Serine/threonine-protein kinase receptor R3

Details

Name
Serine/threonine-protein kinase receptor R3
Synonyms
  • 2.7.11.30
  • Activin receptor-like kinase 1
  • ACVRLK1
  • ALK-1
  • ALK1
  • SKR3
  • TGF-B superfamily receptor type I
  • TSR-I
Gene Name
ACVRL1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010321|Serine/threonine-protein kinase receptor R3
MTLGSPRKGLLMLLMALVTQGDPVKPSRGPLVTCTCESPHCKGPTCRGAWCTVVLVREEG
RHPQEHRGCGNLHRELCRGRPTEFVNHYCCDSHLCNHNVSLVLEATQPPSEQPGTDGQLA
LILGPVLALLALVALGVLGLWHVRRRQEKQRGLHSELGESSLILKASEQGDSMLGDLLDS
DCTTGSGSGLPFLVQRTVARQVALVECVGKGRYGEVWRGLWHGESVAVKIFSSRDEQSWF
RETEIYNTVLLRHDNILGFIASDMTSRNSSTQLWLITHYHEHGSLYDFLQRQTLEPHLAL
RLAVSAACGLAHLHVEIFGTQGKPAIAHRDFKSRNVLVKSNLQCCIADLGLAVMHSQGSD
YLDIGNNPRVGTKRYMAPEVLDEQIRTDCFESYKWTDIWAFGLVLWEIARRTIVNGIVED
YRPPFYDVVPNDPSFEDMKKVVCVDQQTPTIPNRLAADPVLSGLAQMMRECWYPNPSARL
TALRIKKTLQKISNSPEKPKVIQ
Number of residues
503
Molecular Weight
56124.03
Theoretical pI
7.64
GO Classification
Functions
activin binding / activin receptor activity, type I / ATP binding / metal ion binding / protein kinase binding / protein serine/threonine kinase activity / receptor signaling protein serine/threonine kinase activity / SMAD binding / transforming growth factor beta binding / transforming growth factor beta-activated receptor activity / transmembrane receptor protein serine/threonine kinase activity
Processes
activin receptor signaling pathway / angiogenesis / artery development / blood circulation / blood vessel endothelial cell proliferation involved in sprouting angiogenesis / blood vessel maturation / blood vessel remodeling / BMP signaling pathway / cellular response to BMP stimulus / cellular response to transforming growth factor beta stimulus / endothelial tube morphogenesis / in utero embryonic development / lymphangiogenesis / lymphatic endothelial cell differentiation / negative regulation of blood vessel endothelial cell migration / negative regulation of cell adhesion / negative regulation of cell growth / negative regulation of cell migration / negative regulation of cell proliferation / negative regulation of DNA biosynthetic process / negative regulation of endothelial cell differentiation / negative regulation of endothelial cell migration / negative regulation of endothelial cell proliferation / negative regulation of focal adhesion assembly / positive regulation of angiogenesis / positive regulation of BMP signaling pathway / positive regulation of chondrocyte differentiation / positive regulation of endothelial cell differentiation / positive regulation of endothelial cell proliferation / positive regulation of pathway-restricted SMAD protein phosphorylation / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transcription, DNA-templated / protein phosphorylation / regulation of blood pressure / regulation of blood vessel endothelial cell migration / regulation of DNA replication / regulation of endothelial cell proliferation / regulation of transcription, DNA-templated / retina vasculature development in camera-type eye / signal transduction / transforming growth factor beta receptor signaling pathway / venous blood vessel development / wound healing, spreading of epidermal cells
Components
cell surface / integral component of plasma membrane
General Function
Transmembrane receptor protein serine/threonine kinase activity
Specific Function
Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well.
