Reviewed, UniProtKB/Swiss-Prot P12644 (BMP4_HUMAN)

Names and origin

Protein names

Recommended name:
    Bone morphogenetic protein 4
      Short name=BMP-4
Alternative name(s):
    BMP-2B

Gene names

Name:	BMP4
Synonyms:	BMP2B, DVR4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	408 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. Also act in mesoderm induction, tooth development, limb formation and fracture repair.
Subunit structure	Homodimer; disulfide-linked By similarity. Interacts with GREM2 By similarity and SOSTDC1. Part of a complex consisting of TWSG1 and CHRD By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix.
Tissue specificity	Expressed in the lung and lower levels seen in the kidney. Present also in normal and neoplastic prostate tissues, and prostate cancer cell lines.
Involvement in disease	Defects in BMP4 are the cause of syndromic microphthalmia type 6 (MCOPS6) [MIM:607932]; also known as microphthalmia and pituitary anomalies or microphthalmia with brain and digit developmental anomalies or clinical anophthalmia with micrognathia, malformed ears, digital anomalies, and abnormal external genitalia. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Up to 80% of cases of microphthalia occur in association with syndromes that include non-ocular abnormalities.
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Biological process	Chondrogenesis Differentiation Osteogenesis
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Cytokine Developmental protein Growth factor
PTM	Cleavage on pair of basic residues Glycoprotein
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of cell cycle Inferred from direct assay. Source: HGNC positive regulation of bone mineralization Inferred from direct assay. Source: UniProtKB positive regulation of osteoblast differentiation Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB signal transducer activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Propeptide	20 – 292	273
	Chain	293 – 408	116	Bone morphogenetic protein 4
Amino acid modifications
	Glycosylation	143	1	N-linked (GlcNAc...) Potential
	Glycosylation	208	1	N-linked (GlcNAc...) Potential
	Glycosylation	350	1	N-linked (GlcNAc...) Potential
	Glycosylation	365	1	N-linked (GlcNAc...) Potential
	Disulfide bond	308 ↔ 373		By similarity
	Disulfide bond	337 ↔ 405		By similarity
	Disulfide bond	341 ↔ 407		By similarity
	Disulfide bond	372		Interchain By similarity
Natural variations
	Natural variant	91	1	S → C in renal hypodysplasia patients.
	Natural variant	93	1	E → G in MCOPS6.
	Natural variant	116	1	T → S in a renal hypodysplasia patient.
	Natural variant	150	1	N → K in a renal hypodysplasia patient.
	Natural variant	152	1	V → A: dbSNP rs17563.
	Natural variant	225	1	T → A
	Natural variant	226	1	R → W
	Natural variant	367	1	S → T

Sequences

	Sequence		Length	Mass (Da)
	P12644-1 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 79B01179DBB98204	FASTA	408	46,555
	10 20 30 40 50 60 MIPGNRMLMV VLLCQVLLGG ASHASLIPET GKKKVAEIQG HAGGRRSGQS HELLRDFEAT 70 80 90 100 110 120 LLQMFGLRRR PQPSKSAVIP DYMRDLYRLQ SGEEEEEQIH STGLEYPERP ASRANTVRSF 130 140 150 160 170 180 HHEEHLENIP GTSENSAFRF LFNLSSIPEN EVISSAELRL FREQVDQGPD WERGFHRINI 190 200 210 220 230 240 YEVMKPPAEV VPGHLITRLL DTRLVHHNVT RWETFDVSPA VLRWTREKQP NYGLAIEVTH 250 260 270 280 290 300 LHQTRTHQGQ HVRISRSLPQ GSGNWAQLRP LLVTFGHDGR GHALTRRRRA KRSPKHHSQR 310 320 330 340 350 360 ARKKNKNCRR HSLYVDFSDV GWNDWIVAPP GYQAFYCHGD CPFPLADHLN STNHAIVQTL 370 380 390 400 VNSVNSSIPK ACCVPTELSA ISMLYLDEYD KVVLKNYQEM VVEGCGCR

