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Protein

Vascular endothelial growth factor C

Gene

Vegfc

Organism
Rattus norvegicus (Rat)
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 KDR/VEGFR2 and FLT4/VEGFR3 receptors.By similarity

Miscellaneous

Indolinones; MAE87, MAE106 and MAZ51 inhibit VEGF-C induced activation of VEGFR-3.

GO - Molecular functioni

  • chemoattractant activity Source: Ensembl
  • growth factor activity Source: RGD
  • vascular endothelial growth factor receptor 3 binding Source: RGD

GO - Biological processi

  • angiogenesis Source: RGD
  • animal organ morphogenesis Source: Ensembl
  • induction of positive chemotaxis Source: GO_Central
  • morphogenesis of embryonic epithelium Source: Ensembl
  • negative regulation of blood pressure Source: RGD
  • negative regulation of cell proliferation Source: Ensembl
  • positive regulation of angiogenesis Source: GO_Central
  • positive regulation of blood vessel endothelial cell migration Source: RGD
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of cell-matrix adhesion Source: Ensembl
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of endothelial cell proliferation Source: GO_Central
  • positive regulation of epithelial cell proliferation Source: RGD
  • positive regulation of lymphangiogenesis Source: Ensembl
  • positive regulation of mast cell chemotaxis Source: GO_Central
  • positive regulation of neuroblast proliferation Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
  • positive regulation of protein autophosphorylation Source: RGD
  • positive regulation of protein secretion Source: RGD
  • regulation of angiogenesis Source: RGD
  • regulation of vascular endothelial growth factor receptor signaling pathway Source: RGD
  • response to drug Source: RGD
  • response to hypoxia Source: GO_Central
  • vascular endothelial growth factor receptor signaling pathway Source: Ensembl

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-114608. Platelet degranulation.
R-RNO-194313. VEGF ligand-receptor interactions.
R-RNO-195399. VEGF binds to VEGFR leading to receptor dimerization.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi619800. Vegfc.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi152C → S: Inhibits ability to activate VEGFR-2. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31By similarityAdd BLAST31
PropeptideiPRO_000004517532 – 107Sequence analysisAdd BLAST76
ChainiPRO_0000023406108 – 223Vascular endothelial growth factor CAdd BLAST116
PropeptideiPRO_0000023407224 – 415Sequence analysisAdd BLAST192

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi127 ↔ 169By similarity
Disulfide bondi152InterchainBy similarity
Disulfide bondi158 ↔ 205By similarity
Disulfide bondi161InterchainBy similarity
Disulfide bondi162 ↔ 207By similarity
Glycosylationi171N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi201N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi236N-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-223 and Ser-224 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 (By similarity).By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO35757.

PTM databases

PhosphoSitePlusiO35757.

Expressioni

Tissue specificityi

Highly expressed in the lung, ovary, preputial gland and the adrenal gland. Expressed in the post-pubertal mammary glands.2 Publications

Developmental stagei

Increases moderately during pregnancy (2.8-fold increase on day 4) and lactation (1.9-fold increase on day 2).1 Publication

Gene expression databases

BgeeiENSRNOG00000011416.
GenevisibleiO35757. RN.

Interactioni

Subunit structurei

Homodimer; non-covalent and antiparallel. Interacts with FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3 homodimarization and activation.By similarity

GO - Molecular functioni

  • growth factor activity Source: RGD
  • vascular endothelial growth factor receptor 3 binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000015529.

Structurei

3D structure databases

ProteinModelPortaliO35757.
SMRiO35757.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati276 – 2911Add BLAST16
Repeati300 – 3152Add BLAST16
Repeati324 – 3393Add BLAST16
Repeati343 – 3584Add BLAST16

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni276 – 3584 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.
InParanoidiO35757.
KOiK05449.
OMAiTCQCVCK.
OrthoDBiEOG091G07BT.
PhylomeDBiO35757.
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.

O35757-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHLLCFLSLA CSLLAAALIP GPREAPATVA AFESGLGFSE AEPDGGEVKG
60 70 80 90 100
FEGKDLEEQL RSVSSVDELM SVLYPDYWKM YKCQLRKGGW QQPSLNMRTG
110 120 130 140 150
DTVKLAAAHY NTEILKSIDN EWRKTQCMPR EVCIDVGKEF GAATNTFFKP
160 170 180 190 200
PCVSVYRCGG CCNSEGLQCM NTSTGYLSKT LFEITVPLSQ GPKPVTISFA
210 220 230 240 250
NHTSCRCMSK LDVYRQVHSI IRRSLPATLP QCQAANKTCP ANYVWNNYMC
260 270 280 290 300
QCLAQQDFIF YSNVEDDSSN GFHDVCGPNK ELDEDTCQCV CKGGLRPSSC
310 320 330 340 350
GPHKELDRDS CQCVCKNKLF LNSCGANREF DENTCQCVCK RTCPRNQPLN
360 370 380 390 400
PGKCACECTE NTQKCFLKGK KFHHQTCSCY RRPCTNRLKH CDPGLSFSEE
410
VCRCVPSYWK RPHLN
Length:415
Mass (Da):46,397
Last modified:December 20, 2005 - v2
Checksum:i1EB677F5B260A525
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY032729 mRNA. Translation: AAK96009.1.
AF010302 mRNA. Translation: AAB63248.1.
RefSeqiNP_446105.1. NM_053653.1.
UniGeneiRn.6913.

Genome annotation databases

EnsembliENSRNOT00000015529; ENSRNOP00000015529; ENSRNOG00000011416.
GeneIDi114111.
KEGGirno:114111.

Similar proteinsi

Entry informationi

Entry nameiVEGFC_RAT
AccessioniPrimary (citable) accession number: O35757
Secondary accession number(s): Q91ZE3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: December 20, 2005
Last modified: August 30, 2017
This is version 119 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families