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P12643 (BMP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bone morphogenetic protein 2

Short name=BMP-2
Alternative name(s):
Bone morphogenetic protein 2A
Short name=BMP-2A
Gene names
Name:BMP2
Synonyms:BMP2A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length396 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Induces cartilage and bone formation.

Subunit structure

Homodimer; disulfide-linked. Interacts with SOSTDC1. Interacts with GREM2, RGMA, RGMB and RGMC. Interacts with ASPN By similarity. Ref.5

Subcellular location

Secreted.

Tissue specificity

Particularly abundant in lung, spleen and colon and in low but significant levels in heart, brain, placenta, liver, skeletal muscle, kidney, pancreas, prostate, ovary and small intestine.

Pharmaceutical use

Available under the name Infuse (Medtronic Sofamor Danek). Used for treating open tibial shaft fractures.

Sequence similarities

Belongs to the TGF-beta family.

Ontologies

Keywords
   Biological processChondrogenesis
Differentiation
Osteogenesis
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionCytokine
Developmental protein
Growth factor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Pharmaceutical
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from direct assay PubMed 16049014PubMed 18436533PubMed 20843790. Source: BHF-UCL

BMP signaling pathway involved in heart induction

Inferred from direct assay PubMed 19736317. Source: BHF-UCL

Notch signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

SMAD protein signal transduction

Inferred from direct assay PubMed 17244894. Source: UniProtKB

activation of MAPK activity

Inferred from direct assay PubMed 17202865. Source: AgBase

atrioventricular valve morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

bone mineralization

Inferred from sequence or structural similarity. Source: UniProtKB

bone mineralization involved in bone maturation

Inferred from direct assay PubMed 16433617. Source: BHF-UCL

branching involved in ureteric bud morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cardiac epithelial to mesenchymal transition

Inferred from direct assay PubMed 18184661. Source: BHF-UCL

cardiac muscle cell differentiation

Inferred from mutant phenotype PubMed 21311046. Source: BHF-UCL

cardiac muscle tissue morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cardiocyte differentiation

Inferred from mutant phenotype PubMed 19736317. Source: BHF-UCL

cell fate commitment

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell signaling

Traceable author statement PubMed 2315314. Source: ProtInc

cellular response to BMP stimulus

Inferred from direct assay PubMed 20843790. Source: BHF-UCL

cellular response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

chondrocyte differentiation

Inferred from direct assay PubMed 16194878. Source: AgBase

corticotropin hormone secreting cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

embryo development

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic heart tube anterior/posterior pattern specification

Inferred from sequence or structural similarity. Source: UniProtKB

endocardial cushion morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial to mesenchymal transition

Inferred from direct assay PubMed 18184661. Source: BHF-UCL

extracellular matrix organization

Traceable author statement. Source: Reactome

growth

Inferred from electronic annotation. Source: InterPro

heart development

Inferred from sequence or structural similarity. Source: UniProtKB

in utero embryonic development

Inferred from sequence or structural similarity. Source: UniProtKB

inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

inner ear development

Inferred from sequence or structural similarity. Source: UniProtKB

mesenchymal cell differentiation

Inferred from direct assay PubMed 9693150. Source: UniProtKB

mesenchymal cell proliferation involved in ureteric bud development

Inferred from sequence or structural similarity. Source: UniProtKB

mesenchyme development

Inferred from mutant phenotype PubMed 20890042. Source: BHF-UCL

negative regulation of Wnt signaling pathway involved in heart development

Inferred from direct assay PubMed 18545679. Source: BHF-UCL

negative regulation of aldosterone biosynthetic process

Inferred from direct assay PubMed 19584291. Source: BHF-UCL

negative regulation of calcium-independent cell-cell adhesion

Inferred from direct assay PubMed 16194878. Source: AgBase

negative regulation of canonical Wnt signaling pathway

Inferred from expression pattern PubMed 17202865. Source: AgBase

negative regulation of cardiac muscle cell differentiation

Inferred from direct assay PubMed 18545679. Source: BHF-UCL

negative regulation of cell cycle

Inferred from direct assay PubMed 11502704. Source: HGNC

negative regulation of cell proliferation

Inferred from direct assay PubMed 19584291. Source: BHF-UCL

negative regulation of cortisol biosynthetic process

Inferred from direct assay PubMed 19584291. Source: BHF-UCL

negative regulation of insulin-like growth factor receptor signaling pathway

Inferred from direct assay PubMed 19584291. Source: BHF-UCL

negative regulation of steroid biosynthetic process

Inferred from direct assay PubMed 19584291. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19736317. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15254224. Source: BHF-UCL

odontogenesis of dentin-containing tooth

Inferred from sequence or structural similarity. Source: UniProtKB

organ morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

osteoblast differentiation

Inferred from direct assay PubMed 15150273PubMed 22705305. Source: MGI

oxidation-reduction process

Inferred from sequence or structural similarity. Source: GOC

pathway-restricted SMAD protein phosphorylation

Inferred from direct assay PubMed 16049014PubMed 18184661. Source: BHF-UCL

pericardium development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 22540193. Source: DFLAT

positive regulation of MAPK cascade

Inferred from direct assay PubMed 22540193. Source: DFLAT

positive regulation of Wnt signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Wnt signaling pathway by BMP signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay PubMed 9187146. Source: MGI

positive regulation of astrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of bone mineralization

