platelet-derived growth factor C; PDGF-C; spinal cord-derived growth factor; SCDGF; fallotein; VEGF-E; contains: platelet-derived growth factor C, latent form; PDGFC latent form; contains: platelet-derived growth factor C, receptor-binding form; PDGFC receptor-binding form (PDGFC, SCDGF, UNQ174/PRO200)

Function: - potent mitogen & chemoattractant for cells of mesenchymal origin - binding of PDGFC to its affinity receptor elicits a variety of cellular responses. - appears to be involved in the 3 stages of wound healing: inflammation, proliferation & remodeling - role in fibrotic processes, in which transformation of interstitial fibroblasts into myofibroblasts plus collagen deposition occurs - acts as a specific ligand for PDGFR alpha homodimer, & alpha & beta heterodimer - binding to receptors induces their activation by Tyr phosphorylation - the CUB domain has mitogenic activity in coronary artery smooth muscle cells, suggesting a role beyond the maintenance of the latency of the PDGF domain - in the nucleus, PDGFC seems to have additional function - seems to be involved in palatogenesis (putative) - proteolytic removal of the N-terminal CUB domain releasing the core domain is necessary for unmasking the receptor- binding epitopes of the core domain - cleavage after basic residues in the hinge region (region connecting the CUB & growth factor domains) gives rise to the receptor-binding form - cleaved by PLAT & PLG - sumoylated by SUMO1 - interacts (via CUB domain) with PLAT (via kringle domain) Structure: - N-glycosylated - homodimer; disulfide-linked. - belongs to the PDGF/VEGF growth factor family - contains 1 CUB domain Compartment: - cytoplasm, secreted, nucleus, cytoplasmic granule - sumoylated form is predominant in the nucleus - stored in alpha granules in platelets - membrane associated when bound to receptors Alternative splicing: named isoforms=3 Expression: - expressed in the fallopian tube, vascular smooth muscle cells in kidney, breast & colon & in visceral smooth muscle of the gastrointestinal tract - highly expressed in retinal pigment epithelia - expressed in medulloblastoma - in the kidney, constitutively expressed in parietal epithelial cells of Bowman's capsule, tubular epithelial cells & in arterial endothelial cells (at protein level) - highly expressed in platelets, prostate, testis & uterus - weaker expression in the spleen, thymus, heart, pancreas, liver, ovary cells & small intestine - negligible expression in the colon & peripheral blood leukocytes - in the fetal kidney, detected in the developing mesangium, ureteric bud epithelium & the undifferentiated mesenchyme (at protein level) - up-regulated by EWS-FLI1 chimeric transcription factor in tumor derived cells - up-regulated in podocytes & interstitial cells after injury/activation of these cells - FGF2 activates PDGFC transcription via EGR1 - up-regulated by TGFB1 in concert with FGF2 Pathology: - predominant PDGF isoform present in patients with proliferative vitreoretinopathy (PVR); plasmin is the major protease that processes PDGFC in the vitreous of PVR patients - expression increased in patients with uterine leiomyoma - downstream target of EWSR1 fusion proteins, contributing to the Ewing family tumors (EFT) malignant phenotype - the medulloblastoma phenotype is associated with PDGFR alpha expression & activation, with PDGFC as a major player in such endogenous autocrine loop - lower molecular weight form (around 43 kD) is present in patients with papillary thyroid carcinoma

General

glycoprotein receptor

Properties

SIZE: entity length = 345 aa MW = 39 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: signal sequence {1-22} N-glycosylation site {N25} CUB domain {46-163} MOTIF: N-glycosylation site {N55} cysteine residue {C104} MODIFICATION: cysteine residue {C124} cysteine residue {C124} MODIFICATION: cysteine residue {C104} peptide motif {225-226} peptide motif {231-232} peptide motif {234-235} cysteine residue {C250} MODIFICATION: cysteine residue {C294} cysteine residue {C274} MODIFICATION: cysteine residue {C286) (PROBABLE} cysteine residue {C280} MODIFICATION: cysteine residue {C335} cysteine residue {C286} MODIFICATION: cysteine residue {C274) (PROBABLE} cysteine residue {C287} MODIFICATION: cysteine residue {C337} cysteine residue {C294} MODIFICATION: cysteine residue {C250} cysteine residue {C335} MODIFICATION: cysteine residue {C280} cysteine residue {C337} MODIFICATION: cysteine residue {C287}

Database Correlations

UniProt Q9NRA1 PFAM correlations Kegg hsa:5603

References

UniProt :accession Q9NRA1