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Protein

Vascular endothelial growth factor C

Gene

Vegfc

Organism
Mus musculus (Mouse)
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 VEGFR-2 (KDR/FLK1) and VEGFR-3 (FLT4) receptors.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Angiogenesis, Differentiation

Enzyme and pathway databases

ReactomeiREACT_293283. VEGF binds to VEGFR leading to receptor dimerization.
REACT_307071. Platelet degranulation.
REACT_343634. VEGF ligand-receptor interactions.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:109124. Vegfc.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: BHF-UCL
  • membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131By similarityAdd
BLAST
Propeptidei32 – 10776Sequence AnalysisPRO_0000023403Add
BLAST
Chaini108 – 223116Vascular endothelial growth factor CPRO_0000023404Add
BLAST
Propeptidei224 – 415192Sequence AnalysisPRO_0000023405Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi127 ↔ 169By similarity
Disulfide bondi152 – 152InterchainBy similarity
Disulfide bondi158 ↔ 205By similarity
Disulfide bondi161 – 161InterchainBy similarity
Disulfide bondi162 ↔ 207By similarity
Glycosylationi171 – 1711N-linked (GlcNAc...)Sequence Analysis
Glycosylationi201 – 2011N-linked (GlcNAc...)Sequence Analysis
Glycosylationi236 – 2361N-linked (GlcNAc...)Sequence Analysis

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

PRIDEiP97953.

PTM databases

PhosphoSiteiP97953.

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

BgeeiP97953.
CleanExiMM_VEGFC.
GenevisibleiP97953. MM.

Interactioni

Subunit structurei

Homodimer; non-covalent and antiparallel.1 Publication

Protein-protein interaction databases

BioGridi204514. 1 interaction.
STRINGi10090.ENSMUSP00000033919.

Structurei

3D structure databases

ProteinModelPortaliP97953.
SMRiP97953. Positions 113-211.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati276 – 291161Add
BLAST
Repeati300 – 315162Add
BLAST
Repeati324 – 339163Add
BLAST
Repeati343 – 358164Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni276 – 358834 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-CAdd
BLAST

Sequence similaritiesi

Belongs to the PDGF/VEGF growth factor family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG79308.
GeneTreeiENSGT00730000110889.
HOGENOMiHOG000231512.
HOVERGENiHBG073119.
InParanoidiP97953.
KOiK05449.
OMAiTCPRNQP.
OrthoDBiEOG7J17ZS.
PhylomeDBiP97953.
TreeFamiTF319554.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR004153. CXCXC_repeat.
IPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamiPF03128. CXCXC. 3 hits.
PF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei50 – 6213AFEGK…EQLRS → LLQKTVCESTEAL in isoform 4. 1 PublicationVSP_053477Add
BLAST
Alternative sequencei63 – 12967Missing in isoform 4. 1 PublicationVSP_053478Add
BLAST
Alternative sequencei117 – 12913SIDNE…TQCMP → NVGVAATARGCSA in isoform 3. 1 PublicationVSP_053479Add
BLAST
Alternative sequencei130 – 18455Missing in isoform 3 and isoform 4. 1 PublicationVSP_053480Add
BLAST
Alternative sequencei181 – 1844LFEI → VSGS in isoform 2. 1 PublicationVSP_053481
Alternative sequencei185 – 415231Missing in isoform 2, isoform 3 and isoform 4. 1 PublicationVSP_053482Add
BLAST

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]
GeneIDi22341.
KEGGimmu:22341.
UCSCiuc009lsc.1. mouse. [P97953-1]
uc029wsy.1. mouse. [P97953-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP97953.
SMRiP97953. Positions 113-211.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204514. 1 interaction.
STRINGi10090.ENSMUSP00000033919.

PTM databases

PhosphoSiteiP97953.

Proteomic databases

PRIDEiP97953.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7424.
MGIiMGI:109124. Vegfc.

Phylogenomic databases

eggNOGiNOG79308.
GeneTreeiENSGT00730000110889.
HOGENOMiHOG000231512.
HOVERGENiHBG073119.
InParanoidiP97953.
KOiK05449.
OMAiTCPRNQP.
OrthoDBiEOG7J17ZS.
PhylomeDBiP97953.
TreeFamiTF319554.

Enzyme and pathway databases

ReactomeiREACT_293283. VEGF binds to VEGFR leading to receptor dimerization.
REACT_307071. Platelet degranulation.
REACT_343634. VEGF ligand-receptor interactions.

Miscellaneous databases

NextBioi302605.
PROiP97953.
SOURCEiSearch...

Gene expression databases

BgeeiP97953.
CleanExiMM_VEGFC.
GenevisibleiP97953. MM.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR004153. CXCXC_repeat.
IPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamiPF03128. CXCXC. 3 hits.
PF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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.

Entry informationi

Entry nameiVEGFC_MOUSE
AccessioniPrimary (citable) accession number: P97953
Secondary accession number(s): C6F5S8
, C6F5S9, C6F5T0, Q543R6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: July 22, 2015
This is version 127 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.