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 27-MAR-2024, entry version 223. 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 TSC22D1. RX PubMed=21791611; DOI=10.1128/mcb.05448-11; RA Yan X., Zhang J., Pan L., Wang P., Xue H., Zhang L., Gao X., Zhao X., RA Ning Y., Chen Y.G.; RT "TSC-22 promotes transforming growth factor beta-mediated cardiac RT myofibroblast differentiation by antagonizing Smad7 activity."; RL Mol. Cell. Biol. 31:3700-3709(2011). RN [11] 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 [12] 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 [13] RP INTERACTION WITH BMP6. RX PubMed=31800957; DOI=10.1182/blood.2019002620; RA Wang C.Y., Xu Y., Traeger L., Dogan D.Y., Xiao X., Steinbicker A.U., RA Babitt J.L.; RT "Erythroferrone lowers hepcidin by sequestering BMP2/6 heterodimer from RT binding to the BMP type I receptor ALK3."; RL Blood 135:453-456(2020). RN [14] 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 [15] {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 [16] 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 [17] 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 [18] 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 [19] 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). May CC promote the expression of HAMP, potentially via its interaction with CC BMP6 (By similarity). {ECO:0000250|UniProtKB:P15261, CC ECO:0000250|UniProtKB:P37172, 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.14). 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 (when glycosylated); the CC interaction may induce HAMP expression (PubMed:18070108, CC PubMed:31800957). Interacts with TSC22D1/TSC-22 (PubMed:21791611). CC {ECO:0000269|PubMed:17911401, ECO:0000269|PubMed:18070108, CC ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:21791611, CC ECO:0000269|PubMed:22484487, ECO:0000269|PubMed:31800957, CC ECO:0000269|PubMed:8555189, ECO:0000269|PubMed:9748228, CC ECO:0000269|Ref.14}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7YRU; X-ray; 2.60 A; A=21-123. DR PDB; 8C7W; X-ray; 2.26 A; A=201-499. DR PDB; 8C7Z; X-ray; 2.23 A; A=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 PDBsum; 7YRU; -. DR PDBsum; 8C7W; -. DR PDBsum; 8C7Z; -. DR AlphaFoldDB; Q04771; -. DR SMR; Q04771; -. DR BioGRID; 106605; 111. DR DIP; DIP-212N; -. DR IntAct; Q04771; 21. DR MINT; Q04771; -. DR STRING; 9606.ENSP00000405004; -. 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 GlyCosmos; Q04771; 1 site, No reported glycans. DR GlyGen; Q04771; 1 site. DR iPTMnet; Q04771; -. DR PhosphoSitePlus; Q04771; -. DR SwissPalm; Q04771; -. DR BioMuta; ACVR1; -. DR DMDM; 462447; -. DR CPTAC; CPTAC-2848; -. DR CPTAC; CPTAC-2849; -. DR EPD; Q04771; -. DR jPOST; Q04771; -. DR MassIVE; Q04771; -. DR MaxQB; Q04771; -. DR PaxDb; 9606-ENSP00000263640; -. DR PeptideAtlas; Q04771; -. DR ProteomicsDB; 58283; -. DR Pumba; Q04771; -. DR Antibodypedia; 2371; 694 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 AGR; HGNC:171; -. 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; VFERGCI; -. DR OrthoDB; 3900892at2759; -. 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; 18 hits in 1201 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 209 other cell types or tissues. DR ExpressionAtlas; Q04771; baseline and differential. 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:0005886; C:plasma membrane; IDA:UniProtKB. 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:0098821; F:BMP receptor activity; IDA:ARUK-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; IDA:BHF-UCL. 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:HGNC-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: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:0003272; P:endocardial cushion formation; ISS:BHF-UCL. DR GO; GO:0003274; P:endocardial cushion fusion; 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:0060037; P:pharyngeal system development; IEA:Ensembl. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:BHF-UCL. DR GO; GO:0062043; P:positive regulation of cardiac epithelial to mesenchymal transition; ISS: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:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:ARUK-UCL. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0030278; P:regulation of ossification; IMP:UniProtKB. 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:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL. DR CDD; cd14142; STKc_ACVR1_ALK1; 1. DR Gene3D; 2.10.60.10; CD59; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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:SF69; ACTIVIN RECEPTOR TYPE-1; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 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; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF57302; Snake toxin-like; 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. DR Genevisible; Q04771; HS. 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 STRAND 33..36 FT /evidence="ECO:0007829|PDB:7YRU" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:7YRU" FT STRAND 46..60 FT /evidence="ECO:0007829|PDB:7YRU" FT STRAND 63..71 FT /evidence="ECO:0007829|PDB:7YRU" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:7YRU" FT STRAND 89..94 FT /evidence="ECO:0007829|PDB:7YRU" FT TURN 97..102 FT /evidence="ECO:0007829|PDB:7YRU" 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 //