ACVR1_HUMAN
ID ACVR1_HUMAN Reviewed; 509 AA.
AC Q04771;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Activin receptor type-1;
DE EC=2.7.11.30 {ECO:0000269|PubMed:9748228};
DE AltName: Full=Activin receptor type I;
DE Short=ACTR-I;
DE AltName: Full=Activin receptor-like kinase 2;
DE Short=ALK-2;
DE AltName: Full=Serine/threonine-protein kinase receptor R1;
DE Short=SKR1;
DE AltName: Full=TGF-B superfamily receptor type I;
DE Short=TSR-I;
DE Flags: Precursor;
GN Name=ACVR1; Synonyms=ACVRLK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8389764; DOI=10.1016/s0021-9258(18)31447-9;
RA Matsuzaki K., McKeehan W.L.;
RT "A widely expressed transmembrane serine/threonine kinase that does not
RT bind activin, inhibin, transforming growth factor beta, or bone morphogenic
RT factor.";
RL J. Biol. Chem. 268:12719-12723(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=8397373;
RA ten Dijke P., Ichijo H., Franzen P., Schulz P., Saras J., Toyoshima H.,
RA Heldin C.-H., Miyazono K.;
RT "Activin receptor-like kinases: a novel subclass of cell-surface receptors
RT with predicted serine/threonine kinase activity.";
RL Oncogene 8:2879-2887(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH CLU.
RX PubMed=8555189; DOI=10.1021/bi951880a;
RA Reddy K.B., Karode M.C., Harmony A.K., Howe P.H.;
RT "Interaction of transforming growth factor beta receptors with
RT apolipoprotein J/clusterin.";
RL Biochemistry 35:309-314(1996).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH BMP7, AND MUTAGENESIS OF
RP GLN-207.
RX PubMed=9748228; DOI=10.1074/jbc.273.40.25628;
RA Macias-Silva M., Hoodless P.A., Tang S.J., Buchwald M., Wrana J.L.;
RT "Specific activation of Smad1 signaling pathways by the BMP7 type I
RT receptor, ALK2.";
RL J. Biol. Chem. 273:25628-25636(1998).
RN [6]
RP FUNCTION, AND INTERACTION WITH ACVR2A AND AMHR2.
RX PubMed=17911401; DOI=10.1677/joe-07-0281;
RA Renlund N., O'Neill F.H., Zhang L., Sidis Y., Teixeira J.;
RT "Activin receptor-like kinase-2 inhibits activin signaling by blocking the
RT binding of activin to its type II receptor.";
RL J. Endocrinol. 195:95-103(2007).
RN [7]
RP INTERACTION WITH BMP6.
RX PubMed=18070108; DOI=10.1111/j.1742-4658.2007.06187.x;
RA Saremba S., Nickel J., Seher A., Kotzsch A., Sebald W., Mueller T.D.;
RT "Type I receptor binding of bone morphogenetic protein 6 is dependent on N-
RT glycosylation of the ligand.";
RL FEBS J. 275:172-183(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [9]
RP FUNCTION, AND INTERACTION WITH GDF2/BMP9.
RX PubMed=20628059; DOI=10.1074/jbc.m110.130518;
RA Luo J., Tang M., Huang J., He B.C., Gao J.L., Chen L., Zuo G.W., Zhang W.,
RA Luo Q., Shi Q., Zhang B.Q., Bi Y., Luo X., Jiang W., Su Y., Shen J.,
RA Kim S.H., Huang E., Gao Y., Zhou J.Z., Yang K., Luu H.H., Pan X.,
RA Haydon R.C., Deng Z.L., He T.C.;
RT "TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced
RT osteogenic signaling in mesenchymal stem cells.";
RL J. Biol. Chem. 285:29588-29598(2010).
RN [10]
RP INTERACTION WITH FCHO1.
RX PubMed=22484487; DOI=10.1038/ncb2473;
RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B.,
RA Tsang M., Traub L.M.;
RT "Distinct and separable activities of the endocytic clathrin-coat
RT components Fcho1/2 and AP-2 in developmental patterning.";
RL Nat. Cell Biol. 14:488-501(2012).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF THR-203 AND GLY-325.
RX PubMed=25354296; DOI=10.1210/me.2014-1301;
RA Fujimoto M., Ohte S., Osawa K., Miyamoto A., Tsukamoto S., Mizuta T.,
RA Kokabu S., Suda N., Katagiri T.;
RT "Mutant activin-like kinase 2 in fibrodysplasia ossificans progressiva are
RT activated via T203 by BMP type II receptors.";
RL Mol. Endocrinol. 29:140-152(2015).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 172-499 IN COMPLEX WITH FKBP1A.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the kinase domain of type I activin receptor (ACVR1)
RT in complex with FKBP12 and dorsomorphin.";
RL Submitted (JUN-2009) to the PDB data bank.
RN [13] {ECO:0007744|PDB:3H9R}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 172-499, AND FUNCTION.
RX PubMed=22977237; DOI=10.1074/jbc.m112.365932;
RA Chaikuad A., Alfano I., Kerr G., Sanvitale C.E., Boergermann J.H.,
RA Triffitt J.T., von Delft F., Knapp S., Knaus P., Bullock A.N.;
RT "Structure of the bone morphogenetic protein receptor ALK2 and implications
RT for fibrodysplasia ossificans progressiva.";
RL J. Biol. Chem. 287:36990-36998(2012).
RN [14]
RP VARIANT FOP HIS-206.
RX PubMed=16642017; DOI=10.1038/ng1783;
RA Shore E.M., Xu M., Feldman G.J., Fenstermacher D.A., Brown M.A.,
RA Kaplan F.S.;
RT "A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and
RT sporadic fibrodysplasia ossificans progressiva.";
RL Nat. Genet. 38:525-527(2006).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-15; PHE-41; GLN-47 AND SER-115.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [16]
RP VARIANTS FOP 197-PRO-PHE-198 DELINS LEU; HIS-206; GLU-207; ARG-328;
RP TRP-328; GLU-328; ASP-356 AND PRO-375.
RX PubMed=19085907; DOI=10.1002/humu.20868;
RA Kaplan F.S., Xu M., Seemann P., Connor J.M., Glaser D.L., Carroll L.,
RA Delai P., Fastnacht-Urban E., Forman S.J., Gillessen-Kaesbach G.,
RA Hoover-Fong J., Koester B., Pauli R.M., Reardon W., Zaidi S.A., Zasloff M.,
RA Morhart R., Mundlos S., Groppe J., Shore E.M.;
RT "Classic and atypical fibrodysplasia ossificans progressiva (FOP)
RT phenotypes are caused by mutations in the bone morphogenetic protein (BMP)
RT type I receptor ACVR1.";
RL Hum. Mutat. 30:379-390(2009).
RN [17]
RP VARIANTS FOP ILE-202 AND GLU-328.
RX PubMed=19330033; DOI=10.1371/journal.pone.0005005;
RA Petrie K.A., Lee W.H., Bullock A.N., Pointon J.J., Smith R., Russell R.G.,
RA Brown M.A., Wordsworth B.P., Triffitt J.T.;
RT "Novel mutations in ACVR1 result in atypical features in two fibrodysplasia
RT ossificans progressiva patients.";
RL PLoS ONE 4:E5005-E5005(2009).
CC -!- FUNCTION: Bone morphogenetic protein (BMP) type I receptor that is
CC involved in a wide variety of biological processes, including bone,
CC heart, cartilage, nervous, and reproductive system development and
CC regulation (PubMed:20628059, PubMed:22977237). As a type I receptor,
CC forms heterotetrameric receptor complexes with the type II receptors
CC AMHR2, ACVR2A or ACVR2B (PubMed:17911401). Upon binding of ligands such
CC as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors
CC transphosphorylate ACVR1 intracellular domain (PubMed:25354296). In
CC turn, ACVR1 kinase domain is activated and subsequently phosphorylates
CC SMAD1/5/8 proteins that transduce the signal (PubMed:9748228). In
CC addition to its role in mediating BMP pathway-specific signaling,
CC suppresses TGFbeta/activin pathway signaling by interfering with the
CC binding of activin to its type II receptor (PubMed:17911401). Besides
CC canonical SMAD signaling, can activate non-canonical pathways such as
CC p38 mitogen-activated protein kinases/MAPKs (By similarity).
