BMP4_SUNMU
ID BMP4_SUNMU Reviewed; 409 AA.
AC Q8MJV5;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Bone morphogenetic protein 4;
DE Short=BMP-4;
DE Short=sBmp4;
DE Flags: Precursor;
GN Name=BMP4;
OS Suncus murinus (Asian house shrew) (Musk shrew).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Eulipotyphla; Soricidae; Crocidurinae; Suncus.
OX NCBI_TaxID=9378;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12643446;
RA Ogi H., Tabata M.J., Yamanaka A., Yasui K., Uemura M.;
RT "Comparison of expression patterns of fibroblast growth factor 8, bone
RT morphogenetic protein 4 and sonic hedgehog in jaw development of the house
RT shrew, Suncus murinus.";
RL Cell. Mol. Biol. 48:289-296(2002).
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).
CC {ECO:0000250|UniProtKB:P12644, 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB081499; BAC02895.1; -; mRNA.
DR AlphaFoldDB; Q8MJV5; -.
DR SMR; Q8MJV5; -.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0070700; F:BMP receptor binding; ISS:UniProtKB.
DR GO; GO:0042056; F:chemoattractant activity; 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:0030509; P:BMP signaling pathway; 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: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: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:0048392; P:intermediate mesodermal 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:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; ISS:UniProtKB.
DR GO; GO:0001823; P:mesonephros development; 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: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: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: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:0042476; P:odontogenesis; ISS:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; 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: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:0090184; P:positive regulation of kidney development; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
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: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:0048745; P:smooth muscle tissue development; ISS:UniProtKB.
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: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; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..293
FT /evidence="ECO:0000250"
FT /id="PRO_0000253022"
FT CHAIN 294..409
FT /note="Bone morphogenetic protein 4"
FT /id="PRO_0000253023"
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; 46848 MW; ADB69DE60C38C9FA CRC64;
MIPGNRMLMV VLLCQVLLGG ASHASLIPET GKKKVAEIQG HAGGRRSGQS HELLRDFEAT
LLQMFGLRRR PQPSKSAVIP DYMRDLYRLQ SGEEEEEEQI RSIDLEYPER PTSRANTVRS
FHHEEHLEDI PGTSENSAFR FFFNLSSIPE NEVISSAELR LFREQVDQGP DWEQGFHRIN
IYEVMKPPAE VVPGHLITRL LDTRLVHHNV TRWETFDVSP AVLRWTREKQ PNYGLAIEVT
HLHQTRTHQG QHVRISRSLP QGNGDWAQLR PLLVTFGHDG RGHALTRRRR AKRSPKHHPQ
RARKKNKNCR RHSLYVDFSD VGWNDWIVAP PGYQAFYCHG DCPFPLADHL NSTNHAIVQT
LVNSVNSSIP KACCVPTELS AISMLYLDEY DKVVLKNYQE MVVEGCGCR
