Not to be confused with anaplastic lymphoma kinase (ALK) )
ALK4 is ACVR1B, ALK7 is ACVR1C, and ALK5 is [part of] the TGF-β type I receptor.^[7]

See also

• TGF_beta_signaling_pathway, see summary table for ALK*

References

1. ten Dijke P, Ichijo H, Franzen P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K (Oct 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.
2. 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 (Jul 1996). "Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2". Nat Genet 13 (2): 189–95. doi:10.1038/ng0696-189. PMID 8640225.
3. "Entrez Gene: ACVRL1 activin A receptor type II-like 1".
4. Olivieri C, Mira E, Delù G, Pagella F, Zambelli A, Malvezzi L, Buscarini E, Danesino C (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.
5. Vandenbriele C, Peerlinck K, de Ravel T, Verhamme P, Vanassche T (2014). "Pulmonary arterio-venous malformations in a patient with a novel mutation in exon 10 of the ACVRL1 gene". Acta Clin Belg 69 (2): 139–41. doi:10.1179/0001551213Z.00000000012. PMID 24724759.
6. Jones G, Robertson L, Harrison R, Ridout C, Vasudevan P (April 2014). "Somatic mosaicism in ACVRL1 with transmission to several offspring affected with severe pulmonary arterial hypertension". American Journal of Medical Genetics Part A. doi:10.1002/ajmg.a.36568.
7. 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 (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.

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.