P12645 (BMP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bone morphogenetic protein 3
Short name=BMP-3

Alternative name(s):
Bone morphogenetic protein 3A
Short name=BMP-3A
Osteogenin

Gene names

Name:	BMP3
Synonyms:	BMP3A

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	472 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	Negatively regulates bone density. Antagonizes the ability of certain osteogenic BMPs to induce osteoprogenitor differentitation and ossification. Ref.4 Ref.6
Subunit structure	Homodimer; disulfide-linked By similarity. Ref.8
Subcellular location	Secreted.
Tissue specificity	Expressed in adult and fetal cartilage. Ref.7
Induction	Highly expressed in fracture tissue, particularly in osteoblasts, osteoclasts and chondroblasts. Ref.5
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 Reference proteome
Gene Ontology (GO)
Biological_process	cartilage development Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell-cell signaling Traceable author statement Ref.1. Source: ProtInc growth Inferred from electronic annotation. Source: InterPro ossification Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara skeletal system development Traceable author statement Ref.1. Source: ProtInc
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	receptor binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Propeptide

23 – 362

340

By similarity

PRO_0000033836

Chain

363 – 472

110

Bone morphogenetic protein 3

PRO_0000033837

Amino acid modifications

Glycosylation

117

1

N-linked (GlcNAc...) Potential

Glycosylation

141

1

N-linked (GlcNAc...) Potential

Glycosylation

175

1

N-linked (GlcNAc...) Potential

Glycosylation

220

1

N-linked (GlcNAc...) Potential

Glycosylation

463

1

N-linked (GlcNAc...) Potential

Disulfide bond

370 ↔ 437

Ref.8

Disulfide bond

399 ↔ 469

Ref.8

Disulfide bond

403 ↔ 471

Ref.8

Disulfide bond

436

Interchain Ref.8

Natural variations

Natural variant

176

1

Q → K.
Corresponds to variant rs34213771 [ dbSNP | Ensembl ].

VAR_047418

Natural variant

176

1

Q → L.
Corresponds to variant rs34847147 [ dbSNP | Ensembl ].

VAR_047419

Natural variant

192

1

R → Q.
Corresponds to variant rs3733549 [ dbSNP | Ensembl ].

VAR_020063

Natural variant

205

1

L → F. Ref.1 Ref.2 Ref.3
Corresponds to variant rs6831040 [ dbSNP | Ensembl ].

VAR_047420

Natural variant

222

1

T → M.
Corresponds to variant rs34505126 [ dbSNP | Ensembl ].

VAR_047421

Secondary structure

1

.

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472

Helix Strand Turn

Details...

Beta strand

368 – 373

6

Beta strand

376 – 378

3

Turn

379 – 383

5

Turn

385 – 387

3

Beta strand

388 – 390

3

Beta strand

392 – 395

4

Beta strand

398 – 400

3

Helix

409 – 411

3

Helix

415 – 425

11

Beta strand

437 – 439

3

Beta strand

441 – 450

10

Beta strand

456 – 466

11

Beta strand

469 – 471

3

Sequences

	Sequence		Length	Mass (Da)
	P12645 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 2809B7EF5E37596A	FASTA	472	53,372
	10 20 30 40 50 60 MAGASRLLFL WLGCFCVSLA QGERPKPPFP ELRKAVPGDR TAGGGPDSEL QPQDKVSEHM 70 80 90 100 110 120 LRLYDRYSTV QAARTPGSLE GGSQPWRPRL LREGNTVRSF RAAAAETLER KGLYIFNLTS 130 140 150 160 170 180 LTKSENILSA TLYFCIGELG NISLSCPVSG GCSHHAQRKH IQIDLSAWTL KFSRNQSQLL 190 200 210 220 230 240 GHLSVDMAKS HRDIMSWLSK DITQLLRKAK ENEEFLIGFN ITSKGRQLPK RRLPFPEPYI 250 260 270 280 290 300 LVYANDAAIS EPESVVSSLQ GHRNFPTGTV PKWDSHIRAA LSIERRKKRS TGVLLPLQNN 310 320 330 340 350 360 ELPGAEYQYK KDEVWEERKP YKTLQAQAPE KSKNKKKQRK GPHRKSQTLQ FDEQTLKKAR 370 380 390 400 410 420 RKQWIEPRNC ARRYLKVDFA DIGWSEWIIS PKSFDAYYCS GACQFPMPKS LKPSNHATIQ 430 440 450 460 470 SIVRAVGVVP GIPEPCCVPE KMSSLSILFF DENKNVVLKV YPNMTVESCA CR

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], VARIANT PHE-205.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PHE-205.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PHE-205.
[4]	"Bone morphogenetic protein-3 is a negative regulator of bone density." Daluiski A., Engstrand T., Bahamonde M.E., Gamer L.W., Agius E., Stevenson S.L., Cox K., Rosen V., Lyons K.M. Nat. Genet. 27:84-88(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"BMP signaling components are expressed in human fracture callus." Kloen P., Di Paola M., Borens O., Richmond J., Perino G., Helfet D.L., Goumans M.J. Bone 33:362-371(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[6]	"Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery." Kang Q., Sun M.H., Cheng H., Peng Y., Montag A.G., Deyrup A.T., Jiang W., Luu H.H., Luo J., Szatkowski J.P., Vanichakarn P., Park J.Y., Li Y., Haydon R.C., He T.-C. Gene Ther. 11:1312-1320(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Expression of bone morphogenetic proteins, receptors, and tissue inhibitors in human fetal, adult, and osteoarthritic articular cartilage." Chen A.L., Fang C., Liu C., Leslie M.P., Chang E., Di Cesare P.E. J. Orthop. Res. 22:1188-1192(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"BMP-3 and BMP-6 structures illuminate the nature of binding specificity with receptors." Allendorph G.P., Isaacs M.J., Kawakami Y., Izpisua Belmonte J.C., Choe S. Biochemistry 46:12238-12247(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 363-472, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

Wikipedia

Bone morphogenetic protein 3 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M22491 mRNA. Translation: AAA51836.1.
AC093883 Genomic DNA. No translation available.
BC096269 mRNA. Translation: AAH96269.1.
BC096270 mRNA. Translation: AAH96270.1.
BC096271 mRNA. Translation: AAH96271.1.
BC117514 mRNA. Translation: AAI17515.1.

IPI

IPI00025073.

PIR

BMHU3. D37278.

RefSeq

NP_001192.2. NM_001201.2.

UniGene

Hs.387411.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QCQ	X-ray	2.21	A/B	363-472	[»]

ProteinModelPortal

P12645.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000282701.

PTM databases

PhosphoSite

P12645.

Polymorphism databases

DMDM

215273985.

Proteomic databases

PaxDb

P12645.

PRIDE

P12645.

Protocols and materials databases

DNASU

651.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000282701; ENSP00000282701; ENSG00000152785.

GeneID

651.

KEGG

hsa:651.

UCSC

uc003hmg.4. human.

Organism-specific databases

CTD

651.

GeneCards

GC04P081952.

HGNC

HGNC:1070. BMP3.

HPA

HPA045344.

MIM

112263. gene.

neXtProt

NX_P12645.

PharmGKB

PA25380.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG300136.

HOGENOM

HOG000232003.

HOVERGEN

HBG004857.

InParanoid

P12645.

KO

K05496.

OMA

LPFPEPY.

OrthoDB

EOG4P5K8Z.

PhylomeDB

P12645.

Gene expression databases

ArrayExpress

P12645.

Bgee

P12645.

CleanEx

HS_BMP3.

Genevestigator

P12645.

GermOnline

ENSG00000152785. Homo sapiens.

Family and domain databases

InterPro

IPR017197. BMP3/GDF10.
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]

PIRSF

PIRSF037403. BMP3/GDF10. 1 hit.

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

EvolutionaryTrace

P12645.

GenomeRNAi

651.

NextBio

2644.

SOURCE

Search...

Entry information

Entry name

BMP3_HUMAN

Accession

Primary (citable) accession number: P12645
Secondary accession number(s): Q4VAS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 128 of the entry and version 2 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.