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Protein

Vascular endothelial growth factor C

Gene

VEGFC

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

Functioni

Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates VEGFR-2 (KDR/FLK1) and VEGFR-3 (FLT4) receptors.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Angiogenesis, Differentiation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000150630-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-194313. VEGF ligand-receptor interactions.
R-HSA-195399. VEGF binds to VEGFR leading to receptor dimerization.
SIGNORiP49767.

Protein family/group databases

TCDBi9.B.88.2.1. the selenoprotein p hydrogen selenide uptake protein (selp) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Vascular endothelial growth factor C
Short name:
VEGF-C
Alternative name(s):
Flt4 ligand
Short name:
Flt4-L
Vascular endothelial growth factor-related protein
Short name:
VRP
Gene namesi
Name:VEGFC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:12682. VEGFC.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Lymphedema, hereditary, 1D (LMPH1D)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment.
See also OMIM:615907

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi227R → S: No proteolytic processing and lower effect on VEGFR-2 and VEGFR-3. 1 Publication1

Organism-specific databases

DisGeNETi7424.
MalaCardsiVEGFC.
MIMi615907. phenotype.
OpenTargetsiENSG00000150630.
Orphaneti79452. Milroy disease.
PharmGKBiPA37304.

Polymorphism and mutation databases

DMDMi1718154.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 312 PublicationsAdd BLAST31
PropeptideiPRO_000002340032 – 111Or 1021 PublicationAdd BLAST80
ChainiPRO_0000023401112 – 227Vascular endothelial growth factor CAdd BLAST116
PropeptideiPRO_0000023402228 – 419Add BLAST192

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi131 ↔ 1731 Publication
Disulfide bondi156Interchain1 Publication
Disulfide bondi162 ↔ 2091 Publication
Disulfide bondi165Interchain1 Publication
Disulfide bondi166 ↔ 2111 Publication
Glycosylationi175N-linked (GlcNAc...)1 Publication1
Glycosylationi205N-linked (GlcNAc...)1 Publication1
Glycosylationi240N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3, but only the fully processed form could activate VEGFR-2. VEGF-C first form an antiparallel homodimer linked by disulfide bonds. Before secretion, a cleavage occurs between Arg-227 and Ser-228 producing a heterotetramer. The next extracellular step of the processing removes the N-terminal propeptide. Finally the mature VEGF-C is composed mostly of two VEGF homology domains (VHDs) bound by non-covalent interactions.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP49767.
PeptideAtlasiP49767.
PRIDEiP49767.

PTM databases

iPTMnetiP49767.
PhosphoSitePlusiP49767.

Miscellaneous databases

PMAP-CutDBP49767.

Expressioni

Tissue specificityi

Spleen, lymph node, thymus, appendix, bone marrow, heart, placenta, ovary, skeletal muscle, prostate, testis, colon and small intestine and fetal liver, lung and kidney, but not in peripheral blood lymphocyte.

Gene expression databases

BgeeiENSG00000150630.
CleanExiHS_VEGFC.
GenevisibleiP49767. HS.

Interactioni

Subunit structurei

Homodimer; non-covalent and antiparallel.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FLT4P359162EBI-3405539,EBI-1005467

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113267. 2 interactors.
DIPiDIP-5738N.
IntActiP49767. 2 interactors.
STRINGi9606.ENSP00000280193.

Structurei

Secondary structure

1419
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi117 – 129Combined sources13
Beta strandi130 – 139Combined sources10
Turni140 – 142Combined sources3
Beta strandi151 – 163Combined sources13
Beta strandi167 – 170Combined sources4
Beta strandi172 – 188Combined sources17
Beta strandi190 – 194Combined sources5
Beta strandi197 – 212Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2X1WX-ray2.70A/B/C/D112-215[»]
2X1XX-ray3.10E112-215[»]
4BSKX-ray4.20C103-215[»]
ProteinModelPortaliP49767.
SMRiP49767.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49767.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati280 – 2951Add BLAST16
Repeati304 – 3192Add BLAST16
Repeati328 – 3433Add BLAST16
Repeati347 – 3624Add BLAST16

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni280 – 3624 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-CAdd BLAST83

Sequence similaritiesi

Belongs to the PDGF/VEGF growth factor family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IFTP. Eukaryota.
ENOG410YGVZ. LUCA.
GeneTreeiENSGT00730000110889.
HOGENOMiHOG000231512.
HOVERGENiHBG073119.
InParanoidiP49767.
KOiK05449.
OMAiTCPRNQP.
OrthoDBiEOG091G07BT.
PhylomeDBiP49767.
TreeFamiTF319554.

Family and domain databases

CDDicd00135. PDGF. 1 hit.
Gene3Di2.10.90.10. 1 hit.
InterProiIPR004153. CXCXC_repeat.
IPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamiPF03128. CXCXC. 2 hits.
PF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P49767-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHLLGFFSVA CSLLAAALLP GPREAPAAAA AFESGLDLSD AEPDAGEATA
60 70 80 90 100
YASKDLEEQL RSVSSVDELM TVLYPEYWKM YKCQLRKGGW QHNREQANLN
110 120 130 140 150
SRTEETIKFA AAHYNTEILK SIDNEWRKTQ CMPREVCIDV GKEFGVATNT
160 170 180 190 200
FFKPPCVSVY RCGGCCNSEG LQCMNTSTSY LSKTLFEITV PLSQGPKPVT
210 220 230 240 250
ISFANHTSCR CMSKLDVYRQ VHSIIRRSLP ATLPQCQAAN KTCPTNYMWN
260 270 280 290 300
NHICRCLAQE DFMFSSDAGD DSTDGFHDIC GPNKELDEET CQCVCRAGLR
310 320 330 340 350
PASCGPHKEL DRNSCQCVCK NKLFPSQCGA NREFDENTCQ CVCKRTCPRN
360 370 380 390 400
QPLNPGKCAC ECTESPQKCL LKGKKFHHQT CSCYRRPCTN RQKACEPGFS
410
YSEEVCRCVP SYWKRPQMS
Length:419
Mass (Da):46,883
Last modified:October 1, 1996 - v1
Checksum:i9F598719DB3E014F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94216 mRNA. Translation: CAA63907.1.
U43142 mRNA. Translation: AAA85214.1.
U58111 mRNA. Translation: AAB02909.1.
AK313879 mRNA. Translation: BAG36605.1.
AC092673 Genomic DNA. No translation available.
AC093801 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04717.1.
BC035212 mRNA. Translation: AAH35212.1.
BC063685 mRNA. Translation: AAH63685.1.
CCDSiCCDS43285.1.
PIRiS69207.
RefSeqiNP_005420.1. NM_005429.4.
UniGeneiHs.435215.

Genome annotation databases

EnsembliENST00000618562; ENSP00000480043; ENSG00000150630.
GeneIDi7424.
KEGGihsa:7424.
UCSCiuc032ufc.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94216 mRNA. Translation: CAA63907.1.
U43142 mRNA. Translation: AAA85214.1.
U58111 mRNA. Translation: AAB02909.1.
AK313879 mRNA. Translation: BAG36605.1.
AC092673 Genomic DNA. No translation available.
AC093801 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04717.1.
BC035212 mRNA. Translation: AAH35212.1.
BC063685 mRNA. Translation: AAH63685.1.
CCDSiCCDS43285.1.
PIRiS69207.
RefSeqiNP_005420.1. NM_005429.4.
UniGeneiHs.435215.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2X1WX-ray2.70A/B/C/D112-215[»]
2X1XX-ray3.10E112-215[»]
4BSKX-ray4.20C103-215[»]
ProteinModelPortaliP49767.
SMRiP49767.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113267. 2 interactors.
DIPiDIP-5738N.
IntActiP49767. 2 interactors.
STRINGi9606.ENSP00000280193.

Protein family/group databases

TCDBi9.B.88.2.1. the selenoprotein p hydrogen selenide uptake protein (selp) family.

PTM databases

iPTMnetiP49767.
PhosphoSitePlusiP49767.

Polymorphism and mutation databases

DMDMi1718154.

Proteomic databases

PaxDbiP49767.
PeptideAtlasiP49767.
PRIDEiP49767.

Protocols and materials databases

DNASUi7424.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000618562; ENSP00000480043; ENSG00000150630.
GeneIDi7424.
KEGGihsa:7424.
UCSCiuc032ufc.2. human.

Organism-specific databases

CTDi7424.
DisGeNETi7424.
GeneCardsiVEGFC.
HGNCiHGNC:12682. VEGFC.
MalaCardsiVEGFC.
MIMi601528. gene.
615907. phenotype.
neXtProtiNX_P49767.
OpenTargetsiENSG00000150630.
Orphaneti79452. Milroy disease.
PharmGKBiPA37304.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFTP. Eukaryota.
ENOG410YGVZ. LUCA.
GeneTreeiENSGT00730000110889.
HOGENOMiHOG000231512.
HOVERGENiHBG073119.
InParanoidiP49767.
KOiK05449.
OMAiTCPRNQP.
OrthoDBiEOG091G07BT.
PhylomeDBiP49767.
TreeFamiTF319554.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000150630-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-194313. VEGF ligand-receptor interactions.
R-HSA-195399. VEGF binds to VEGFR leading to receptor dimerization.
SIGNORiP49767.

Miscellaneous databases

ChiTaRSiVEGFC. human.
EvolutionaryTraceiP49767.
GeneWikiiVascular_endothelial_growth_factor_C.
GenomeRNAii7424.
PMAP-CutDBP49767.
PROiP49767.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150630.
CleanExiHS_VEGFC.
GenevisibleiP49767. HS.

Family and domain databases

CDDicd00135. PDGF. 1 hit.
Gene3Di2.10.90.10. 1 hit.
InterProiIPR004153. CXCXC_repeat.
IPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamiPF03128. CXCXC. 2 hits.
PF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVEGFC_HUMAN
AccessioniPrimary (citable) accession number: P49767
Secondary accession number(s): B2R9Q8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 152 of the entry and version 1 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.