VEGFC_HUMAN
ID VEGFC_HUMAN Reviewed; 419 AA.
AC P49767; B2R9Q8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 185.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 103-120.
RX PubMed=8617204; DOI=10.1002/j.1460-2075.1996.tb00359.x;
RA Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E.,
RA Saksela O., Kalkkinen N., Alitalo K.;
RT "A novel vascular endothelial growth factor, VEGF-C, is a ligand for the
RT Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.";
RL EMBO J. 15:290-298(1996).
RN [2]
RP ERRATUM OF PUBMED:8617204.
RX PubMed=8612600; DOI=10.1002/j.1460-2075.1996.tb00521.x;
RA Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E.,
RA Saksela O., Kalkkinen N., Alitalo K.;
RL EMBO J. 15:1751-1751(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Glial tumor;
RX PubMed=8700872; DOI=10.1073/pnas.93.5.1988;
RA Lee J., Gray A., Yuan J., Luoh S.-M., Avraham H., Wood W.I.;
RT "Vascular endothelial growth factor-related protein: a ligand and specific
RT activator of the tyrosine kinase receptor Flt4.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1988-1992(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin, and Urinary bladder;
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).
RN [9]
RP PROTEIN SEQUENCE OF 32-41; 112-121 AND 228-233, AND MUTAGENESIS OF ARG-227.
RX PubMed=9233800; DOI=10.1093/emboj/16.13.3898;
RA Joukov V., Sorsa T., Kumar V., Jeltsch M., Claesson-Welsh L., Cao Y.,
RA Saksela O., Kalkkinen N., Alitalo K.;
RT "Proteolytic processing regulates receptor specificity and activity of
RT VEGF-C.";
RL EMBO J. 16:3898-3911(1997).
RN [10]
RP PROTEIN SEQUENCE OF 32-46.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [11]
RP INVOLVEMENT IN LMPHM4.
RX PubMed=23410910; DOI=10.1161/circresaha.113.300350;
RA Gordon K., Schulte D., Brice G., Simpson M.A., Roukens M.G., van Impel A.,
RA Connell F., Kalidas K., Jeffery S., Mortimer P.S., Mansour S.,
RA Schulte-Merker S., Ostergaard P.;
RT "Mutation in vascular endothelial growth factor-C, a ligand for vascular
RT endothelial growth factor receptor-3, is associated with autosomal dominant
RT milroy-like primary lymphedema.";
RL Circ. Res. 112:956-960(2013).
RN [12]
RP INVOLVEMENT IN LMPHM4.
RX PubMed=24744435; DOI=10.1136/jmedgenet-2013-102020;
RA Balboa-Beltran E., Fernandez-Seara M.J., Perez-Munuzuri A., Lago R.,
RA Garcia-Magan C., Couce M.L., Sobrino B., Amigo J., Carracedo A., Barros F.;
RT "A novel stop mutation in the vascular endothelial growth factor-C gene
RT (VEGFC) results in Milroy-like disease.";
RL J. Med. Genet. 51:475-478(2014).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 112-215 IN COMPLEX WITH KDR,
RP FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-175 AND ASN-205, AND
RP SUBUNIT.
RX PubMed=20145116; DOI=10.1073/pnas.0914318107;
RA Leppanen V.M., Prota A.E., Jeltsch M., Anisimov A., Kalkkinen N.,
RA Strandin T., Lankinen H., Goldman A., Ballmer-Hofer K., Alitalo K.;
RT "Structural determinants of growth factor binding and specificity by VEGF
RT receptor 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2425-2430(2010).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (4.20 ANGSTROMS) OF 103-215 IN COMPLEX WITH FLT4,
RP GLYCOSYLATION AT ASN-175 AND ASN-205, AND DISULFIDE BOND.
RX PubMed=23878260; DOI=10.1073/pnas.1301415110;
RA Leppanen V.M., Tvorogov D., Kisko K., Prota A.E., Jeltsch M., Anisimov A.,
RA Markovic-Mueller S., Stuttfeld E., Goldie K.N., Ballmer-Hofer K.,
RA Alitalo K.;
RT "Structural and mechanistic insights into VEGF receptor 3 ligand binding
RT and activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:12960-12965(2013).
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:20145116}.
CC -!- SUBUNIT: Homodimer; non-covalent and antiparallel (PubMed:20145116).
CC Interacts with FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3
CC homodimarization and activation (PubMed:23878260).
CC {ECO:0000269|PubMed:20145116, ECO:0000269|PubMed:23878260}.
