VEGFC_RAT
ID VEGFC_RAT Reviewed; 415 AA.
AC O35757; Q91ZE3;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 139.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND MUTAGENESIS OF CYS-152.
RC STRAIN=Sprague-Dawley;
RX PubMed=11683876; DOI=10.1046/j.1432-1033.2001.02476.x;
RA Kirkin V., Mazitschek R., Krishnan J., Steffen A., Waltenberger J.,
RA Pepper M.S., Giannis A., Sleeman J.P.;
RT "Characterization of indolinones which preferentially inhibit VEGF-C- and
RT VEGF-D-induced activation of VEGFR-3 rather than VEGFR-2.";
RL Eur. J. Biochem. 268:5530-5540(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 153-278, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=10878616;
RX DOI=10.1002/1097-0177(200007)218:3<507::aid-dvdy1012>3.0.co;2-5;
RA Pepper M.S., Baetens D., Mandriota S.J., Di Sanza C., Oikemus S.,
RA Lane T.F., Soriano J.V., Montesano R., Iruela-Arispe M.L.;
RT "Regulation of VEGF and VEGF receptor expression in the rodent mammary
RT gland during pregnancy, lactation, and involution.";
RL Dev. Dyn. 218:507-524(2000).
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:0000250|UniProtKB:P49767}.
CC -!- SUBUNIT: Homodimer; non-covalent and antiparallel. Interacts with
CC FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3
CC homodimarization and activation. {ECO:0000250|UniProtKB:P49767}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highly expressed in the lung, ovary, preputial
CC gland and the adrenal gland. Expressed in the post-pubertal mammary
CC glands. {ECO:0000269|PubMed:10878616, ECO:0000269|PubMed:11683876}.
CC -!- DEVELOPMENTAL STAGE: Increases moderately during pregnancy (2.8-fold
CC increase on day 4) and lactation (1.9-fold increase on day 2).
CC {ECO:0000269|PubMed:10878616}.
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 -!- MISCELLANEOUS: Indolinones; MAE87, MAE106 and MAZ51 inhibit VEGF-C
CC induced activation of VEGFR-3.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; AY032729; AAK96009.1; -; mRNA.
DR EMBL; AF010302; AAB63248.1; -; mRNA.
DR RefSeq; NP_446105.1; NM_053653.1.
DR AlphaFoldDB; O35757; -.
DR SMR; O35757; -.
DR STRING; 10116.ENSRNOP00000015529; -.
DR GlyGen; O35757; 3 sites.
DR PhosphoSitePlus; O35757; -.
DR PaxDb; O35757; -.
DR Ensembl; ENSRNOT00000015529; ENSRNOP00000015529; ENSRNOG00000011416.
DR GeneID; 114111; -.
DR KEGG; rno:114111; -.
DR CTD; 7424; -.
DR RGD; 619800; Vegfc.
DR eggNOG; ENOG502QVXE; Eukaryota.
DR GeneTree; ENSGT00940000156167; -.
DR HOGENOM; CLU_061712_1_0_1; -.
DR InParanoid; O35757; -.
DR OMA; TCQCICK; -.
DR OrthoDB; 1364454at2759; -.
DR PhylomeDB; O35757; -.
DR TreeFam; TF319554; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-194313; VEGF ligand-receptor interactions.
DR Reactome; R-RNO-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR PRO; PR:O35757; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000011416; Expressed in liver and 18 other tissues.
DR Genevisible; O35757; RN.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0042056; F:chemoattractant activity; ISO:RGD.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0043185; F:vascular endothelial growth factor receptor 3 binding; IMP:RGD.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IMP:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl.
DR GO; GO:0050930; P:induction of positive chemotaxis; ISO:RGD.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; ISO:RGD.
DR GO; GO:0045776; P:negative regulation of blood pressure; IMP:RGD.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:RGD.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA: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; IMP:RGD.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:1901492; P:positive regulation of lymphangiogenesis; ISO:RGD.
DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; ISO:RGD.
DR GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; ISO:RGD.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IDA:MGI.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IMP:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:RGD.
DR GO; GO:0045765; P:regulation of angiogenesis; TAS:RGD.
DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; IMP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0002040; P:sprouting angiogenesis; IBA:GO_Central.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
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 Angiogenesis; Cleavage on pair of basic residues; Developmental protein;
KW Differentiation; Disulfide bond; Glycoprotein; Growth factor; Mitogen;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000250"
FT PROPEP 32..107
FT /evidence="ECO:0000255"
FT /id="PRO_0000045175"
FT CHAIN 108..223
FT /note="Vascular endothelial growth factor C"
FT /id="PRO_0000023406"
FT PROPEP 224..415
FT /evidence="ECO:0000255"
FT /id="PRO_0000023407"
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 MUTAGEN 152
FT /note="C->S: Inhibits ability to activate VEGFR-2."
FT /evidence="ECO:0000269|PubMed:11683876"
SQ SEQUENCE 415 AA; 46397 MW; 1EB677F5B260A525 CRC64;
MHLLCFLSLA CSLLAAALIP GPREAPATVA AFESGLGFSE AEPDGGEVKG FEGKDLEEQL
RSVSSVDELM SVLYPDYWKM YKCQLRKGGW QQPSLNMRTG DTVKLAAAHY NTEILKSIDN
EWRKTQCMPR EVCIDVGKEF GAATNTFFKP PCVSVYRCGG CCNSEGLQCM NTSTGYLSKT
LFEITVPLSQ GPKPVTISFA NHTSCRCMSK LDVYRQVHSI IRRSLPATLP QCQAANKTCP
ANYVWNNYMC QCLAQQDFIF YSNVEDDSSN GFHDVCGPNK ELDEDTCQCV CKGGLRPSSC
GPHKELDRDS CQCVCKNKLF LNSCGANREF DENTCQCVCK RTCPRNQPLN PGKCACECTE
NTQKCFLKGK KFHHQTCSCY RRPCTNRLKH CDPGLSFSEE VCRCVPSYWK RPHLN