Pfam Domain Function
Transmembrane Regions
119-141
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0010322|Serine/threonine-protein kinase receptor R3 (ACVRL1)
ATGACCTTGGGCTCCCCCAGGAAAGGCCTTCTGATGCTGCTGATGGCCTTGGTGACCCAG
GGAGACCCTGTGAAGCCGTCTCGGGGCCCGCTGGTGACCTGCACGTGTGAGAGCCCACAT
TGCAAGGGGCCTACCTGCCGGGGGGCCTGGTGCACAGTAGTGCTGGTGCGGGAGGAGGGG
AGGCACCCCCAGGAACATCGGGGCTGCGGGAACTTGCACAGGGAGCTCTGCAGGGGGCGC
CCCACCGAGTTCGTCAACCACTACTGCTGCGACAGCCACCTCTGCAACCACAACGTGTCC
CTGGTGCTGGAGGCCACCCAACCTCCTTCGGAGCAGCCGGGAACAGATGGCCAGCTGGCC
CTGATCCTGGGCCCCGTGCTGGCCTTGCTGGCCCTGGTGGCCCTGGGTGTCCTGGGCCTG
TGGCATGTCCGACGGAGGCAGGAGAAGCAGCGTGGCCTGCACAGCGAGCTGGGAGAGTCC
AGTCTCATCCTGAAAGCATCTGAGCAGGGCGACAGCATGTTGGGGGACCTCCTGGACAGT
GACTGCACCACAGGGAGTGGCTCAGGGCTCCCCTTCCTGGTGCAGAGGACAGTGGCACGG
CAGGTTGCCTTGGTGGAGTGTGTGGGAAAAGGCCGCTATGGCGAAGTGTGGCGGGGCTTG
TGGCACGGTGAGAGTGTGGCCGTCAAGATCTTCTCCTCGAGGGATGAACAGTCCTGGTTC
CGGGAGACTGAGATCTATAACACAGTGTTGCTCAGACACGACAACATCCTAGGCTTCATC
GCCTCAGACATGACCTCCCGCAACTCGAGCACGCAGCTGTGGCTCATCACGCACTACCAC
GAGCACGGCTCCCTCTACGACTTTCTGCAGAGACAGACGCTGGAGCCCCATCTGGCTCTG
AGGCTAGCTGTGTCCGCGGCATGCGGCCTGGCGCACCTGCACGTGGAGATCTTCGGTACA
CAGGGCAAACCAGCCATTGCCCACCGCGACTTCAAGAGCCGCAATGTGCTGGTCAAGAGC
AACCTGCAGTGTTGCATCGCCGACCTGGGCCTGGCTGTGATGCACTCACAGGGCAGCGAT
TACCTGGACATCGGCAACAACCCGAGAGTGGGCACCAAGCGGTACATGGCACCCGAGGTG
CTGGACGAGCAGATCCGCACGGACTGCTTTGAGTCCTACAAGTGGACTGACATCTGGGCC
TTTGGCCTGGTGCTGTGGGAGATTGCCCGCCGGACCATCGTGAATGGCATCGTGGAGGAC
TATAGACCACCCTTCTATGATGTGGTGCCCAATGACCCCAGCTTTGAGGACATGAAGAAG
GTGGTGTGTGTGGATCAGCAGACCCCCACCATCCCTAACCGGCTGGCTGCAGACCCGGTC
CTCTCAGGCCTAGCTCAGATGATGCGGGAGTGCTGGTACCCAAACCCCTCTGCCCGACTC
ACCGCGCTGCGGATCAAGAAGACACTACAAAAAATTAGCAACAGTCCAGAGAAGCCTAAA
GTGATTCAATAG
Chromosome Location
12
Locus
12q11-q14
External Identifiers
ResourceLink
UniProtKB IDP37023
UniProtKB Entry NameACVL1_HUMAN
GenBank Protein ID402197
GenBank Gene IDZ22533
GenAtlas IDACVRL1
HGNC IDHGNC:175
General References
  1. ten Dijke P, Ichijo H, Franzen P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K: Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity. Oncogene. 1993 Oct;8(10):2879-87. [Article]
  2. Attisano L, Carcamo J, Ventura F, Weis FM, Massague J, Wrana JL: Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors. Cell. 1993 Nov 19;75(4):671-80. [Article]
  3. Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA: The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet. 1997 Jul;61(1):60-7. [Article]
  4. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. [Article]
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  6. Mahlawat P, Ilangovan U, Biswas T, Sun LZ, Hinck AP: Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties. Biochemistry. 2012 Aug 14;51(32):6328-41. Epub 2012 Aug 2. [Article]
  7. Townson SA, Martinez-Hackert E, Greppi C, Lowden P, Sako D, Liu J, Ucran JA, Liharska K, Underwood KW, Seehra J, Kumar R, Grinberg AV: Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex. J Biol Chem. 2012 Aug 10;287(33):27313-25. doi: 10.1074/jbc.M112.377960. Epub 2012 Jun 20. [Article]
  8. 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: Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996 Jun;13(2):189-95. [Article]
  9. Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA: 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. 1998;12(2):137. [Article]
  10. Abdalla SA, Pece-Barbara N, Vera S, Tapia E, Paez E, Bernabeu C, Letarte M: Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2. Hum Mol Genet. 2000 May 1;9(8):1227-37. [Article]
  11. Kjeldsen AD, Brusgaard K, Poulsen L, Kruse T, Rasmussen K, Green A, Vase P: Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families. Am J Med Genet. 2001 Feb 1;98(4):298-302. [Article]
  12. 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: Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2001 Aug 2;345(5):325-34. [Article]
  13. Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Kermeen F, Halme M, Raisanen-Sokolowski A, Laitinen T, Morrell NW, Trembath RC: Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet. 2003 Dec;40(12):865-71. [Article]
  14. Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Riviere S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S: Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004 Apr;23(4):289-99. [Article]
  15. Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M: Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations. Hum Mutat. 2005 Mar;25(3):320. [Article]
  16. Bossler AD, Richards J, George C, Godmilow L, Ganguly A: Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Hum Mutat. 2006 Jul;27(7):667-75. [Article]
  17. Argyriou L, Twelkemeyer S, Panchulidze I, Wehner LE, Teske U, Engel W, Nayernia K: Novel mutations in the ENG and ACVRL1 genes causing hereditary hemorrhagic teleangiectasia. Int J Mol Med. 2006 Apr;17(4):655-9. [Article]
  18. Richards-Yutz J, Grant K, Chao EC, Walther SE, Ganguly A: Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Hum Genet. 2010 Jul;128(1):61-77. doi: 10.1007/s00439-010-0825-4. Epub 2010 Apr 23. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00171ATPinvestigational, nutraceuticalunknownDetails