Inferred from direct assay PubMed 18436533. Source: BHF-UCL

positive regulation of cartilage development

Inferred from direct assay Ref.1. Source: MGI

positive regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell proliferation

Inferred from direct assay PubMed 17992660. Source: UniProtKB

positive regulation of epithelial to mesenchymal transition

Inferred from direct assay PubMed 20890042. Source: BHF-UCL

positive regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 16243309. Source: UniProtKB

positive regulation of neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of odontogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ossification

Inferred from direct assay PubMed 9213002. Source: MGI

positive regulation of osteoblast differentiation

Inferred from direct assay PubMed 15254224PubMed 16433617PubMed 18436533. Source: BHF-UCL

positive regulation of osteoblast proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of p38MAPK cascade

Inferred from direct assay PubMed 22540193. Source: DFLAT

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from direct assay PubMed 17244894. Source: UniProtKB

positive regulation of phosphatase activity

Inferred from direct assay PubMed 9213002. Source: MGI

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 17472960. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16433617PubMed 19736317PubMed 20890042. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus

Inferred from direct assay PubMed 20843790. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 16243309. Source: UniProtKB

protein destabilization

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 22540193. Source: DFLAT

proteoglycan metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15671031. Source: HGNC

response to hypoxia

Inferred from sequence or structural similarity. Source: UniProtKB

skeletal system development

Traceable author statement PubMed 2315314. Source: ProtInc

telencephalon development

Inferred from direct assay PubMed 9187146. Source: MGI

telencephalon regionalization

Inferred from sequence or structural similarity. Source: UniProtKB

thyroid-stimulating hormone-secreting cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell surface

Inferred from direct assay PubMed 22227436. Source: UniProtKB

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionBMP receptor binding

Inferred from direct assay PubMed 7811286. Source: MGI

SMAD binding

Inferred from direct assay PubMed 18184661. Source: BHF-UCL

phosphatase activator activity

Inferred from direct assay PubMed 9213002. Source: MGI

protein binding

Inferred from physical interaction PubMed 20505824. Source: UniProtKB

protein heterodimerization activity

Inferred from direct assay PubMed 7811286. Source: MGI

receptor binding

Traceable author statement PubMed 2315314. Source: ProtInc

retinol dehydrogenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Propeptide24 – 282259Cleaved by PCSK5
PRO_0000033824
Chain283 – 396114Bone morphogenetic protein 2
PRO_0000033825

Amino acid modifications

Glycosylation1351N-linked (GlcNAc...) Potential
Glycosylation1631N-linked (GlcNAc...) Potential
Glycosylation1641N-linked (GlcNAc...) Potential
Glycosylation2001N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) (high mannose) Ref.4
Disulfide bond296 ↔ 361
Disulfide bond325 ↔ 393
Disulfide bond329 ↔ 395
Disulfide bond360Interchain

Natural variations

Natural variant371S → A.
Corresponds to variant rs2273073 [ dbSNP | Ensembl ].
VAR_020061
Natural variant771P → S.
Corresponds to variant rs36105541 [ dbSNP | Ensembl ].
VAR_052568
Natural variant1061A → T.
Corresponds to variant rs2273074 [ dbSNP | Ensembl ].
VAR_020062
Natural variant1611L → S.
Corresponds to variant rs34183594 [ dbSNP | Ensembl ].
VAR_052569
Natural variant1901R → S.
Corresponds to variant rs235768 [ dbSNP | Ensembl ].
VAR_024232
Natural variant3871D → G.
Corresponds to variant rs11545591 [ dbSNP | Ensembl ].
VAR_052570

Secondary structure

...................... 396
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P12643 [UniParc].

Last modified October 1, 1989. Version 1.
Checksum: 20653A3987B25E60

FASTA39644,702
        10         20         30         40         50         60 
MVAGTRCLLA LLLPQVLLGG AAGLVPELGR RKFAAASSGR PSSQPSDEVL SEFELRLLSM 

        70         80         90        100        110        120 
FGLKQRPTPS RDAVVPPYML DLYRRHSGQP GSPAPDHRLE RAASRANTVR SFHHEESLEE 

       130        140        150        160        170        180 
LPETSGKTTR RFFFNLSSIP TEEFITSAEL QVFREQMQDA LGNNSSFHHR INIYEIIKPA 

       190        200        210        220        230        240 
TANSKFPVTR LLDTRLVNQN ASRWESFDVT PAVMRWTAQG HANHGFVVEV AHLEEKQGVS 

       250        260        270        280        290        300 
KRHVRISRSL HQDEHSWSQI RPLLVTFGHD GKGHPLHKRE KRQAKHKQRK RLKSSCKRHP 