CC {ECO:0000250|UniProtKB:P15261, ECO:0000269|PubMed:17911401,
CC ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:22977237,
CC ECO:0000269|PubMed:25354296, ECO:0000269|PubMed:9748228}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho-
CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA-
CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.30;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L-
CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022,
CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC EC=2.7.11.30; Evidence={ECO:0000269|PubMed:9748228};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBUNIT: Interacts with FKBP1A (PubMed:22484487, Ref.12). Interacts
CC with FCHO1 (PubMed:22484487). Interacts with CLU (PubMed:8555189).
CC Interacts with type II receptors AMHR2 and ACVR2A (PubMed:17911401).
CC Interacts with BMP7 (PubMed:9748228). Interacts with GDF2/BMP9
CC (PubMed:20628059). Interacts with BMP6 (PubMed:18070108).
CC {ECO:0000269|PubMed:17911401, ECO:0000269|PubMed:18070108,
CC ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:22484487,
CC ECO:0000269|PubMed:8555189, ECO:0000269|PubMed:9748228,
CC ECO:0000269|Ref.12}.
CC -!- INTERACTION:
CC Q04771; Q9UF33: EPHA6; NbExp=2; IntAct=EBI-1383616, EBI-3950019;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in normal parenchymal cells, endothelial
CC cells, fibroblasts and tumor-derived epithelial cells.
CC {ECO:0000269|PubMed:8389764}.
CC -!- DISEASE: Fibrodysplasia ossificans progressiva (FOP) [MIM:135100]: A
CC rare autosomal dominant connective tissue disorder resulting in
CC skeletal malformations and progressive extraskeletal ossification.
CC Heterotopic ossification begins in childhood and can be induced by
CC trauma or may occur without warning. Bone formation is episodic and
CC progressive, leading to a debilitating ankylosis of all major joints of
CC the axial and appendicular skeleton, rendering movement impossible.
CC {ECO:0000269|PubMed:16642017, ECO:0000269|PubMed:19085907,
CC ECO:0000269|PubMed:19330033}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}.
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DR EMBL; L02911; AAA36614.1; -; mRNA.
DR EMBL; Z22534; CAA80256.1; -; mRNA.
DR EMBL; BC033867; AAH33867.1; -; mRNA.
DR CCDS; CCDS2206.1; -.
DR PIR; A45992; A45992.
DR RefSeq; NP_001096.1; NM_001105.4.
DR RefSeq; NP_001104537.1; NM_001111067.2.
DR RefSeq; NP_001334592.1; NM_001347663.1.
DR RefSeq; NP_001334593.1; NM_001347664.1.
DR RefSeq; NP_001334594.1; NM_001347665.1.
DR RefSeq; NP_001334595.1; NM_001347666.1.
DR RefSeq; NP_001334596.1; NM_001347667.1.
DR RefSeq; XP_006712888.1; XM_006712825.3.
DR RefSeq; XP_011510410.1; XM_011512108.2.
DR PDB; 3H9R; X-ray; 2.35 A; A=172-499.
DR PDB; 3MTF; X-ray; 2.15 A; A/B=201-499.
DR PDB; 3OOM; X-ray; 2.00 A; A=201-499.
DR PDB; 3Q4U; X-ray; 1.82 A; A/B/C/D=201-499.
DR PDB; 4BGG; X-ray; 2.56 A; A/B/C/D=201-499.
DR PDB; 4C02; X-ray; 2.17 A; A=172-499.
