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Protein

Vascular endothelial growth factor C

Gene

Vegfc

Organism
Mus musculus (Mouse)
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.2 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-114608 Platelet degranulation
R-MMU-194313 VEGF ligand-receptor interactions
R-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:109124 Vegfc

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31By similarityAdd BLAST31
PropeptideiPRO_000002340332 – 107Sequence analysisAdd BLAST76
ChainiPRO_0000023404108 – 223Vascular endothelial growth factor CAdd BLAST116
PropeptideiPRO_0000023405224 – 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

MaxQBiP97953
PaxDbiP97953
PeptideAtlasiP97953
PRIDEiP97953

PTM databases

PhosphoSitePlusiP97953

Expressioni

Tissue specificityi

Expressed in adult heart, brain, spleen, lung, liver, skeletal muscle, kidney, testis and intestine with higher levels in heart, brain and kidney. Isoform 4 levels are very low. Isoform 3 is mostly expressed in liver and has reduced expression level in other tissues. Isoform 2 is mostly expressed in brain and kidney, although a lower level expression in other tissues is also detectable.3 Publications

Developmental stagei

Expression detected in mesenchymal cells of postimplantation embryos, particularly in the regions where the lymphatic vessels undergo sprouting from embryonic veins, such as the perimetanephric, axillary and jugular regions, and in the developing mesenterium. Also detected between vertebral corpuscles, in lung mesenchyme, in neck region and in developing forehead. Not detected in the blood islands of the yolk sac.1 Publication

Gene expression databases

BgeeiENSMUSG00000031520
CleanExiMM_VEGFC
GenevisibleiP97953 MM

Interactioni

Subunit structurei

Homodimer; non-covalent and antiparallel (PubMed:9247316). Interacts with FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3 homodimarization and activation (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
NRP2O604623EBI-16148671,EBI-12586256From Homo sapiens.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204514, 1 interactor
DIPiDIP-61403N
IntActiP97953, 2 interactors
STRINGi10090.ENSMUSP00000033919

Structurei

3D structure databases

ProteinModelPortaliP97953
SMRiP97953
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
InParanoidiP97953
KOiK05449
OMAiTCQCVCK
OrthoDBiEOG091G07BT
PhylomeDBiP97953
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

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: P97953-1) [UniParc]FASTAAdd to basket
Also known as: Vegf-C

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
MHLLCFLSLA CSLLAAALIP SPREAPATVA AFESGLGFSE AEPDGGEVKA
60 70 80 90 100
FEGKDLEEQL RSVSSVDELM SVLYPDYWKM YKCQLRKGGW QQPTLNTRTG
110 120 130 140 150
DSVKFAAAHY NTEILKSIDN EWRKTQCMPR EVCIDVGKEF GAATNTFFKP
160 170 180 190 200
PCVSVYRCGG CCNSEGLQCM NTSTGYLSKT LFEITVPLSQ GPKPVTISFA
210 220 230 240 250
NHTSCRCMSK LDVYRQVHSI IRRSLPATLP QCQAANKTCP TNYVWNNYMC
260 270 280 290 300
RCLAQQDFIF YSNVEDDSTN GFHDVCGPNK ELDEDTCQCV CKGGLRPSSC
310 320 330 340 350
GPHKELDRDS CQCVCKNKLF PNSCGANREF DENTCQCVCK RTCPRNQPLN
360 370 380 390 400
PGKCACECTE NTQKCFLKGK KFHHQTCSCY RRPCANRLKH CDPGLSFSEE
410
VCRCVPSYWK RPHLN
Length:415
Mass (Da):46,471
Last modified:May 1, 1997 - v1
Checksum:iD9D3DD3CECC659D6
GO
Isoform 2 (identifier: P97953-2) [UniParc]FASTAAdd to basket
Also known as: Vegf-C184

The sequence of this isoform differs from the canonical sequence as follows:
     181-184: LFEI → VSGS
     185-415: Missing.

Show »
Length:184
Mass (Da):20,120
Checksum:i244E323EA999A516
GO
Isoform 3 (identifier: P97953-3) [UniParc]FASTAAdd to basket
Also known as: Vegf-C129

The sequence of this isoform differs from the canonical sequence as follows:
     117-129: SIDNEWRKTQCMP → NVGVAATARGCSA
     130-184: Missing.
     185-415: Missing.

Show »
Length:129
Mass (Da):13,902
Checksum:i83AA659AA707FD1F
GO
Isoform 4 (identifier: P97953-4) [UniParc]FASTAAdd to basket
Also known as: Vegf-C62

The sequence of this isoform differs from the canonical sequence as follows:
     50-62: AFEGKDLEEQLRS → LLQKTVCESTEAL
     63-129: Missing.
     130-184: Missing.
     185-415: Missing.

Show »
Length:62
Mass (Da):6,405
Checksum:i08538283DAC3AEB2
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05347750 – 62AFEGK…EQLRS → LLQKTVCESTEAL in isoform 4. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_05347863 – 129Missing in isoform 4. 1 PublicationAdd BLAST67
Alternative sequenceiVSP_053479117 – 129SIDNE…TQCMP → NVGVAATARGCSA in isoform 3. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_053480130 – 184Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_053481181 – 184LFEI → VSGS in isoform 2. 1 Publication4
Alternative sequenceiVSP_053482185 – 415Missing in isoform 2, isoform 3 and isoform 4. 1 PublicationAdd BLAST231

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73620 mRNA Translation: AAC52984.1
U58112 mRNA Translation: AAB46707.1
EU862553 mRNA Translation: ACJ54375.1
EU862554 mRNA Translation: ACJ54376.1
EU862555 mRNA Translation: ACJ54377.1
AK047844 mRNA Translation: BAC33172.1
CH466554 Genomic DNA Translation: EDL35638.1
BC096377 mRNA Translation: AAH96377.1
CCDSiCCDS22306.1 [P97953-1]
RefSeqiNP_033532.1, NM_009506.2 [P97953-1]
UniGeneiMm.1402

Genome annotation databases

EnsembliENSMUST00000033919; ENSMUSP00000033919; ENSMUSG00000031520 [P97953-1]
ENSMUST00000210831; ENSMUSP00000148210; ENSMUSG00000031520 [P97953-2]
GeneIDi22341
KEGGimmu:22341
UCSCiuc009lsc.1 mouse [P97953-1]
uc029wsy.1 mouse [P97953-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiVEGFC_MOUSE
AccessioniPrimary (citable) accession number: P97953
Secondary accession number(s): C6F5S8
, C6F5S9, C6F5T0, Q543R6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: June 20, 2018
This is version 145 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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