Reviewed, UniProtKB/Swiss-Prot O00238 (BMR1B_HUMAN)

Names and origin

Protein names

Recommended name:
    Bone morphogenetic protein receptor type-1B
      Short name=BMP type-1B receptor
      Short name=BMPR-1B
    EC=2.7.11.30
Alternative name(s):
    CD_antigen=CDw293

Gene names

Name:

BMPR1B

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	502 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 BMPS/OP-1.
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Involvement in disease	Defects in BMPR1B are the cause of acromesomelic chondrodysplasia with genital anomalies (AMDGA) [MIM:609441]. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs, and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). Ref.7 Defects in BMPR1B are a cause of brachydactyly type A2 (BDA2) [MIM:112600]. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits. BDA2 was described first in a large Norwegian kindred. BDA2 is caused by mutations in BMPR1B gene and studies demonstrate that these mutations function as dominant negatives in vitro and in vivo. Ref.6
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

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
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	BMP signaling pathway Ref.2 Non-traceable author statement. Source: UniProtKB cartilage condensation Ref.6 Non-traceable author statement. Source: UniProtKB limb morphogenesis Ref.6 Inferred from mutant phenotype. Source: UniProtKB ovarian cumulus expansion Inferred from sequence or structural similarity. 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
Cellular component	integral to plasma membrane Ref.6 Inferred by curator. Source: UniProtKB receptor complex Ref.6 Traceable author statement. Source: UniProtKB
Molecular function	ATP binding Inferred from direct assay. Source: HGNC SMAD binding Inferred from direct assay. Source: HGNC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 13	13	Potential
	Chain	14 – 502	489	Bone morphogenetic protein receptor type-1B		PRO_0000024412
Regions
	Topological domain	14 – 126	113	Extracellular Potential
	Transmembrane	127 – 148	22	Potential
	Topological domain	149 – 502	354	Cytoplasmic Potential
	Domain	174 – 203	30	GS
	Domain	204 – 494	291	Protein kinase
	Nucleotide binding	210 – 218	9	ATP By similarity
Sites
	Active site	332	1	Proton acceptor By similarity
	Binding site	231	1	ATP By similarity
Natural variations
	Natural variant	31	1	R → H in a gastric adenocarcinoma sample; somatic mutation. Ref.9		VAR_041401
	Natural variant	149	1	R → W: dbSNP rs34231464. Ref.9		VAR_041402
	Natural variant	200	1	I → K in BDA2. dbSNP rs28939703. Ref.6		VAR_023819
	Natural variant	224	1	R → H: dbSNP rs35973133. Ref.9		VAR_041403
	Natural variant	297	1	D → N in a metastatic melanoma sample; somatic mutation. Ref.9		VAR_041404
	Natural variant	371	1	R → Q: dbSNP rs34970181. Ref.9		VAR_041405
	Natural variant	486	1	R → Q in brachydactyly type C and BDA2; with also additional features of symphalangism-1. Ref.8		VAR_037967
	Natural variant	486	1	R → W in BDA2. dbSNP rs28939704. Ref.6		VAR_023820

