Human Gene BMPR1B (uc003htm.4)
  Description: Homo sapiens bone morphogenetic protein receptor, type IB (BMPR1B), transcript variant 2, mRNA.
RefSeq Summary (NM_001203): 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 chr4:95,679,128-96,079,601 Size: 400,474 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg19 chr4:96,025,576-96,075,824 Size: 50,249 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:95,679,128-96,079,601)mRNA (may differ from genome)Protein (502 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): BMPR1B
CDC HuGE Published Literature: BMPR1B
Positive Disease Associations: Attention Deficit Disorder with Hyperactivity , Hypertension , increased ovulation rate
Related Studies:
  1. 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.
  2. 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]
  3. 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]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: BMPR1B
Diseases sorted by gene-association score: acromesomelic dysplasia, demirhan type* (1330), brachydactyly, type a1, d* (1200), brachydactyly, type a2* (1195), chondrodysplasia acromesomelic with genital anomalies* (400), chondrodysplasia, grebe type* (247), du pan syndrome* (247), brachydactyly, type a1* (219), acromesomelic dysplasia (32), brachydactyly, type c* (30), brachydactyly (16), parietal foramina (13), multiple synostoses syndrome (10), proximal symphalangism (7), osteochondroma (5), pulmonary hypertension (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.18 RPKM in Prostate
Total median expression: 87.33 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -88.70274-0.324 Picture PostScript Text
3' UTR -966.033777-0.256 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000333 - Activin_II/TGFBeta-II_recpt
IPR000472 - Activin_rcpt
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR008271 - Ser/Thr_kinase_AS
IPR003605 - TGF_beta_rcpt_GS

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

SCOP Domains:
56112 - Protein kinase-like (PK-like)
57302 - Snake toxin-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3MDY - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O00238
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo 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

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030425 dendrite
GO:0043025 neuronal cell body
GO:0043235 receptor complex
GO:1990712 HFE-transferrin receptor complex


-  Descriptions from all associated GenBank mRNAs
  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.
JD195944 - Sequence 176968 from Patent EP1572962.
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

-  Other Names for This Gene
  Alternate Gene Symbols: B2R953, BMR1B_HUMAN, NM_001203, NP_001243723, O00238, P78366
UCSC ID: uc003htm.4
RefSeq Accession: NM_001203
Protein: O00238 (aka BMR1B_HUMAN or BMRB_HUMAN)
CCDS: CCDS3642.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene BMPR1B:
pph (Heritable Pulmonary Arterial Hypertension Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001203.2
exon count: 13CDS single in 3' UTR: no RNA size: 5560
ORF size: 1509CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3182.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.