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Reviewed, UniProtKB/Swiss-Prot P49767 (VEGFC_HUMAN)

Last modified November 25, 2008. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Vascular endothelial growth factor C
      Short name=VEGF-C
Alternative name(s):
    Vascular endothelial growth factor-related protein
      Short name=VRP
    Flt4 ligand
      Short name=Flt4-L
Gene names
Name: VEGFC
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length419 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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 (Flk1) and VEGFR-3 (Flt4) receptors.

Subunit structure

Homodimer; non-covalent and antiparallel.

Subcellular location

Secreted.

Tissue specificity

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.

Post-translational modification

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 an 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.

Sequence similarities

Belongs to the PDGF/VEGF growth factor family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131
Propeptide32 – 11180Or 102
PRO_0000023400
Chain112 – 227116Vascular endothelial growth factor C
PRO_0000023401
Propeptide228 – 419192
PRO_0000023402

Regions

Repeat280 – 295161
Repeat304 – 319162
Repeat328 – 343163
Repeat347 – 362164
Region280 – 362834 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C

Amino acid modifications

Glycosylation1751N-linked (GlcNAc...) Potential
Glycosylation2051N-linked (GlcNAc...) Potential
Glycosylation2401N-linked (GlcNAc...) Potential
Disulfide bond131 ↔ 173 By similarity
Disulfide bond156Interchain By similarity
Disulfide bond162 ↔ 209 By similarity
Disulfide bond165Interchain By similarity
Disulfide bond166 ↔ 211 By similarity

Experimental info

Mutagenesis2271R → S: No proteolytic processing and lower effect on VEGFR-2 and VEGFR-3

Sequences

Sequence LengthMass (Da)Tools
P49767-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 9F598719DB3E014F

FASTA41946,883
        10         20         30         40         50         60 
MHLLGFFSVA CSLLAAALLP GPREAPAAAA AFESGLDLSD AEPDAGEATA YASKDLEEQL 

        70         80         90        100        110        120 
RSVSSVDELM TVLYPEYWKM YKCQLRKGGW QHNREQANLN SRTEETIKFA AAHYNTEILK 

       130        140        150        160        170        180 
SIDNEWRKTQ CMPREVCIDV GKEFGVATNT FFKPPCVSVY RCGGCCNSEG LQCMNTSTSY 

       190        200        210        220        230        240 
LSKTLFEITV PLSQGPKPVT ISFANHTSCR CMSKLDVYRQ VHSIIRRSLP ATLPQCQAAN 

       250        260        270        280        290        300 
KTCPTNYMWN NHICRCLAQE DFMFSSDAGD DSTDGFHDIC GPNKELDEET CQCVCRAGLR 

       310        320        330        340        350        360 
PASCGPHKEL DRNSCQCVCK NKLFPSQCGA NREFDENTCQ CVCKRTCPRN QPLNPGKCAC 

       370        380        390        400        410 
ECTESPQKCL LKGKKFHHQT CSCYRRPCTN RQKACEPGFS YSEEVCRCVP SYWKRPQMS 

« Hide

References

« Hide 'large scale' references
[1]"A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases."
Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E., Saksela O., Kalkkinen N., Alitalo K.
EMBO J. 15:290-298(1996) [PubMed: 8617204] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 103-120.
[2]Erratum
Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E., Saksela O., Kalkkinen N., Alitalo K.
EMBO J. 15:1751-1751(1996) [PubMed: 8612600] [Abstract]
[3]"Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4."
Lee J., Gray A., Yuan J., Luoh S.-M., Avraham H., Wood W.I.
Proc. Natl. Acad. Sci. U.S.A. 93:1988-1992(1996) [PubMed: 8700872] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE.
Tissue: Glial tumor.
[4]"Characterization of murine Flt4 ligand/VEGF-C."
Fitz L.J., Morris J.C., Towler P., Long A., Burgess P., Greco R., Wang J., Gassaway R., Nickbarg E., Kovacic S., Ciarletta A., Giannotti J., Finnerty H., Zollner R., Beier D.R., Leak L.V., Turner K.J., Wood C.R.
Oncogene 15:613-618(1997) [PubMed: 9247316] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin and Urinary bladder.
[6]"Proteolytic processing regulates receptor specificity and activity of VEGF-C."
Joukov V., Sorsa T., Kumar V., Jeltsch M., Claesson-Welsh L., Cao Y., Saksela O., Kalkkinen N., Alitalo K.
EMBO J. 16:3898-3911(1997) [PubMed: 9233800] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-41; 112-121 AND 228-233, MUTAGENESIS OF ARG-227.
[7]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-46.
+Additional computationally mapped references.

Cross-references

Sequence databases

X94216 mRNA. Translation: CAA63907.1.
U43142 Unassigned DNA. Translation: AAA85214.1.
U58111 mRNA. Translation: AAB02909.1.
BC035212 mRNA. Translation: AAH35212.1.
BC063685 mRNA. Translation: AAH63685.1.
PIRS69207.
RefSeqNP_005420.1.
UniGeneHs.435215

3D structure databases

HSSPHSSP built from PDB template 1FZV based on UniProtKB P49763.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:5738N.
DIP:5747N.

PTM databases

PhosphoSiteP49767.

Genome annotation databases

EnsemblENSG00000150630. Homo sapiens. [Contig view]
GeneID7424.
KEGGhsa:7424.

Organism-specific databases

H-InvDBHIX0024599.
HGNCHGNC:12682. VEGFC.
MIM601528. gene.
PharmGKBPA37304.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP49767.
HOVERGENP49767.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.

Gene expression databases

ArrayExpressP49767.
CleanExHS_VEGFC.
GermOnlineENSG00000150630. Homo sapiens.

Family and domain databases

InterProIPR004153. CXCXC_repeat.
IPR002400. GF_cysknot.
IPR000072. PD_growth_factor.
[Graphical view]
PfamPF03128. CXCXC. 5 hits.
PF00341. PDGF. 1 hit.
[Graphical view]
PRINTSPR00438. GFCYSKNOT.
ProDomPD001629. PD_growth_factor. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00141. PDGF. 1 hit.
[Graphical view]
PROSITEPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio29082.
SOURCESearch...

Entry information

Entry nameVEGFC_HUMAN
AccessionPrimary (citable) accession number: P49767
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 25, 2008
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents