Q9EQX6 (PDGFC_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Platelet-derived growth factor C
Short name=PDGF-C

Alternative name(s):
Fallotein
Spinal cord-derived growth factor
Short name=rScdfg
VEGF-E

Cleaved into the following 2 chains:

1. Platelet-derived growth factor C, latent form
   Short name=PDGFC latent form
2. Platelet-derived growth factor C, receptor-binding form
   Short name=PDGFC receptor-binding form

Gene names

Name:	Pdgfc
Synonyms:	Scdgf

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	345 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen and chemoattractant for cells of mesenchymal origin. Required for normal skeleton formation during embryonic development, especially for normal development of the craniofacial skeleton and for normal development of the palate. Required for normal skin morphogenesis during embryonic development. Plays an important role in wound healing, where it appears to be involved in three stages: inflammation, proliferation and remodeling. Plays an important role in angiogenesis and blood vessel development. Involved in fibrotic processes, in which transformation of interstitial fibroblasts into myofibroblasts plus collagen deposition occurs. 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 By similarity.
Subunit structure	Homodimer; disulfide-linked. Interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB domain) with PLAT (via kringle domain) By similarity.
Subcellular location	Cytoplasm By similarity. Secreted By similarity. Nucleus By similarity. Cytoplasmic granule By similarity. Note: Sumoylated form is predominant in the nucleus By similarity. Stored in alpha granules in platelets By similarity. Membrane associated when bound to receptors By similarity.
Tissue specificity	Highly expressed in the kidney and adrenal gland. In the kidney, it is expressed in arteriolar smooth muscle cells and in epithelial cells of individual segments (at protein level). Ref.3 Ref.4
Developmental stage	Expressed in the floor plate of the spinal cord at E11 and also in the ventricular zone at E16, but not in adult. In the brain, expression is more significant at E16 than at adult, with high expression in the cortex, pontine area and choroid plexus. Detected in the otocyst at E16. Ref.4 Ref.5 Ref.8
Induction	Up-regulated in mesangial, visceral epithelial, and interstitial cells after predominant injury to these cells. Expression levels increase in hepatic cells undergoing in vitro transdifferentiation, which represents a model for hepatic fibrogenesis. Expression induced by indoxyl sulfate. Expression induced by angiotensin-2 via EGR1 in smooth muscle cells in neonatal but not in adult rats. Ref.3 Ref.6 Ref.7
Post-translational modification	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 and growth factor domains) gives rise to the receptor-binding form. Cleaved by PLAT and PLG By similarity. Sumoylated with SUMO1 By similarity. N-glycosylated By similarity.
Sequence similarities	Belongs to the PDGF/VEGF growth factor family. Contains 1 CUB domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Secreted
Domain	Signal
Molecular function	Developmental protein Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: Compara cellular response to amino acid stimulus Inferred from electronic annotation. Source: Compara organ morphogenesis Inferred from electronic annotation. Source: Compara platelet-derived growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of DNA replication Inferred from electronic annotation. Source: Compara positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: Compara membrane Inferred from electronic annotation. Source: InterPro nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cell surface binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 345	323	Platelet-derived growth factor C, latent form		PRO_0000343875
	Chain	? – 345		Platelet-derived growth factor C, receptor-binding form		PRO_0000343876
Regions
	Domain	46 – 163	118	CUB
Sites
	Site	225 – 226	2	Cleavage By similarity
	Site	231 – 232	2	Cleavage By similarity
	Site	234 – 235	2	Cleavage By similarity
Amino acid modifications
	Glycosylation	25	1	N-linked (GlcNAc...) Potential
	Glycosylation	55	1	N-linked (GlcNAc...) Potential
	Disulfide bond	104 ↔ 124		By similarity
	Disulfide bond	250 ↔ 294		By similarity
	Disulfide bond	274		Interchain (with C-286) By similarity
	Disulfide bond	280 ↔ 335		By similarity
	Disulfide bond	286		Interchain (with C-274) By similarity
	Disulfide bond	287 ↔ 337		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9EQX6 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: F296DA6E9B765D10	FASTA	345	38,734
	10 20 30 40 50 60 MLLLGLLLLT SALAGQRTGT RAESNLSSKL QLSSDKEQNG VQDPRHERVV TISGNGSIHS 70 80 90 100 110 120 PKFPHTYPRN TVLVWRLVAV DENVRIQLTF DERFGLEDPE DDLCKYDFVE VEEPSDGSVL 130 140 150 160 170 180 GRWCGSGTVP GKQTSKGNHI RIRFVSDEYF PSEPGFCIHY SIIMPQVTET TSPSVLPPSA 190 200 210 220 230 240 LSLDLLNNAV TAFSTVEELI RFLEPDRWQI DLDSLYKPTW PLLGKAFLYG KKSKAVNLNL 250 260 270 280 290 300 LKEEVKLYSC TPRNFSVSIR EELKRTDTIF WPGCLLVKRC GGNCACCLHN CNECQCVPRK 310 320 330 340 VTKKYHEVLQ LRPKIGVKGL HKSLTDVALE HHEECDCVCR GNTEG

References

[1]	"Molecular cloning of SCDGF-B, a novel growth factor homologous to SCDGF/PDGF-C/fallotein." Hamada T., Ui-Tei K., Imaki J., Miyata Y. Biochem. Biophys. Res. Commun. 280:733-737(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Kidney.
[2]	"Platelet derived growth factor C (PDGF-C) expression in wound healing." Brown S.A., Coberly D.M., Rohrich R.R., Chao J.J. Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 42-299. Strain: Sprague-Dawley. Tissue: Skin.
[3]	"Expression of a novel PDGF isoform, PDGF-C, in normal and diseased rat kidney." Eitner F., Ostendorf T., Van Roeyen C., Kitahara M., Li X., Aase K., Grone H.J., Eriksson U., Floege J. J. Am. Soc. Nephrol. 13:910-917(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[4]	"The expression of SCDGF/PDGF-C/fallotein and SCDGF-B/PDGF-D in the rat central nervous system." Hamada T., Ui-Tei K., Imaki J., Takahashi F., Onodera H., Mishima T., Miyata Y. Mech. Dev. 112:161-164(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[5]	"Expression of platelet-derived growth factor in the developing cochlea of rats." Lee Y.W., Ozeki M., Juhn S.K., Lin J. Acta Oto-Laryngol. 124:558-562(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[6]	"Expression patterns of PDGF-A, -B, -C and -D and the PDGF-receptors alpha and beta in activated rat hepatic stellate cells (HSC)." Breitkopf K., Roeyen C., Sawitza I., Wickert L., Floege J., Gressner A.M. Cytokine 31:349-357(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY FIBROGENESIS.
[7]	"Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells." Yamamoto H., Tsuruoka S., Ioka T., Ando H., Ito C., Akimoto T., Fujimura A., Asano Y., Kusano E. Kidney Int. 69:1780-1785(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY INDOXYL SULFATE.
[8]	"Angiotensin II induction of PDGF-C expression is mediated by AT1 receptor-dependent Egr-1 transactivation." Sanchez-Guerrero E., Midgley V.C., Khachigian L.M. Nucleic Acids Res. 36:1941-1951(2008) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB033830 mRNA. Translation: BAB19969.1. AF508348 mRNA. Translation: AAM47265.1.
IPI	IPI00190558.
RefSeq	NP_112607.1. NM_031317.1.
UniGene	Rn.211987.
3D structure databases
HSSP	HSSP built from PDB template 1SZB based on UniProtKB Q9UBP3.
ProteinModelPortal	Q9EQX6.
ModBase	Search...
Proteomic databases
PRIDE	Q9EQX6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000015081; ENSRNOP00000015081; ENSRNOG00000010695.
GeneID	79429.
KEGG	rno:79429.
UCSC	RGD:68410. rat.
Organism-specific databases
CTD	56034.
RGD	68410. Pdgfc.
Phylogenomic databases
eggNOG	NOG74970.
GeneTree	ENSGT00390000005171.
HOGENOM	HOG000261610.
HOVERGEN	HBG057324.
InParanoid	Q9EQX6.
KO	K05450.
OMA	HEVLQLK.
OrthoDB	EOG47D9GQ.
Gene expression databases
Genevestigator	Q9EQX6.
Family and domain databases
Gene3D	2.60.120.290. 1 hit.
InterPro	IPR000859. CUB_dom. IPR000072. PD_growth_factor. [Graphical view]
Pfam	PF00431. CUB. 1 hit. PF00341. PDGF. 1 hit. [Graphical view]
SMART	SM00042. CUB. 1 hit. SM00141. PDGF. 1 hit. [Graphical view]
SUPFAM	SSF49854. CUB. 1 hit.
PROSITE	PS01180. CUB. 1 hit. PS00249. PDGF_1. False negative. PS50278. PDGF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	614787.

Entry information

Entry name

PDGFC_RAT

Accession

Primary (citable) accession number: Q9EQX6
Secondary accession number(s): Q8K429

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 22, 2008
Last sequence update:	March 1, 2001
Last modified:	April 3, 2013
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program