ID PDGFB_MOUSE Reviewed; 241 AA. AC P31240; Q6P3C4; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 1. DT 09-DEC-2015, entry version 137. DE RecName: Full=Platelet-derived growth factor subunit B; DE Short=PDGF subunit B; DE AltName: Full=PDGF-2; DE AltName: Full=Platelet-derived growth factor B chain; DE AltName: Full=Platelet-derived growth factor beta polypeptide; DE AltName: Full=Proto-oncogene c-Sis; DE Flags: Precursor; GN Name=Pdgfb; Synonyms=Sis; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2045107; DOI=10.1016/0888-7543(91)90515-G; RA Bonthron D.T., Sultan P., Collins T.; RT "Structure of the murine c-sis proto-oncogene (Sis, PDGFB) encoding RT the B chain of platelet-derived growth factor."; RL Genomics 10:287-292(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Embryo, and Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=7958863; DOI=10.1101/gad.8.16.1875; RA Leveen P., Pekny M., Gebre-Medhin S., Swolin B., Larsson E., RA Betsholtz C.; RT "Mice deficient for PDGF B show renal, cardiovascular, and RT hematological abnormalities."; RL Genes Dev. 8:1875-1887(1994). RN [4] RP DISRUPTION PHENOTYPE. RX PubMed=9211853; DOI=10.1126/science.277.5323.242; RA Lindahl P., Johansson B.R., Leveen P., Betsholtz C.; RT "Pericyte loss and microaneurysm formation in PDGF-B-deficient mice."; RL Science 277:242-245(1997). RN [5] RP FUNCTION. RX PubMed=10734101; DOI=10.1074/jbc.275.13.9527; RA Arar M., Xu Y.C., Elshihabi I., Barnes J.L., Choudhury G.G., RA Abboud H.E.; RT "Platelet-derived growth factor receptor beta regulates migration and RT DNA synthesis in metanephric mesenchymal cells."; RL J. Biol. Chem. 275:9527-9533(2000). RN [6] RP DISRUPTION PHENOTYPE. RX PubMed=11264163; DOI=10.1182/blood.V97.7.1990; RA Kaminski W.E., Lindahl P., Lin N.L., Broudy V.C., Crosby J.R., RA Hellstrom M., Swolin B., Bowen-Pope D.F., Martin P.J., Ross R., RA Betsholtz C., Raines E.W.; RT "Basis of hematopoietic defects in platelet-derived growth factor RT (PDGF)-B and PDGF beta-receptor null mice."; RL Blood 97:1990-1998(2001). RN [7] RP TISSUE SPECIFICITY. RX PubMed=14514732; DOI=10.1097/01.ASN.0000089828.73014.C8; RA Taneda S., Hudkins K.L., Topouzis S., Gilbertson D.G., RA Ophascharoensuk V., Truong L., Johnson R.J., Alpers C.E.; RT "Obstructive uropathy in mice and humans: potential role for PDGF-D in RT the progression of tubulointerstitial injury."; RL J. Am. Soc. Nephrol. 14:2544-2555(2003). RN [8] RP FUNCTION. RX PubMed=14561699; DOI=10.1172/JCI200318549; RA Abramsson A., Lindblom P., Betsholtz C.; RT "Endothelial and nonendothelial sources of PDGF-B regulate pericyte RT recruitment and influence vascular pattern formation in tumors."; RL J. Clin. Invest. 112:1142-1151(2003). RN [9] RP REVIEW. RX PubMed=15207812; DOI=10.1016/j.cytogfr.2004.03.003; RA Tallquist M., Kazlauskas A.; RT "PDGF signaling in cells and mice."; RL Cytokine Growth Factor Rev. 15:205-213(2004). RN [10] RP REVIEW ON FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=15207813; DOI=10.1016/j.cytogfr.2004.03.005; RA Betsholtz C.; RT "Insight into the physiological functions of PDGF through genetic RT studies in mice."; RL Cytokine Growth Factor Rev. 15:215-228(2004). RN [11] RP FUNCTION. RX PubMed=19030102; DOI=10.1371/journal.pone.0003794; RA Wu E., Palmer N., Tian Z., Moseman A.P., Galdzicki M., Wang X., RA Berger B., Zhang H., Kohane I.S.; RT "Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR RT genetically defined cells."; RL PLoS ONE 3:E3794-E3794(2008). CC -!