Q8CI19 (PDGFC_MOUSE) 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=SCDGF
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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

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. Ref.6 Ref.7 Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.22
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. Ref.6 Ref.7
Subcellular location	Cytoplasm. Secreted. Nucleus. Cytoplasmic granule By similarity. Note: Sumoylated form is predominant in the nucleus. Stored in alpha granules in platelets By similarity. Membrane associated when bound to receptors By similarity. Secretion increased by TGFB1. Ref.14 Ref.20
Tissue specificity	Mainly expressed in kidney, testis, liver, heart and brain (at protein level). Highly expressed in airway epithelium, interstitial cells and alveolar macrophages in the lung of mice overexpressing IL13. Expressed in the ovaries. Ref.7 Ref.9 Ref.19 Ref.21 Ref.22
Developmental stage	In stage E9.5-E15.5, widely expressed in the surface ectoderm and later in the germinal layer of the skin, the olfactory and otic placode and their derivatives and the lining of the oral cavity. In stages E14.5-17.5 expressed in ducts connected to epidermis, and in developing epidermal openings. Highly expressed in the early stages of the developing kidney, in the metanephric mesenchymal aggregates, prefusion skeletal muscle, cardiac myoblasts, and in visceral and vascular smooth muscle. Ref.1 Ref.6 Ref.12 Ref.14
Induction	Expression decreased by hypoxia. Up-regulated by EWS-FLI1 transcription factor in tumor-derived cells. Up-regulated by IL13 overexpression in the lung via STAT6 and EGR1. Elevated expression induced by coxsackievirus B3 infection in immunodeficient mice. Overexpressed in the renal fibrosis. Expression in the lung is significantly increased after bleomycin treatment. Down-regulated by retinoic acid and gonadotropin. Ref.8 Ref.11 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21
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 by SUMO1. Ref.20 N-glycosylated By similarity.
Involvement in disease	Involved in the development of myocarditis and subsequent fibrosis in the experimental model of coxsackievirus B3-induced chronic myocarditis. Ref.16
Disruption phenotype	Perinatal lethality. Mice have feeding and respiratory difficulties due to a complete cleft of the secondary palate. However, they have reduction of renal fibrogenesis. Mice lacking both PDGFA and PDGFC develop a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects. Ref.15 Ref.22
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 direct assay Ref.6. Source: MGI cellular response to amino acid stimulus Inferred from direct assay PubMed 20548288. Source: MGI organ morphogenesis Inferred from mutant phenotype Ref.15. Source: MGI platelet-derived growth factor receptor signaling pathway Inferred from direct assay Ref.14. Source: MGI 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 cell proliferation Inferred from direct assay Ref.6PubMed 15234987. Source: MGI positive regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 11940581. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from direct assay Ref.6. Source: MGI 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 platelet-derived growth factor receptor binding Inferred from direct assay Ref.6Ref.14. Source: MGI
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_0000343873
	Chain	? – 345		Platelet-derived growth factor C, receptor-binding form		PRO_0000343874
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
Experimental info
	Sequence conflict	86	1	I → T in AAF91483. Ref.1
	Sequence conflict	103	1	I → L in AAH37696. Ref.5
	Sequence conflict	127	1	G → E in AAF91483. Ref.1
	Sequence conflict	230	1	G → V in AAF91483. Ref.1
	Sequence conflict	269	1	I → R in AAF91483. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8CI19 [UniParc]. Last modified July 22, 2008. Version 2. Checksum: 3A58A1F701B84EA2	FASTA	345	38,741
	10 20 30 40 50 60 MLLLGLLLLT SALAGQRTGT RAESNLSSKL QLSSDKEQNG VQDPRHERVV TISGNGSIHS 70 80 90 100 110 120 PKFPHTYPRN MVLVWRLVAV DENVRIQLTF DERFGLEDPE DDICKYDFVE VEEPSDGSVL 130 140 150 160 170 180 GRWCGSGTVP GKQTSKGNHI RIRFVSDEYF PSEPGFCIHY SIIMPQVTET TSPSVLPPSS 190 200 210 220 230 240 LSLDLLNNAV TAFSTLEELI RYLEPDRWQV DLDSLYKPTW QLLGKAFLYG KKSKVVNLNL 250 260 270 280 290 300 LKEEVKLYSC TPRNFSVSIR EELKRTDTIF WPGCLLVKRC GGNCACCLHN CNECQCVPRK 310 320 330 340 VTKKYHEVLQ LRPKTGVKGL HKSLTDVALE HHEECDCVCR GNAGG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The mouse Pdgfc gene: dynamic expression in embryonic tissues during organogenesis." Ding H., Wu X., Kim I., Tam P.P., Koh G.Y., Nagy A. Mech. Dev. 96:209-213(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE. Strain: Swiss Webster / NIH.
[2]	"cDNA cloning of fallotein from mouse ovary." Tsai Y.-J., Lee R.K.-K., Chen Y.-H., Lin S.-P., Cheng W.T.-K. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ovary.
[3]	"Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha receptor." Gao Z., Hart C., Piddington C., Sheppard P., Shoemaker K., Gilbertson D., West J., O'Hara P.J. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6J.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Cecum, Cerebellum and Head.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Czech II and FVB/N. Tissue: Mammary tumor.
[6]	"PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor." Li X., Ponten A., Aase K., Karlsson L., Abramsson A., Uutela M., Backstrom G., Hellstrom M., Bostrom H., Li H., Soriano P., Betsholtz C., Heldin C.H., Alitalo K., Ostman A., Eriksson U. Nat. Cell Biol. 2:302-309(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, DEVELOPMENTAL STAGE.
[7]	"Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor." Gilbertson D.G., Duff M.E., West J.W., Kelly J.D., Sheppard P.O., Hofstrand P.D., Gao Z., Shoemaker K., Bukowski T.R., Moore M., Feldhaus A.L., Humes J.M., Palmer T.E., Hart C.E. J. Biol. Chem. 276:27406-27414(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
[8]	"PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family tumors." Zwerner J.P., May W.A. Oncogene 20:626-633(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[9]	"Expression analysis of PDGF-C in adult and developing mouse tissues." Aase K., Abramsson A., Karlsson L., Betsholtz C., Eriksson U. Mech. Dev. 110:187-191(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Transgenic overexpression of platelet-derived growth factor-C in the mouse heart induces cardiac fibrosis, hypertrophy, and dilated cardiomyopathy." Ponten A., Li X., Thoren P., Aase K., Sjoblom T., Ostman A., Eriksson U. Am. J. Pathol. 163:673-682(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Modulation of PDGF-C and PDGF-D expression during bleomycin-induced lung fibrosis." Zhuo Y., Zhang J., Laboy M., Lasky J.A. Am. J. Physiol. 286:L182-L188(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION BY BLEOMYCIN.
[12]	"PDGF C is a selective alpha platelet-derived growth factor receptor agonist that is highly expressed in platelet alpha granules and vascular smooth muscle." Fang L., Yan Y., Komuves L.G., Yonkovich S., Sullivan C.M., Stringer B., Galbraith S., Lokker N.A., Hwang S.S., Nurden P., Phillips D.R., Giese N.A. Arterioscler. Thromb. Vasc. Biol. 24:787-792(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[13]	"PDGF signaling in cells and mice." Tallquist M., Kazlauskas A. Cytokine Growth Factor Rev. 15:205-213(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[14]	"Tissue plasminogen activator is a potent activator of PDGF-CC." Fredriksson L., Li H., Fieber C., Li X., Eriksson U. EMBO J. 23:3793-3802(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, ACTIVATION BY PROTEOLYTIC CLEAVAGE.
[15]	"A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling." Ding H., Wu X., Bostrom H., Kim I., Wong N., Tsoi B., O'Rourke M., Koh G.Y., Soriano P., Betsholtz C., Hart T.C., Marazita M.L., Field L.L., Tam P.P., Nagy A. Nat. Genet. 36:1111-1116(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[16]	"Linkage between elevated PDGF-C expression and myocardial fibrogenesis in coxsackievirus B3-induced chronic myocarditis." Yang D., Qiu D. Eur. Heart J. 26:642-643(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION BY COXSACKIEVIRUS B3 INFECTION, DISEASE.
[17]	"Structural requirements for activation of latent platelet-derived growth factor CC by tissue plasminogen activator." Fredriksson L., Ehnman M., Fieber C., Eriksson U. J. Biol. Chem. 280:26856-26862(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[18]	"PDGF-C controls proliferation and is down-regulated by retinoic acid in mouse embryonic palatal mesenchymal cells." Han J., Xiao Y., Lin J., Li Y. Birth Defects Res. B Dev. Reprod. Toxicol. 77:438-444(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY RETINOIC ACID.
[19]	"Aberrant expression of PDGF ligands and receptors in the tumor prone ovary of follitropin receptor knockout (FORKO) mouse." Chen X., Aravindakshan J., Yang Y., Tiwari-Pandey R., Sairam M.R. Carcinogenesis 27:903-915(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION BY GONADOTROPIN.
[20]	"Nuclear localisation of endogenous SUMO-1-modified PDGF-C in human thyroid tissue and cell lines." Reigstad L.J., Martinez A., Varhaug J.E., Lillehaug J.R. Exp. Cell Res. 312:782-795(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, SUMOYLATION.
[21]	"Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts." Ingram J.L., Antao-Menezes A., Mangum J.B., Lyght O., Lee P.J., Elias J.A., Bonner J.C. J. Immunol. 177:4141-4148(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION BY IL13.
[22]	"PDGF-C is a proinflammatory cytokine that mediates renal interstitial fibrosis." Eitner F., Bucher E., van Roeyen C., Kunter U., Rong S., Seikrit C., Villa L., Boor P., Fredriksson L., Backstrom G., Eriksson U., Ostman A., Floege J., Ostendorf T. J. Am. Soc. Nephrol. 19:281-289(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF286725 mRNA. Translation: AAF91483.1. AF117608 mRNA. Translation: AAF22516.1. AF266467 mRNA. Translation: AAK58566.1. AK033734 mRNA. Translation: BAC28455.1. AK042767 mRNA. Translation: BAC31358.1. AK052947 mRNA. Translation: BAC35216.1. BC006027 mRNA. Translation: AAH06027.1. BC037696 mRNA. Translation: AAH37696.1.
IPI	IPI00461914.
RefSeq	NP_064355.1. NM_019971.2.
UniGene	Mm.331089.
3D structure databases
HSSP	HSSP built from PDB template 1SZB based on UniProtKB Q9UBP3.
ProteinModelPortal	Q8CI19.
SMR	Q8CI19. Positions 10-198, 236-338.
ModBase	Search...
PTM databases
PhosphoSite	Q8CI19.
Proteomic databases
PRIDE	Q8CI19.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000029652; ENSMUSP00000029652; ENSMUSG00000028019.
GeneID	54635.
KEGG	mmu:54635.
UCSC	uc008poi.1. mouse.
Organism-specific databases
CTD	56034.
MGI	MGI:1859631. Pdgfc.
Phylogenomic databases
eggNOG	NOG74970.
GeneTree	ENSGT00390000005171.
HOGENOM	HOG000261610.
HOVERGEN	HBG057324.
InParanoid	Q8CI19.
KO	K05450.
OMA	HEVLQLK.
OrthoDB	EOG47D9GQ.
Gene expression databases
ArrayExpress	Q8CI19.
Bgee	Q8CI19.
Genevestigator	Q8CI19.
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
ChiTaRS	PDGFC. mouse.
NextBio	311464.
SOURCE	Search...

Entry information

Entry name

PDGFC_MOUSE

Accession

Primary (citable) accession number: Q8CI19
Secondary accession number(s): Q99JM4, Q9JHV8, Q9QY71

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 22, 2008
Last sequence update:	July 22, 2008
Last modified:	May 1, 2013
This is version 75 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program