P22004 (BMP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bone morphogenetic protein 6
Short name=BMP-6

Alternative name(s):
VG-1-related protein
Short name=VG-1-R
Short name=VGR-1

Gene names

Name:	BMP6
Synonyms:	VGR

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	513 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	Interacts with SOSTDC1 By similarity.
Subcellular location	Secreted By similarity.
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	BMP signaling pathway Inferred from direct assay PubMed 18436533. Source: BHF-UCL SMAD protein signal transduction Inferred from direct assay PubMed 17244894. Source: UniProtKB cartilage development Inferred from electronic annotation. Source: UniProtKB-KW endochondral ossification Inferred from electronic annotation. Source: Compara eye development Inferred from electronic annotation. Source: Compara growth Inferred from electronic annotation. Source: InterPro immune response Inferred from mutant phenotype PubMed 16886151. Source: BHF-UCL inflammatory response Inferred from electronic annotation. Source: Compara kidney development Inferred from electronic annotation. Source: Compara male genitalia development Inferred from electronic annotation. Source: Compara osteoblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of DNA-dependent DNA replication Non-traceable author statement PubMed 15516325. Source: BHF-UCL positive regulation of aldosterone biosynthetic process Inferred from direct assay PubMed 16527843. Source: UniProtKB positive regulation of bone mineralization Inferred from direct assay PubMed 18436533. Source: BHF-UCL positive regulation of endothelial cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of endothelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell proliferation Inferred from direct assay PubMed 11865031. Source: BHF-UCL positive regulation of neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from direct assay PubMed 18436533. Source: BHF-UCL positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 17244894. Source: UniProtKB positive regulation of protein secretion Non-traceable author statement PubMed 15516325. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 16527843. Source: UniProtKB response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to retinoic acid Inferred from electronic annotation. Source: Compara skeletal system development Traceable author statement PubMed 8089189. Source: ProtInc type B pancreatic cell development Inferred from direct assay PubMed 11865031. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: UniProtKB-KW membrane-bounded vesicle Inferred from electronic annotation. Source: Compara
Molecular_function	protein heterodimerization activity Inferred from direct assay PubMed 7811286. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Propeptide

21 – 374

354

Potential

PRO_0000033870

Chain

375 – 513

139

Bone morphogenetic protein 6

PRO_0000033871

Amino acid modifications

Glycosylation

241

1

N-linked (GlcNAc...) Potential

Glycosylation

269

1

N-linked (GlcNAc...) Potential

Glycosylation

386

1

N-linked (GlcNAc...) Potential

Glycosylation

404

1

N-linked (GlcNAc...) Potential

Glycosylation

454

1

N-linked (GlcNAc...) Potential

Disulfide bond

412 ↔ 478

By similarity

Disulfide bond

441 ↔ 510

By similarity

Disulfide bond

445 ↔ 512

By similarity

Disulfide bond

477

Interchain By similarity

Natural variations

Natural variant

257

1

R → C.
Corresponds to variant rs10458105 [ dbSNP | Ensembl ].

VAR_047055

Natural variant

343

1

A → D in a colorectal cancer sample; somatic mutation. Ref.3

VAR_036200

Natural variant

476

1

P → L in a colorectal cancer sample; somatic mutation. Ref.3

VAR_036201

Secondary structure

1

.

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513

Helix Strand Turn

Details...

