Reviewed,
UniProtKB/Swiss-Prot Q13873 (BMPR2_HUMAN)
Last modified
June 16, 2009.
Version 105.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Bone morphogenetic protein receptor type-2 EC=2.7.11.30 Alternative name(s): Bone morphogenetic protein receptor type II BMP type II receptor BMPR-II | ||||
| Gene names |
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| 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 | 1038 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. Binds to BMP-7, BMP-2 and, less efficiently, BMP-4. Binding is weak but enhanced by the presence of type I receptors for BMPs. |
| Catalytic activity | ATP + [receptor-protein] = ADP + [receptor-protein] phosphate. |
| Cofactor | Magnesium or manganese By similarity. |
| Subcellular location | |
| Tissue specificity | Highly expressed in heart and liver. |
| Involvement in disease | Defects in BMPR2 are the cause of primary pulmonary hypertension (PPH1) [MIM:178600]. PPH1 is a rare autosomal dominant disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial PPH1 is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Defects in BMPR2 are a cause of pulmonary venoocclusive disease (PVOD) [MIM:265450]. PVOD is a rare form of pulmonary hypertension in which the vascular changes originate in the small pulmonary veins and venules. The pathogenesis is unknown and any link with PPH1 has been speculative. The finding of PVOD associated with a BMPR2 mutation reveals a possible pathogenetic connection with PPH1. Ref.11 Ref.13 |
| Sequence similarities | Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. Contains 1 protein kinase domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| C4bp | Q91X48 | 1 | EBI-527196,EBI-527325 | From a different organism. |
| Prkcb | P68404 | 2 | EBI-527196,EBI-397048 | From a different organism. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 26 | 26 | Potential | ||||||||
| Chain | 27 – 1038 | 1012 | Bone morphogenetic protein receptor type-2 | PRO_0000024415 | |||||||
Regions | |||||||||||
| Topological domain | 27 – 150 | 124 | Extracellular Potential | ||||||||
| Transmembrane | 151 – 171 | 21 | Potential | ||||||||
| Topological domain | 172 – 1038 | 867 | Cytoplasmic Potential | ||||||||
| Domain | 203 – 504 | 302 | Protein kinase | ||||||||
| Nucleotide binding | 209 – 217 | 9 | ATP By similarity | ||||||||
| Compositional bias | 547 – 550 | 4 | Poly-Ser | ||||||||
| Compositional bias | 610 – 618 | 9 | Poly-Thr | ||||||||
| Compositional bias | 901 – 908 | 8 | Poly-Asn | ||||||||
Sites | |||||||||||
| Active site | 333 | 1 | Proton acceptor By similarity | ||||||||
| Binding site | 230 | 1 | ATP By similarity | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 586 | 1 | Phosphoserine Ref.5 | ||||||||
| Modified residue | 680 | 1 | Phosphoserine Ref.5 | ||||||||
| Modified residue | 681 | 1 | Phosphoserine Ref.5 | ||||||||
| Modified residue | 757 | 1 | Phosphoserine Ref.5 | ||||||||
| Modified residue | 863 | 1 | Phosphoserine Ref.5 | ||||||||
| Glycosylation | 55 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 110 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 126 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Disulfide bond | 34 ↔ 66 | By similarity | |||||||||
| Disulfide bond | 94 ↔ 117 | By similarity | |||||||||
Natural variations | |||||||||||
| Natural variant | 60 | 1 | C → Y in PPH1. Ref.7 | VAR_013670 | |||||||
| Natural variant | 82 | 1 | Q → H in PPH1. Ref.10 | VAR_033109 | |||||||
| Natural variant | 117 | 1 | C → Y in PPH1. Ref.7 | VAR_013671 | |||||||
| Natural variant | 118 | 1 | C → W in PPH1. Ref.8 | VAR_013672 | |||||||
| Natural variant | 123 | 1 | C → R in PPH1. Ref.9 | VAR_013673 | |||||||
| Natural variant | 123 | 1 | C → S in PPH1. Ref.9 | VAR_013674 | |||||||
| Natural variant | 182 | 1 | G → D in PPH1. Ref.10 | VAR_033110 | |||||||
| Natural variant | 224 | 1 | E → D Ref.9 | VAR_013675 | |||||||
| Natural variant | 347 | 1 | C → Y in PPH1. Ref.8 | VAR_013676 | |||||||
| Natural variant | 420 | 1 | C → R in PPH1. Ref.9 | VAR_013677 | |||||||
| Natural variant | 483 | 1 | C → R in PPH1; sporadic. Ref.7 Ref.10 | VAR_013678 | |||||||
| Natural variant | 485 | 1 | D → G in PPH1; complete loss of function. Ref.8 Ref.9 | VAR_013679 | |||||||
| Natural variant | 491 | 1 | R → Q in PPH1; sporadic. Ref.6 | VAR_013680 | |||||||
| Natural variant | 491 | 1 | R → W in PPH1. Ref.6 | VAR_013681 | |||||||
| Natural variant | 512 | 1 | K → T in PPH1. Ref.9 | VAR_013682 | |||||||
| Natural variant | 519 | 1 | N → K in PPH1. | VAR_013683 | |||||||
| Natural variant | 775 | 1 | S → N: dbSNP rs2228545. Ref.14 | VAR_019996 | |||||||
| Natural variant | 899 | 1 | R → P in PPH1; leads to constitutive activation of the MAPK14 pathway. Ref.12 | VAR_033111 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 828 | 1 | G → R in CAA88759. Ref.1 | ||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning and characterization of a human type II receptor for bone morphogenetic proteins." Rosenzweig B.L., Imamura T., Okadome T., Cox G.N., Yamashita H., ten Dijke P., Heldin C., Miyazono K. Proc. Natl. Acad. Sci. U.S.A. 92:7632-7636(1995) [PubMed: 7644468] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Substantia nigra. |
| [2] | "Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors." Nohno T., Ishikawa T., Saito T., Hosokawa K., Noji S., Wosing D.H., Rosenbaum J.S. J. Biol. Chem. 270:22522-22526(1995) [PubMed: 7673243] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skin fibroblast. |
| [3] | "Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor." Kawabata M., Chytil A., Moses H.L. J. Biol. Chem. 270:5625-5630(1995) [PubMed: 7890683] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [4] | "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: Skin. |
| [5] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-586; SER-680; SER-681; SER-757 AND SER-863, MASS SPECTROMETRY. |
| [6] | "Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene." Deng Z., Morse J.H., Slager S.L., Cuervo N., Moore K.J., Venetos G., Kalachikov S., Cayanis E., Fischer S.G., Barst R.J., Hodge S.E., Knowles J.A. Am. J. Hum. Genet. 67:737-744(2000) [PubMed: 10903931] [Abstract] Cited for: VARIANTS PPH1 GLN-491 AND TRP-491. |
| [7] | "Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family." Thomson J.R., Machado R.D., Pauciulo M.W., Morgan N.V., Humbert M., Elliott G.C., Ward K., Yacoub M., Mikhail G., Rogers P., Newman J.H., Wheeler L., Higenbottam T., Gibbs J.S.R., Egan J., Crozier A., Peacock A., Allcock R. Nichols W.C.J. Med. Genet. 37:741-745(2000) [PubMed: 11015450] [Abstract] Cited for: VARIANTS PPH1 TYR-60; TYR-117 AND ARG-483. |
| [8] | "Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension." Lane K.B., Machado R.D., Pauciulo M.W., Thomson J.R., Phillips J.A. III, Loyd J.E., Nichols W.C., Trembath R.C., Aldred M., Brannon C.A., Conneally P.M., Foroud T., Fretwell N., Gaddipati R., Koller D., Loyd E.J., Morgan N.V., Newman J.H. Wheeler L.Nat. Genet. 26:81-84(2000) [PubMed: 10973254] [Abstract] Cited for: VARIANTS PPH1 TRP-118; TYR-347 AND GLY-485. |
| [9] | "BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension." Machado R.D., Pauciulo M.W., Thomson J.R., Lane K.B., Morgan N.V., Wheeler L., Phillips J.A. III, Newman J.H., Williams D., Galie N., Manes A., McNeil K., Yacoub M., Mikhail G., Rogers P., Corris P., Humbert M., Donnai D. Nichols W.C.Am. J. Hum. Genet. 68:92-102(2001) [PubMed: 11115378] [Abstract] Cited for: VARIANTS PPH1 ARG-123; SER-123; ARG-420 AND THR-512, VARIANT ASP-224, CHARACTERIZATION OF VARIANT PPH1 GLY-485. |
