BMR1A_HUMAN
ID BMR1A_HUMAN Reviewed; 532 AA.
AC P36894; A8K6U9; Q8NEN8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 240.
DE RecName: Full=Bone morphogenetic protein receptor type-1A;
DE Short=BMP type-1A receptor;
DE Short=BMPR-1A;
DE EC=2.7.11.30;
DE AltName: Full=Activin receptor-like kinase 3;
DE Short=ALK-3;
DE AltName: Full=Serine/threonine-protein kinase receptor R5;
DE Short=SKR5;
DE AltName: CD_antigen=CD292;
DE Flags: Precursor;
GN Name=BMPR1A; Synonyms=ACVRLK3, ALK3;
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 VARIANT THR-2.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-2.
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 BMP4.
RX PubMed=8006002; DOI=10.1016/s0021-9258(17)32506-1;
RA ten Dijke P., Yamashita H., Sampath T.K., Reddi A.H., Estevez M.,
RA Riddle D.L., Ichijo H., Heldin C.H., Miyazono K.;
RT "Identification of type I receptors for osteogenic protein-1 and bone
RT morphogenetic protein-4.";
RL J. Biol. Chem. 269:16985-16988(1994).
RN [5]
RP INTERACTION WITH BMP2, AND MUTAGENESIS OF 107-ASP--GLN-109.
RX PubMed=22799562; DOI=10.1021/bi300942x;
RA Mahlawat P., Ilangovan U., Biswas T., Sun L.Z., Hinck A.P.;
RT "Structure of the Alk1 extracellular domain and characterization of its
RT bone morphogenetic protein (BMP) binding properties.";
RL Biochemistry 51:6328-6341(2012).
RN [6]
RP INTERACTION WITH GDF5.
RX PubMed=24098149; DOI=10.1371/journal.pgen.1003846;
RA Degenkolbe E., Konig J., Zimmer J., Walther M., Reissner C., Nickel J.,
RA Ploger F., Raspopovic J., Sharpe J., Dathe K., Hecht J.T., Mundlos S.,
RA Doelken S.C., Seemann P.;
RT "A GDF5 point mutation strikes twice--causing BDA1 and SYNS2.";
RL PLoS Genet. 9:E1003846-E1003846(2013).
RN [7]
RP INTERACTION WITH SCUBE3.
RX PubMed=33308444; DOI=10.1016/j.ajhg.2020.11.015;
RG Genomics England Research Consortium;
RA Lin Y.C., Niceta M., Muto V., Vona B., Pagnamenta A.T., Maroofian R.,
RA Beetz C., van Duyvenvoorde H., Dentici M.L., Lauffer P., Vallian S.,
RA Ciolfi A., Pizzi S., Bauer P., Gruening N.M., Bellacchio E.,
RA Del Fattore A., Petrini S., Shaheen R., Tiosano D., Halloun R.,
RA Pode-Shakked B., Albayrak H.M., Isik E., Wit J.M., Dittrich M.,
RA Freire B.L., Bertola D.R., Jorge A.A.L., Barel O., Sabir A.H.,
RA Al Tenaiji A.M.J., Taji S.M., Al-Sannaa N., Al-Abdulwahed H., Digilio M.C.,
RA Irving M., Anikster Y., Bhavani G.S.L., Girisha K.M., Haaf T., Taylor J.C.,
RA Dallapiccola B., Alkuraya F.S., Yang R.B., Tartaglia M.;
RT "SCUBE3 loss-of-function causes a recognizable recessive developmental
RT disorder due to defective bone morphogenetic protein signaling.";
RL Am. J. Hum. Genet. 108:115-133(2021).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 55-143 IN COMPLEX WITH BMP2,
RP DISULFIDE BOND, AND INTERACTION WITH BMP2.
RX PubMed=10881198; DOI=10.1038/75903;
RA Kirsch T., Sebald W., Dreyer M.K.;
RT "Crystal structure of the BMP-2-BRIA ectodomain complex.";
RL Nat. Struct. Biol. 7:492-496(2000).
RN [9] {ECO:0007744|PDB:1REW}
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 24-152, AND INTERACTION WITH
RP BMP2.
RX PubMed=15064755; DOI=10.1038/nsmb756;
RA Keller S., Nickel J., Zhang J.L., Sebald W., Mueller T.D.;
RT "Molecular recognition of BMP-2 and BMP receptor IA.";
RL Nat. Struct. Mol. Biol. 11:481-488(2004).
RN [10] {ECO:0007744|PDB:2H62, ECO:0007744|PDB:2H64}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 24-152, AND INTERACTION WITH
RP BMP2.
RX PubMed=17295905; DOI=10.1186/1472-6807-7-6;
RA Weber D., Kotzsch A., Nickel J., Harth S., Seher A., Mueller U., Sebald W.,
RA Mueller T.D.;
RT "A silent H-bond can be mutationally activated for high-affinity
RT interaction of BMP-2 and activin type IIB receptor.";
RL BMC Struct. Biol. 7:6-6(2007).
RN [11]
RP DISEASE.
RX PubMed=11381269; DOI=10.1038/88919;
RA Howe J.R., Bair J.L., Sayed M.G., Anderson M.E., Mitros F.A.,
RA Petersen G.M., Velculescu V.E., Traverso G., Vogelstein B.;
RT "Germline mutations of the gene encoding bone morphogenetic protein
RT receptor 1A in juvenile polyposis.";
RL Nat. Genet. 28:184-187(2001).
RN [12]
RP STRUCTURE BY NMR OF 51-152, DISULFIDE BONDS, AND INTERACTION WITH BMP2.
RX PubMed=18937504; DOI=10.1021/bi801059j;
RA Klages J., Kotzsch A., Coles M., Sebald W., Nickel J., Muller T.,
RA Kessler H.;
RT "The solution structure of BMPR-IA reveals a local disorder-to-order
RT transition upon BMP-2 binding.";
RL Biochemistry 47:11930-11939(2008).
RN [13]
RP VARIANTS JPS ARG-124; ASP-338 AND TYR-376.
RX PubMed=11536076; DOI=10.1086/323703;
RA Zhou X.-P., Woodford-Richens K., Lehtonen R., Kurose K., Aldred M.,
RA Hampel H., Launonen V., Virta S., Pilarski R., Salovaara R., Bodmer W.F.,
RA Conrad B.A., Dunlop M., Hodgson S.V., Iwama T., Jaervinen H.,
RA Kellokumpu I., Kim J.C., Leggett B., Markie D., Mecklin J.-P., Neale K.,
RA Phillips R., Piris J., Rozen P., Houlston R.S., Aaltonen L.A.,
RA Tomlinson I.P.M., Eng C.;
RT "Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile
RT polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes.";
RL Am. J. Hum. Genet. 69:704-711(2001).
RN [14]
RP VARIANTS JPS ASP-62; TYR-82 AND CYS-443.
RX PubMed=12417513; DOI=10.1007/bf02557528;
RA Sayed M.G., Ahmed A.F., Ringold J.R., Anderson M.E., Bair J.L.,
RA Mitros F.A., Lynch H.T., Tinley S.T., Petersen G.M., Giardiello F.M.,
RA Vogelstein B., Howe J.R.;
RT "Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis.";
RL Ann. Surg. Oncol. 9:901-906(2002).
RN [15]
RP VARIANT JPS ARG-130.
RX PubMed=12136244; DOI=10.1007/s00439-002-0748-9;
RA Friedl W., Uhlhaas S., Schulmann K., Stolte M., Loff S., Back W.,
RA Mangold E., Stern M., Knaebel H.P., Sutter C., Weber R.G., Pistorius S.,
RA Burger B., Propping P.;
RT "Juvenile polyposis: massive gastric polyposis is more common in MADH4
RT mutation carriers than in BMPR1A mutation carriers.";
RL Hum. Genet. 111:108-111(2002).
RN [16]
RP VARIANT JPS THR-470.
RX PubMed=12630959; DOI=10.1034/j.1399-0004.2003.00008.x;
RA Kim I.J., Park J.H., Kang H.C., Kim K.H., Kim J.H., Ku J.L., Kang S.B.,
RA Park S.Y., Lee J.S., Park J.G.;
RT "Identification of a novel BMPR1A germline mutation in a Korean juvenile
RT polyposis patient without SMAD4 mutation.";
RL Clin. Genet. 63:126-130(2003).
RN [17]
RP INVOLVEMENT IN JUVENILE POLYPOSIS OF INFANCY.
RX PubMed=16685657; DOI=10.1086/504301;
RA Delnatte C., Sanlaville D., Mougenot J.-F., Vermeesch J.-R., Houdayer C.,
RA Blois M.-C., Genevieve D., Goulet O., Fryns J.-P., Jaubert F., Vekemans M.,
RA Lyonnet S., Romana S., Eng C., Stoppa-Lyonnet D.;
RT "Contiguous gene deletion within chromosome arm 10q is associated with
RT juvenile polyposis of infancy, reflecting cooperation between the BMPR1A
RT and PTEN tumor-suppressor genes.";
RL Am. J. Hum. Genet. 78:1066-1074(2006).
RN [18]
RP INVOLVEMENT IN HEREDITARY MIXED POLYPOSIS SYNDROME 2.
RX PubMed=16525031; DOI=10.1136/jmg.2005.034827;
RA Cao X., Eu K.W., Kumarasinghe M.P., Li H.H., Loi C., Cheah P.Y.;
RT "Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23
RT by genomewide high-density single nucleotide polymorphism (SNP) scan and
RT identification of BMPR1A loss of function.";
RL J. Med. Genet. 43:E13-E13(2006).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-2; TYR-58; CYS-443; MET-450 AND
RP GLN-486.
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 [20]
RP VARIANT THR-460.
RX PubMed=25860647; DOI=10.1007/s10689-015-9803-2;
RA Hansen M.F., Johansen J., Bjoernevoll I., Sylvander A.E., Steinsbekk K.S.,
RA Saetrom P., Sandvik A.K., Drabloes F., Sjursen W.;
RT "A novel POLE mutation associated with cancers of colon, pancreas, ovaries
RT and small intestine.";
RL Fam. Cancer 14:437-448(2015).
CC -!- FUNCTION: On ligand binding, forms a receptor complex consisting of two
CC type II and two type I transmembrane serine/threonine kinases. Type II
CC receptors phosphorylate and activate type I receptors which
CC autophosphorylate, then bind and activate SMAD transcriptional
CC regulators. Receptor for BMP2, BMP4, GDF5 and GDF6. Positively
CC regulates chondrocyte differentiation through GDF5 interaction.
CC Mediates induction of adipogenesis by GDF6.
CC {ECO:0000250|UniProtKB:P36895}.
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;
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 BMP2 (PubMed:10881198, PubMed:15064755,
CC PubMed:17295905, PubMed:18937504). Interacts with low affinity with
CC GDF5; positively regulates chondrocyte differentiation
CC (PubMed:24098149). Interacts with BMP4 (PubMed:8006002). Interacts with
CC SCUBE3 (PubMed:33308444). {ECO:0000269|PubMed:10881198,
CC ECO:0000269|PubMed:18937504, ECO:0000269|PubMed:24098149,
CC ECO:0000269|PubMed:33308444, ECO:0000269|PubMed:8006002}.
CC -!- INTERACTION:
CC P36894; P12643: BMP2; NbExp=17; IntAct=EBI-1029237, EBI-1029262;
CC P36894; P12644: BMP4; NbExp=2; IntAct=EBI-1029237, EBI-1998134;
CC P36894; P43026: GDF5; NbExp=4; IntAct=EBI-1029237, EBI-8571476;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P36898};
CC Single-pass type I membrane protein {ECO:0000255}. Cell surface
CC {ECO:0000250|UniProtKB:P36895}.
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P36895}.
CC -!- DISEASE: Juvenile polyposis syndrome (JPS) [MIM:174900]: Autosomal
CC dominant gastrointestinal hamartomatous polyposis syndrome in which
CC patients are at risk for developing gastrointestinal cancers. The
CC lesions are typified by a smooth histological appearance, predominant
CC stroma, cystic spaces and lack of a smooth muscle core. Multiple
CC juvenile polyps usually occur in a number of Mendelian disorders.
CC Sometimes, these polyps occur without associated features as in JPS;
CC here, polyps tend to occur in the large bowel and are associated with
CC an increased risk of colon and other gastrointestinal cancers.
CC {ECO:0000269|PubMed:11536076, ECO:0000269|PubMed:12136244,
CC ECO:0000269|PubMed:12417513, ECO:0000269|PubMed:12630959}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Polyposis syndrome, mixed hereditary 2 (HMPS2) [MIM:610069]: A
CC disease is characterized by atypical juvenile polyps, colonic adenomas,
CC and colorectal carcinomas. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=A microdeletion of chromosome 10q23 involving BMPR1A and
CC PTEN is a cause of chromosome 10q23 deletion syndrome, which shows
CC overlapping features of the following three disorders: Bannayan-Zonana
CC syndrome, Cowden disease and juvenile polyposis syndrome.
CC {ECO:0000269|PubMed:11381269, ECO:0000269|PubMed:16525031}.
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; Z22535; CAA80257.1; -; mRNA.
