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Protein

Bone morphogenetic protein 4

Gene

BMP4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Induces cartilage and bone formation. Also act in mesoderm induction, tooth development, limb formation and fracture repair. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity).By similarity

GO - Molecular functioni

  • BMP receptor binding Source: MGI
  • chemoattractant activity Source: UniProtKB
  • co-receptor binding Source: BHF-UCL
  • cytokine activity Source: MGI
  • heparin binding Source: Ensembl
  • transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Developmental protein, Growth factor

Keywords - Biological processi

Chondrogenesis, Differentiation, Osteogenesis

Enzyme and pathway databases

ReactomeiR-HSA-2129379. Molecules associated with elastic fibres.
SignaLinkiP12644.
SIGNORiP12644.

Names & Taxonomyi

Protein namesi
Recommended name:
Bone morphogenetic protein 4
Short name:
BMP-4
Alternative name(s):
Bone morphogenetic protein 2B
Short name:
BMP-2B
Gene namesi
Name:BMP4
Synonyms:BMP2B, DVR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:1071. BMP4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Microphthalmia, syndromic, 6 (MCOPS6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by microphthalmia/anophthalmia associated with facial, genital, skeletal, neurologic and endocrine anomalies. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
See also OMIM:607932
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti93 – 931E → G in MCOPS6. 1 Publication
Corresponds to variant rs121912765 [ dbSNP | Ensembl ].
VAR_043532
Non-syndromic orofacial cleft 11 (OFC11)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.
See also OMIM:600625
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti91 – 911S → C in OFC11; also found in renal hypodysplasia patients. 3 Publications
Corresponds to variant rs121912767 [ dbSNP | Ensembl ].
VAR_043531
Natural varianti162 – 1621R → Q in OFC11. 1 Publication
Corresponds to variant rs770493925 [ dbSNP | Ensembl ].
VAR_058315
Natural varianti287 – 2871R → H in OFC11. 1 Publication
Corresponds to variant rs121912768 [ dbSNP | Ensembl ].
VAR_058317
Natural varianti346 – 3461A → V in OFC11. 1 Publication
Corresponds to variant rs121912766 [ dbSNP | Ensembl ].
VAR_058318

Keywords - Diseasei

Disease mutation, Microphthalmia

Organism-specific databases

MalaCardsiBMP4.
MIMi600625. phenotype.
607932. phenotype.
Orphaneti264200. 14q22q23 microdeletion syndrome.
1991. Cleft lip with or without cleft palate.
139471. Microphthalmia with brain and digit anomalies.
93100. Unilateral renal agenesis.
PharmGKBiPA25381.

Chemistry

ChEMBLiCHEMBL5350.

Polymorphism and mutation databases

BioMutaiBMP4.
DMDMi115073.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Propeptidei20 – 292273PRO_0000033856Add
BLAST
Chaini293 – 408116Bone morphogenetic protein 4PRO_0000033857Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei91 – 911Phosphoserine; by FAM20C1 Publication
Glycosylationi143 – 1431N-linked (GlcNAc...)Sequence analysis
Glycosylationi208 – 2081N-linked (GlcNAc...)Sequence analysis
Disulfide bondi308 ↔ 373By similarity
Disulfide bondi337 ↔ 405By similarity
Disulfide bondi341 ↔ 407By similarity
Glycosylationi350 – 3501N-linked (GlcNAc...)Sequence analysis
Glycosylationi365 – 3651N-linked (GlcNAc...)Sequence analysis
Disulfide bondi372 – 372InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP12644.
PeptideAtlasiP12644.
PRIDEiP12644.

PTM databases

iPTMnetiP12644.
PhosphoSiteiP12644.

Expressioni

Tissue specificityi

Expressed in the lung and lower levels seen in the kidney. Present also in normal and neoplastic prostate tissues, and prostate cancer cell lines.

Gene expression databases

BgeeiENSG00000125378.
CleanExiHS_BMP4.
ExpressionAtlasiP12644. baseline and differential.
GenevisibleiP12644. HS.

Organism-specific databases

HPAiCAB006863.
HPA066235.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (By similarity). Interacts with GREM2. Part of a complex consisting of TWSG1 and CHRD. Interacts with the serine proteases, HTRA1 and HTRA3; the interaction with either inhibits BMP4-mediated signaling. The HTRA protease activity is required for this inhibition (By similarity). Interacts with SOSTDC1.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
BMPR1AP368942EBI-1998134,EBI-1029237

GO - Molecular functioni

  • BMP receptor binding Source: MGI
  • co-receptor binding Source: BHF-UCL
  • cytokine activity Source: MGI
  • transforming growth factor beta receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi107120. 13 interactions.
DIPiDIP-5795N.
IntActiP12644. 8 interactions.
MINTiMINT-1184353.
STRINGi9606.ENSP00000245451.

Chemistry

BindingDBiP12644.

Structurei

3D structure databases

ProteinModelPortaliP12644.
SMRiP12644. Positions 80-278, 307-408.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000249478.
HOVERGENiHBG004860.
InParanoidiP12644.
KOiK04662.
OMAiTRLVRHN.
OrthoDBiEOG091G0K7Z.
PhylomeDBiP12644.
TreeFamiTF351789.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P12644-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIPGNRMLMV VLLCQVLLGG ASHASLIPET GKKKVAEIQG HAGGRRSGQS
60 70 80 90 100
HELLRDFEAT LLQMFGLRRR PQPSKSAVIP DYMRDLYRLQ SGEEEEEQIH
110 120 130 140 150
STGLEYPERP ASRANTVRSF HHEEHLENIP GTSENSAFRF LFNLSSIPEN
160 170 180 190 200
EVISSAELRL FREQVDQGPD WERGFHRINI YEVMKPPAEV VPGHLITRLL
210 220 230 240 250
DTRLVHHNVT RWETFDVSPA VLRWTREKQP NYGLAIEVTH LHQTRTHQGQ
260 270 280 290 300
HVRISRSLPQ GSGNWAQLRP LLVTFGHDGR GHALTRRRRA KRSPKHHSQR
310 320 330 340 350
ARKKNKNCRR HSLYVDFSDV GWNDWIVAPP GYQAFYCHGD CPFPLADHLN
360 370 380 390 400
STNHAIVQTL VNSVNSSIPK ACCVPTELSA ISMLYLDEYD KVVLKNYQEM

VVEGCGCR
Length:408
Mass (Da):46,555
Last modified:October 1, 1989 - v1
Checksum:i79B01179DBB98204
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti91 – 911S → C in OFC11; also found in renal hypodysplasia patients. 3 Publications
Corresponds to variant rs121912767 [ dbSNP | Ensembl ].
VAR_043531
Natural varianti93 – 931E → G in MCOPS6. 1 Publication
Corresponds to variant rs121912765 [ dbSNP | Ensembl ].
VAR_043532
Natural varianti102 – 1021T → A.1 Publication
Corresponds to variant rs202159001 [ dbSNP | Ensembl ].
VAR_058314
Natural varianti116 – 1161T → S in a renal hypodysplasia patient. 1 Publication
Corresponds to variant rs750427266 [ dbSNP | Ensembl ].
VAR_043533
Natural varianti150 – 1501N → K in a renal hypodysplasia patient. 1 Publication
Corresponds to variant rs767216159 [ dbSNP | Ensembl ].
VAR_043534
Natural varianti152 – 1521V → A.4 Publications
Corresponds to variant rs17563 [ dbSNP | Ensembl ].
VAR_016174
Natural varianti162 – 1621R → Q in OFC11. 1 Publication
Corresponds to variant rs770493925 [ dbSNP | Ensembl ].
VAR_058315
Natural varianti168 – 1681G → A.1 Publication
VAR_058316
Natural varianti225 – 2251T → A.1 Publication
Corresponds to variant rs144556455 [ dbSNP | Ensembl ].
VAR_043535
Natural varianti226 – 2261R → W.1 Publication
Corresponds to variant rs140590144 [ dbSNP | Ensembl ].
VAR_043536
Natural varianti287 – 2871R → H in OFC11. 1 Publication
Corresponds to variant rs121912768 [ dbSNP | Ensembl ].
VAR_058317
Natural varianti346 – 3461A → V in OFC11. 1 Publication
Corresponds to variant rs121912766 [ dbSNP | Ensembl ].
VAR_058318
Natural varianti367 – 3671S → T.1 Publication
VAR_043537

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22490 mRNA. Translation: AAA51835.1.
U43842 Genomic DNA. Translation: AAC72278.1.
BC020546 mRNA. Translation: AAH20546.1.
D30751 mRNA. Translation: BAA06410.1.
CCDSiCCDS9715.1.
PIRiC37278. BMHU4.
RefSeqiNP_001193.2. NM_001202.4.
NP_570911.2. NM_130850.3.
XP_005268072.1. XM_005268015.4.
UniGeneiHs.68879.

Genome annotation databases

EnsembliENST00000245451; ENSP00000245451; ENSG00000125378.
ENST00000417573; ENSP00000394165; ENSG00000125378.
ENST00000558984; ENSP00000454134; ENSG00000125378.
ENST00000559087; ENSP00000453485; ENSG00000125378.
GeneIDi652.
KEGGihsa:652.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Bone morphogenetic protein 4 entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22490 mRNA. Translation: AAA51835.1.
U43842 Genomic DNA. Translation: AAC72278.1.
BC020546 mRNA. Translation: AAH20546.1.
D30751 mRNA. Translation: BAA06410.1.
CCDSiCCDS9715.1.
PIRiC37278. BMHU4.
RefSeqiNP_001193.2. NM_001202.4.
NP_570911.2. NM_130850.3.
XP_005268072.1. XM_005268015.4.
UniGeneiHs.68879.

3D structure databases

ProteinModelPortaliP12644.
SMRiP12644. Positions 80-278, 307-408.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107120. 13 interactions.
DIPiDIP-5795N.
IntActiP12644. 8 interactions.
MINTiMINT-1184353.
STRINGi9606.ENSP00000245451.

Chemistry

BindingDBiP12644.
ChEMBLiCHEMBL5350.

PTM databases

iPTMnetiP12644.
PhosphoSiteiP12644.

Polymorphism and mutation databases

BioMutaiBMP4.
DMDMi115073.

Proteomic databases

PaxDbiP12644.
PeptideAtlasiP12644.
PRIDEiP12644.

Protocols and materials databases

DNASUi652.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245451; ENSP00000245451; ENSG00000125378.
ENST00000417573; ENSP00000394165; ENSG00000125378.
ENST00000558984; ENSP00000454134; ENSG00000125378.
ENST00000559087; ENSP00000453485; ENSG00000125378.
GeneIDi652.
KEGGihsa:652.

Organism-specific databases

CTDi652.
GeneCardsiBMP4.
GeneReviewsiBMP4.
HGNCiHGNC:1071. BMP4.
HPAiCAB006863.
HPA066235.
MalaCardsiBMP4.
MIMi112262. gene.
600625. phenotype.
607932. phenotype.
neXtProtiNX_P12644.
Orphaneti264200. 14q22q23 microdeletion syndrome.
1991. Cleft lip with or without cleft palate.
139471. Microphthalmia with brain and digit anomalies.
93100. Unilateral renal agenesis.
PharmGKBiPA25381.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000249478.
HOVERGENiHBG004860.
InParanoidiP12644.
KOiK04662.
OMAiTRLVRHN.
OrthoDBiEOG091G0K7Z.
PhylomeDBiP12644.
TreeFamiTF351789.

Enzyme and pathway databases

ReactomeiR-HSA-2129379. Molecules associated with elastic fibres.
SignaLinkiP12644.
SIGNORiP12644.

Miscellaneous databases

GeneWikiiBone_morphogenetic_protein_4.
GenomeRNAii652.
PROiP12644.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125378.
CleanExiHS_BMP4.
ExpressionAtlasiP12644. baseline and differential.
GenevisibleiP12644. HS.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBMP4_HUMAN
AccessioniPrimary (citable) accession number: P12644
Secondary accession number(s): Q9UM80
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: September 7, 2016
This is version 187 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.