DR PDB; 4DYM; X-ray; 2.42 A; A=201-499.
DR PDB; 5OXG; X-ray; 2.13 A; A/B/C/D=201-499.
DR PDB; 5OY6; X-ray; 2.56 A; A/B/C/D=201-499.
DR PDB; 5S75; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S76; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S77; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S78; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S79; X-ray; 1.50 A; A/B=201-499.
DR PDB; 5S7A; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S7B; X-ray; 1.32 A; A/B=201-499.
DR PDB; 5S7C; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S7D; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S7E; X-ray; 1.32 A; A/B=201-499.
DR PDB; 5S7F; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S7G; X-ray; 1.78 A; A/B=201-499.
DR PDB; 5S7H; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S7I; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S7J; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S7K; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S7L; X-ray; 1.36 A; A/B=201-499.
DR PDB; 5S7M; X-ray; 1.32 A; A/B=201-499.
DR PDB; 5S7N; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S7O; X-ray; 1.43 A; A/B=201-499.
DR PDB; 5S7P; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S7Q; X-ray; 1.53 A; A/B=201-499.
DR PDB; 5S7R; X-ray; 1.46 A; A/B=201-499.
DR PDB; 5S7S; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S7T; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S7U; X-ray; 1.59 A; A/B=201-499.
DR PDB; 5S7V; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S7W; X-ray; 1.33 A; A/B=201-499.
DR PDB; 5S7X; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S7Y; X-ray; 1.37 A; A/B=201-499.
DR PDB; 5S7Z; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S80; X-ray; 1.67 A; A/B=201-499.
DR PDB; 5S81; X-ray; 1.43 A; A/B=201-499.
DR PDB; 5S82; X-ray; 1.71 A; A/B=201-499.
DR PDB; 5S83; X-ray; 1.33 A; A/B=201-499.
DR PDB; 5S84; X-ray; 1.35 A; A/B=201-499.
DR PDB; 5S85; X-ray; 1.33 A; A/B=201-499.
DR PDB; 5S86; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S87; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S88; X-ray; 1.31 A; A/B=201-499.
DR PDB; 5S89; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S8A; X-ray; 1.30 A; A/B=201-499.
DR PDB; 5S8B; X-ray; 1.64 A; A/B=201-499.
DR PDB; 5S9K; X-ray; 1.35 A; A/B=201-499.
DR PDB; 6ACR; X-ray; 2.01 A; A/B=201-499.
DR PDB; 6EIX; X-ray; 2.30 A; A=172-509.
DR PDB; 6GI6; X-ray; 1.98 A; A=201-499.
DR PDB; 6GIN; X-ray; 2.20 A; A/B=201-499.
DR PDB; 6GIP; X-ray; 2.17 A; A=201-499.
DR PDB; 6I1S; X-ray; 1.52 A; A=172-499.
DR PDB; 6JUX; X-ray; 1.75 A; A=201-499.
DR PDB; 6SRH; X-ray; 1.25 A; A/B=201-499.
DR PDB; 6SZM; X-ray; 1.42 A; A/B=201-499.
DR PDB; 6T6D; X-ray; 2.56 A; A/B/C/D=201-499.
DR PDB; 6T8N; X-ray; 1.77 A; A/B=201-499.
DR PDB; 6TN8; X-ray; 1.63 A; A=201-499.
DR PDB; 6UNQ; X-ray; 2.40 A; A=201-499.
DR PDB; 6UNR; X-ray; 2.20 A; A=201-499.
DR PDB; 6UNS; X-ray; 2.30 A; A/B=201-499.
DR PDB; 6Z36; X-ray; 1.37 A; A/B=201-499.
DR PDB; 6ZGC; X-ray; 2.67 A; A/B/C/D=201-499.
DR PDB; 7A21; X-ray; 2.14 A; A/B=201-499.
DR PDB; 7C3G; X-ray; 1.80 A; A/B=201-499.
DR PDB; 7NNS; X-ray; 2.14 A; B=201-499.