- FUNCTION: Growth factor that plays an essential role in the CC regulation of embryonic development, cell proliferation, cell CC migration, survival and chemotaxis. Potent mitogen for cells of CC mesenchymal origin. Required for normal proliferation and CC recruitment of pericytes and vascular smooth muscle cells in the CC central nervous system, skin, lung, heart and placenta. Required CC for normal blood vessel development, and for normal development of CC kidney glomeruli. Plays an important role in wound healing. CC Signaling is modulated by the formation of heterodimers with CC PDGFA. {ECO:0000269|PubMed:10734101, ECO:0000269|PubMed:14561699, CC ECO:0000269|PubMed:19030102, ECO:0000269|PubMed:7958863}. CC -!- SUBUNIT: Homodimer; antiparallel disulfide-linked dimer. CC Heterodimer with PDGFA; antiparallel disulfide-linked dimer. The CC PDGFB homodimer interacts with PDGFRA and PDGFRB homodimers, and CC with heterodimers formed by PDGFRA and PDGFRB. The heterodimer CC composed of PDGFA and PDGFB interacts with PDGFRB homodimers, and CC with heterodimers formed by PDGFRA and PDGFRB. Interacts with CC XLKD1 (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Secreted. Note=Released by platelets upon CC wounding. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Localized to vascular smooth muscle cells. CC Also weakly expressed by cortical interstitial cells but absent in CC tubules. Up-regulated in areas of renal fibrosis. In mice with CC unilateral ureteral obstruction, an increased expression in CC interstitial cells and in some tubules observed after day 4. CC {ECO:0000269|PubMed:14514732}. CC -!- DISRUPTION PHENOTYPE: Perinatal lethality, due to severe CC hemorrhages shortly before birth. Kidney glomerular tufts do not CC form, apparently because of absence of mesangial cells. The heart CC and some large arteries are dilated in late-stage embryos. Mice CC lack microvascular pericytes, which normally form part of the CC capillary wall, and develop numerous capillary microaneurysms, CC leading to hemorrhages. Mice display erythroblastosis, macrocytic CC anemia, and thrombocytopenia. {ECO:0000269|PubMed:11264163, CC ECO:0000269|PubMed:15207813, ECO:0000269|PubMed:7958863, CC ECO:0000269|PubMed:9211853}. CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family. CC {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; M84453; AAA40113.1; -; Genomic_DNA. DR EMBL; M84448; AAA40113.1; JOINED; Genomic_DNA. DR EMBL; M84449; AAA40113.1; JOINED; Genomic_DNA. DR EMBL; M84450; AAA40113.1; JOINED; Genomic_DNA. DR EMBL; M84451; AAA40113.1; JOINED; Genomic_DNA. DR EMBL; M84452; AAA40113.1; JOINED; Genomic_DNA. DR EMBL; M64849; AAA37485.1; -; Genomic_DNA. DR EMBL; M64844; AAA37485.1; JOINED; Genomic_DNA. DR EMBL; M64845; AAA37485.1; JOINED; Genomic_DNA. DR EMBL; M64846; AAA37485.1; JOINED; Genomic_DNA. DR EMBL; M64847; AAA37485.1; JOINED; Genomic_DNA. DR EMBL; M64848; AAA37485.1; JOINED; Genomic_DNA. DR EMBL; BC053430; AAH53430.1; -; mRNA. DR EMBL; BC064056; AAH64056.1; -; mRNA. DR CCDS; CCDS27656.1; -. DR PIR; A39073; PFMSGB. DR RefSeq; NP_035187.2; NM_011057.3. DR UniGene; Mm.144089; -. DR PDB; 2DZ4; Model; -; A=90-185. DR PDB; 2DZ5; Model; -; A=90-185. DR PDBsum; 2DZ4; -. DR PDBsum; 2DZ5; -. DR ProteinModelPortal; P31240; -. DR SMR; P31240; 25-182. DR IntAct; P31240; 1. DR STRING; 10090.ENSMUSP00000000500; -. DR PhosphoSite; P31240; -. DR MaxQB; P31240; -. DR PaxDb; P31240; -. DR PRIDE; P31240; -. DR GeneID; 18591; -. DR KEGG; mmu:18591; -. DR UCSC; uc007wuz.1; mouse. DR CTD; 5155; -. DR MGI; MGI:97528; Pdgfb. DR eggNOG; ENOG410IJ45; Eukaryota. DR eggNOG; ENOG410XWTB; LUCA. DR HOGENOM; HOG000286027; -. DR HOVERGEN; HBG053546; -. DR InParanoid; P31240; -. DR KO; K17386; -. DR OrthoDB; EOG78H3VV; -. DR PhylomeDB; P31240; -. DR TreeFam; TF319554; -. DR NextBio; 294476; -. DR PRO; PR:P31240; -. DR Proteomes; UP000000589; Unplaced. DR Bgee; P31240; -. DR CleanEx; MM_PDGFB; -. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0042056; F:chemoattractant activity; ISO:MGI. DR GO; GO:0005518; F:collagen binding; ISO:MGI. DR GO; GO:0008083; F:growth factor activity; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0048407; F:platelet-derived growth factor binding; ISO:MGI. DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISS:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; ISS:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:MGI. DR GO; GO:0032147; P:activation of protein kinase activity; ISS:UniProtKB. DR GO; GO:0032148; P:activation of protein kinase B activity; ISS:UniProtKB. DR GO; GO:0001568; P:blood vessel development; IEP:UniProtKB. DR GO; GO:0048514; P:blood vessel morphogenesis; IDA:MGI. DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IMP:MGI. DR GO; GO:0060947; P:cardiac vascular smooth muscle cell differentiation; TAS:DFLAT. DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB. DR GO; GO:0030031; P:cell projection assembly; IDA:MGI. DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:MGI. DR GO; GO:0071506; P:cellular response to mycophenolic acid; ISS:UniProtKB. DR GO; GO:0001892; P:embryonic placenta development; IMP:UniProtKB. DR GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IMP:MGI. DR GO; GO:0042462; P:eye photoreceptor cell development; IMP:MGI. DR GO; GO:0021782; P:glial cell development; IMP:MGI. DR GO; GO:0007507; P:heart development; IMP:UniProtKB. DR GO; GO:0072264; P:metanephric glomerular endothelium development; IEP:UniProtKB. DR GO; GO:0072255; P:metanephric glomerular mesangial cell development; IMP:UniProtKB. DR GO; GO:0072262; P:metanephric glomerular mesangial cell proliferation involved in metanephros development; IMP:UniProtKB. DR GO; GO:0002548; P:monocyte chemotaxis; ISS:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; IGI:MGI. DR GO; GO:0010512; P:negative regulation of phosphatidylinositol biosynthetic process; ISS:UniProtKB. DR GO; GO:0010544; P:negative regulation of platelet activation; ISS:UniProtKB. DR GO; GO:0032091; P:negative regulation of protein binding; ISO:MGI. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0045908; P:negative regulation of vasodilation; TAS:DFLAT. DR GO; GO:0016322; P:neuron remodeling; IMP:MGI. DR GO; GO:0038001; P:paracrine signaling; IMP:UniProtKB. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0050918; P:positive chemotaxis; ISO:MGI. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISS:UniProtKB. DR GO; GO:0090280; P:positive regulation of calcium ion import; ISS:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IGI:MGI. DR GO; GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB. DR GO; GO:0050921; P:positive regulation of chemotaxis; ISS:UniProtKB. DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISS:UniProtKB. DR GO; GO:0045740; P:positive regulation of DNA replication; ISS:UniProtKB. DR GO; GO:0038033; P:positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway; TAS:BHF-UCL. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IGI:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0045743; P:positive regulation of fibroblast growth factor receptor signaling pathway; IDA:MGI. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0003104; P:positive regulation of glomerular filtration; IMP:UniProtKB. DR GO; GO:0072126; P:positive regulation of glomerular mesangial cell proliferation; ISS:UniProtKB. DR GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; ISS:UniProtKB. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB. DR GO; GO:2000591; P:positive regulation of metanephric mesenchymal cell migration; ISO:MGI. DR GO; GO:0035793; P:positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway; ISS:UniProtKB. DR GO; GO:0045977; P:positive regulation of mitotic cell cycle, embryonic; IGI:MGI. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISS:UniProtKB. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI. DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB. DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB. DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISS:UniProtKB. DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:UniProtKB. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0045907; P:positive regulation of vasoconstriction; TAS:DFLAT. DR GO; GO:0070528; P:protein kinase C signaling; ISO:MGI. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISS:UniProtKB. DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IDA:MGI. DR GO; GO:0009611; P:response to wounding; ISS:UniProtKB. DR GO; GO:0060041; P:retina development in camera-type eye; IMP:MGI. DR GO; GO:0061298; P:retina vasculature development in camera-type eye; IMP:MGI. DR GO; GO:0006929; P:substrate-dependent cell migration; IDA:MGI. DR GO; GO:0007416; P:synapse assembly; IMP:MGI. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB. DR Gene3D; 2.10.90.10; -; 1. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR023581; PD_growth_factor_CS. DR InterPro; IPR000072; PDGF/VEGF_dom. DR InterPro; IPR006782; PDGF_N. DR Pfam; PF00341; PDGF; 1. DR Pfam; PF04692; PDGF_N; 1. DR SMART; SM00141; PDGF; 1. DR SUPFAM; SSF57501; SSF57501; 1. DR PROSITE; PS00249; PDGF_1; 1. DR PROSITE; PS50278; PDGF_2; 1. PE 2: Evidence at transcript level; KW 3D-structure; Cleavage on pair of basic residues; Complete proteome; KW Developmental protein; Disulfide bond; Glycoprotein; Growth factor; KW Mitogen; Proto-oncogene; Reference proteome; Secreted; Signal. FT SIGNAL 1 20 {ECO:0000250}. FT PROPEP 21 81 Removed in mature form. {ECO:0000250}. FT /FTId=PRO_0000023374. FT CHAIN 82 190 Platelet-derived growth factor subunit B. FT /FTId=PRO_0000023375. FT PROPEP 191 241 Removed in mature form. {ECO:0000250}. FT /FTId=PRO_0000023376. FT SITE 108 108 Involved in receptor binding. FT SITE 111 111 Involved in receptor binding. FT CARBOHYD 63 63 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 97 141 {ECO:0000250}. FT DISULFID 124 124 Interchain. {ECO:0000250}. FT DISULFID 130 178 {ECO:0000250}. FT DISULFID 133 133 Interchain. {ECO:0000250}. FT DISULFID 134 180 {ECO:0000250}. FT CONFLICT 183 183 I -> V (in Ref. 2; AAH53430/AAH64056). FT {ECO:0000305}. SQ SEQUENCE 241 AA; 27382 MW; 3C5EB7A2DAD64178 CRC64; MNRCWALFLP LCCYLRLVSA EGDPIPEELY EMLSDHSIRS FDDLQRLLHR DSVDEDGAEL DLNMTRAHSG VELESSSRGR RSLGSLAAAE PAVIAECKTR TEVFQISRNL IDRTNANFLV WPPCVEVQRC SGCCNNRNVQ CRASQVQMRP VQVRKIEIVR KKPIFKKATV TLEDHLACKC ETIVTPRPVT RSPGTSREQR AKTPQARVTI RTVRIRRPPK GKHRKFKHTH DKAALKETLG A //