       310        320        330        340        350        360 
LYVDFSDVGW NDWIVAPPGY HAFYCHGECP FPLADHLNST NHAIVQTLVN SVNSKIPKAC 

       370        380        390 
CVPTELSAIS MLYLDENEKV VLKNYQDMVV EGCGCR 

« Hide

References

« Hide 'large scale' references
[1]"Novel regulators of bone formation: molecular clones and activities."
Wozney J.M., Rosen V., Celeste A.J., Mitsock L.M., Whitters M.J., Kriz R.W., Hewick R.M., Wang E.A.
Science 242:1528-1534(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Human bone morphogenetic protein 2 (BMP-2) genomic DNA sequence."
Shore E.M., Xu M.-Q., Calvert G., Moriatis J., Kaplan F.S.
Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Direct isoform analysis of high-mannose-containing glycoproteins by on-line capillary electrophoresis electrospray mass spectrometry."
Yeung B., Porter T.J., Vath J.E.
Anal. Chem. 69:2510-2516(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-338.
[5]"USAG-1: a bone morphogenetic protein antagonist abundantly expressed in the kidney."
Yanagita M., Oka M., Watabe T., Iguchi H., Niida A., Takahashi S., Akiyama T., Miyazono K., Yanagisawa M., Sakurai T.
Biochem. Biophys. Res. Commun. 316:490-500(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SOSTDC1.
[6]"Posttranslational activation of bone morphogenetic protein 2 is mediated by proprotein convertase 6 during decidualization for pregnancy establishment."
Heng S., Paule S., Hardman B., Li Y., Singh H., Rainczuk A., Stephens A.N., Nie G.
Endocrinology 151:3909-3917(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, PROPEPTIDE.
[7]"Crystal structure of human bone morphogenetic protein-2 at 2.7 A resolution."
Scheufler C., Sebald W., Huelsmeyer M.
J. Mol. Biol. 287:103-115(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 292-396.
+Additional computationally mapped references.

Web resources

Wikipedia

Bone morphogenetic protein 2 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M22489 mRNA. Translation: AAA51834.1.
AF040249 Genomic DNA. Translation: AAF21646.1.
AL035668 Genomic DNA. Translation: CAB82007.1.
CCDSCCDS13099.1.
PIRBMHU2. B37278.
RefSeqNP_001191.1. NM_001200.2.
UniGeneHs.73853.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ES7X-ray2.90A/C283-396[»]
1REUX-ray2.65A294-396[»]
1REWX-ray1.86A/B283-396[»]
2GOOX-ray2.20A/D283-396[»]
2H62X-ray1.85A/B283-396[»]
2H64X-ray1.92A283-396[»]
2QJ9X-ray2.44A/B283-396[»]
2QJAX-ray2.60A/B283-396[»]
2QJBX-ray2.50A/B283-396[»]
3BK3X-ray2.70A/B283-396[»]
3BMPX-ray2.70A283-396[»]
4MIDX-ray2.14A283-395[»]
4N1DX-ray1.91A283-305[»]
A362-396[»]
ProteinModelPortalP12643.
SMRP12643. Positions 293-396.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107118. 8 interactions.
DIPDIP-5792N.
IntActP12643. 7 interactions.
MINTMINT-6772716.
STRING9606.ENSP00000368104.

Chemistry

ChEMBLCHEMBL1926496.
DrugBankDB00641. Simvastatin.

PTM databases

PhosphoSiteP12643.

Polymorphism databases

DMDM115068.

Proteomic databases

PaxDbP12643.
PRIDEP12643.

Protocols and materials databases

DNASU650.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000378827; ENSP00000368104; ENSG00000125845.
GeneID650.
KEGGhsa:650.
UCSCuc002wmu.1. human.

Organism-specific databases

CTD650.
GeneCardsGC20P006696.
HGNCHGNC:1069. BMP2.
MIM112261. gene.
neXtProtNX_P12643.
Orphanet261295. 20p12.3 microdeletion syndrome.
93396. Brachydactyly type A2.
907. Wolff-Parkinson-White syndrome.
PharmGKBPA25379.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243555.
HOGENOMHOG000249478.
HOVERGENHBG004860.
InParanoidP12643.
KOK04662.
OMADEHSWSQ.
OrthoDBEOG7WHH9D.
PhylomeDBP12643.
TreeFamTF351789.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_118779. Extracellular matrix organization.
SignaLinkP12643.

Gene expression databases

ArrayExpressP12643.
BgeeP12643.
CleanExHS_BMP2.
GenevestigatorP12643.

Family and domain databases

Gene3D2.10.90.10. 1 hit.
InterProIPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERPTHR11848. PTHR11848. 1 hit.
PfamPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
PRINTSPR00669. INHIBINA.
SMARTSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMSSF57501. SSF57501. 1 hit.
PROSITEPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP12643.
GeneWikiBone_morphogenetic_protein_2.
GenomeRNAi650.
NextBio2640.
PROP12643.
SOURCESearch...

Entry information

Entry nameBMP2_HUMAN
AccessionPrimary (citable) accession number: P12643
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: July 9, 2014
This is version 169 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM