P12643 (BMP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	396 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	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.4
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 process	Chondrogenesis Differentiation Osteogenesis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine Developmental protein Growth factor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	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 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 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: Compara chondrocyte differentiation Inferred from direct assay PubMed 16194878. Source: AgBase corticotropin hormone secreting cell differentiation 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 extracellular matrix organization Traceable author statement. Source: Reactome growth Inferred from electronic annotation. Source: InterPro 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 proliferation involved in ureteric bud development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of Wnt receptor 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 receptor 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 transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19736317. Source: BHF-UCL odontogenesis of dentin-containing tooth Inferred from sequence or structural similarity. Source: UniProtKB osteoblast differentiation Inferred from direct assay PubMed 15150273PubMed 22705305. Source: MGI 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 Wnt receptor 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 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 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 transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Inferred from direct assay PubMed 20843790. Source: BHF-UCL protein destabilization Inferred from electronic annotation. Source: Compara proteoglycan metabolic process Inferred from electronic annotation. Source: Compara regulation of odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from sequence or structural similarity. Source: UniProtKB 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_component	cell 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_function	BMP 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 heterodimerization activity Inferred from direct assay PubMed 7811286. Source: MGI retinol dehydrogenase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BMPR1A	P36894	2	EBI-1029262,EBI-1029237

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Propeptide

24 – 282

259

Cleaved by PCSK5

PRO_0000033824

Chain

283 – 396

114

Bone morphogenetic protein 2

PRO_0000033825

Amino acid modifications

Glycosylation

135

1

N-linked (GlcNAc...) Potential

Glycosylation

163

1

N-linked (GlcNAc...) Potential

Glycosylation

164

1

N-linked (GlcNAc...) Potential

Glycosylation

200

1

N-linked (GlcNAc...) Potential

Disulfide bond

296 ↔ 361

Disulfide bond

325 ↔ 393

Disulfide bond

329 ↔ 395

Disulfide bond

360

Interchain

Natural variations

Natural variant

37

1

S → A.
Corresponds to variant rs2273073 [ dbSNP | Ensembl ].

VAR_020061

Natural variant

77

1

P → S.
Corresponds to variant rs36105541 [ dbSNP | Ensembl ].

VAR_052568

Natural variant

106

1

A → T.
Corresponds to variant rs2273074 [ dbSNP | Ensembl ].

VAR_020062

Natural variant

161

1

L → S.
Corresponds to variant rs34183594 [ dbSNP | Ensembl ].

VAR_052569

Natural variant

190

1

R → S.
Corresponds to variant rs235768 [ dbSNP | Ensembl ].

VAR_024232

Natural variant

387

1

D → G.
Corresponds to variant rs11545591 [ dbSNP | Ensembl ].

VAR_052570

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

396

Helix Strand Turn

Details...

Beta strand

295 – 299

5

Beta strand

302 – 304

3

Helix

305 – 308

4

Turn

311 – 313

3

Beta strand

314 – 316

3

Beta strand

318 – 321

4

Beta strand

324 – 326

3

Beta strand

337 – 339

3

Helix

341 – 352

12

Beta strand

354 – 356

3

Beta strand

360 – 374

15

Beta strand

380 – 396

17

Sequences

	Sequence		Length	Mass (Da)
	P12643 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 20653A3987B25E60	FASTA	396	44,702
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
[5]	"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.
[6]	"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.

IPI

IPI00025069.

PIR

BMHU2. B37278.

RefSeq

NP_001191.1. NM_001200.2.

UniGene

Hs.73853.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ES7	X-ray	2.90	A/C	283-396	[»]
1REU	X-ray	2.65	A	294-396	[»]
1REW	X-ray	1.86	A/B	283-396	[»]
2GOO	X-ray	2.20	A/D	283-396	[»]
2H62	X-ray	1.85	A/B	283-396	[»]
2H64	X-ray	1.92	A	283-396	[»]
2QJ9	X-ray	2.44	A/B	283-396	[»]
2QJA	X-ray	2.60	A/B	283-396	[»]
2QJB	X-ray	2.50	A/B	283-396	[»]
3BK3	X-ray	2.70	A/B	283-396	[»]
3BMP	X-ray	2.70	A	283-396	[»]

ProteinModelPortal

P12643.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5792N.

IntAct

P12643. 1 interaction.

MINT

MINT-6772716.

STRING

9606.ENSP00000368104.

PTM databases

PhosphoSite

P12643.

Polymorphism databases

DMDM

115068.

Proteomic databases

PaxDb

P12643.

PRIDE

P12643.

Protocols and materials databases

DNASU

650.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000378827; ENSP00000368104; ENSG00000125845.

GeneID

650.

KEGG

hsa:650.

UCSC

uc002wmu.1. human.

Organism-specific databases

CTD

650.

GeneCards

GC20P006696.

HGNC

HGNC:1069. BMP2.

MIM

112261. gene.

neXtProt

NX_P12643.

Orphanet

261295. 20p12.3 microdeletion syndrome.
93396. Brachydactyly type A2.
907. Wolff-Parkinson-White syndrome.

PharmGKB

PA25379.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG243555.

HOGENOM

HOG000249478.

HOVERGEN

HBG004860.

InParanoid

P12643.

KO

K04662.

OMA

DEHSWSQ.

OrthoDB

EOG4C2H9R.

PhylomeDB

P12643.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_118779. Extracellular matrix organization.

SignaLink

P12643.

Gene expression databases

ArrayExpress

P12643.

Bgee

P12643.

CleanEx

HS_BMP2.

Genevestigator

P12643.

GermOnline

ENSG00000125845. Homo sapiens.

Family and domain databases

InterPro

IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]

PANTHER

PTHR11848. PTHR11848. 1 hit.

Pfam

PF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]

PRINTS

PR00669. INHIBINA.

SMART

SM00204. TGFB. 1 hit.
[Graphical view]

PROSITE

PS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1926496.

DrugBank

DB00641. Simvastatin.

EvolutionaryTrace

P12643.

GenomeRNAi

650.

NextBio

2640.

SOURCE

Search...

Entry information

Entry name

BMP2_HUMAN

Accession

Primary (citable) accession number: P12643

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	May 29, 2013
This is version 158 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.