Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P97953 (VEGFC_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length415 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.1 Ref.2

Subunit structure

Homodimer; non-covalent and antiparallel. Ref.2

Subcellular location

Secreted.

Tissue specificity

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. Ref.1 Ref.2 Ref.3

Developmental stage

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. Ref.1

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-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.

Sequence similarities

Belongs to the PDGF/VEGF growth factor family.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
   Molecular functionDevelopmental protein
Growth factor
Mitogen
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

induction of positive chemotaxis

Inferred from electronic annotation. Source: Ensembl

morphogenesis of embryonic epithelium

Inferred from mutant phenotype PubMed 14634646. Source: MGI

negative regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from direct assay Ref.3. Source: MGI

organ morphogenesis

Inferred from mutant phenotype PubMed 14634646. Source: MGI

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

Inferred from mutant phenotype PubMed 16462734. Source: MGI

positive regulation of cell-matrix adhesion

Inferred from direct assay Ref.3. Source: MGI

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of lymphangiogenesis

Inferred from direct assay PubMed 20133819. Source: MGI

positive regulation of mast cell chemotaxis

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuroblast proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.3. Source: MGI

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

vascular endothelial growth factor receptor signaling pathway

Inferred from direct assay Ref.1. Source: MGI

   Cellular_componentextracellular space

Inferred from direct assay Ref.2. Source: MGI

membrane

Inferred from electronic annotation. Source: InterPro

   Molecular_functionchemoattractant activity

Inferred from electronic annotation. Source: Ensembl

vascular endothelial growth factor receptor 3 binding

Inferred from physical interaction Ref.1Ref.2. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P97953-1)

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.
Isoform 2 (identifier: P97953-2)

Also known as: Vegf-C184;

The sequence of this isoform differs from the canonical sequence as follows:
     181-184: LFEI → VSGS
     185-415: Missing.
Isoform 3 (identifier: P97953-3)

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.
Isoform 4 (identifier: P97953-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 By similarity
Propeptide32 – 10776 Potential
PRO_0000023403
Chain108 – 223116Vascular endothelial growth factor C
PRO_0000023404
Propeptide224 – 415192 Potential
PRO_0000023405

Regions

Repeat276 – 291161
Repeat300 – 315162
Repeat324 – 339163
Repeat343 – 358164
Region276 – 358834 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C

Amino acid modifications

Glycosylation1711N-linked (GlcNAc...) Potential
Glycosylation2011N-linked (GlcNAc...) Potential
Glycosylation2361N-linked (GlcNAc...) Potential
Disulfide bond127 ↔ 169 By similarity
Disulfide bond152Interchain By similarity
Disulfide bond158 ↔ 205 By similarity
Disulfide bond161Interchain By similarity
Disulfide bond162 ↔ 207 By similarity

Natural variations

Alternative sequence50 – 6213AFEGK…EQLRS → LLQKTVCESTEAL in isoform 4.
VSP_053477
Alternative sequence63 – 12967Missing in isoform 4.
VSP_053478
Alternative sequence117 – 12913SIDNE…TQCMP → NVGVAATARGCSA in isoform 3.
VSP_053479
Alternative sequence130 – 18455Missing in isoform 3 and isoform 4.
VSP_053480
Alternative sequence181 – 1844LFEI → VSGS in isoform 2.
VSP_053481
Alternative sequence185 – 415231Missing in isoform 2, isoform 3 and isoform 4.
VSP_053482

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Vegf-C) [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: D9D3DD3CECC659D6

FASTA41546,471
        10         20         30         40         50         60 
MHLLCFLSLA CSLLAAALIP SPREAPATVA AFESGLGFSE AEPDGGEVKA FEGKDLEEQL 

        70         80         90        100        110        120 
RSVSSVDELM SVLYPDYWKM YKCQLRKGGW QQPTLNTRTG DSVKFAAAHY NTEILKSIDN 

       130        140        150        160        170        180 
EWRKTQCMPR EVCIDVGKEF GAATNTFFKP PCVSVYRCGG CCNSEGLQCM NTSTGYLSKT 

       190        200        210        220        230        240 
LFEITVPLSQ GPKPVTISFA NHTSCRCMSK LDVYRQVHSI IRRSLPATLP QCQAANKTCP 

       250        260        270        280        290        300 
TNYVWNNYMC RCLAQQDFIF YSNVEDDSTN GFHDVCGPNK ELDEDTCQCV CKGGLRPSSC 

       310        320        330        340        350        360 
GPHKELDRDS CQCVCKNKLF PNSCGANREF DENTCQCVCK RTCPRNQPLN PGKCACECTE 

       370        380        390        400        410 
NTQKCFLKGK KFHHQTCSCY RRPCANRLKH CDPGLSFSEE VCRCVPSYWK RPHLN 

« Hide

Isoform 2 (Vegf-C184) [UniParc].

Checksum: 244E323EA999A516
Show »

FASTA18420,120
Isoform 3 (Vegf-C129) [UniParc].

Checksum: 83AA659AA707FD1F
Show »

FASTA12913,902
Isoform 4 (Vegf-C62) [UniParc].

Checksum: 08538283DAC3AEB2
Show »

FASTA626,405

References

« Hide 'large scale' references
[1]"VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development."
Kukk E., Lymboussaki A., Taira S., Kaipainen A., Jeltsch M., Joukov V., Alitalo K.
Development 122:3829-3837(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: BALB/c.
[2]"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] (ISOFORM 1), PROTEIN SEQUENCE OF 108-126, FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
Strain: BALB/c.
[3]"Characterization of novel VEGF (vascular endothelial growth factor)-C splicing isoforms from mouse."
Wang Z.G., Puri T.S., Quigg R.J.
Biochem. J. 428:347-354(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), TISSUE SPECIFICITY.
Tissue: Kidney proximal tubule.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Head.
[5]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1).
Strain: FVB/N-3.
Tissue: Mammary tumor.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_033532.1. NM_009506.2.
UniGeneMm.1402.

3D structure databases

ProteinModelPortalP97953.
SMRP97953. Positions 113-211.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204514. 1 interaction.
STRING10090.ENSMUSP00000033919.

PTM databases

PhosphoSiteP97953.

Proteomic databases

PRIDEP97953.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033919; ENSMUSP00000033919; ENSMUSG00000031520. [P97953-1]
GeneID22341.
KEGGmmu:22341.
UCSCuc009lsc.1. mouse. [P97953-1]

Organism-specific databases

CTD7424.
MGIMGI:109124. Vegfc.

Phylogenomic databases

eggNOGNOG79308.
GeneTreeENSGT00730000110889.
HOGENOMHOG000231512.
HOVERGENHBG073119.
InParanoidP97953.
KOK05449.
OMATCPRNQP.
OrthoDBEOG7J17ZS.
PhylomeDBP97953.
TreeFamTF319554.

Gene expression databases

BgeeP97953.
CleanExMM_VEGFC.
GenevestigatorP97953.

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

NextBio302605.
PROP97953.
SOURCESearch...

Entry information

Entry nameVEGFC_MOUSE
AccessionPrimary (citable) accession number: P97953
Secondary accession number(s): C6F5S8 expand/collapse secondary AC list , C6F5S9, C6F5T0, Q543R6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot