PDGFC_RAT
ID PDGFC_RAT Reviewed; 345 AA.
AC Q9EQX6; Q8K429;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Platelet-derived growth factor C;
DE Short=PDGF-C;
DE AltName: Full=Fallotein;
DE AltName: Full=Spinal cord-derived growth factor;
DE Short=rScdfg;
DE AltName: Full=VEGF-E;
DE Contains:
DE RecName: Full=Platelet-derived growth factor C, latent form;
DE Short=PDGFC latent form;
DE Contains:
DE RecName: Full=Platelet-derived growth factor C, receptor-binding form;
DE Short=PDGFC receptor-binding form;
DE Flags: Precursor;
GN Name=Pdgfc; Synonyms=Scdgf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Kidney;
RX PubMed=11162582; DOI=10.1006/bbrc.2000.4187;
RA Hamada T., Ui-Tei K., Imaki J., Miyata Y.;
RT "Molecular cloning of SCDGF-B, a novel growth factor homologous to
RT SCDGF/PDGF-C/fallotein.";
RL Biochem. Biophys. Res. Commun. 280:733-737(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-299.
RC STRAIN=Sprague-Dawley; TISSUE=Skin;
RA Brown S.A., Coberly D.M., Rohrich R.R., Chao J.J.;
RT "Platelet derived growth factor C (PDGF-C) expression in wound healing.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11912250; DOI=10.1681/asn.v134910;
RA Eitner F., Ostendorf T., Van Roeyen C., Kitahara M., Li X., Aase K.,
RA Grone H.J., Eriksson U., Floege J.;
RT "Expression of a novel PDGF isoform, PDGF-C, in normal and diseased rat
RT kidney.";
RL J. Am. Soc. Nephrol. 13:910-917(2002).
RN [4]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11850188; DOI=10.1016/s0925-4773(01)00625-6;
RA Hamada T., Ui-Tei K., Imaki J., Takahashi F., Onodera H., Mishima T.,
RA Miyata Y.;
RT "The expression of SCDGF/PDGF-C/fallotein and SCDGF-B/PDGF-D in the rat
RT central nervous system.";
RL Mech. Dev. 112:161-164(2002).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=15267171; DOI=10.1080/00016480410016577;
RA Lee Y.W., Ozeki M., Juhn S.K., Lin J.;
RT "Expression of platelet-derived growth factor in the developing cochlea of
RT rats.";
RL Acta Oto-Laryngol. 124:558-562(2004).
RN [6]
RP INDUCTION BY FIBROGENESIS.
RX PubMed=16039137; DOI=10.1016/j.cyto.2005.06.005;
RA Breitkopf K., Roeyen C., Sawitza I., Wickert L., Floege J., Gressner A.M.;
RT "Expression patterns of PDGF-A, -B, -C and -D and the PDGF-receptors alpha
RT and beta in activated rat hepatic stellate cells (HSC).";
RL Cytokine 31:349-357(2005).
RN [7]
RP INDUCTION BY INDOXYL SULFATE.
RX PubMed=16612331; DOI=10.1038/sj.ki.5000340;
RA Yamamoto H., Tsuruoka S., Ioka T., Ando H., Ito C., Akimoto T.,
RA Fujimura A., Asano Y., Kusano E.;
RT "Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle
RT cells.";
RL Kidney Int. 69:1780-1785(2006).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=18272536; DOI=10.1093/nar/gkm923;
RA Sanchez-Guerrero E., Midgley V.C., Khachigian L.M.;
RT "Angiotensin II induction of PDGF-C expression is mediated by AT1 receptor-
RT dependent Egr-1 transactivation.";
RL Nucleic Acids Res. 36:1941-1951(2008).
CC -!- FUNCTION: Growth factor that plays an essential role in the regulation
CC of embryonic development, cell proliferation, cell migration, survival
CC and chemotaxis. Potent mitogen and chemoattractant for cells of
CC mesenchymal origin. Required for normal skeleton formation during
CC embryonic development, especially for normal development of the
CC craniofacial skeleton and for normal development of the palate.
CC Required for normal skin morphogenesis during embryonic development.
CC Plays an important role in wound healing, where it appears to be
CC involved in three stages: inflammation, proliferation and remodeling.
CC Plays an important role in angiogenesis and blood vessel development.
CC Involved in fibrotic processes, in which transformation of interstitial
CC fibroblasts into myofibroblasts plus collagen deposition occurs. The
CC CUB domain has mitogenic activity in coronary artery smooth muscle
CC cells, suggesting a role beyond the maintenance of the latency of the
CC PDGF domain. In the nucleus, PDGFC seems to have additional function
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with PDGFRA homodimers,
CC and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB
CC domain) with PLAT (via kringle domain) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9NRA1}. Secreted
CC {ECO:0000250|UniProtKB:Q9NRA1}. Nucleus {ECO:0000250|UniProtKB:Q9NRA1}.
CC Cytoplasmic granule {ECO:0000250|UniProtKB:Q9NRA1}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9NRA1}. Note=Sumoylated form is predominant in
CC the nucleus. Stored in alpha granules in platelets.
CC {ECO:0000250|UniProtKB:Q9NRA1}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the kidney and adrenal gland.
CC In the kidney, it is expressed in arteriolar smooth muscle cells and in
CC epithelial cells of individual segments (at protein level).
