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Protein

Vascular endothelial growth factor C

Gene

VEGFC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 KDR/VEGFR2 and FLT4/VEGFR3 receptors.1 Publication

GO - Molecular functioni

  • chemoattractant activity Source: UniProtKB
  • growth factor activity Source: GO_Central
  • vascular endothelial growth factor receptor 3 binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Growth factor, Mitogen
Biological processAngiogenesis, Differentiation

Enzyme and pathway databases

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 putative 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

EuPathDBiHostDB:ENSG00000150630.3
HGNCiHGNC:12682 VEGFC
MIMi601528 gene
neXtProtiNX_P49767

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Chemistry databases

ChEMBLiCHEMBL3714157

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 ↔ 1732 Publications
Disulfide bondi156Interchain2 Publications
Disulfide bondi162 ↔ 2092 Publications
Disulfide bondi165Interchain2 Publications
Disulfide bondi166 ↔ 2112 Publications
Glycosylationi175N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi205N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi240N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi56105

PTM databases

iPTMnetiP49767
PhosphoSitePlusiP49767

Miscellaneous databases

PMAP-CutDBiP49767

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 Expressed in 175 organ(s), highest expression level in layer of synovial tissue
CleanExiHS_VEGFC
GenevisibleiP49767 HS

Interactioni

Subunit structurei

Homodimer; non-covalent and antiparallel (PubMed:20145116). Interacts with FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3 homodimarization and activation (PubMed:23878260).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113267, 2 interactors
CORUMiP49767
DIPiDIP-5738N
IntActiP49767, 3 interactors
STRINGi9606.ENSP00000280193

Structurei

Secondary structure

1419
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiTCQCVCK
OrthoDBiEOG091G07BT
PhylomeDBiP49767
TreeFamiTF319554

Family and domain databases

CDDicd00135 PDGF, 1 hit
Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR004153 CXCXC_repeat
IPR029034 Cystine-knot_cytokine
IPR023581 PD_growth_factor_CS
IPR000072 PDGF/VEGF_dom
PfamiView protein in Pfam
PF03128 CXCXC, 2 hits
PF00341 PDGF, 1 hit
SMARTiView protein in SMART
SM00141 PDGF, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00249 PDGF_1, 1 hit
PS50278 PDGF_2, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiVEGFC_HUMAN
AccessioniPrimary (citable) accession number: P49767
Secondary accession number(s): B2R9Q8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 12, 2018
This is version 162 of the entry and version 1 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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