CC -!- INTERACTION:
CC P49767; P35916: FLT4; NbExp=2; IntAct=EBI-3405539, EBI-1005467;
CC P49767; P35968: KDR; NbExp=6; IntAct=EBI-3405539, EBI-1005487;
CC P49767; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-3405539, EBI-744081;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Spleen, lymph node, thymus, appendix, bone marrow,
CC heart, placenta, ovary, skeletal muscle, prostate, testis, colon and
CC small intestine and fetal liver, lung and kidney, but not in peripheral
CC blood lymphocyte.
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-227 and Ser-228
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.
CC -!- DISEASE: Lymphatic malformation 4 (LMPHM4) [MIM:615907]: A form of
CC primary lymphedema, a disease characterized by swelling of body parts
CC due to developmental anomalies and functional defects of the lymphatic
CC system. Patients with lymphedema may suffer from recurrent local
CC infections. LMPHM4 is an autosomal dominant form with onset at birth or
CC in early childhood. Affected individuals manifest lymphedema of lower
CC limbs with prominent veins, and impaired lymphatic uptake and drainage.
CC Additional features are nail dysplasia, skin hyperkeratosis and
CC papillomatosis. {ECO:0000269|PubMed:23410910,
CC ECO:0000269|PubMed:24744435}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; X94216; CAA63907.1; -; mRNA.
DR EMBL; U43142; AAA85214.1; -; mRNA.
DR EMBL; U58111; AAB02909.1; -; mRNA.
DR EMBL; AK313879; BAG36605.1; -; mRNA.
DR EMBL; AC092673; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX04717.1; -; Genomic_DNA.
DR EMBL; BC035212; AAH35212.1; -; mRNA.
DR EMBL; BC063685; AAH63685.1; -; mRNA.
DR CCDS; CCDS43285.1; -.
DR PIR; S69207; S69207.
DR RefSeq; NP_005420.1; NM_005429.4.
DR PDB; 2X1W; X-ray; 2.70 A; A/B/C/D=112-215.
DR PDB; 2X1X; X-ray; 3.10 A; E=112-215.
DR PDB; 4BSK; X-ray; 4.20 A; C=103-215.
DR PDB; 6TJT; X-ray; 1.31 A; D/F=223-227.
DR PDBsum; 2X1W; -.
DR PDBsum; 2X1X; -.
DR PDBsum; 4BSK; -.
DR PDBsum; 6TJT; -.
DR AlphaFoldDB; P49767; -.
DR SMR; P49767; -.
DR BioGRID; 113267; 4.
DR CORUM; P49767; -.
DR DIP; DIP-5738N; -.
DR IntAct; P49767; 3.
DR STRING; 9606.ENSP00000480043; -.
DR ChEMBL; CHEMBL3714157; -.
DR TCDB; 9.B.88.2.1; the putative selenoprotein p hydrogen selenide uptake protein (selp) family.
DR GlyGen; P49767; 3 sites.
DR iPTMnet; P49767; -.
DR PhosphoSitePlus; P49767; -.
DR BioMuta; VEGFC; -.
DR DMDM; 1718154; -.
DR MassIVE; P49767; -.
DR PaxDb; P49767; -.
DR PeptideAtlas; P49767; -.
DR PRIDE; P49767; -.
DR ProteomicsDB; 56105; -.
DR Antibodypedia; 28667; 982 antibodies from 38 providers.
DR DNASU; 7424; -.
DR Ensembl; ENST00000618562.2; ENSP00000480043.1; ENSG00000150630.4.
DR GeneID; 7424; -.
DR KEGG; hsa:7424; -.
DR MANE-Select; ENST00000618562.2; ENSP00000480043.1; NM_005429.5; NP_005420.1.
DR UCSC; uc032ufc.2; human.
DR CTD; 7424; -.
DR DisGeNET; 7424; -.
DR GeneCards; VEGFC; -.
DR HGNC; HGNC:12682; VEGFC.
DR HPA; ENSG00000150630; Low tissue specificity.
DR MalaCards; VEGFC; -.
DR MIM; 601528; gene.
DR MIM; 615907; phenotype.
DR neXtProt; NX_P49767; -.
DR OpenTargets; ENSG00000150630; -.
DR Orphanet; 569821; Congenital primary lymphedema of Gordon.
DR PharmGKB; PA37304; -.
DR VEuPathDB; HostDB:ENSG00000150630; -.
DR eggNOG; ENOG502QVXE; Eukaryota.
DR GeneTree; ENSGT00940000156167; -.
DR HOGENOM; CLU_061712_1_0_1; -.
DR InParanoid; P49767; -.
DR OMA; TCQCICK; -.
DR OrthoDB; 1364454at2759; -.
DR PhylomeDB; P49767; -.
DR TreeFam; TF319554; -.
DR PathwayCommons; P49767; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-194313; VEGF ligand-receptor interactions.
DR Reactome; R-HSA-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR SignaLink; P49767; -.
DR SIGNOR; P49767; -.
DR BioGRID-ORCS; 7424; 11 hits in 1068 CRISPR screens.
DR ChiTaRS; VEGFC; human.
DR EvolutionaryTrace; P49767; -.
DR GeneWiki; Vascular_endothelial_growth_factor_C; -.
DR GenomeRNAi; 7424; -.
DR Pharos; P49767; Tbio.
DR PRO; PR:P49767; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P49767; protein.
DR Bgee; ENSG00000150630; Expressed in stromal cell of endometrium and 144 other tissues.
DR Genevisible; P49767; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0042056; F:chemoattractant activity; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0043185; F:vascular endothelial growth factor receptor 3 binding; IPI:UniProtKB.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; IEA:Ensembl.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl.
DR GO; GO:0050930; P:induction of positive chemotaxis; IDA:UniProtKB.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IEA:Ensembl.
DR GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IBA:GO_Central.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IEA:Ensembl.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IBA:GO_Central.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:1901492; P:positive regulation of lymphangiogenesis; IEA:Ensembl.
DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; IDA:UniProtKB.
DR GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; IEA:Ensembl.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0050714; P:positive regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; IEA:Ensembl.
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:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0002040; P:sprouting angiogenesis; IBA:GO_Central.
DR GO; GO:0006929; P:substrate-dependent cell migration; TAS:ProtInc.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IDA: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 3D-structure; 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:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:9233800"
FT PROPEP 32..111
FT /note="Or 102"
FT /evidence="ECO:0000269|PubMed:9233800"
FT /id="PRO_0000023400"
FT CHAIN 112..227
FT /note="Vascular endothelial growth factor C"
FT /id="PRO_0000023401"
FT PROPEP 228..419
FT /id="PRO_0000023402"
FT REPEAT 280..295
FT /note="1"
FT REPEAT 304..319
FT /note="2"
FT REPEAT 328..343
FT /note="3"
FT REPEAT 347..362
FT /note="4"
FT REGION 280..362
FT /note="4 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20145116,
FT ECO:0000269|PubMed:23878260"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20145116,
FT ECO:0000269|PubMed:23878260"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 131..173
FT /evidence="ECO:0000269|PubMed:20145116,
FT ECO:0000269|PubMed:23878260"
FT DISULFID 156
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:20145116,
FT ECO:0000269|PubMed:23878260"
FT DISULFID 162..209
FT /evidence="ECO:0000269|PubMed:20145116,
FT ECO:0000269|PubMed:23878260"
FT DISULFID 165
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:20145116,
FT ECO:0000269|PubMed:23878260"
FT DISULFID 166..211
FT /evidence="ECO:0000269|PubMed:20145116,
FT ECO:0000269|PubMed:23878260"
FT MUTAGEN 227
FT /note="R->S: No proteolytic processing and lower effect on
FT VEGFR-2 and VEGFR-3."
FT /evidence="ECO:0000269|PubMed:9233800"
FT HELIX 117..129
FT /evidence="ECO:0007829|PDB:2X1W"
FT STRAND 130..139
FT /evidence="ECO:0007829|PDB:2X1W"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:2X1W"
FT STRAND 151..163
FT /evidence="ECO:0007829|PDB:2X1W"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:2X1W"
FT STRAND 172..188
FT /evidence="ECO:0007829|PDB:2X1W"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:2X1W"
FT STRAND 197..212
FT /evidence="ECO:0007829|PDB:2X1W"
SQ SEQUENCE 419 AA; 46883 MW; 9F598719DB3E014F CRC64;
MHLLGFFSVA CSLLAAALLP GPREAPAAAA AFESGLDLSD AEPDAGEATA YASKDLEEQL
RSVSSVDELM TVLYPEYWKM YKCQLRKGGW QHNREQANLN SRTEETIKFA AAHYNTEILK
SIDNEWRKTQ CMPREVCIDV GKEFGVATNT FFKPPCVSVY RCGGCCNSEG LQCMNTSTSY
LSKTLFEITV PLSQGPKPVT ISFANHTSCR CMSKLDVYRQ VHSIIRRSLP ATLPQCQAAN
KTCPTNYMWN NHICRCLAQE DFMFSSDAGD DSTDGFHDIC GPNKELDEET CQCVCRAGLR
PASCGPHKEL DRNSCQCVCK NKLFPSQCGA NREFDENTCQ CVCKRTCPRN QPLNPGKCAC
ECTESPQKCL LKGKKFHHQT CSCYRRPCTN RQKACEPGFS YSEEVCRCVP SYWKRPQMS
