BMP4_RABIT
ID BMP4_RABIT Reviewed; 409 AA.
AC O46576;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 112.
DE RecName: Full=Bone morphogenetic protein 4;
DE Short=BMP-4;
DE Flags: Precursor;
GN Name=BMP4; Synonyms=BMP-4;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Ocular ciliary epithelium;
RA Wan X.L., Sears J., Chen S., Sears M.;
RT "Cloning and expression of BMP-2/-4 from rabbit ocular ciliary
RT epithelium.";
RL Submitted (JAN-1998) 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; AF042497; AAB97467.1; -; mRNA.
DR AlphaFoldDB; O46576; -.
DR SMR; O46576; -.
DR STRING; 9986.ENSOCUP00000009545; -.
DR PRIDE; O46576; -.
DR eggNOG; KOG3900; Eukaryota.
DR InParanoid; O46576; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0070700; F:BMP receptor binding; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISS:UniProtKB.
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:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0007182; P:common-partner SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0035993; P:deltoid tuberosity development; ISS:UniProtKB.
DR GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB.
DR GO; GO:0072104; P:glomerular capillary formation; ISS:UniProtKB.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; ISS:UniProtKB.
DR GO; GO:0072205; P:metanephric collecting duct development; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0090191; P:negative regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:2000137; P:negative regulation of cell proliferation involved in heart morphogenesis; ISS:UniProtKB.
DR GO; GO:0072125; P:negative regulation of glomerular mesangial cell proliferation; 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:0045839; P:negative regulation of mitotic nuclear division; ISS:UniProtKB.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; 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:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:UniProtKB.
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:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
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:0010453; P:regulation of cell fate commitment; ISS:CAFA.
DR GO; GO:0060393; P:regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
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:0043401; P:steroid hormone mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0035990; P:tendon cell differentiation; ISS:UniProtKB.
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..19
FT /evidence="ECO:0000255"
FT PROPEP 20..293
FT /evidence="ECO:0000250"
FT /id="PRO_0000033860"
FT CHAIN 294..409
FT /note="Bone morphogenetic protein 4"
FT /id="PRO_0000033861"
FT REGION 91..110
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; 46641 MW; 35557561447AD625 CRC64;
MIPGNRMLMV VLLCQVLLGG ASHASLIPET GKKKVAEIQG HAGGRRSGQS HELLRDFEAT
LLQMFGLRRH PQPSKSAVIP DYMRDLYRLQ SGEEEEEEQM PSGGLEYPER PASRANTVRS
FHHEEHLENI PGTSENSAFR FLFNLSSIPE NEAISSAELR LFREQVDQGP DWERGFHRIN
IYEVMKPPAE AVPGHLITRL LDTRLVHHNV TRWETFDVSP AVLRWTREKQ PNHGLAVEVT
HFHHTRTHQG QHVRLSRSLL QGSGDWAQFR PLLVTFGHDG RGHALTRRRR AKRSLKHHPQ
RARKKNKNCR RHALYVDFSD VGWNDWIVAP PGYQAFYCHG DCPFPLADHF NSTNHAIVQT
LVNSVNSSIP KACCVPTELS AISMLYLDEY DKVVLKNYQE MVVEGCGCR
