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P49767 (VEGFC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:VEGFC
OrganismHomo sapiens (Human) [Reference proteome]
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 (KDR/FLK1) and VEGFR-3 (FLT4) receptors. Ref.11

Subunit structure

Homodimer; non-covalent and antiparallel. Ref.11

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 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.

Sequence similarities

Belongs to the PDGF/VEGF growth factor family.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
   Cellular componentSecreted
   DomainRepeat
Signal
   Molecular functionDevelopmental protein
Growth factor
Mitogen
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

blood coagulation

Traceable author statement. Source: Reactome

induction of positive chemotaxis

Inferred from direct assay PubMed 19275959. Source: UniProtKB

morphogenesis of embryonic epithelium

Inferred from electronic annotation. Source: Ensembl

negative regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

platelet activation

Traceable author statement. Source: Reactome

platelet degranulation

Traceable author statement. Source: Reactome

positive chemotaxis

Inferred from direct assay PubMed 19275959. Source: GOC

positive regulation of blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of cell proliferation

Traceable author statement Ref.1. Source: ProtInc

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of lymphangiogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of mast cell chemotaxis

Inferred from direct assay PubMed 19275959. Source: UniProtKB

positive regulation of neuroblast proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein secretion

Inferred from electronic annotation. Source: Ensembl

regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

substrate-dependent cell migration

Traceable author statement Ref.1. Source: ProtInc

vascular endothelial growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from electronic annotation. Source: InterPro

platelet alpha granule lumen

Traceable author statement. Source: Reactome

   Molecular_functionchemoattractant activity

Inferred from direct assay PubMed 19275959. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FLT4P359162EBI-3405539,EBI-1005467

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Ref.9 Ref.10
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...) Ref.11
Glycosylation2051N-linked (GlcNAc...) Ref.11
Glycosylation2401N-linked (GlcNAc...) Potential
Disulfide bond131 ↔ 173 Ref.11
Disulfide bond156Interchain Ref.11
Disulfide bond162 ↔ 209 Ref.11
Disulfide bond165Interchain Ref.11
Disulfide bond166 ↔ 211 Ref.11

Experimental info

Mutagenesis2271R → S: No proteolytic processing and lower effect on VEGFR-2 and VEGFR-3. Ref.9

Secondary structure

............... 419
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P49767 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Trachea.
[6]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin and Urinary bladder.
[9]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-41; 112-121 AND 228-233, MUTAGENESIS OF ARG-227.
[10]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-46.
[11]"Structural determinants of growth factor binding and specificity by VEGF receptor 2."
Leppanen V.M., Prota A.E., Jeltsch M., Anisimov A., Kalkkinen N., Strandin T., Lankinen H., Goldman A., Ballmer-Hofer K., Alitalo K.
Proc. Natl. Acad. Sci. U.S.A. 107:2425-2430(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 112-215 IN COMPLEX WITH KDR, FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-175 AND ASN-205, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS69207.
RefSeqNP_005420.1. NM_005429.3.
UniGeneHs.435215.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2X1WX-ray2.70A/B/C/D112-215[»]
2X1XX-ray3.10E112-215[»]
4BSKX-ray4.20C103-215[»]
ProteinModelPortalP49767.
SMRP49767. Positions 117-215.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113267. 2 interactions.
DIPDIP-5738N.
IntActP49767. 1 interaction.
STRING9606.ENSP00000280193.

Protein family/group databases

TCDB9.B.88.2.1. the selenoprotein p hydrogen selenide uptake protein (selp) family.

PTM databases

PhosphoSiteP49767.

Polymorphism databases

DMDM1718154.

Proteomic databases

PaxDbP49767.
PRIDEP49767.

Protocols and materials databases

DNASU7424.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000280193; ENSP00000280193; ENSG00000150630.
GeneID7424.
KEGGhsa:7424.
UCSCuc003ius.1. human.

Organism-specific databases

CTD7424.
GeneCardsGC04M177604.
HGNCHGNC:12682. VEGFC.
MIM601528. gene.
neXtProtNX_P49767.
Orphanet79452. Milroy disease.
PharmGKBPA37304.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG79308.
HOGENOMHOG000231512.
HOVERGENHBG073119.
InParanoidP49767.
KOK05449.
OrthoDBEOG7J17ZS.
PhylomeDBP49767.
TreeFamTF319554.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

BgeeP49767.
CleanExHS_VEGFC.
GenevestigatorP49767.

Family and domain databases

InterProIPR004153. CXCXC_repeat.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamPF03128. CXCXC. 3 hits.
PF00341. PDGF. 1 hit.
[Graphical view]
SMARTSM00141. PDGF. 1 hit.
[Graphical view]
PROSITEPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP49767.
GeneWikiVascular_endothelial_growth_factor_C.
GenomeRNAi7424.
NextBio29082.
PMAP-CutDBP49767.
PROP49767.
SOURCESearch...

Entry information

Entry nameVEGFC_HUMAN
AccessionPrimary (citable) accession number: P49767
Secondary accession number(s): B2R9Q8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 4

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