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Protein

Platelet-derived growth factor C

Gene

PDGFC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.12 Publications

GO - Molecular functioni

  • platelet-derived growth factor receptor binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Enzyme and pathway databases

ReactomeiR-HSA-186797. Signaling by PDGF.
SignaLinkiQ9NRA1.

Names & Taxonomyi

Protein namesi
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:
Platelet-derived growth factor C, receptor-binding form
Short name:
PDGFC receptor-binding form
Gene namesi
Name:PDGFC
Synonyms:SCDGF
ORF Names:UNQ174/PRO200
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:8801. PDGFC.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • cytoplasm Source: HPA
  • cytosol Source: UniProtKB-SubCell
  • endoplasmic reticulum lumen Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • Golgi membrane Source: Reactome
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi124C → S: Loss of mitogenic activity of CUB domain in coronary artery smooth muscle cells. 1 Publication1
Mutagenesisi231R → A: Essential for cleavage by PLAT. 1 Publication1
Mutagenesisi232K → A: Not essential for cleavage by PLAT. 1 Publication1
Mutagenesisi234R → A: Not essential for cleavage by PLAT. 1 Publication1

Organism-specific databases

DisGeNETi56034.
OpenTargetsiENSG00000145431.
PharmGKBiPA33146.

Polymorphism and mutation databases

BioMutaiPDGFC.
DMDMi205830662.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000343872? – 345Platelet-derived growth factor C, receptor-binding form
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000034387123 – 345Platelet-derived growth factor C, latent formAdd BLAST323

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi25N-linked (GlcNAc...)Sequence analysis1
Glycosylationi55N-linked (GlcNAc...)By similarity1
Disulfide bondi104 ↔ 124PROSITE-ProRule annotation
Disulfide bondi250 ↔ 2941 Publication
Disulfide bondi274Interchain (with C-286)1 Publication
Disulfide bondi280 ↔ 3351 Publication
Disulfide bondi286Interchain (with C-274)1 Publication
Disulfide bondi287 ↔ 3371 Publication

Post-translational modificationi

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.
Sumoylated with SUMO1.1 Publication
N-glycosylated.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei225 – 226Cleavage2
Sitei231 – 232CleavageSequence analysis2
Sitei234 – 235CleavageSequence analysis2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9NRA1.
PeptideAtlasiQ9NRA1.
PRIDEiQ9NRA1.

PTM databases

iPTMnetiQ9NRA1.
PhosphoSitePlusiQ9NRA1.

Expressioni

Tissue specificityi

Expressed in the fallopian tube, vascular smooth muscle cells in kidney, breast and colon and 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 and in arterial endothelial cells (at protein level). Highly expressed in the platelets, prostate, testis and uterus. Higher expression is observed in uterine leiomyomata. Weaker expression in the spleen, thymus, heart, pancreas, liver, ovary cells and small intestine, and negligible expression in the colon and peripheral blood leukocytes.9 Publications

Developmental stagei

In the fetal kidney, detected in the developing mesangium, ureteric bud epithelium and the undifferentiated mesenchyme (at protein level).1 Publication

Inductioni

Up-regulated by EWS-FLI1 chimeric transcription factor in tumor derived cells. Up-regulated in podocytes and interstitial cells after injury/activation of these cells. FGF2 activates PDGFC transcription via EGR1. Up-regulated by TGFB1 in concert with FGF2.4 Publications

Gene expression databases

BgeeiENSG00000145431.
CleanExiHS_PDGFC.
ExpressionAtlasiQ9NRA1. baseline and differential.
GenevisibleiQ9NRA1. HS.

Organism-specific databases

HPAiHPA009134.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB domain) with PLAT (via kringle domain).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PDGFRAP162342EBI-8833587,EBI-2861522

GO - Molecular functioni

  • platelet-derived growth factor receptor binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi121032. 6 interactors.
DIPiDIP-59339N.
IntActiQ9NRA1. 2 interactors.
STRINGi9606.ENSP00000422464.

Structurei

3D structure databases

ProteinModelPortaliQ9NRA1.
SMRiQ9NRA1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 163CUBPROSITE-ProRule annotationAdd BLAST118

Sequence similaritiesi

Belongs to the PDGF/VEGF growth factor family.Curated
Contains 1 CUB domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IETQ. Eukaryota.
ENOG410XQ91. LUCA.
GeneTreeiENSGT00390000005171.
HOGENOMiHOG000185996.
HOVERGENiHBG057324.
InParanoidiQ9NRA1.
KOiK05450.
OMAiDCVCRGN.
OrthoDBiEOG091G0BFZ.
PhylomeDBiQ9NRA1.
TreeFamiTF332130.

Family and domain databases

CDDicd00041. CUB. 1 hit.
cd00135. PDGF. 1 hit.
Gene3Di2.10.90.10. 1 hit.
2.60.120.290. 1 hit.
InterProiIPR000859. CUB_dom.
IPR029034. Cystine-knot_cytokine.
IPR029817. PDGF-C.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PANTHERiPTHR11633:SF5. PTHR11633:SF5. 1 hit.
PfamiPF00431. CUB. 1 hit.
PF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00042. CUB. 1 hit.
SM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 1 hit.
SSF57501. SSF57501. 1 hit.
PROSITEiPS01180. CUB. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NRA1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSLFGLLLLT SALAGQRQGT QAESNLSSKF QFSSNKEQNG VQDPQHERII
60 70 80 90 100
TVSTNGSIHS PRFPHTYPRN TVLVWRLVAV EENVWIQLTF DERFGLEDPE
110 120 130 140 150
DDICKYDFVE VEEPSDGTIL GRWCGSGTVP GKQISKGNQI RIRFVSDEYF
160 170 180 190 200
PSEPGFCIHY NIVMPQFTEA VSPSVLPPSA LPLDLLNNAI TAFSTLEDLI
210 220 230 240 250
RYLEPERWQL DLEDLYRPTW QLLGKAFVFG RKSRVVDLNL LTEEVRLYSC
260 270 280 290 300
TPRNFSVSIR EELKRTDTIF WPGCLLVKRC GGNCACCLHN CNECQCVPSK
310 320 330 340
VTKKYHEVLQ LRPKTGVRGL HKSLTDVALE HHEECDCVCR GSTGG
Length:345
Mass (Da):39,029
Last modified:July 22, 2008 - v2
Checksum:iCDE9E51F40633E78
GO
Isoform 2 (identifier: Q9NRA1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     244-306: Missing.

Note: No experimental confirmation available.
Show »
Length:282
Mass (Da):31,808
Checksum:i8426CEB8FF9AA45B
GO
Isoform 3 (identifier: Q9NRA1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     155-167: GFCIHYNIVMPQF → SNRGGKIIQLHTS
     168-345: Missing.

Note: No experimental confirmation available.
Show »
Length:167
Mass (Da):18,784
Checksum:i60023851D9FE5E65
GO
Isoform 4 (identifier: Q9NRA1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: Missing.

Note: No experimental confirmation available.
Show »
Length:182
Mass (Da):20,609
Checksum:iF5B9733D3794B1B7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9L → V in AAF80597 (PubMed:10806482).Curated1
Sequence conflicti18Q → R in AAF80597 (PubMed:10806482).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0476061 – 163Missing in isoform 4. 2 PublicationsAdd BLAST163
Alternative sequenceiVSP_034701155 – 167GFCIH…VMPQF → SNRGGKIIQLHTS in isoform 3. CuratedAdd BLAST13
Alternative sequenceiVSP_034702168 – 345Missing in isoform 3. CuratedAdd BLAST178
Alternative sequenceiVSP_034703244 – 306Missing in isoform 2. CuratedAdd BLAST63

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF091434 mRNA. Translation: AAF00049.1.
AB033831 mRNA. Translation: BAB03266.1.
AF244813 mRNA. Translation: AAF80597.1.
AF260738 mRNA. Translation: AAK51637.1.
AM922296 mRNA. Translation: CAP58278.1.
AY358493 mRNA. Translation: AAQ88857.1.
AK300480 mRNA. Translation: BAG62196.1.
AC092608 Genomic DNA. Translation: AAY40906.1.
AC093325 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04874.1.
CH471056 Genomic DNA. Translation: EAX04875.1.
BC136662 mRNA. Translation: AAI36663.1.
CCDSiCCDS3795.1. [Q9NRA1-1]
RefSeqiNP_057289.1. NM_016205.2. [Q9NRA1-1]
XP_016863945.1. XM_017008456.1. [Q9NRA1-2]
UniGeneiHs.570855.