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: 3201241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation." Shore E.M., Xu M., Shah P.B., Janoff H.B., Hahn G.V., Deardorff M.A., Sovinsky L., Spinner N.B., Zasloff M.A., Wozney J.M., Kaplan F.S. Calcif. Tissue Int. 63:221-229(1998) [PubMed: 9701626] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-152.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-152. Tissue: Duodenum.
[4]	"Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library." Oida S., Iimura T., Maruoka Y., Takeda K., Sasaki S. DNA Seq. 5:273-275(1995) [PubMed: 7579580] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-408. Tissue: Placenta.
[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: 15020244] [Abstract] Cited for: INTERACTION WITH SOSTDC1.
[6]	"Evaluation of BMP4 and its specific inhibitor NOG as candidates in human neural tube defects (NTDs)." Felder B., Stegmann K., Schultealbert A., Geller F., Strehl E., Ermert A., Koch M.C. Eur. J. Hum. Genet. 10:753-756(2002) [PubMed: 12404109] [Abstract] Cited for: VARIANTS CYS-91; ALA-152; ALA-225; TRP-226 AND THR-367.
[7]	"Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways." Bakrania P., Efthymiou M., Klein J.C., Salt A., Bunyan D.J., Wyatt A., Ponting C.P., Martin A., Williams S., Lindley V., Gilmore J., Restori M., Robson A.G., Neveu M.M., Holder G.E., Collin J.R.O., Robinson D.O., Farndon P. , Johansen-Berg H., Gerrelli D., Ragge N.K. Am. J. Hum. Genet. 82d:304-319(2008) [PubMed: 18252212] [Abstract] Cited for: VARIANT MCOPS6 GLY-93.
[8]	"SIX2 and BMP4 mutations associate with anomalous kidney development." Weber S., Taylor J.C., Winyard P., Baker K.F., Sullivan-Brown J., Schild R., Knueppel T., Zurowska A.M., Caldas-Alfonso A., Litwin M., Emre S., Ghiggeri G.M., Bakkaloglu A., Mehls O., Antignac C., Schaefer F., Burdine R.D. J. Am. Soc. Nephrol. 19:891-903(2008) [PubMed: 18305125] [Abstract] Cited for: VARIANTS CYS-91; SER-116 AND LYS-150.
+	Additional computationally mapped references.

Web resources

Wikipedia

Bone morphogenetic protein 4 entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	M22490 mRNA. Translation: AAA51835.1. U43842 Genomic DNA. Translation: AAC72278.1. BC020546 mRNA. Translation: AAH20546.1. D30751 mRNA. Translation: BAA06410.1.
PIR	BMHU4. C37278.
RefSeq	NP_001193.2. NP_570911.2. NP_570912.2.
UniGene	Hs.68879
3D structure databases
HSSP	HSSP built from PDB template 1ES7 based on UniProtKB P12643.
SMR	P12644. Positions 307-408.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:5795N.
Genome annotation databases
Ensembl	ENSG00000125378. Homo sapiens. [Contig view]
GeneID	652.
KEGG	hsa:652.
Organism-specific databases
H-InvDB	HIX0011668.
HGNC	HGNC:1071. BMP4.
HPA	CAB006863.
MIM	112262. gene. 607932. phenotype.
Orphanet	139471. Bakrania-Ragge syndrome.
PharmGKB	PA25381.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P12644.
HOVERGEN	P12644.
Gene expression databases
ArrayExpress	P12644.
CleanEx	HS_BMP4.
GermOnline	ENSG00000125378. Homo sapiens.
Family and domain databases
InterPro	IPR001839. TGFb. IPR001111. TGFb_N. IPR015615. TGFbeta. [Graphical view]
PANTHER	PTHR11848. TGFbeta. 1 hit.
Pfam	PF00019. TGF_beta. 1 hit. PF00688. TGFb_propeptide. 1 hit. [Graphical view]
ProDom	PD000357. TGFb. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00204. TGFB. 1 hit. [Graphical view]
PROSITE	PS00250. TGF_BETA_1. 1 hit. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
LinkHub	P12644.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

BMP4_HUMAN

Accession

Primary (citable) accession number: P12644
Secondary accession number(s): Q9UM80

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	September 2, 2008
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)