DR EMBL; AK291764; BAF84453.1; -; mRNA.
DR EMBL; BC028383; AAH28383.1; -; mRNA.
DR CCDS; CCDS7378.1; -.
DR PIR; I37163; I37163.
DR RefSeq; NP_004320.2; NM_004329.2.
DR RefSeq; XP_011538405.1; XM_011540103.2.
DR RefSeq; XP_011538406.1; XM_011540104.2.
DR PDB; 1ES7; X-ray; 2.90 A; B/D=55-143.
DR PDB; 1REW; X-ray; 1.86 A; C/D=24-152.
DR PDB; 2GOO; X-ray; 2.20 A; B/E=24-152.
DR PDB; 2H62; X-ray; 1.85 A; C=24-152.
DR PDB; 2H64; X-ray; 1.92 A; B=24-152.
DR PDB; 2K3G; NMR; -; A=51-152.
DR PDB; 2QJ9; X-ray; 2.44 A; C/D=24-152.
DR PDB; 2QJA; X-ray; 2.60 A; C/D=24-152.
DR PDB; 2QJB; X-ray; 2.50 A; C/D=24-152.
DR PDB; 3NH7; X-ray; 2.70 A; A/B/C/D=24-152.
DR PDB; 3QB4; X-ray; 2.28 A; B/D=24-152.
DR PDBsum; 1ES7; -.
DR PDBsum; 1REW; -.
DR PDBsum; 2GOO; -.
DR PDBsum; 2H62; -.
DR PDBsum; 2H64; -.
DR PDBsum; 2K3G; -.
DR PDBsum; 2QJ9; -.
DR PDBsum; 2QJA; -.
DR PDBsum; 2QJB; -.
DR PDBsum; 3NH7; -.
DR PDBsum; 3QB4; -.
DR AlphaFoldDB; P36894; -.
DR BMRB; P36894; -.
DR SMR; P36894; -.
DR BioGRID; 107125; 210.
DR CORUM; P36894; -.
DR DIP; DIP-5793N; -.
DR IntAct; P36894; 65.
DR MINT; P36894; -.
DR STRING; 9606.ENSP00000361107; -.
DR BindingDB; P36894; -.
DR ChEMBL; CHEMBL5275; -.
DR DrugBank; DB11639; Dibotermin alfa.
DR DrugCentral; P36894; -.
DR GuidetoPHARMACOLOGY; 1786; -.
DR GlyGen; P36894; 1 site.
DR iPTMnet; P36894; -.
DR PhosphoSitePlus; P36894; -.
DR SwissPalm; P36894; -.
DR BioMuta; BMPR1A; -.
DR DMDM; 61252444; -.
DR EPD; P36894; -.
DR jPOST; P36894; -.
DR MassIVE; P36894; -.
DR MaxQB; P36894; -.
DR PaxDb; P36894; -.
DR PeptideAtlas; P36894; -.
DR PRIDE; P36894; -.
DR ProteomicsDB; 55228; -.
DR ABCD; P36894; 1 sequenced antibody.
DR Antibodypedia; 4524; 791 antibodies from 39 providers.
DR DNASU; 657; -.
DR Ensembl; ENST00000372037.8; ENSP00000361107.2; ENSG00000107779.14.
DR Ensembl; ENST00000635816.1; ENSP00000489707.1; ENSG00000107779.14.
DR Ensembl; ENST00000636056.1; ENSP00000490273.1; ENSG00000107779.14.
DR Ensembl; ENST00000638429.1; ENSP00000492290.1; ENSG00000107779.14.
DR GeneID; 657; -.
DR KEGG; hsa:657; -.
DR MANE-Select; ENST00000372037.8; ENSP00000361107.2; NM_004329.3; NP_004320.2.
DR UCSC; uc001kdy.4; human.
DR CTD; 657; -.
DR DisGeNET; 657; -.
DR GeneCards; BMPR1A; -.
DR GeneReviews; BMPR1A; -.
DR HGNC; HGNC:1076; BMPR1A.
DR HPA; ENSG00000107779; Low tissue specificity.
DR MalaCards; BMPR1A; -.
DR MIM; 174900; phenotype.
DR MIM; 601299; gene.
DR MIM; 610069; phenotype.
DR MIM; 612242; phenotype.
DR neXtProt; NX_P36894; -.
DR OpenTargets; ENSG00000107779; -.
DR Orphanet; 440437; Familial colorectal cancer Type X.
DR Orphanet; 329971; Generalized juvenile polyposis/juvenile polyposis coli.
DR Orphanet; 157794; Hereditary mixed polyposis syndrome.
DR Orphanet; 79076; Juvenile polyposis of infancy.
DR PharmGKB; PA25386; -.
DR VEuPathDB; HostDB:ENSG00000107779; -.
DR eggNOG; KOG2052; Eukaryota.
DR GeneTree; ENSGT00940000156225; -.
DR HOGENOM; CLU_000288_8_1_1; -.
DR InParanoid; P36894; -.
DR OMA; VMGPFFD; -.
DR OrthoDB; 776697at2759; -.
DR PhylomeDB; P36894; -.
DR TreeFam; TF314724; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P36894; -.
DR Reactome; R-HSA-201451; Signaling by BMP.
DR SignaLink; P36894; -.
DR SIGNOR; P36894; -.
DR BioGRID-ORCS; 657; 84 hits in 1108 CRISPR screens.
DR ChiTaRS; BMPR1A; human.
DR EvolutionaryTrace; P36894; -.
DR GeneWiki; BMPR1A; -.
DR GenomeRNAi; 657; -.
DR Pharos; P36894; Tchem.
DR PRO; PR:P36894; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P36894; protein.
DR Bgee; ENSG00000107779; Expressed in secondary oocyte and 209 other tissues.
DR ExpressionAtlas; P36894; baseline and differential.
DR Genevisible; P36894; HS.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; IC:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC-UCL.
DR GO; GO:0036122; F:BMP binding; IEA:Ensembl.
DR GO; GO:0098821; F:BMP receptor activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019211; F:phosphatase activator activity; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:HGNC-UCL.
DR GO; GO:0046332; F:SMAD binding; IDA:HGNC-UCL.
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; TAS:Reactome.
DR GO; GO:0060928; P:atrioventricular node cell development; ISS:BHF-UCL.
DR GO; GO:0003171; P:atrioventricular valve development; 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:0003161; P:cardiac conduction system development; ISS:BHF-UCL.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; ISS: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:0021953; P:central nervous system neuron differentiation; IEA:Ensembl.
DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0048589; P:developmental growth; IEA:Ensembl.
DR GO; GO:0035912; P:dorsal aorta morphogenesis; ISS:BHF-UCL.
DR GO; GO:0009950; P:dorsal/ventral axis specification; IEA:Ensembl.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central.
DR GO; GO:0007398; P:ectoderm development; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0048568; P:embryonic organ development; ISS:BHF-UCL.
DR GO; GO:0003272; P:endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:1905285; P:fibrous ring of heart morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060914; P:heart formation; IEA:Ensembl.
DR GO; GO:0035137; P:hindlimb morphogenesis; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IMP:BHF-UCL.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0048368; P:lateral mesoderm development; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0048382; P:mesendoderm development; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0003183; P:mitral valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001880; P:Mullerian duct regression; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IMP:BHF-UCL.
DR GO; GO:0014032; P:neural crest cell development; IEA:Ensembl.
DR GO; GO:0021998; P:neural plate mediolateral regionalization; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0048352; P:paraxial mesoderm structural organization; IEA:Ensembl.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISS:BHF-UCL.
DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:BHF-UCL.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:BHF-UCL.
DR GO; GO:1904414; P:positive regulation of cardiac ventricle development; ISS:BHF-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
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: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; IMP:BHF-UCL.
DR GO; GO:0032915; P:positive regulation of transforming growth factor beta2 production; ISS:BHF-UCL.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:HGNC-UCL.
DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; ISS:BHF-UCL.
DR GO; GO:2000772; P:regulation of cellular senescence; IEA:Ensembl.
DR GO; GO:0048378; P:regulation of lateral mesodermal cell fate specification; IEA:Ensembl.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0003186; P:tricuspid valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; ISS:BHF-UCL.
DR DisProt; DP01990; -.