CC {ECO:0000269|PubMed:11850188, ECO:0000269|PubMed:11912250}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the floor plate of the spinal cord at
CC E11 and also in the ventricular zone at E16, but not in adult. In the
CC brain, expression is more significant at E16 than at adult, with high
CC expression in the cortex, pontine area and choroid plexus. Detected in
CC the otocyst at E16. {ECO:0000269|PubMed:11850188,
CC ECO:0000269|PubMed:15267171, ECO:0000269|PubMed:18272536}.
CC -!- INDUCTION: Up-regulated in mesangial, visceral epithelial, and
CC interstitial cells after predominant injury to these cells. Expression
CC levels increase in hepatic cells undergoing in vitro
CC transdifferentiation, which represents a model for hepatic
CC fibrogenesis. Expression induced by indoxyl sulfate. Expression induced
CC by angiotensin-2 via EGR1 in smooth muscle cells in neonatal but not in
CC adult rats. {ECO:0000269|PubMed:11912250, ECO:0000269|PubMed:16039137,
CC ECO:0000269|PubMed:16612331}.
CC -!- PTM: Proteolytic removal of the N-terminal CUB domain releasing the
CC core domain is necessary for unmasking the receptor-binding epitopes of
CC the core domain. Cleavage after basic residues in the hinge region
CC (region connecting the CUB and growth factor domains) gives rise to the
CC receptor-binding form. Cleaved by PLAT and PLG (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Sumoylated with SUMO1. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; AB033830; BAB19969.1; -; mRNA.
DR EMBL; AF508348; AAM47265.1; -; mRNA.
DR RefSeq; NP_112607.1; NM_031317.1.
DR AlphaFoldDB; Q9EQX6; -.
DR SMR; Q9EQX6; -.
DR STRING; 10116.ENSRNOP00000015081; -.
DR GlyGen; Q9EQX6; 2 sites.
DR PaxDb; Q9EQX6; -.
DR Ensembl; ENSRNOT00000015081; ENSRNOP00000015081; ENSRNOG00000010695.
DR GeneID; 79429; -.
DR KEGG; rno:79429; -.
DR UCSC; RGD:68410; rat.
DR CTD; 56034; -.
DR RGD; 68410; Pdgfc.
DR eggNOG; ENOG502QUUR; Eukaryota.
DR GeneTree; ENSGT00940000158645; -.
DR HOGENOM; CLU_037859_0_0_1; -.
DR InParanoid; Q9EQX6; -.
DR OMA; LDENVWI; -.
DR OrthoDB; 962163at2759; -.
DR PhylomeDB; Q9EQX6; -.
DR TreeFam; TF332130; -.
DR Reactome; R-RNO-186797; Signaling by PDGF.
DR PRO; PR:Q9EQX6; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000010695; Expressed in adult mammalian kidney and 18 other tissues.
DR ExpressionAtlas; Q9EQX6; baseline and differential.
DR Genevisible; Q9EQX6; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0070851; F:growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0060348; P:bone development; ISO:RGD.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:RGD.
DR GO; GO:0048565; P:digestive tract development; ISO:RGD.
DR GO; GO:0048568; P:embryonic organ development; IEA:InterPro.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IBA:GO_Central.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR CDD; cd00041; CUB; 1.
DR CDD; cd00135; PDGF; 1.
DR Gene3D; 2.10.90.10; -; 1.
DR Gene3D; 2.60.120.290; -; 1.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR029817; PDGF-C.
DR InterPro; IPR000072; PDGF/VEGF_dom.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR PANTHER; PTHR11633:SF5; PTHR11633:SF5; 1.
DR Pfam; PF00431; CUB; 1.
DR Pfam; PF00341; PDGF; 1.
DR SMART; SM00042; CUB; 1.
DR SMART; SM00141; PDGF; 1.
DR SUPFAM; SSF49854; SSF49854; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS01180; CUB; 1.
DR PROSITE; PS50278; PDGF_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cleavage on pair of basic residues; Cytoplasm;
KW Developmental protein; Disulfide bond; Glycoprotein; Growth factor;
KW Membrane; Mitogen; Nucleus; Reference proteome; Secreted; Signal;
KW Ubl conjugation.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..345
FT /note="Platelet-derived growth factor C, latent form"
FT /id="PRO_0000343875"
FT CHAIN ?..345
FT /note="Platelet-derived growth factor C, receptor-binding
FT form"
FT /id="PRO_0000343876"
FT DOMAIN 46..163
FT /note="CUB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT REGION 24..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 225..226
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT SITE 231..232
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT SITE 234..235
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 104..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 250..294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 274
FT /note="Interchain (with C-286)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 280..335
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 286
FT /note="Interchain (with C-274)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 287..337
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
SQ SEQUENCE 345 AA; 38734 MW; F296DA6E9B765D10 CRC64;
MLLLGLLLLT SALAGQRTGT RAESNLSSKL QLSSDKEQNG VQDPRHERVV TISGNGSIHS
PKFPHTYPRN TVLVWRLVAV DENVRIQLTF DERFGLEDPE DDLCKYDFVE VEEPSDGSVL
GRWCGSGTVP GKQTSKGNHI RIRFVSDEYF PSEPGFCIHY SIIMPQVTET TSPSVLPPSA
LSLDLLNNAV TAFSTVEELI RFLEPDRWQI DLDSLYKPTW PLLGKAFLYG KKSKAVNLNL
LKEEVKLYSC TPRNFSVSIR EELKRTDTIF WPGCLLVKRC GGNCACCLHN CNECQCVPRK
VTKKYHEVLQ LRPKIGVKGL HKSLTDVALE HHEECDCVCR GNTEG
