Reviewed,
UniProtKB/Swiss-Prot P36894 (BMR1A_HUMAN)
Last modified
July 22, 2008.
Version 104.
History...
Clusters with 100%,
90%,
50% identity |
Documents (9) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Bone morphogenetic protein receptor type-1A EC=2.7.11.30 Alternative name(s): Serine/threonine-protein kinase receptor R5 Short name(s)=SKR5 Activin receptor-like kinase 3 Short name(s)=ALK-3 CD_antigen=CD292 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 532 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP-2 and BMP-4. |
| Catalytic activity | ATP + [receptor-protein] = ADP + [receptor-protein] phosphate. |
| Cofactor | Magnesium or manganese By similarity. |
| Subcellular location | |
| Tissue specificity | Highly expressed in skeletal muscle. |
| Involvement in disease | Defects in BMPR1A are a cause of juvenile polyposis syndrome (JPS) [MIM:174900]; also known as juvenile intestinal polyposis (JIP). JPS is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers. Defects in BMPR1A are a cause of Cowden disease (CD) [MIM:158350]. CD is an autosomal dominant cancer syndrome characterized by multiple hamartomas and by a high risk for breast, thyroid and endometrial cancers. Defects in BMPR1A are the cause of hereditary mixed polyposis syndrome 2 (HMPS2) [MIM:610069]. Hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas. |
| Sequence similarities | Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. Contains 1 GS domain. Contains 1 protein kinase domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | ||||||||||||||||||
Molecule processing | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 23 | 23 | Potential | |||||||||||||||||||
| Chain | 24 – 532 | 509 | Bone morphogenetic protein receptor type-1A | |||||||||||||||||||
Regions | ||||||||||||||||||||||
| Topological domain | 24 – 152 | 129 | Extracellular Potential | |||||||||||||||||||
| Transmembrane | 153 – 176 | 24 | Potential | |||||||||||||||||||
| Topological domain | 177 – 532 | 356 | Cytoplasmic Potential | |||||||||||||||||||
| Domain | 204 – 233 | 30 | GS | |||||||||||||||||||
| Domain | 234 – 525 | 292 | Protein kinase | |||||||||||||||||||
| Nucleotide binding | 240 – 248 | 9 | ATP By similarity | |||||||||||||||||||
Sites | ||||||||||||||||||||||
| Active site | 362 | 1 | Proton acceptor By similarity | |||||||||||||||||||
| Binding site | 261 | 1 | ATP By similarity | |||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||
| Modified residue | 215 | 1 | Phosphoserine | |||||||||||||||||||
| Modified residue | 216 | 1 | Phosphoserine | |||||||||||||||||||
| Modified residue | 218 | 1 | Phosphoserine | |||||||||||||||||||
| Modified residue | 220 | 1 | Phosphoserine | |||||||||||||||||||
| Glycosylation | 73 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||
| Disulfide bond | 61 ↔ 82 | |||||||||||||||||||||
| Disulfide bond | 63 ↔ 67 | |||||||||||||||||||||
| Disulfide bond | 76 ↔ 100 | |||||||||||||||||||||
| Disulfide bond | 110 ↔ 124 | |||||||||||||||||||||
| Disulfide bond | 125 ↔ 130 | |||||||||||||||||||||
Natural variations | ||||||||||||||||||||||
| Natural variant | 2 | 1 | P → T | |||||||||||||||||||
| Natural variant | 58 | 1 | F → Y in a renal clear cell carcinoma sample; somatic mutation. | |||||||||||||||||||
| Natural variant | 62 | 1 | Y → D in JPS. | |||||||||||||||||||
| Natural variant | 82 | 1 | C → Y in JPS. | |||||||||||||||||||
| Natural variant | 124 | 1 | C → R in JPS. | |||||||||||||||||||
| Natural variant | 130 | 1 | C → R in JPS. | |||||||||||||||||||
| Natural variant | 338 | 1 | A → D in CD. | |||||||||||||||||||
| Natural variant | 376 | 1 | C → Y in JPS. | |||||||||||||||||||
| Natural variant | 443 | 1 | R → C in JPS. | |||||||||||||||||||
| Natural variant | 450 | 1 | V → M | |||||||||||||||||||
| Natural variant | 470 | 1 | M → T in JPS. | |||||||||||||||||||
| Natural variant | 486 | 1 | R → Q in a gastric adenocarcinoma sample; somatic mutation. | |||||||||||||||||||
Secondary structure | ||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||
| Beta strand | 59 – 62 | 4 | ||||||||||||||||||||
| Beta strand | 64 – 66 | 3 | ||||||||||||||||||||
| Beta strand | 75 – 88 | 14 | ||||||||||||||||||||
| Beta strand | 94 – 101 | 8 | ||||||||||||||||||||
| Helix | 106 – 111 | 6 | ||||||||||||||||||||
| Beta strand | 120 – 125 | 6 | ||||||||||||||||||||
| Helix | 130 – 133 | 4 | ||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity." ten Dijke P., Ichijo H., Franzen P., Schulz P., Saras J., Toyoshima H., Heldin C.-H., Miyazono K. Oncogene 8:2879-2887(1993) [PubMed: 8397373] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-2. Tissue: Placenta. |
| [2] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis. |
| [3] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-216; SER-218 AND SER-220, MASS SPECTROMETRY. Tissue: Epithelium. |
| [4] | "Crystal structure of the BMP-2-BRIA ectodomain complex." Kirsch T., Sebald W., Dreyer M.K. Nat. Struct. Biol. 7:492-496(2000) [PubMed: 10881198] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 55-143 IN COMPLEX WITH BMP-2. |
