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   24-JAN-2024, entry version 130.
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       11 dpc and also in the ventricular zone at 16 dpc, but not in adult. In
CC       the brain, expression is more significant at 16 dpc than at adult, with
CC       high expression in the cortex, pontine area and choroid plexus.
CC       Detected in the otocyst at 16 dpc. {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   GlyCosmos; Q9EQX6; 2 sites, No reported glycans.
DR   GlyGen; Q9EQX6; 2 sites.
DR   PhosphoSitePlus; Q9EQX6; -.
DR   PaxDb; 10116-ENSRNOP00000015081; -.
DR   Ensembl; ENSRNOT00000015081.5; ENSRNOP00000015081.3; ENSRNOG00000010695.5.
DR   Ensembl; ENSRNOT00055002407; ENSRNOP00055001825; ENSRNOG00055001486.
DR   Ensembl; ENSRNOT00060011691; ENSRNOP00060008801; ENSRNOG00060007117.
DR   Ensembl; ENSRNOT00065052511; ENSRNOP00065043156; ENSRNOG00065030449.
DR   GeneID; 79429; -.
DR   KEGG; rno:79429; -.
DR   UCSC; RGD:68410; rat.
DR   AGR; RGD:68410; -.
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; MCVVIQT; -.
DR   OrthoDB; 3908391at2759; -.
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 cell types or tissues.
DR   ExpressionAtlas; Q9EQX6; baseline and differential.
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:0005161; F:platelet-derived growth factor receptor binding; ISO:RGD.
DR   GO; GO:0042803; F:protein homodimerization 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:0048144; P:fibroblast proliferation; ISO:RGD.
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:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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; Cystine-knot cytokines; 1.
DR   Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 1.
DR   InterPro; IPR000859; CUB_dom.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR000072; PDGF/VEGF_dom.
DR   InterPro; IPR035914; Sperma_CUB_dom_sf.
DR   PANTHER; PTHR11633; PLATELET-DERIVED GROWTH FACTOR; 1.
DR   PANTHER; PTHR11633:SF5; PLATELET-DERIVED GROWTH FACTOR C; 1.
DR   Pfam; PF00431; CUB; 1.
DR   Pfam; PF00341; PDGF; 1.
DR   SMART; SM00042; CUB; 1.
DR   SMART; SM00141; PDGF; 1.
DR   SUPFAM; SSF57501; Cystine-knot cytokines; 1.
DR   SUPFAM; SSF49854; Spermadhesin, CUB domain; 1.
DR   PROSITE; PS01180; CUB; 1.
DR   PROSITE; PS50278; PDGF_2; 1.
DR   Genevisible; Q9EQX6; RN.
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
//