DR PDBsum; 3H9R; -.
DR PDBsum; 3MTF; -.
DR PDBsum; 3OOM; -.
DR PDBsum; 3Q4U; -.
DR PDBsum; 4BGG; -.
DR PDBsum; 4C02; -.
DR PDBsum; 4DYM; -.
DR PDBsum; 5OXG; -.
DR PDBsum; 5OY6; -.
DR PDBsum; 5S75; -.
DR PDBsum; 5S76; -.
DR PDBsum; 5S77; -.
DR PDBsum; 5S78; -.
DR PDBsum; 5S79; -.
DR PDBsum; 5S7A; -.
DR PDBsum; 5S7B; -.
DR PDBsum; 5S7C; -.
DR PDBsum; 5S7D; -.
DR PDBsum; 5S7E; -.
DR PDBsum; 5S7F; -.
DR PDBsum; 5S7G; -.
DR PDBsum; 5S7H; -.
DR PDBsum; 5S7I; -.
DR PDBsum; 5S7J; -.
DR PDBsum; 5S7K; -.
DR PDBsum; 5S7L; -.
DR PDBsum; 5S7M; -.
DR PDBsum; 5S7N; -.
DR PDBsum; 5S7O; -.
DR PDBsum; 5S7P; -.
DR PDBsum; 5S7Q; -.
DR PDBsum; 5S7R; -.
DR PDBsum; 5S7S; -.
DR PDBsum; 5S7T; -.
DR PDBsum; 5S7U; -.
DR PDBsum; 5S7V; -.
DR PDBsum; 5S7W; -.
DR PDBsum; 5S7X; -.
DR PDBsum; 5S7Y; -.
DR PDBsum; 5S7Z; -.
DR PDBsum; 5S80; -.
DR PDBsum; 5S81; -.
DR PDBsum; 5S82; -.
DR PDBsum; 5S83; -.
DR PDBsum; 5S84; -.
DR PDBsum; 5S85; -.
DR PDBsum; 5S86; -.
DR PDBsum; 5S87; -.
DR PDBsum; 5S88; -.
DR PDBsum; 5S89; -.
DR PDBsum; 5S8A; -.
DR PDBsum; 5S8B; -.
DR PDBsum; 5S9K; -.
DR PDBsum; 6ACR; -.
DR PDBsum; 6EIX; -.
DR PDBsum; 6GI6; -.
DR PDBsum; 6GIN; -.
DR PDBsum; 6GIP; -.
DR PDBsum; 6I1S; -.
DR PDBsum; 6JUX; -.
DR PDBsum; 6SRH; -.
DR PDBsum; 6SZM; -.
DR PDBsum; 6T6D; -.
DR PDBsum; 6T8N; -.
DR PDBsum; 6TN8; -.
DR PDBsum; 6UNQ; -.
DR PDBsum; 6UNR; -.
DR PDBsum; 6UNS; -.
DR PDBsum; 6Z36; -.
DR PDBsum; 6ZGC; -.
DR PDBsum; 7A21; -.
DR PDBsum; 7C3G; -.
DR PDBsum; 7NNS; -.
DR AlphaFoldDB; Q04771; -.
DR SMR; Q04771; -.
DR BioGRID; 106605; 106.
DR DIP; DIP-212N; -.
DR IntAct; Q04771; 21.
DR MINT; Q04771; -.
DR STRING; 9606.ENSP00000263640; -.
DR BindingDB; Q04771; -.
DR ChEMBL; CHEMBL5903; -.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB08597; Dorsomorphin.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q04771; -.
DR GuidetoPHARMACOLOGY; 1785; -.
DR GlyGen; Q04771; 1 site.
DR iPTMnet; Q04771; -.
DR PhosphoSitePlus; Q04771; -.
DR BioMuta; ACVR1; -.
DR DMDM; 462447; -.
DR EPD; Q04771; -.
DR jPOST; Q04771; -.
DR MassIVE; Q04771; -.
DR MaxQB; Q04771; -.
DR PaxDb; Q04771; -.
DR PeptideAtlas; Q04771; -.
DR PRIDE; Q04771; -.
DR ProteomicsDB; 58283; -.
DR Antibodypedia; 2371; 626 antibodies from 41 providers.
DR DNASU; 90; -.
DR Ensembl; ENST00000263640.7; ENSP00000263640.3; ENSG00000115170.16.
DR Ensembl; ENST00000409283.6; ENSP00000387273.2; ENSG00000115170.16.
DR Ensembl; ENST00000410057.6; ENSP00000387127.2; ENSG00000115170.16.
DR Ensembl; ENST00000424669.6; ENSP00000400767.2; ENSG00000115170.16.
DR Ensembl; ENST00000434821.7; ENSP00000405004.1; ENSG00000115170.16.
DR Ensembl; ENST00000539637.6; ENSP00000440091.2; ENSG00000115170.16.
DR Ensembl; ENST00000672582.1; ENSP00000500605.1; ENSG00000115170.16.
DR Ensembl; ENST00000673324.1; ENSP00000500109.1; ENSG00000115170.16.
DR Ensembl; ENST00000682025.1; ENSP00000507086.1; ENSG00000115170.16.
DR Ensembl; ENST00000682300.1; ENSP00000507102.1; ENSG00000115170.16.
DR Ensembl; ENST00000683441.1; ENSP00000508189.1; ENSG00000115170.16.
DR Ensembl; ENST00000683487.1; ENSP00000507113.1; ENSG00000115170.16.
DR Ensembl; ENST00000683820.1; ENSP00000507727.1; ENSG00000115170.16.
DR Ensembl; ENST00000684348.1; ENSP00000508136.1; ENSG00000115170.16.
DR Ensembl; ENST00000684595.1; ENSP00000507730.1; ENSG00000115170.16.
DR GeneID; 90; -.
DR KEGG; hsa:90; -.
DR MANE-Select; ENST00000434821.7; ENSP00000405004.1; NM_001111067.4; NP_001104537.1.
DR UCSC; uc002tzm.4; human.
DR CTD; 90; -.
DR DisGeNET; 90; -.
DR GeneCards; ACVR1; -.
DR GeneReviews; ACVR1; -.
DR HGNC; HGNC:171; ACVR1.
DR HPA; ENSG00000115170; Low tissue specificity.
DR MalaCards; ACVR1; -.
DR MIM; 102576; gene.
DR MIM; 135100; phenotype.
DR neXtProt; NX_Q04771; -.
DR OpenTargets; ENSG00000115170; -.
DR Orphanet; 337; Fibrodysplasia ossificans progressiva.
DR PharmGKB; PA24492; -.
DR VEuPathDB; HostDB:ENSG00000115170; -.
DR eggNOG; KOG2052; Eukaryota.
DR GeneTree; ENSGT00940000160160; -.
DR HOGENOM; CLU_000288_8_5_1; -.
DR InParanoid; Q04771; -.
DR OMA; NQAVECC; -.
DR OrthoDB; 1299087at2759; -.
DR PhylomeDB; Q04771; -.
DR TreeFam; TF314724; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; Q04771; -.
DR SignaLink; Q04771; -.
DR SIGNOR; Q04771; -.
DR BioGRID-ORCS; 90; 16 hits in 1117 CRISPR screens.
DR ChiTaRS; ACVR1; human.
DR EvolutionaryTrace; Q04771; -.
DR GeneWiki; ACVR1; -.
DR GenomeRNAi; 90; -.
DR Pharos; Q04771; Tchem.
DR PRO; PR:Q04771; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q04771; protein.
DR Bgee; ENSG00000115170; Expressed in cartilage tissue and 207 other tissues.
DR ExpressionAtlas; Q04771; baseline and differential.
DR Genevisible; Q04771; HS.
DR GO; GO:0048179; C:activin receptor complex; IDA:UniProtKB.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0070724; C:BMP receptor complex; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0048185; F:activin binding; IDA:UniProtKB.
