Description: Homo sapiens bone morphogenetic protein receptor, type IB (BMPR1B), transcript variant 4, mRNA. RefSeq Summary (NM_001256794): This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. Mutations in this gene have been associated with primary pulmonary hypertension. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]. Transcript (Including UTRs) Position: hg19 chr4:96,012,642-96,079,601 Size: 66,960 Total Exon Count: 11 Strand: + Coding Region Position: hg19 chr4:96,025,576-96,075,824 Size: 50,249 Coding Exon Count: 10
ID:BMR1B_HUMAN DESCRIPTION: RecName: Full=Bone morphogenetic protein receptor type-1B; Short=BMP type-1B receptor; Short=BMPR-1B; EC=2.7.11.30; AltName: CD_antigen=CDw293; Flags: Precursor; 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 BMP7/OP-1 and GDF5. CATALYTIC ACTIVITY: ATP + [receptor-protein] = ADP + [receptor- protein] phosphate. COFACTOR: Magnesium or manganese (By similarity). SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. 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). DISEASE: 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. SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. SIMILARITY: Contains 1 GS domain. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/BMPR1B";
Attention Deficit Disorder with Hyperactivity Eric Mick et al. Journal of the American Academy of Child and Adolescent Psychiatry 2010, Family-based genome-wide association scan of attention-deficit/hyperactivity disorder., Journal of the American Academy of Child and Adolescent Psychiatry.
[PubMed 20732626]
We and our colleagues in the Psychiatric GWAS Consortium are working to pool together GWAS samples to establish the large data sets needed to follow-up on these results and to identify genes for ADHD and other disorders.
Hypertension Youling Guo et al. PloS one 2012, A genome-wide linkage and association scan reveals novel loci for hypertension and blood pressure traits., PloS one.
[PubMed 22384028]
increased ovulation rate Mulsant P et al. 2001, Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes., Proc Natl Acad Sci U S A.
[PubMed 11320249]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF01064 - Activin types I and II receptor domain PF07714 - Protein tyrosine kinase PF08515 - Transforming growth factor beta type I GS-motif
ModBase Predicted Comparative 3D Structure on O00238
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Mouse
Rat
Zebrafish
D. melanogaster
C. elegans
S. cerevisiae
No ortholog
No ortholog
No ortholog
No ortholog
No ortholog
No ortholog
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000166 nucleotide binding GO:0004672 protein kinase activity GO:0004674 protein serine/threonine kinase activity GO:0004675 transmembrane receptor protein serine/threonine kinase activity GO:0005025 transforming growth factor beta receptor activity, type I GO:0005515 protein binding GO:0005524 ATP binding GO:0016301 kinase activity GO:0016740 transferase activity GO:0046332 SMAD binding GO:0046872 metal ion binding
Biological Process: GO:0001501 skeletal system development GO:0001502 cartilage condensation GO:0001550 ovarian cumulus expansion GO:0001654 eye development GO:0002062 chondrocyte differentiation GO:0002063 chondrocyte development GO:0006468 protein phosphorylation GO:0006954 inflammatory response GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0009953 dorsal/ventral pattern formation GO:0016310 phosphorylation GO:0030154 cell differentiation GO:0030166 proteoglycan biosynthetic process GO:0030501 positive regulation of bone mineralization GO:0030509 BMP signaling pathway GO:0031290 retinal ganglion cell axon guidance GO:0032332 positive regulation of chondrocyte differentiation GO:0035108 limb morphogenesis GO:0042698 ovulation cycle GO:0043010 camera-type eye development GO:0045597 positive regulation of cell differentiation GO:0045669 positive regulation of osteoblast differentiation GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051216 cartilage development GO:0060041 retina development in camera-type eye GO:0060350 endochondral bone morphogenesis GO:0061036 positive regulation of cartilage development GO:0071363 cellular response to growth factor stimulus GO:0071773 cellular response to BMP stimulus GO:1902043 positive regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902731 negative regulation of chondrocyte proliferation
U89326 - Homo sapiens bone morphogenetic protein receptor type I ALK-6 mRNA, complete cds. BC069796 - Homo sapiens bone morphogenetic protein receptor, type IB, mRNA (cDNA clone MGC:97235 IMAGE:7262484), complete cds. BC069803 - Homo sapiens bone morphogenetic protein receptor, type IB, mRNA (cDNA clone MGC:97247 IMAGE:7262496), complete cds. AK313642 - Homo sapiens cDNA, FLJ94217, Homo sapiens bone morphogenetic protein receptor, type IB (BMPR1B),mRNA. AK299930 - Homo sapiens cDNA FLJ59749 complete cds, highly similar to Bone morphogenetic protein receptor type IB precursor (EC 2.7.11.30). AK293008 - Homo sapiens cDNA FLJ78585 complete cds, highly similar to Homo sapiens bone morphogenetic protein receptor, type IB (BMPR1B), mRNA. BC047773 - Homo sapiens bone morphogenetic protein receptor, type IB, mRNA (cDNA clone MGC:54267 IMAGE:6202951), complete cds. D89675 - Homo sapiens mRNA for bone morphogenetic protein type IB receptor, complete cds. AB527519 - Synthetic construct DNA, clone: pF1KB5905, Homo sapiens BMPR1B gene for bone morphogenetic protein receptor, type IB, without stop codon, in Flexi system. KJ890774 - Synthetic construct Homo sapiens clone ccsbBroadEn_00168 BMPR1B gene, encodes complete protein. KJ905149 - Synthetic construct Homo sapiens clone ccsbBroadEn_14550 BMPR1B gene, encodes complete protein. KR711062 - Synthetic construct Homo sapiens clone CCSBHm_00019497 BMPR1B (BMPR1B) mRNA, encodes complete protein. KR711063 - Synthetic construct Homo sapiens clone CCSBHm_00019498 BMPR1B (BMPR1B) mRNA, encodes complete protein. KR711064 - Synthetic construct Homo sapiens clone CCSBHm_00019499 BMPR1B (BMPR1B) mRNA, encodes complete protein. CU690498 - Synthetic construct Homo sapiens gateway clone IMAGE:100021426 5' read BMPR1B mRNA. JD325826 - Sequence 306850 from Patent EP1572962. JD227224 - Sequence 208248 from Patent EP1572962. JD323104 - Sequence 304128 from Patent EP1572962. JD204364 - Sequence 185388 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04060 - Cytokine-cytokine receptor interaction hsa04350 - TGF-beta signaling pathway
Reactome (by CSHL, EBI, and GO)
Protein O00238 (Reactome details) participates in the following event(s):
R-HSA-202604 Formation of a heteromeric BMP receptor complex R-HSA-201457 BMP2 binds to the receptor complex R-HSA-201475 I-Smad competes with R-Smad1/5/8 for type I receptor R-HSA-201648 An anchoring protein, Endofin, recruits R-Smad1/5/8 R-HSA-201821 I-Smad binds to type I receptor, preventing Smad1/5/8 from being activated R-HSA-201443 Type II receptor phosphorylates type I receptor R-HSA-201453 Phospho-R-Smad1/5/8 dissociates from the receptor complex R-HSA-201476 Activated type I receptor phosphorylates R-Smad1/5/8 directly R-HSA-201451 Signaling by BMP R-HSA-9006936 Signaling by TGF-beta family members R-HSA-162582 Signal Transduction