Activin receptor type-1

Details

Name
Activin receptor type-1
Synonyms
  • 2.7.11.30
  • Activin receptor type I
  • Activin receptor-like kinase 2
  • ACTR-I
  • ACVRLK2
  • ALK-2
  • Serine/threonine-protein kinase receptor R1
  • SKR1
  • TGF-B superfamily receptor type I
  • TSR-I
Gene Name
ACVR1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010226|Activin receptor type-1
MVDGVMILPVLIMIALPSPSMEDEKPKVNPKLYMCVCEGLSCGNEDHCEGQQCFSSLSIN
DGFHVYQKGCFQVYEQGKMTCKTPPSPGQAVECCQGDWCNRNITAQLPTKGKSFPGTQNF
HLEVGLIILSVVFAVCLLACLLGVALRKFKRRNQERLNPRDVEYGTIEGLITTNVGDSTL
ADLLDHSCTSGSGSGLPFLVQRTVARQITLLECVGKGRYGEVWRGSWQGENVAVKIFSSR
DEKSWFRETELYNTVMLRHENILGFIASDMTSRHSSTQLWLITHYHEMGSLYDYLQLTTL
DTVSCLRIVLSIASGLAHLHIEIFGTQGKPAIAHRDLKSKNILVKKNGQCCIADLGLAVM
HSQSTNQLDVGNNPRVGTKRYMAPEVLDETIQVDCFDSYKRVDIWAFGLVLWEVARRMVS
NGIVEDYKPPFYDVVPNDPSFEDMRKVVCVDQQRPNIPNRWFSDPTLTSLAKLMKECWYQ
NPSARLTALRIKKTLTKIDNSLDKLKTDC
Number of residues
509
Molecular Weight
57152.41
Theoretical pI
7.36
GO Classification
Functions
activin binding / activin receptor activity, type I / ATP binding / metal ion binding / peptide hormone binding / protein homodimerization activity / protein kinase activity / protein serine/threonine kinase activity / receptor signaling protein serine/threonine kinase activity / SMAD binding / transforming growth factor beta binding / transforming growth factor beta receptor activity, type I / transmembrane receptor protein serine/threonine kinase activity
Processes
activin receptor signaling pathway / acute inflammatory response / atrial septum primum morphogenesis / BMP signaling pathway / cardiac muscle cell fate commitment / cellular response to BMP stimulus / determination of left/right symmetry / embryonic heart tube morphogenesis / endocardial cushion cell fate commitment / G1/S transition of mitotic cell cycle / gastrulation with mouth forming second / germ cell development / in utero embryonic development / mesoderm formation / mitral valve morphogenesis / negative regulation of activin receptor signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / negative regulation of signal transduction / neural crest cell migration / pathway-restricted SMAD protein phosphorylation / patterning of blood vessels / peptidyl-threonine phosphorylation / pharyngeal system development / positive regulation of bone mineralization / positive regulation of cell migration / positive regulation of determination of dorsal identity / positive regulation of osteoblast differentiation / 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 ossification / smooth muscle cell differentiation / transforming growth factor beta receptor signaling pathway
Components
activin receptor complex / apical part of cell / integral component of plasma membrane
General Function
Transmembrane receptor protein serine/threonine kinase activity
Specific Function
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. Receptor for activin. May be involved for left-right pattern formation during embryogenesis (By similarity).
