Bone morphogenetic protein receptor type-1A precursor

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Reviewed, UniProtKB/Swiss-Prot P36894 (BMR1A_HUMAN)

Last modified July 22, 2008. Version 104. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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

Name:	BMPR1A
Synonyms:	ACVRLK3, ALK3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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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.

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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	Membrane; Single-pass type I membrane protein.
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.

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Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of bone mineralization Inferred from mutant phenotype. Source: UniProtKB positive regulation of osteoblast differentiation Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from direct assay. Source: HGNC transforming growth factor beta receptor signaling pathway Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Ref.1 Traceable author statement. Source: ProtInc plasma membrane Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from direct assay. Source: HGNC SMAD binding Inferred from direct assay. Source: HGNC protein homodimerization activity Inferred from direct assay. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay. Source: HGNC
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 23

Potential

Chain

24 – 532

509

Bone morphogenetic protein receptor type-1A

Regions

Topological domain

24 – 152

129

Extracellular Potential

Transmembrane

153 – 176

Potential

Topological domain

177 – 532

356

Cytoplasmic Potential

Domain

204 – 233

Domain

234 – 525

292

Protein kinase

Nucleotide binding

240 – 248

ATP By similarity

Sites

Active site

362

Proton acceptor By similarity

Binding site

261

ATP By similarity

Amino acid modifications

Modified residue

215

Phosphoserine

Modified residue

216

Phosphoserine

Modified residue

218

Phosphoserine

Modified residue

220

Phosphoserine

Glycosylation

N-linked (GlcNAc...) Potential

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Natural variations

Natural variant

P → T

Natural variant

F → Y in a renal clear cell carcinoma sample; somatic mutation.

Natural variant

Y → D in JPS.

Natural variant

C → Y in JPS.

Natural variant

124

C → R in JPS.

Natural variant

130

C → R in JPS.

Natural variant

338

A → D in CD.

Natural variant

376

C → Y in JPS.

Natural variant

443

R → C in JPS.

Natural variant

450

V → M

Natural variant

470

M → T in JPS.

Natural variant

486

R → Q in a gastric adenocarcinoma sample; somatic mutation.

Secondary structure

532

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P36894-1 [UniParc].

Last modified March 15, 2005. Version 2.
Checksum: 00CE2DDDA3A44170
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FASTA

532

60,198

        10         20         30         40         50         60 
MPQLYIYIRL LGAYLFIISR VQGQNLDSML HGTGMKSDSD QKKSENGVTL APEDTLPFLK 

        70         80         90        100        110        120 
CYCSGHCPDD AINNTCITNG HCFAIIEEDD QGETTLASGC MKYEGSDFQC KDSPKAQLRR 

       130        140        150        160        170        180 
TIECCRTNLC NQYLQPTLPP VVIGPFFDGS IRWLVLLISM AVCIIAMIIF SSCFCYKHYC 

       190        200        210        220        230        240 
KSISSRRRYN RDLEQDEAFI PVGESLKDLI DQSQSSGSGS GLPLLVQRTI AKQIQMVRQV 

       250        260        270        280        290        300 
GKGRYGEVWM GKWRGEKVAV KVFFTTEEAS WFRETEIYQT VLMRHENILG FIAADIKGTG 

       310        320        330        340        350        360 
SWTQLYLITD YHENGSLYDF LKCATLDTRA LLKLAYSAAC GLCHLHTEIY GTQGKPAIAH 

       370        380        390        400        410        420 
RDLKSKNILI KKNGSCCIAD LGLAVKFNSD TNEVDVPLNT RVGTKRYMAP EVLDESLNKN 

       430        440        450        460        470        480 
HFQPYIMADI YSFGLIIWEM ARRCITGGIV EEYQLPYYNM VPSDPSYEDM REVVCVKRLR 

       490        500        510        520        530 
PIVSNRWNSD ECLRAVLKLM SECWAHNPAS RLTALRIKKT LAKMVESQDV KI

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References

	« Hide 'large scale' referencesShow '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.

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Web resources

GeneReviews

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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

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ES7	X-ray	2.90	B/D	55-143	[»]
1REW	X-ray	1.86	C/D	24-152	[»]
2GOO	X-ray	2.20	B/E	24-152	[»]
2H62	X-ray	1.85	C	24-152	[»]
2H64	X-ray	1.92	B	24-152	[»]

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

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GeneCards

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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

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Other Resources

LinkHub

P36894.

SOURCE

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ProtoNet

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Entry information

Entry name	BMR1A_HUMAN
Accession	Primary (citable) accession number: P36894 Secondary accession number(s): Q8NEN8

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information