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Bone morphogenetic protein 4 (BMP-4)

 BMP4_BOVIN              Reviewed;         409 AA.
Q2KJH1;
27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
07-MAR-2006, sequence version 1.
27-SEP-2017, entry version 90.
RecName: Full=Bone morphogenetic protein 4;
Short=BMP-4;
Flags: Precursor;
Name=BMP4;
Bos taurus (Bovine).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
Pecora; Bovidae; Bovinae; Bos.
NCBI_TaxID=9913;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=Crossbred X Angus; TISSUE=Ileum;
NIH - Mammalian Gene Collection (MGC) project;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: Induces cartilage and bone formation. Acts in concert
with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic
mammary development and to inhibit hair follicle induction (By
similarity). {ECO:0000250}.
-!- SUBUNIT: Homodimer; disulfide-linked. Interacts with SOSTDC1,
GREM2, RGMA, RGMB and RGMC. 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. Interacts with FBN1 (via N-terminal domain) and
FBN2. {ECO:0000250|UniProtKB:P12644,
ECO:0000250|UniProtKB:P21275}.
-!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
matrix {ECO:0000250}.
-!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
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EMBL; BC105344; AAI05345.1; -; mRNA.
RefSeq; NP_001039342.1; NM_001045877.1.
RefSeq; XP_005211850.1; XM_005211793.3.
RefSeq; XP_005211851.1; XM_005211794.3.
RefSeq; XP_010807631.1; XM_010809329.2.
RefSeq; XP_010807633.1; XM_010809331.2.
UniGene; Bt.28459; -.
ProteinModelPortal; Q2KJH1; -.
STRING; 9913.ENSBTAP00000004992; -.
PaxDb; Q2KJH1; -.
PRIDE; Q2KJH1; -.
Ensembl; ENSBTAT00000004992; ENSBTAP00000004992; ENSBTAG00000003835.
GeneID; 407216; -.
KEGG; bta:407216; -.
CTD; 652; -.
eggNOG; KOG3900; Eukaryota.
eggNOG; ENOG410XT8Z; LUCA.
GeneTree; ENSGT00760000118883; -.
HOGENOM; HOG000249478; -.
HOVERGEN; HBG004860; -.
InParanoid; Q2KJH1; -.
KO; K04662; -.
OMA; QGFHRIN; -.
OrthoDB; EOG091G0K7Z; -.
TreeFam; TF351789; -.
Reactome; R-BTA-2129379; Molecules associated with elastic fibres.
Reactome; R-BTA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
Reactome; R-BTA-8957275; Post-translational protein phosphorylation.
Proteomes; UP000009136; Chromosome 10.
Bgee; ENSBTAG00000003835; -.
GO; GO:0005615; C:extracellular space; IBA:GO_Central.
GO; GO:0005578; C:proteinaceous extracellular matrix; IEA:UniProtKB-SubCell.
GO; GO:0070700; F:BMP receptor binding; ISS:UniProtKB.
GO; GO:0042056; F:chemoattractant activity; ISS:UniProtKB.
GO; GO:0039706; F:co-receptor binding; IEA:Ensembl.
GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
GO; GO:0008201; F:heparin binding; IEA:Ensembl.
GO; GO:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central.
GO; GO:0000186; P:activation of MAPKK activity; ISS:UniProtKB.
GO; GO:0009948; P:anterior/posterior axis specification; IEA:Ensembl.
GO; GO:0003180; P:aortic valve morphogenesis; IEA:Ensembl.
GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISS:UniProtKB.
GO; GO:0030509; P:BMP signaling pathway; ISS:UniProtKB.
GO; GO:0061312; P:BMP signaling pathway involved in heart development; IEA:Ensembl.
GO; GO:0003130; P:BMP signaling pathway involved in heart induction; ISS:UniProtKB.
GO; GO:0071893; P:BMP signaling pathway involved in nephric duct formation; ISS:UniProtKB.
GO; GO:0061151; P:BMP signaling pathway involved in renal system segmentation; ISS:UniProtKB.
GO; GO:0061149; P:BMP signaling pathway involved in ureter morphogenesis; ISS:UniProtKB.
GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IEA:Ensembl.
GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:UniProtKB.
GO; GO:0060433; P:bronchus development; IEA:Ensembl.
GO; GO:0060503; P:bud dilation involved in lung branching; IEA:Ensembl.
GO; GO:0060449; P:bud elongation involved in lung branching; IEA:Ensembl.
GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
GO; GO:0048468; P:cell development; IBA:GO_Central.
GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
GO; GO:0060197; P:cloacal septation; IEA:Ensembl.
GO; GO:0007182; P:common-partner SMAD protein phosphorylation; ISS:UniProtKB.
GO; GO:0060976; P:coronary vasculature development; IEA:Ensembl.
GO; GO:0060363; P:cranial suture morphogenesis; IEA:Ensembl.
GO; GO:0035993; P:deltoid tuberosity development; ISS:UniProtKB.
GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl.
GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl.
GO; GO:0060272; P:embryonic skeletal joint morphogenesis; IEA:Ensembl.
GO; GO:0003197; P:endocardial cushion development; IEA:Ensembl.
GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB.
GO; GO:0007492; P:endoderm development; IEA:Ensembl.
GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; IEA:Ensembl.
GO; GO:0060684; P:epithelial-mesenchymal cell signaling; IEA:Ensembl.
GO; GO:0030218; P:erythrocyte differentiation; IEA:Ensembl.
GO; GO:0007281; P:germ cell development; IEA:Ensembl.
GO; GO:0072104; P:glomerular capillary formation; ISS:UniProtKB.
GO; GO:0072015; P:glomerular visceral epithelial cell development; IEA:Ensembl.
GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISS:UniProtKB.
GO; GO:0060113; P:inner ear receptor cell differentiation; IEA:Ensembl.
GO; GO:0048392; P:intermediate mesodermal cell differentiation; ISS:UniProtKB.
GO; GO:0001822; P:kidney development; ISS:UniProtKB.
GO; GO:0060235; P:lens induction in camera-type eye; IEA:Ensembl.
GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
GO; GO:0002320; P:lymphoid progenitor cell differentiation; ISS:UniProtKB.
GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl.
GO; GO:0060592; P:mammary gland formation; IEA:Ensembl.
GO; GO:0003149; P:membranous septum morphogenesis; IEA:Ensembl.
GO; GO:0072161; P:mesenchymal cell differentiation involved in kidney development; IEA:Ensembl.
GO; GO:0072198; P:mesenchymal cell proliferation involved in ureter development; IEA:Ensembl.
GO; GO:0072138; P:mesenchymal cell proliferation involved in ureteric bud development; IEA:Ensembl.
GO; GO:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; ISS:UniProtKB.
GO; GO:0007500; P:mesodermal cell fate determination; IEA:Ensembl.
GO; GO:0001823; P:mesonephros development; ISS:UniProtKB.
GO; GO:0072205; P:metanephric collecting duct development; ISS:UniProtKB.
GO; GO:0030224; P:monocyte differentiation; IEA:Ensembl.
GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
GO; GO:0072097; P:negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway; ISS:UniProtKB.
GO; GO:0090191; P:negative regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
GO; GO:0045786; P:negative regulation of cell cycle; ISS:UniProtKB.
GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
GO; GO:2000137; P:negative regulation of cell proliferation involved in heart morphogenesis; ISS:UniProtKB.
GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IEA:Ensembl.
GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
GO; GO:0072125; P:negative regulation of glomerular mesangial cell proliferation; ISS:UniProtKB.
GO; GO:0090194; P:negative regulation of glomerulus development; ISS:UniProtKB.
GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; ISS:UniProtKB.
GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
GO; GO:0072200; P:negative regulation of mesenchymal cell proliferation involved in ureter development; ISS:UniProtKB.
GO; GO:2000007; P:negative regulation of metanephric comma-shaped body morphogenesis; ISS:UniProtKB.
GO; GO:2000005; P:negative regulation of metanephric S-shaped body morphogenesis; ISS:UniProtKB.
GO; GO:0045839; P:negative regulation of mitotic nuclear division; ISS:UniProtKB.
GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
GO; GO:0042326; P:negative regulation of phosphorylation; ISS:UniProtKB.
GO; GO:0060686; P:negative regulation of prostatic bud formation; IEA:Ensembl.
GO; GO:0045843; P:negative regulation of striated muscle tissue development; IEA:Ensembl.
GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; ISS:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IBA:GO_Central.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
GO; GO:0048663; P:neuron fate commitment; IEA:Ensembl.
GO; GO:0042476; P:odontogenesis; ISS:UniProtKB.
GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
GO; GO:0003148; P:outflow tract septum morphogenesis; IEA:Ensembl.
GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IEA:Ensembl.
GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISS:UniProtKB.
GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
GO; GO:0061047; P:positive regulation of branching involved in lung morphogenesis; ISS:UniProtKB.
GO; GO:0055020; P:positive regulation of cardiac muscle fiber development; ISS:UniProtKB.
GO; GO:1905312; P:positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis; IEA:Ensembl.
GO; GO:0061036; P:positive regulation of cartilage development; IEA:Ensembl.
GO; GO:1901964; P:positive regulation of cell proliferation involved in outflow tract morphogenesis; IEA:Ensembl.
GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:UniProtKB.
GO; GO:2000105; P:positive regulation of DNA-dependent DNA replication; ISS:UniProtKB.
GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IEA:Ensembl.
GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
GO; GO:0045606; P:positive regulation of epidermal cell differentiation; ISS:UniProtKB.
GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:BHF-UCL.
GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IEA:Ensembl.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
GO; GO:0090184; P:positive regulation of kidney development; ISS:UniProtKB.
GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
GO; GO:1902895; P:positive regulation of pri-miRNA transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:1903800; P:positive regulation of production of miRNAs involved in gene silencing by miRNA; IEA:Ensembl.
GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
GO; GO:0060391; P:positive regulation of SMAD protein import into nucleus; ISS:UniProtKB.
GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
GO; GO:0034504; P:protein localization to nucleus; ISS:UniProtKB.
GO; GO:0061155; P:pulmonary artery endothelial tube morphogenesis; ISS:UniProtKB.
GO; GO:0003184; P:pulmonary valve morphogenesis; IEA:Ensembl.
GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IEA:Ensembl.
GO; GO:0010453; P:regulation of cell fate commitment; ISS:UniProtKB.
GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl.
GO; GO:0060393; P:regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
GO; GO:0051150; P:regulation of smooth muscle cell differentiation; IEA:Ensembl.
GO; GO:0003014; P:renal system process; IEA:Ensembl.
GO; GO:0003139; P:secondary heart field specification; ISS:UniProtKB.
GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB.
GO; GO:0048745; P:smooth muscle tissue development; ISS:UniProtKB.
GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
GO; GO:0010159; P:specification of animal organ position; IEA:Ensembl.
GO; GO:0072101; P:specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway; ISS:UniProtKB.
GO; GO:0043401; P:steroid hormone mediated signaling pathway; ISS:UniProtKB.
GO; GO:0021978; P:telencephalon regionalization; IEA:Ensembl.
GO; GO:0035990; P:tendon cell differentiation; ISS:UniProtKB.
GO; GO:0060440; P:trachea formation; IEA:Ensembl.
GO; GO:0003323; P:type B pancreatic cell development; ISS:UniProtKB.
GO; GO:0072192; P:ureter epithelial cell differentiation; ISS:UniProtKB.
GO; GO:0072193; P:ureter smooth muscle cell differentiation; ISS:UniProtKB.
Gene3D; 2.10.90.10; -; 1.
InterPro; IPR029034; Cystine-knot_cytokine.
InterPro; IPR001839; TGF-b_C.
InterPro; IPR001111; TGF-b_propeptide.
InterPro; IPR015615; TGF-beta-rel.
InterPro; IPR017948; TGFb_CS.
PANTHER; PTHR11848; PTHR11848; 1.
Pfam; PF00019; TGF_beta; 1.
Pfam; PF00688; TGFb_propeptide; 1.
SMART; SM00204; TGFB; 1.
SUPFAM; SSF57501; SSF57501; 1.
PROSITE; PS00250; TGF_BETA_1; 1.
PROSITE; PS51362; TGF_BETA_2; 1.
2: Evidence at transcript level;
Chondrogenesis; Cleavage on pair of basic residues; Complete proteome;
Cytokine; Developmental protein; Differentiation; Disulfide bond;
Extracellular matrix; Glycoprotein; Growth factor; Osteogenesis;
Phosphoprotein; Reference proteome; Secreted; Signal.
SIGNAL 1 24 {ECO:0000255}.
PROPEP 25 293 {ECO:0000250}.
/FTId=PRO_0000244401.
CHAIN 294 409 Bone morphogenetic protein 4.
/FTId=PRO_0000244402.
MOD_RES 91 91 Phosphoserine.
{ECO:0000250|UniProtKB:P12644}.
CARBOHYD 144 144 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 209 209 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 351 351 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 366 366 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 309 374 {ECO:0000250}.
DISULFID 338 406 {ECO:0000250}.
DISULFID 342 408 {ECO:0000250}.
DISULFID 373 373 Interchain. {ECO:0000250}.
SEQUENCE 409 AA; 46626 MW; 5450B9A831D4EE0C CRC64;
MIPGNRMLMV VLLCQVLLGG ASHASLIPET GKKKVAEIQG HAGGRRSGQS HELLRDFEAT
LLQMFGLRRR PQPSKSAVIP DYMRDLYRLQ SGEEEEEEQI QGIGLEYPER PASRANTVRS
FHHEEHLENI PGTSENSAFR FLFNLSSIPE NEVISSAELR LFREQVDQGP DWDQGFHRIN
IYEVMKPPAE VVPGHLITRL LDTRLVHHNV TRWETFDVSP AVLRWTREKQ PNYGLAIEVT
HLHQTRTHQG QHVRISRSLP QGSGDWAQLR PLLVTFGHDG RGHALTRRRR AKRSPKHHPQ
RARKKNKNCR RHSLYVDFSD VGWNDWIVAP PGYQAFYCHG DCPFPLADHL NSTNHAIVQT
LVNSVNSSIP KACCVPTELS AISMLYLDEY DKVVLKNYQE MVVEGCGCR


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