| [10] | "BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives." Humbert M., Deng Z., Simonneau G., Barst R.J., Sitbon O., Wolf M., Cuervo N., Moore K.J., Hodge S.E., Knowles J.A., Morse J.H. Eur. Respir. J. 20:518-523(2002) [PubMed: 12358323] [Abstract] Cited for: VARIANTS PPH1 HIS-82; ASP-182 AND ARG-483. |
| [11] | "Pulmonary veno-occlusive disease caused by an inherited mutation in bone morphogenetic protein receptor II." Runo J.R., Vnencak-Jones C.L., Prince M., Loyd J.E., Wheeler L., Robbins I.M., Lane K.B., Newman J.H., Johnson J., Nichols W.C., Phillips J.A. III Am. J. Respir. Crit. Care Med. 167:889-894(2003) [PubMed: 12446270] [Abstract] Cited for: INVOLVEMENT IN PVOD. |
| [12] | "BMPR2 mutations have short lifetime expectancy in primary pulmonary hypertension." Sankelo M., Flanagan J.A., Machado R., Harrison R., Rudarakanchana N., Morrell N., Dixon M., Halme M., Puolijoki H., Kere J., Elomaa O., Kupari M., Raeisaenen-Sokolowski A., Trembath R.C., Laitinen T. Hum. Mutat. 26:119-124(2005) [PubMed: 15965979] [Abstract] Cited for: VARIANT PPH1 PRO-899, CHARACTERIZATION OF VARIANT PPH1 PRO-899. |
| [13] | "Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension." Machado R.D., Aldred M.A., James V., Harrison R.E., Patel B., Schwalbe E.C., Gruenig E., Janssen B., Koehler R., Seeger W., Eickelberg O., Olschewski H., Elliott C.G., Glissmeyer E., Carlquist J., Kim M., Torbicki A., Fijalkowska A. Trembath R.C.Hum. Mutat. 27:121-132(2006) [PubMed: 16429395] [Abstract] Cited for: INVOLVEMENT IN PVOD. |
| [14] | "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: VARIANT [LARGE SCALE ANALYSIS] ASN-775. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Z48923 mRNA. Translation: CAA88759.1. D50516 mRNA. Translation: BAA09094.1. U20165 mRNA. Translation: AAC50105.1. BC052985 mRNA. Translation: AAH52985.1. | |||||||||||||
| IPI | IPI00783156. | ||||||||||||
| PIR | I38935. | ||||||||||||
| RefSeq | NP_001195.2. | ||||||||||||
| UniGene | Hs.471119 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| SMR | Q13873. Positions 33-131. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP:5794N. DIP:5941N. DIP:5942N. | ||||||||||||
| IntAct | Q13873. 30 interactions. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q13873. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | Q13873. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000204217. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 659. | ||||||||||||
| KEGG | hsa:659. | ||||||||||||
Organism-specific databases | |||||||||||||
| GeneCards | GC02P202950. | ||||||||||||
| H-InvDB | HIX0002749. | ||||||||||||
| HGNC | HGNC:1078. BMPR2. | ||||||||||||
| HPA | HPA017385. | ||||||||||||
| MIM | 178600. phenotype. 265450. phenotype. 600799. gene. | ||||||||||||
| Orphanet | 422. Pulmonary arterial hypertension. 31837. Pulmonary venoocclusive disease. | ||||||||||||
| PharmGKB | PA25388. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOVERGEN | Q13873. | ||||||||||||
| OMA | Q13873. ELPRGDH. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 2.7.11.30. 247. | ||||||||||||
| Pathway_Interaction_DB | bmppathway. BMP receptor signaling. | ||||||||||||
| Reactome | REACT_12034. Signaling by BMP. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q13873. | ||||||||||||
| Bgee | Q13873. | ||||||||||||
| CleanEx | HS_BMPR2. | ||||||||||||
| GermOnline | ENSG00000204217. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR000472. Activin_rcpt. IPR015770. BMPRII. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view] | ||||||||||||
| PANTHER | PTHR23255:SF12. BMPRII. 1 hit. | ||||||||||||
| Pfam | PF01064. Activin_recp. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view] | ||||||||||||
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 2680. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | BMPR2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13873 Secondary accession number(s): Q16569 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


