BMP4_BOVIN
ID BMP4_BOVIN Reviewed; 409 AA.
AC Q2KJH1;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Bone morphogenetic protein 4;
DE Short=BMP-4;
DE Flags: Precursor;
GN Name=BMP4;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Growth factor of the TGF-beta superfamily that plays
CC essential roles in many developmental processes, including
CC neurogenesis, vascular development, angiogenesis and osteogenesis (By
CC similarity). Acts in concert with PTHLH/PTHRP to stimulate ductal
CC outgrowth during embryonic mammary development and to inhibit hair
CC follicle induction (By similarity). Initiates the canonical BMP
CC signaling cascade by associating with type I receptor BMPR1A and type
CC II receptor BMPR2. Once all three components are bound together in a
CC complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A.
CC In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that
CC travel to the nucleus and act as activators and repressors of
CC transcription of target genes. Can also signal through non-canonical
CC BMP pathways such as ERK/MAP kinase, PI3K/Akt, or SRC cascades. For
CC example, induces SRC phosphorylation which, in turn, activates VEGFR2,
CC leading to an angiogenic response (By similarity).
CC {ECO:0000250|UniProtKB:P12644, ECO:0000250|UniProtKB:P21275}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC GREM2. Part of a complex consisting of TWSG1 and CHRD. Interacts with
CC the serine proteases, HTRA1 and HTRA3; the interaction with either
CC inhibits BMP4-mediated signaling. The HTRA protease activity is
CC required for this inhibition (By similarity). Interacts with SOSTDC1.
CC Interacts with FBN1 (via N-terminal domain) and FBN2. Interacts with
CC type I receptor BMPR1A. Interacts with type II receptor BMPR2.
CC Interacts with FSTL1; this interaction inhibits the activation of the
CC BMP4/Smad1/5/8 signaling pathway (By similarity). Interacts with SCUBE3
CC (By similarity). {ECO:0000250|UniProtKB:P12644,
CC ECO:0000250|UniProtKB:P21275}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; BC105344; AAI05345.1; -; mRNA.
DR RefSeq; NP_001039342.1; NM_001045877.1.
DR RefSeq; XP_005211850.1; XM_005211793.3.
DR RefSeq; XP_005211851.1; XM_005211794.3.
DR RefSeq; XP_010807631.1; XM_010809329.2.
DR RefSeq; XP_010807633.1; XM_010809331.2.
DR AlphaFoldDB; Q2KJH1; -.
DR SMR; Q2KJH1; -.
DR STRING; 9913.ENSBTAP00000004992; -.
DR PaxDb; Q2KJH1; -.
DR Ensembl; ENSBTAT00000004992; ENSBTAP00000004992; ENSBTAG00000003835.
DR GeneID; 407216; -.
DR KEGG; bta:407216; -.
DR CTD; 652; -.
DR VEuPathDB; HostDB:ENSBTAG00000003835; -.
DR VGNC; VGNC:26519; BMP4.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000159502; -.
DR HOGENOM; CLU_020515_4_2_1; -.
DR InParanoid; Q2KJH1; -.
DR OMA; HEEHMEQ; -.
DR OrthoDB; 962484at2759; -.
DR TreeFam; TF351789; -.
DR Reactome; R-BTA-2129379; Molecules associated with elastic fibres.
DR Reactome; R-BTA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-BTA-8957275; Post-translational protein phosphorylation.
DR Proteomes; UP000009136; Chromosome 10.
DR Bgee; ENSBTAG00000003835; Expressed in fornix of vagina and 106 other tissues.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0070700; F:BMP receptor binding; ISS:UniProtKB.
DR GO; GO:0042056; F:chemoattractant activity; ISS:UniProtKB.
DR GO; GO:0039706; F:co-receptor binding; IEA:Ensembl.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IEA:Ensembl.
DR GO; GO:0036305; P:ameloblast differentiation; IEA:Ensembl.
DR GO; GO:0009948; P:anterior/posterior axis specification; IEA:Ensembl.
DR GO; GO:0003180; P:aortic valve morphogenesis; IEA:Ensembl.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0061312; P:BMP signaling pathway involved in heart development; IEA:Ensembl.
DR GO; GO:0003130; P:BMP signaling pathway involved in heart induction; ISS:UniProtKB.
DR GO; GO:0071893; P:BMP signaling pathway involved in nephric duct formation; ISS:UniProtKB.
DR GO; GO:0061151; P:BMP signaling pathway involved in renal system segmentation; ISS:UniProtKB.
DR GO; GO:0061149; P:BMP signaling pathway involved in ureter morphogenesis; ISS:UniProtKB.
DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:UniProtKB.
DR GO; GO:0060433; P:bronchus development; IEA:Ensembl.
DR GO; GO:0060503; P:bud dilation involved in lung branching; IEA:Ensembl.
DR GO; GO:0060449; P:bud elongation involved in lung branching; IEA:Ensembl.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0060197; P:cloacal septation; IEA:Ensembl.
DR GO; GO:0007182; P:common-partner SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0060976; P:coronary vasculature development; IEA:Ensembl.
DR GO; GO:0060363; P:cranial suture morphogenesis; IEA:Ensembl.
DR GO; GO:0035993; P:deltoid tuberosity development; ISS:UniProtKB.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl.
DR GO; GO:0060272; P:embryonic skeletal joint morphogenesis; IEA:Ensembl.
DR GO; GO:0003197; P:endocardial cushion development; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB.