Sequences

	Sequence		Length	Mass (Da)
	O00238-1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: B283D9BF45535C79	FASTA	502	56,930
	10 20 30 40 50 60 MLLRSAGKLN VGTKKEDGES TAPTPRPKVL RCKCHHHCPE DSVNNICSTD GYCFTMIEED 70 80 90 100 110 120 DSGLPVVTSG CLGLEGSDFQ CRDTPIPHQR RSIECCTERN ECNKDLHPTL PPLKNRDFVD 130 140 150 160 170 180 GPIHHRALLI SVTVCSLLLV LIILFCYFRY KRQETRPRYS IGLEQDETYI PPGESLRDLI 190 200 210 220 230 240 EQSQSSGSGS GLPLLVQRTI AKQIQMVKQI GKGRYGEVWM GKWRGEKVAV KVFFTTEEAS 250 260 270 280 290 300 WFRETEIYQT VLMRHENILG FIAADIKGTG SWTQLYLITD YHENGSLYDY LKSTTLDAKS 310 320 330 340 350 360 MLKLAYSSVS GLCHLHTEIF STQGKPAIAH RDLKSKNILV KKNGTCCIAD LGLAVKFISD 370 380 390 400 410 420 TNEVDIPPNT RVGTKRYMPP EVLDESLNRN HFQSYIMADM YSFGLILWEV ARRCVSGGIV 430 440 450 460 470 480 EEYQLPYHDL VPSDPSYEDM REIVCIKKLR PSFPNRWSSD ECLRQMGKLM TECWAHNPAS 490 500 RLTALRVKKT LAKMSESQDI KL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB) and its expression in prostate cancer in comparison with other BMPRs." Ide H., Katoh M., Sasaki H., Yoshida T., Aoki K., Nawa Y., Osada Y., Sugimura T., Terada M. Oncogene 14:1377-1382(1997) [PubMed: 9178898] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Prostate.
[2]	"Chromosomal localization of three human genes encoding bone morphogenetic protein receptors." Astroem A.-K., Jin D.F., Imamura T., Roijer E., Rosenzweig B., Miyazono K., ten Dijke P., Stenman G. Mamm. Genome 10:299-302(1999) [PubMed: 10051328] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ovary.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: PNS.
[6]	"Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2." Lehmann K., Seemann P., Stricker S., Sammar M., Meyer B., Suering K., Majewski F., Tinschert S., Grzeschik K.-H., Mueller D., Knaus P., Nuernberg P., Mundlos S. Proc. Natl. Acad. Sci. U.S.A. 100:12277-12282(2003) [PubMed: 14523231] [Abstract] Cited for: VARIANTS BDA2 LYS-200 AND TRP-486.
[7]	"A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies." Demirhan O., Tuerkmen S., Schwabe G.C., Soyupak S., Akguel E., Tastemir D., Karahan D., Mundlos S., Lehmann K. J. Med. Genet. 42:314-317(2005) [PubMed: 15805157] [Abstract] Cited for: INVOLVEMENT IN AMDGA.
[8]	"A novel R486Q mutation in BMPR1B resulting in either a brachydactyly type C/symphalangism-like phenotype or brachydactyly type A2." Lehmann K., Seemann P., Boergermann J., Morin G., Reif S., Knaus P., Mundlos S. Eur. J. Hum. Genet. 14:1248-1254(2006) [PubMed: 16957682] [Abstract] Cited for: VARIANT BRACHYDACTYLY TYPE C/BDA2 GLN-486.
[9]	"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. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-31; TRP-149; HIS-224; ASN-297 AND GLN-371.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	D89675 mRNA. Translation: BAA19765.1. U89326 mRNA. Translation: AAC28131.1. AK313642 mRNA. Translation: BAG36400.1. CH471057 Genomic DNA. Translation: EAX06060.1. BC047773 mRNA. Translation: AAH47773.1. BC069796 mRNA. Translation: AAH69796.1. BC069803 mRNA. Translation: AAH69803.1.
IPI	IPI00939250.
RefSeq	NP_001194.1.
UniGene	Hs.598475
3D structure databases
SMR	O00238. Positions 30-113, 170-498.
ModBase	Search...
Protein-protein interaction databases
STRING	O00238.
Proteomic databases
PRIDE	O00238.
Genome annotation databases
Ensembl	ENST00000264568; ENSP00000264568; ENSG00000138696; Homo sapiens. [Genome view] ENST00000394931; ENSP00000378389; ENSG00000138696; Homo sapiens. [Genome view] ENST00000440890; ENSP00000401907; ENSG00000138696; Homo sapiens. [Genome view]
GeneID	658.
KEGG	hsa:658.
UCSC	uc003htm.2. human.
Organism-specific databases
CTD	658.
GeneCards	GC04P095991.
H-InvDB	HIX0024604.
HGNC	HGNC:1077. BMPR1B.
HPA	CAB009634.
MIM	112600. phenotype. 603248. gene. 609441. phenotype.
Orphanet	69028. Brachydactyly. 93396. Brachydactyly, type A2. 93384. Brachydactyly, type C.
PharmGKB	PA25387.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13312.
HOVERGEN	O00238.
InParanoid	O00238.
OrthoDB	EOG9JHG1D.
PhylomeDB	O00238.
Enzyme and pathway databases
BRENDA	2.7.10.2. 247. 2.7.11.30. 247.
Pathway_Interaction_DB	bmppathway. BMP receptor signaling.
Reactome	REACT_12034. Signaling by BMP.
Gene expression databases
ArrayExpress	O00238.
Bgee	O00238.
CleanEx	HS_BMPR1B.
Genevestigator	O00238.
GermOnline	ENSG00000138696. Homo sapiens.
Family and domain databases
InterPro	IPR000333. Activin_II_recpt. IPR000472. Activin_rcpt. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_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.
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]
ProtoNet	Search...
Other Resources
NextBio	2676.
SOURCE	Search...

Entry information

Entry name

BMR1B_HUMAN

Accession

Primary (citable) accession number: O00238
Secondary accession number(s): B2R953, P78366

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 1, 1997
Last modified:	February 9, 2010
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.