Pfam Domain Function
Transmembrane Regions
124-146
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0010227|Activin receptor type-1 (ACVR1)
ATGGTAGATGGAGTGATGATTCTTCCTGTGCTTATCATGATTGCTCTCCCCTCCCCTAGT
ATGGAAGATGAGAAGCCCAAGGTCAACCCCAAACTCTACATGTGTGTGTGTGAAGGTCTC
TCCTGCGGTAATGAGGACCACTGTGAAGGCCAGCAGTGCTTTTCCTCACTGAGCATCAAC
GATGGCTTCCACGTCTACCAGAAAGGCTGCTTCCAGGTTTATGAGCAGGGAAAGATGACC
TGTAAGACCCCGCCGTCCCCTGGCCAAGCCGTGGAGTGCTGCCAAGGGGACTGGTGTAAC
AGGAACATCACGGCCCAGCTGCCCACTAAAGGAAAATCCTTCCCTGGAACACAGAATTTC
CACTTGGAGGTTGGCCTCATTATTCTCTCTGTAGTGTTCGCAGTATGTCTTTTAGCCTGC
CTGCTGGGAGTTGCTCTCCGAAAATTTAAAAGGCGCAACCAAGAACGCCTCAATCCCCGA
GACGTGGAGTATGGCACTATCGAAGGGCTCATCACCACCAATGTTGGAGACAGCACTTTA
GCAGATTTATTGGATCATTCGTGTACATCAGGAAGTGGCTCTGGTCTTCCTTTTCTGGTA
CAAAGAACAGTGGCTCGCCAGATTACACTGTTGGAGTGTGTCGGGAAAGGCAGGTATGGT
GAGGTGTGGAGGGGCAGCTGGCAAGGGGAGAATGTTGCCGTGAAGATCTTCTCCTCCCGT
GATGAGAAGTCATGGTTCAGGGAAACGGAATTGTACAACACTGTGATGCTGAGGCATGAA
AATATCTTAGGTTTCATTGCTTCAGACATGACATCAAGACACTCCAGTACCCAGCTGTGG
TTAATTACACATTATCATGAAATGGGATCGTTGTACGACTATCTTCAGCTTACTACTCTG
GATACAGTTAGCTGCCTTCGAATAGTGCTGTCCATAGCTAGTGGTCTTGCACATTTGCAC
ATAGAGATATTTGGGACCCAAGGGAAACCAGCCATTGCCCATCGAGATTTAAAGAGCAAA
AATATTCTGGTTAAGAAGAATGGACAGTGTTGCATAGCAGATTTGGGCCTGGCAGTCATG
CATTCCCAGAGCACCAATCAGCTTGATGTGGGGAACAATCCCCGTGTGGGCACCAAGCGC
TACATGGCCCCCGAAGTTCTAGATGAAACCATCCAGGTGGATTGTTTCGATTCTTATAAA
AGGGTCGATATTTGGGCCTTTGGACTTGTTTTGTGGGAAGTGGCCAGGCGGATGGTGAGC
AATGGTATAGTGGAGGATTACAAGCCACCGTTCTACGATGTGGTTCCCAATGACCCAAGT
TTTGAAGATATGAGGAAGGTAGTCTGTGTGGATCAACAAAGGCCAAACATACCCAACAGA
TGGTTCTCAGACCCGACATTAACCTCTCTGGCCAAGCTAATGAAAGAATGCTGGTATCAA
AATCCATCCGCAAGACTCACAGCACTGCGTATCAAAAAGACTTTGACCAAAATTGATAAT
TCCCTCGACAAATTGAAAACTGACTGTTGA
Chromosome Location
2
Locus
2q23-q24
External Identifiers
ResourceLink
UniProtKB IDQ04771
UniProtKB Entry NameACVR1_HUMAN
GenBank Protein ID338219
GenBank Gene IDL02911
GenAtlas IDACVR1
HGNC IDHGNC:171
General References
  1. Matsuzaki K, Xu J, Wang F, McKeehan WL, Krummen L, Kan M: A widely expressed transmembrane serine/threonine kinase that does not bind activin, inhibin, transforming growth factor beta, or bone morphogenic factor. J Biol Chem. 1993 Jun 15;268(17):12719-23. [PubMed:8389764]
  2. 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. [PubMed:8397373]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195]
  5. Umasankar PK, Sanker S, Thieman JR, Chakraborty S, Wendland B, Tsang M, Traub LM: Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning. Nat Cell Biol. 2012 Apr 8;14(5):488-501. doi: 10.1038/ncb2473. [PubMed:22484487]
  6. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS: A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006 May;38(5):525-7. Epub 2006 Apr 23. [PubMed:16642017]
  7. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846]
  8. Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, Delai P, Fastnacht-Urban E, Forman SJ, Gillessen-Kaesbach G, Hoover-Fong J, Koster B, Pauli RM, Reardon W, Zaidi SA, Zasloff M, Morhart R, Mundlos S, Groppe J, Shore EM: Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat. 2009 Mar;30(3):379-90. doi: 10.1002/humu.20868. [PubMed:19085907]
  9. Petrie KA, Lee WH, Bullock AN, Pointon JJ, Smith R, Russell RG, Brown MA, Wordsworth BP, Triffitt JT: Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients. PLoS One. 2009;4(3):e5005. doi: 10.1371/journal.pone.0005005. Epub 2009 Mar 30. [PubMed:19330033]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00171ATPinvestigational, nutraceuticalunknownDetails
DB085976-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidineexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails