VEGFC_MOUSE
ID VEGFC_MOUSE Reviewed; 415 AA.
AC P97953; C6F5S8; C6F5S9; C6F5T0; Q543R6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Vascular endothelial growth factor C;
DE Short=VEGF-C;
DE AltName: Full=Flt4 ligand;
DE Short=Flt4-L;
DE AltName: Full=Vascular endothelial growth factor-related protein;
DE Short=VRP;
DE Flags: Precursor;
GN Name=Vegfc;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ;
RX PubMed=9012504; DOI=10.1242/dev.122.12.3829;
RA Kukk E., Lymboussaki A., Taira S., Kaipainen A., Jeltsch M., Joukov V.,
RA Alitalo K.;
RT "VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a
RT role in lymphatic vascular development.";
RL Development 122:3829-3837(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 108-126,
RP FUNCTION, SUBUNIT, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=9247316; DOI=10.1038/sj.onc.1201191;
RA Fitz L.J., Morris J.C., Towler P., Long A., Burgess P., Greco R., Wang J.,
RA Gassaway R., Nickbarg E., Kovacic S., Ciarletta A., Giannotti J.,
RA Finnerty H., Zollner R., Beier D.R., Leak L.V., Turner K.J., Wood C.R.;
RT "Characterization of murine Flt4 ligand/VEGF-C.";
RL Oncogene 15:613-618(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney proximal tubule;
RX PubMed=20415667; DOI=10.1042/bj20100379;
RA Wang Z.G., Puri T.S., Quigg R.J.;
RT "Characterization of novel VEGF (vascular endothelial growth factor)-C
RT splicing isoforms from mouse.";
RL Biochem. J. 428:347-354(2010).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Growth factor active in angiogenesis, and endothelial cell
CC growth, stimulating their proliferation and migration and also has
CC effects on the permeability of blood vessels. May function in
CC angiogenesis of the venous and lymphatic vascular systems during
CC embryogenesis, and also in the maintenance of differentiated lymphatic
CC endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3
CC receptors. {ECO:0000269|PubMed:9012504, ECO:0000269|PubMed:9247316}.
CC -!- SUBUNIT: Homodimer; non-covalent and antiparallel (PubMed:9247316).
CC Interacts with FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3
CC homodimarization and activation (By similarity).
CC {ECO:0000250|UniProtKB:P49767, ECO:0000269|PubMed:9247316}.
CC -!- INTERACTION:
CC P97953-1; O60462: NRP2; Xeno; NbExp=3; IntAct=EBI-16148671, EBI-12586256;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Vegf-C;
CC IsoId=P97953-1; Sequence=Displayed;
CC Name=2; Synonyms=Vegf-C184;
CC IsoId=P97953-2; Sequence=VSP_053481, VSP_053482;
CC Name=3; Synonyms=Vegf-C129;
CC IsoId=P97953-3; Sequence=VSP_053479, VSP_053480, VSP_053482;
CC Name=4; Synonyms=Vegf-C62;
CC IsoId=P97953-4; Sequence=VSP_053477, VSP_053478, VSP_053480,
CC VSP_053482;
CC -!- TISSUE SPECIFICITY: Expressed in adult heart, brain, spleen, lung,
CC liver, skeletal muscle, kidney, testis and intestine with higher levels
CC in heart, brain and kidney. Isoform 4 levels are very low. Isoform 3 is
CC mostly expressed in liver and has reduced expression level in other
CC tissues. Isoform 2 is mostly expressed in brain and kidney, although a
CC lower level expression in other tissues is also detectable.
CC {ECO:0000269|PubMed:20415667, ECO:0000269|PubMed:9012504,
CC ECO:0000269|PubMed:9247316}.
CC -!- DEVELOPMENTAL STAGE: Expression detected in mesenchymal cells of
CC postimplantation embryos, particularly in the regions where the
CC lymphatic vessels undergo sprouting from embryonic veins, such as the
CC perimetanephric, axillary and jugular regions, and in the developing
CC mesenterium. Also detected between vertebral corpuscles, in lung
CC mesenchyme, in neck region and in developing forehead. Not detected in
CC the blood islands of the yolk sac. {ECO:0000269|PubMed:9012504}.
CC -!- PTM: Undergoes a complex proteolytic maturation which generates a
CC variety of processed secreted forms with increased activity toward
CC VEGFR-3, but only the fully processed form could activate VEGFR-2.
CC VEGF-C first form an antiparallel homodimer linked by disulfide bonds.
CC Before secretion, a cleavage occurs between Arg-223 and Ser-224
CC producing a heterotetramer. The next extracellular step of the
CC processing removes the N-terminal propeptide. Finally the mature VEGF-C
CC is composed mostly of two VEGF homology domains (VHDs) bound by non-
CC covalent interactions (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; U73620; AAC52984.1; -; mRNA.
DR EMBL; U58112; AAB46707.1; -; mRNA.
DR EMBL; EU862553; ACJ54375.1; -; mRNA.
DR EMBL; EU862554; ACJ54376.1; -; mRNA.
DR EMBL; EU862555; ACJ54377.1; -; mRNA.
DR EMBL; AK047844; BAC33172.1; -; mRNA.
DR EMBL; CH466554; EDL35638.1; -; Genomic_DNA.
DR EMBL; BC096377; AAH96377.1; -; mRNA.
DR CCDS; CCDS22306.1; -. [P97953-1]
DR RefSeq; NP_033532.1; NM_009506.2. [P97953-1]
DR AlphaFoldDB; P97953; -.
DR SMR; P97953; -.
DR BioGRID; 204514; 1.
DR DIP; DIP-61403N; -.
DR IntAct; P97953; 2.
DR STRING; 10090.ENSMUSP00000033919; -.
DR GlyGen; P97953; 3 sites.
DR PhosphoSitePlus; P97953; -.
DR MaxQB; P97953; -.
DR PaxDb; P97953; -.
DR PeptideAtlas; P97953; -.
DR PRIDE; P97953; -.
DR ProteomicsDB; 297877; -. [P97953-1]
DR ProteomicsDB; 297878; -. [P97953-2]
DR ProteomicsDB; 297879; -. [P97953-3]
DR Antibodypedia; 28667; 982 antibodies from 38 providers.
DR DNASU; 22341; -.
DR Ensembl; ENSMUST00000033919; ENSMUSP00000033919; ENSMUSG00000031520. [P97953-1]
DR Ensembl; ENSMUST00000210831; ENSMUSP00000148210; ENSMUSG00000031520. [P97953-2]
DR GeneID; 22341; -.
DR KEGG; mmu:22341; -.
DR UCSC; uc009lsc.1; mouse. [P97953-1]
DR UCSC; uc029wsy.1; mouse. [P97953-2]
DR CTD; 7424; -.
DR MGI; MGI:109124; Vegfc.
DR VEuPathDB; HostDB:ENSMUSG00000031520; -.
DR eggNOG; ENOG502QVXE; Eukaryota.
DR GeneTree; ENSGT00940000156167; -.
DR HOGENOM; CLU_061712_1_0_1; -.
DR InParanoid; P97953; -.
DR OMA; TCQCICK; -.
DR OrthoDB; 1364454at2759; -.
DR PhylomeDB; P97953; -.
DR TreeFam; TF319554; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-194313; VEGF ligand-receptor interactions.
DR Reactome; R-MMU-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR BioGRID-ORCS; 22341; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Vegfc; mouse.
DR PRO; PR:P97953; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P97953; protein.
DR Bgee; ENSMUSG00000031520; Expressed in brain blood vessel and 224 other tissues.
DR Genevisible; P97953; MM.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0042056; F:chemoattractant activity; ISO:MGI.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0043185; F:vascular endothelial growth factor receptor 3 binding; IPI:MGI.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0014009; P:glial cell proliferation; IMP:MGI.
DR GO; GO:0050930; P:induction of positive chemotaxis; ISO:MGI.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:MGI.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISO:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:CACAO.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:BHF-UCL.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:CACAO.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IBA:GO_Central.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IMP:MGI.
DR GO; GO:1901492; P:positive regulation of lymphangiogenesis; IDA:BHF-UCL.
DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; ISO:MGI.
DR GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; IDA:CACAO.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISO:MGI.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; ISO:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:CACAO.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:MGI.
DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0002040; P:sprouting angiogenesis; IBA:GO_Central.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IBA:GO_Central.
DR CDD; cd00135; PDGF; 1.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR004153; CXCXC_repeat.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR023581; PD_growth_factor_CS.
DR InterPro; IPR000072; PDGF/VEGF_dom.
DR Pfam; PF03128; CXCXC; 3.
DR Pfam; PF00341; PDGF; 1.
DR SMART; SM00141; PDGF; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00249; PDGF_1; 1.
DR PROSITE; PS50278; PDGF_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Angiogenesis; Cleavage on pair of basic residues;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Growth factor; Mitogen; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000250"
FT PROPEP 32..107
FT /evidence="ECO:0000255"
FT /id="PRO_0000023403"
FT CHAIN 108..223
FT /note="Vascular endothelial growth factor C"
FT /id="PRO_0000023404"
FT PROPEP 224..415
FT /evidence="ECO:0000255"
FT /id="PRO_0000023405"
FT REPEAT 276..291
FT /note="1"
FT REPEAT 300..315
FT /note="2"
FT REPEAT 324..339
FT /note="3"
FT REPEAT 343..358
FT /note="4"
FT REGION 276..358
FT /note="4 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 127..169
FT /evidence="ECO:0000250|UniProtKB:P49767"
FT DISULFID 152
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P49767"
FT DISULFID 158..205
FT /evidence="ECO:0000250|UniProtKB:P49767"
FT DISULFID 161
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P49767"
FT DISULFID 162..207
FT /evidence="ECO:0000250|UniProtKB:P49767"
FT VAR_SEQ 50..62
FT /note="AFEGKDLEEQLRS -> LLQKTVCESTEAL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:20415667"
FT /id="VSP_053477"
FT VAR_SEQ 63..129
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:20415667"
FT /id="VSP_053478"
FT VAR_SEQ 117..129
FT /note="SIDNEWRKTQCMP -> NVGVAATARGCSA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:20415667"
FT /id="VSP_053479"
FT VAR_SEQ 130..184
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:20415667"
FT /id="VSP_053480"
FT VAR_SEQ 181..184
FT /note="LFEI -> VSGS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:20415667"
FT /id="VSP_053481"
FT VAR_SEQ 185..415
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:20415667"
FT /id="VSP_053482"
SQ SEQUENCE 415 AA; 46471 MW; D9D3DD3CECC659D6 CRC64;
MHLLCFLSLA CSLLAAALIP SPREAPATVA AFESGLGFSE AEPDGGEVKA FEGKDLEEQL
RSVSSVDELM SVLYPDYWKM YKCQLRKGGW QQPTLNTRTG DSVKFAAAHY NTEILKSIDN
EWRKTQCMPR EVCIDVGKEF GAATNTFFKP PCVSVYRCGG CCNSEGLQCM NTSTGYLSKT
LFEITVPLSQ GPKPVTISFA NHTSCRCMSK LDVYRQVHSI IRRSLPATLP QCQAANKTCP
TNYVWNNYMC RCLAQQDFIF YSNVEDDSTN GFHDVCGPNK ELDEDTCQCV CKGGLRPSSC
GPHKELDRDS CQCVCKNKLF PNSCGANREF DENTCQCVCK RTCPRNQPLN PGKCACECTE
NTQKCFLKGK KFHHQTCSCY RRPCANRLKH CDPGLSFSEE VCRCVPSYWK RPHLN