| [5] | "Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis." Howe J.R., Bair J.L., Sayed M.G., Anderson M.E., Mitros F.A., Petersen G.M., Velculescu V.E., Traverso G., Vogelstein B. Nat. Genet. 28:184-187(2001) [PubMed: 11381269] [Abstract] Cited for: DISEASE. |
| [6] | "Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes." Zhou X.-P., Woodford-Richens K., Lehtonen R., Kurose K., Aldred M., Hampel H., Launonen V., Virta S., Pilarski R., Salovaara R., Bodmer W.F., Conrad B.A., Dunlop M., Hodgson S.V., Iwama T., Jaervinen H., Kellokumpu I., Kim J.C. Eng C.Am. J. Hum. Genet. 69:704-711(2001) [PubMed: 11536076] [Abstract] Cited for: VARIANTS JPS ARG-124 AND TYR-376, VARIANT CD ASP-338. |
| [7] | "Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis." Sayed M.G., Ahmed A.F., Ringold J.R., Anderson M.E., Bair J.L., Mitros F.A., Lynch H.T., Tinley S.T., Petersen G.M., Giardiello F.M., Vogelstein B., Howe J.R. Ann. Surg. Oncol. 9:901-906(2002) [PubMed: 12417513] [Abstract] Cited for: VARIANTS JPS ASP-62; TYR-82 AND CYS-443. |
| [8] | "Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers." Friedl W., Uhlhaas S., Schulmann K., Stolte M., Loff S., Back W., Mangold E., Stern M., Knaebel H.P., Sutter C., Weber R.G., Pistorius S., Burger B., Propping P. Hum. Genet. 111:108-111(2002) [PubMed: 12136244] [Abstract] Cited for: VARIANT JPS ARG-130. |
| [9] | "Identification of a novel BMPR1A germline mutation in a Korean juvenile polyposis patient without SMAD4 mutation." Kim I.J., Park J.H., Kang H.C., Kim K.H., Kim J.H., Ku J.L., Kang S.B., Park S.Y., Lee J.S., Park J.G. Clin. Genet. 63:126-130(2003) [PubMed: 12630959] [Abstract] Cited for: VARIANT JPS THR-470. |
| [10] | "Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function." Cao X., Eu K.W., Kumarasinghe M.P., Li H.H., Loi C., Cheah P.Y. J. Med. Genet. 43:E13-E13(2006) [PubMed: 16525031] [Abstract] Cited for: INVOLVEMENT IN HEREDITARY MIXED POLYPOSIS SYNDROME 2. |
| [11] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-2; TYR-58; CYS-443; MET-450 AND GLN-486. |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Z22535 mRNA. Translation: CAA80257.1. BC028383 mRNA. Translation: AAH28383.1. | |||||||||||||||||||||||||||||||||||||
| PIR | I37163. | ||||||||||||||||||||||||||||||||||||
| RefSeq | NP_004320.2. | ||||||||||||||||||||||||||||||||||||
| UniGene | Hs.524477 | ||||||||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||||||||
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| ModBase | Search... | ||||||||||||||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||||||||||||||
| DIP | DIP:5793N. | ||||||||||||||||||||||||||||||||||||
| IntAct | P36894. | ||||||||||||||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||||||||||||||
| PhosphoSite | P36894. | ||||||||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||||||||
| Ensembl | ENSG00000107779. Homo sapiens. [Contig view] | ||||||||||||||||||||||||||||||||||||
| GeneID | 657. | ||||||||||||||||||||||||||||||||||||
| KEGG | hsa:657. | ||||||||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||||||||
| H-InvDB | HIX0026073. HIX0036564. | ||||||||||||||||||||||||||||||||||||
| HGNC | HGNC:1076. BMPR1A. | ||||||||||||||||||||||||||||||||||||
| MIM | 158350. phenotype. 174900. phenotype. 601299. gene. 610069. phenotype. | ||||||||||||||||||||||||||||||||||||
| Orphanet | 201. Cowden syndrome. 2929. Juvenile gastrointestinal polyposis. 79076. Juvenile polyposis of infancy. 65285. Lhermitte-Duclos disease. | ||||||||||||||||||||||||||||||||||||
| PharmGKB | PA25386. | ||||||||||||||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||||||||||||||
| GeneCards | Search... | ||||||||||||||||||||||||||||||||||||
| GeneLynx | Search... | ||||||||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||||||||
| HOGENOM | P36894. | ||||||||||||||||||||||||||||||||||||
| HOVERGEN | P36894. | ||||||||||||||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||||||||||||||
| ArrayExpress | P36894. | ||||||||||||||||||||||||||||||||||||
| CleanEx | HS_BMPR1A. | ||||||||||||||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||||||||||||||
| InterPro | IPR000333. Activin_II_recpt. IPR000472. Activin_rcpt. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR003605. TGF_beta_rcpt_GS. [Graphical view] | ||||||||||||||||||||||||||||||||||||
| Pfam | PF01064. Activin_recp. 1 hit. PF00069. Pkinase. 1 hit. PF08515. TGF_beta_GS. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||
| PRINTS | PR00653. ACTIVIN2R. | ||||||||||||||||||||||||||||||||||||
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||||||||||||||||||||||||||
| SMART | SM00467. GS. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||
| PROSITE | PS51256. GS. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||
| BLOCKS | Search... | ||||||||||||||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||||||||||||||
| LinkHub | P36894. | ||||||||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||||||||||||||

Clusters with