DR GO; GO:0016361; F:activin receptor activity, type I; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC-UCL.
DR GO; GO:0045296; F:cadherin binding; IPI:ARUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017046; F:peptide hormone binding; NAS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:HGNC-UCL.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:ARUK-UCL.
DR GO; GO:0046332; F:SMAD binding; IDA:HGNC-UCL.
DR GO; GO:0050431; F:transforming growth factor beta binding; IDA:UniProtKB.
DR GO; GO:0005025; F:transforming growth factor beta receptor activity, type I; IBA:GO_Central.
DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; NAS:UniProtKB.
DR GO; GO:0032924; P:activin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0002526; P:acute inflammatory response; IEA:Ensembl.
DR GO; GO:0003289; P:atrial septum primum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL.
DR GO; GO:0061312; P:BMP signaling pathway involved in heart development; ISS:BHF-UCL.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl.
DR GO; GO:0060923; P:cardiac muscle cell fate commitment; IMP:BHF-UCL.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IMP:BHF-UCL.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central.
DR GO; GO:0003143; P:embryonic heart tube morphogenesis; IMP:BHF-UCL.
DR GO; GO:0061445; P:endocardial cushion cell fate commitment; IMP:BHF-UCL.
DR GO; GO:0003274; P:endocardial cushion fusion; ISS:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0003183; P:mitral valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0032926; P:negative regulation of activin receptor signaling pathway; IMP:HGNC-UCL.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IMP:HGNC-UCL.
DR GO; GO:0009968; P:negative regulation of signal transduction; IMP:HGNC-UCL.
DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0060037; P:pharyngeal system development; IEA:Ensembl.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IGI:BHF-UCL.
DR GO; GO:2000017; P:positive regulation of determination of dorsal identity; IDA:BHF-UCL.
DR GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:HGNC-UCL.
DR GO; GO:0030278; P:regulation of ossification; IMP:UniProtKB.
DR GO; GO:0048641; P:regulation of skeletal muscle tissue development; IEA:Ensembl.
DR GO; GO:0051145; P:smooth muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0001655; P:urogenital system development; IEA:Ensembl.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR000472; Activin_recp.
DR InterPro; IPR003605; GS_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR000333; TGFB_receptor.
DR PANTHER; PTHR23255; PTHR23255; 1.
DR Pfam; PF01064; Activin_recp; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF08515; TGF_beta_GS; 1.
DR PRINTS; PR00653; ACTIVIN2R.
DR SMART; SM00467; GS; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS51256; GS; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Disease variant; Glycoprotein; Kinase;
KW Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome;
KW Serine/threonine-protein kinase; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT CHAIN 21..509
FT /note="Activin receptor type-1"
FT /id="PRO_0000024394"
FT TOPO_DOM 21..123
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 147..509
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 178..207
FT /note="GS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585"
FT DOMAIN 208..502
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 336
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 214..222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 235
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 15
FT /note="A -> G (in dbSNP:rs13406336)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041392"
FT VARIANT 41
FT /note="S -> F (in dbSNP:rs55957214)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041393"
FT VARIANT 47
FT /note="H -> Q (in dbSNP:rs34056189)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041394"
FT VARIANT 115
FT /note="P -> S (in a melanoma sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041395"
FT VARIANT 197..198
FT /note="PF -> L (in FOP; variant phenotype)"
FT /evidence="ECO:0000269|PubMed:19085907"
FT /id="VAR_058418"
FT VARIANT 202
FT /note="R -> I (in FOP; with some atypical features;
FT dbSNP:rs387906591)"
FT /evidence="ECO:0000269|PubMed:19330033"
FT /id="VAR_058419"
FT VARIANT 206
FT /note="R -> H (in FOP; dbSNP:rs121912678)"
FT /evidence="ECO:0000269|PubMed:16642017,
FT ECO:0000269|PubMed:19085907"
FT /id="VAR_028444"
FT VARIANT 207
FT /note="Q -> E (in FOP; with some atypical features)"
FT /evidence="ECO:0000269|PubMed:19085907"
FT /id="VAR_058420"
FT VARIANT 328
FT /note="G -> E (in FOP; variant phenotype;
FT dbSNP:rs387906589)"
FT /evidence="ECO:0000269|PubMed:19085907,
FT ECO:0000269|PubMed:19330033"
FT /id="VAR_058421"
FT VARIANT 328
FT /note="G -> R (in FOP; variant phenotype;
FT dbSNP:rs387906588)"
FT /evidence="ECO:0000269|PubMed:19085907"
FT /id="VAR_058422"
FT VARIANT 328
FT /note="G -> W (in FOP; variant phenotype;
FT dbSNP:rs387906588)"
FT /evidence="ECO:0000269|PubMed:19085907"
FT /id="VAR_058423"
FT VARIANT 356
FT /note="G -> D (in FOP; variant phenotype;
FT dbSNP:rs121912679)"
FT /evidence="ECO:0000269|PubMed:19085907"
FT /id="VAR_058424"
FT VARIANT 375
FT /note="R -> P (in FOP; variant phenotype;
FT dbSNP:rs387906590)"
FT /evidence="ECO:0000269|PubMed:19085907"
FT /id="VAR_058425"
FT MUTAGEN 203
FT /note="T->V: Almost complete loss of alcaline phosphatase
FT induction; in association with A-325."
FT /evidence="ECO:0000269|PubMed:25354296"
FT MUTAGEN 207
FT /note="Q->D: Strong induction of SMAD1 phosphorylation."
FT /evidence="ECO:0000269|PubMed:9748228"
FT MUTAGEN 325
FT /note="G->A: Almost complete loss of alcaline phosphatase
FT induction; in association with V-203."
FT /evidence="ECO:0000269|PubMed:25354296"
FT HELIX 180..184
FT /evidence="ECO:0007829|PDB:6I1S"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:6I1S"
FT HELIX 198..205
FT /evidence="ECO:0007829|PDB:6I1S"
FT STRAND 209..217
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 220..227
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 230..237
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 242..254
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 265..272
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 274..283
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 291..297
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 302..320
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:3MTF"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:6SRH"
FT TURN 363..366
FT /evidence="ECO:0007829|PDB:6SRH"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 384..387
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 396..415
FT /evidence="ECO:0007829|PDB:6SRH"
FT TURN 430..434
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 441..448
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 459..463
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 465..477
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:6SRH"
FT HELIX 488..496
FT /evidence="ECO:0007829|PDB:6SRH"
SQ SEQUENCE 509 AA; 57153 MW; E2B0F051D19DD052 CRC64;
MVDGVMILPV LIMIALPSPS MEDEKPKVNP KLYMCVCEGL SCGNEDHCEG QQCFSSLSIN
DGFHVYQKGC FQVYEQGKMT CKTPPSPGQA VECCQGDWCN RNITAQLPTK GKSFPGTQNF
HLEVGLIILS VVFAVCLLAC LLGVALRKFK RRNQERLNPR DVEYGTIEGL ITTNVGDSTL
ADLLDHSCTS GSGSGLPFLV QRTVARQITL LECVGKGRYG EVWRGSWQGE NVAVKIFSSR
DEKSWFRETE LYNTVMLRHE NILGFIASDM TSRHSSTQLW LITHYHEMGS LYDYLQLTTL
DTVSCLRIVL SIASGLAHLH IEIFGTQGKP AIAHRDLKSK NILVKKNGQC CIADLGLAVM
HSQSTNQLDV GNNPRVGTKR YMAPEVLDET IQVDCFDSYK RVDIWAFGLV LWEVARRMVS
NGIVEDYKPP FYDVVPNDPS FEDMRKVVCV DQQRPNIPNR WFSDPTLTSL AKLMKECWYQ
NPSARLTALR IKKTLTKIDN SLDKLKTDC