Genome annotation databases

EnsembliENST00000422544; ENSP00000410048; ENSG00000145431. [Q9NRA1-2]
ENST00000502773; ENSP00000422464; ENSG00000145431. [Q9NRA1-1]
GeneIDi56034.
KEGGihsa:56034.
UCSCiuc003iph.3. human. [Q9NRA1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF091434 mRNA. Translation: AAF00049.1.
AB033831 mRNA. Translation: BAB03266.1.
AF244813 mRNA. Translation: AAF80597.1.
AF260738 mRNA. Translation: AAK51637.1.
AM922296 mRNA. Translation: CAP58278.1.
AY358493 mRNA. Translation: AAQ88857.1.
AK300480 mRNA. Translation: BAG62196.1.
AC092608 Genomic DNA. Translation: AAY40906.1.
AC093325 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04874.1.
CH471056 Genomic DNA. Translation: EAX04875.1.
BC136662 mRNA. Translation: AAI36663.1.
CCDSiCCDS3795.1. [Q9NRA1-1]
RefSeqiNP_057289.1. NM_016205.2. [Q9NRA1-1]
XP_016863945.1. XM_017008456.1. [Q9NRA1-2]
UniGeneiHs.570855.

3D structure databases

ProteinModelPortaliQ9NRA1.
SMRiQ9NRA1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121032. 6 interactors.
DIPiDIP-59339N.
IntActiQ9NRA1. 2 interactors.
STRINGi9606.ENSP00000422464.

PTM databases

iPTMnetiQ9NRA1.
PhosphoSitePlusiQ9NRA1.

Polymorphism and mutation databases

BioMutaiPDGFC.
DMDMi205830662.

Proteomic databases

PaxDbiQ9NRA1.
PeptideAtlasiQ9NRA1.
PRIDEiQ9NRA1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000422544; ENSP00000410048; ENSG00000145431. [Q9NRA1-2]
ENST00000502773; ENSP00000422464; ENSG00000145431. [Q9NRA1-1]
GeneIDi56034.
KEGGihsa:56034.
UCSCiuc003iph.3. human. [Q9NRA1-1]

Organism-specific databases

CTDi56034.
DisGeNETi56034.
GeneCardsiPDGFC.
HGNCiHGNC:8801. PDGFC.
HPAiHPA009134.
MIMi608452. gene.
neXtProtiNX_Q9NRA1.
OpenTargetsiENSG00000145431.
PharmGKBiPA33146.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IETQ. Eukaryota.
ENOG410XQ91. LUCA.
GeneTreeiENSGT00390000005171.
HOGENOMiHOG000185996.
HOVERGENiHBG057324.
InParanoidiQ9NRA1.
KOiK05450.
OMAiDCVCRGN.
OrthoDBiEOG091G0BFZ.
PhylomeDBiQ9NRA1.
TreeFamiTF332130.

Enzyme and pathway databases

ReactomeiR-HSA-186797. Signaling by PDGF.
SignaLinkiQ9NRA1.

Miscellaneous databases

ChiTaRSiPDGFC. human.
GeneWikiiPDGFC.
GenomeRNAii56034.
PROiQ9NRA1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145431.
CleanExiHS_PDGFC.
ExpressionAtlasiQ9NRA1. baseline and differential.
GenevisibleiQ9NRA1. HS.

Family and domain databases

CDDicd00041. CUB. 1 hit.
cd00135. PDGF. 1 hit.
Gene3Di2.10.90.10. 1 hit.
2.60.120.290. 1 hit.
InterProiIPR000859. CUB_dom.
IPR029034. Cystine-knot_cytokine.
IPR029817. PDGF-C.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PANTHERiPTHR11633:SF5. PTHR11633:SF5. 1 hit.
PfamiPF00431. CUB. 1 hit.
PF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00042. CUB. 1 hit.
SM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 1 hit.
SSF57501. SSF57501. 1 hit.
PROSITEiPS01180. CUB. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDGFC_HUMAN
AccessioniPrimary (citable) accession number: Q9NRA1
Secondary accession number(s): B4DU34
, B9EGR8, Q4W5M9, Q9UL22
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: July 22, 2008
Last modified: November 30, 2016
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

A lower molecular weight form (around 43 kDa) is present in patients with papillary thyroid carcinoma.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.