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 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; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Kinase; Magnesium; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Receptor; Reference proteome;
KW Serine/threonine-protein kinase; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..532
FT /note="Bone morphogenetic protein receptor type-1A"
FT /id="PRO_0000024410"
FT TOPO_DOM 24..152
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..532
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 204..233
FT /note="GS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585"
FT DOMAIN 234..525
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 107..109
FT /note="Mediates specificity for BMP ligand"
FT /evidence="ECO:0000269|PubMed:22799562"
FT ACT_SITE 362
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 240..248
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 61..82
FT /evidence="ECO:0000269|PubMed:10881198,
FT ECO:0000269|PubMed:18937504"
FT DISULFID 63..67
FT /evidence="ECO:0000269|PubMed:10881198,
FT ECO:0000269|PubMed:18937504"
FT DISULFID 76..100
FT /evidence="ECO:0000269|PubMed:10881198,
FT ECO:0000269|PubMed:18937504"
FT DISULFID 110..124
FT /evidence="ECO:0000269|PubMed:10881198,
FT ECO:0000269|PubMed:18937504"
FT DISULFID 125..130
FT /evidence="ECO:0000269|PubMed:10881198,
FT ECO:0000269|PubMed:18937504"
FT VARIANT 2
FT /note="P -> T (in dbSNP:rs11528010)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:8397373"
FT /id="VAR_041397"
FT VARIANT 58
FT /note="F -> Y (in a renal clear cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041398"
FT VARIANT 62
FT /note="Y -> D (in JPS)"
FT /evidence="ECO:0000269|PubMed:12417513"
FT /id="VAR_022828"
FT VARIANT 82
FT /note="C -> Y (in JPS)"
FT /evidence="ECO:0000269|PubMed:12417513"
FT /id="VAR_022829"
FT VARIANT 124
FT /note="C -> R (in JPS; dbSNP:rs199476087)"
FT /evidence="ECO:0000269|PubMed:11536076"
FT /id="VAR_015533"
FT VARIANT 130
FT /note="C -> R (in JPS; dbSNP:rs1131691168)"
FT /evidence="ECO:0000269|PubMed:12136244"
FT /id="VAR_022830"
FT VARIANT 338
FT /note="A -> D (in JPS; dbSNP:rs199476086)"
FT /evidence="ECO:0000269|PubMed:11536076"
FT /id="VAR_015534"
FT VARIANT 376
FT /note="C -> Y (in JPS; dbSNP:rs199476088)"
FT /evidence="ECO:0000269|PubMed:11536076"
FT /id="VAR_015535"
FT VARIANT 443
FT /note="R -> C (in JPS; dbSNP:rs35619497)"
FT /evidence="ECO:0000269|PubMed:12417513,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_022831"
FT VARIANT 450
FT /note="V -> M (in dbSNP:rs55932635)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041399"
FT VARIANT 460
FT /note="M -> T (found in a patient with tubular adenoma and
FT rectal neuroendocrine tumor; unknown pathological
FT significance; dbSNP:rs758309022)"
FT /evidence="ECO:0000269|PubMed:25860647"
FT /id="VAR_077353"
FT VARIANT 470
FT /note="M -> T (in JPS; dbSNP:rs199476089)"
FT /evidence="ECO:0000269|PubMed:12630959"
FT /id="VAR_022832"
FT VARIANT 486
FT /note="R -> Q (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs752802257)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041400"
FT MUTAGEN 107..109
FT /note="DFQ->REL: Affinity for BMP2 decreased by over 200-
FT fold."
FT /evidence="ECO:0000269|PubMed:22799562"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 75..88
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:2H62"
FT HELIX 106..111
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:2QJA"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:2H62"
FT HELIX 130..133
FT /evidence="ECO:0007829|PDB:2H62"
SQ SEQUENCE 532 AA; 60198 MW; 00CE2DDDA3A44170 CRC64;
MPQLYIYIRL LGAYLFIISR VQGQNLDSML HGTGMKSDSD QKKSENGVTL APEDTLPFLK
CYCSGHCPDD AINNTCITNG HCFAIIEEDD QGETTLASGC MKYEGSDFQC KDSPKAQLRR
TIECCRTNLC NQYLQPTLPP VVIGPFFDGS IRWLVLLISM AVCIIAMIIF SSCFCYKHYC
KSISSRRRYN RDLEQDEAFI PVGESLKDLI DQSQSSGSGS GLPLLVQRTI AKQIQMVRQV
GKGRYGEVWM GKWRGEKVAV KVFFTTEEAS WFRETEIYQT VLMRHENILG FIAADIKGTG
SWTQLYLITD YHENGSLYDF LKCATLDTRA LLKLAYSAAC GLCHLHTEIY GTQGKPAIAH
RDLKSKNILI KKNGSCCIAD LGLAVKFNSD TNEVDVPLNT RVGTKRYMAP EVLDESLNKN
HFQPYIMADI YSFGLIIWEM ARRCITGGIV EEYQLPYYNM VPSDPSYEDM REVVCVKRLR
PIVSNRWNSD ECLRAVLKLM SECWAHNPAS RLTALRIKKT LAKMVESQDV KI