DR GO; GO:0007492; P:endoderm development; IEA:Ensembl.
DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; IEA:Ensembl.
DR GO; GO:0060684; P:epithelial-mesenchymal cell signaling; IEA:Ensembl.
DR GO; GO:0030218; P:erythrocyte differentiation; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0072104; P:glomerular capillary formation; ISS:UniProtKB.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISS:UniProtKB.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:0048392; P:intermediate mesodermal cell differentiation; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0060235; P:lens induction in camera-type eye; IEA:Ensembl.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; ISS:UniProtKB.
DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl.
DR GO; GO:0060592; P:mammary gland formation; IEA:Ensembl.
DR GO; GO:0003149; P:membranous septum morphogenesis; IEA:Ensembl.
DR GO; GO:0072161; P:mesenchymal cell differentiation involved in kidney development; IEA:Ensembl.
DR GO; GO:0072198; P:mesenchymal cell proliferation involved in ureter development; IEA:Ensembl.
DR GO; GO:0072138; P:mesenchymal cell proliferation involved in ureteric bud development; IEA:Ensembl.
DR GO; GO:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; ISS:UniProtKB.
DR GO; GO:0007500; P:mesodermal cell fate determination; IEA:Ensembl.
DR GO; GO:0001823; P:mesonephros development; ISS:UniProtKB.
DR GO; GO:0072205; P:metanephric collecting duct development; ISS:UniProtKB.
DR GO; GO:0030224; P:monocyte differentiation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0072097; P:negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0090191; P:negative regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
DR GO; GO:2000137; P:negative regulation of cell proliferation involved in heart morphogenesis; ISS:UniProtKB.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0072125; P:negative regulation of glomerular mesangial cell proliferation; ISS:UniProtKB.
DR GO; GO:0090194; P:negative regulation of glomerulus development; ISS:UniProtKB.
DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; ISS:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0072200; P:negative regulation of mesenchymal cell proliferation involved in ureter development; ISS:UniProtKB.
DR GO; GO:2000007; P:negative regulation of metanephric comma-shaped body morphogenesis; ISS:UniProtKB.
DR GO; GO:2000005; P:negative regulation of metanephric S-shaped body morphogenesis; ISS:UniProtKB.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; ISS:UniProtKB.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0060686; P:negative regulation of prostatic bud formation; IEA:Ensembl.
DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; IEA:Ensembl.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0048663; P:neuron fate commitment; IEA:Ensembl.
DR GO; GO:0042476; P:odontogenesis; ISS:UniProtKB.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; IEA:Ensembl.
DR GO; GO:1904238; P:pericyte cell differentiation; IEA:Ensembl.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IEA:Ensembl.
DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR GO; GO:0072015; P:podocyte development; IEA:Ensembl.
DR GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0061047; P:positive regulation of branching involved in lung morphogenesis; ISS:UniProtKB.
DR GO; GO:0055020; P:positive regulation of cardiac muscle fiber development; ISS:UniProtKB.
DR GO; GO:1905312; P:positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0061036; P:positive regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:1901964; P:positive regulation of cell proliferation involved in outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IEA:Ensembl.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045606; P:positive regulation of epidermal cell differentiation; ISS:CAFA.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0090184; P:positive regulation of kidney development; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:1903800; P:positive regulation of miRNA maturation; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IEA:Ensembl.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0060513; P:prostatic bud formation; IEA:Ensembl.
DR GO; GO:0034504; P:protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0061155; P:pulmonary artery endothelial tube morphogenesis; ISS:UniProtKB.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; IEA:Ensembl.
DR GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IEA:Ensembl.
DR GO; GO:0010453; P:regulation of cell fate commitment; ISS:CAFA.
DR GO; GO:1905770; P:regulation of mesodermal cell differentiation; IEA:Ensembl.
DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0060393; P:regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0042306; P:regulation of protein import into nucleus; IEA:Ensembl.
DR GO; GO:0051150; P:regulation of smooth muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0003014; P:renal system process; IEA:Ensembl.
DR GO; GO:0003139; P:secondary heart field specification; ISS:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0048745; P:smooth muscle tissue development; ISS:UniProtKB.
DR GO; GO:0010159; P:specification of animal organ position; IEA:Ensembl.
DR GO; GO:0072101; P:specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0043401; P:steroid hormone mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0021978; P:telencephalon regionalization; IEA:Ensembl.
DR GO; GO:0035990; P:tendon cell differentiation; ISS:UniProtKB.
DR GO; GO:0060440; P:trachea formation; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0003323; P:type B pancreatic cell development; ISS:UniProtKB.
DR GO; GO:0072192; P:ureter epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0072193; P:ureter smooth muscle cell differentiation; ISS:UniProtKB.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 2: Evidence at transcript level;
KW Chondrogenesis; Cleavage on pair of basic residues; Cytokine;
KW Developmental protein; Differentiation; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Growth factor; Osteogenesis;
KW Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..293
FT /evidence="ECO:0000250"
FT /id="PRO_0000244401"
FT CHAIN 294..409
FT /note="Bone morphogenetic protein 4"
FT /id="PRO_0000244402"
FT REGION 284..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12644"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 351
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 309..374
FT /evidence="ECO:0000250"
FT DISULFID 338..406
FT /evidence="ECO:0000250"
FT DISULFID 342..408
FT /evidence="ECO:0000250"
FT DISULFID 373
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ 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