Beta strand

411 – 415

5

Beta strand

418 – 420

3

Turn

421 – 425

5

Turn

427 – 429

3

Beta strand

430 – 432

3

Beta strand

434 – 437

4

Beta strand

440 – 442

3

Turn

451 – 454

4

Helix

457 – 468

12

Turn

470 – 472

3

Beta strand

477 – 491

15

Beta strand

497 – 513

17

Sequences

	Sequence		Length	Mass (Da)
	P22004 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: 3F19155B36049278	FASTA	513	57,226
	10 20 30 40 50 60 MPGLGRRAQW LCWWWGLLCS CCGPPPLRPP LPAAAAAAAG GQLLGDGGSP GRTEQPPPSP 70 80 90 100 110 120 QSSSGFLYRR LKTQEKREMQ KEILSVLGLP HRPRPLHGLQ QPQPPALRQQ EEQQQQQQLP 130 140 150 160 170 180 RGEPPPGRLK SAPLFMLDLY NALSADNDED GASEGERQQS WPHEAASSSQ RRQPPPGAAH 190 200 210 220 230 240 PLNRKSLLAP GSGSGGASPL TSAQDSAFLN DADMVMSFVN LVEYDKEFSP RQRHHKEFKF 250 260 270 280 290 300 NLSQIPEGEV VTAAEFRIYK DCVMGSFKNQ TFLISIYQVL QEHQHRDSDL FLLDTRVVWA 310 320 330 340 350 360 SEEGWLEFDI TATSNLWVVT PQHNMGLQLS VVTRDGVHVH PRAAGLVGRD GPYDKQPFMV 370 380 390 400 410 420 AFFKVSEVHV RTTRSASSRR RQQSRNRSTQ SQDVARVSSA SDYNSSELKT ACRKHELYVS 430 440 450 460 470 480 FQDLGWQDWI IAPKGYAANY CDGECSFPLN AHMNATNHAI VQTLVHLMNP EYVPKPCCAP 490 500 510 TKLNAISVLY FDDNSNVILK KYRNMVVRAC GCH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone." Celeste A.J., Iannazzi J.A., Taylor R.C., Hewick R.M., Rosen V., Wang E.A., Wozney J.M. Proc. Natl. Acad. Sci. U.S.A. 87:9843-9847(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Bone.
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-343 AND LEU-476.
[4]	"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 (2.49 ANGSTROMS) OF 382-513.
+	Additional computationally mapped references.

Web resources

Wikipedia

Bone morphogenetic protein 6 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M60315 mRNA. Translation: AAA36737.1.
AL135778, AL133541 Genomic DNA. Translation: CAI19426.1.
AL133541, AL135778 Genomic DNA. Translation: CAI19472.1.

IPI

IPI00024887.

PIR

BMHU6. B39263.

RefSeq

NP_001709.1. NM_001718.4.

UniGene

Hs.285671.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QCW	X-ray	2.49	A/B	382-513	[»]
2R52	X-ray	2.50	A/B	375-513	[»]
2R53	X-ray	2.10	A/B	411-513	[»]

ProteinModelPortal

P22004.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5797N.

STRING

9606.ENSP00000283147.

PTM databases

PhosphoSite

P22004.

Polymorphism databases

DMDM

115076.

Proteomic databases

PaxDb

P22004.

PRIDE

P22004.

Protocols and materials databases

DNASU

654.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000283147; ENSP00000283147; ENSG00000153162.

GeneID

654.

KEGG

hsa:654.

UCSC

uc003mxu.4. human.

Organism-specific databases

CTD

654.

GeneCards

GC06P007672.

HGNC

HGNC:1073. BMP6.

HPA

CAB002773.

MIM

112266. gene.

neXtProt

NX_P22004.

PharmGKB

PA25383.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG272883.

HOGENOM

HOG000249476.

HOVERGEN

HBG004860.

InParanoid

P22004.

KO

K16620.

OMA

WWGLLCS.

OrthoDB

EOG4GB76H.

PhylomeDB

P22004.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.

Gene expression databases

ArrayExpress

P22004.

Bgee

P22004.

CleanEx

HS_BMP6.

Genevestigator

P22004.

GermOnline

ENSG00000153162. Homo sapiens.

Family and domain databases

InterPro

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]

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

ChiTaRS

BMP6. human.

EvolutionaryTrace

P22004.

GenomeRNAi

654.

NextBio

2660.

SOURCE

Search...

Entry information

Entry name

BMP6_HUMAN

Accession

Primary (citable) accession number: P22004
Secondary accession number(s): Q5TCP3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	May 1, 2013
This is version 130 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.