VEGFD_RAT
ID VEGFD_RAT Reviewed; 326 AA.
AC O35251; Q91ZE4;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 25-MAY-2022, entry version 123.
DE RecName: Full=Vascular endothelial growth factor D {ECO:0000312|RGD:620695};
DE Short=VEGF-D;
DE AltName: Full=c-Fos-induced growth factor;
DE Short=FIGF;
DE Flags: Precursor;
GN Name=Vegfd {ECO:0000312|RGD:620695}; Synonyms=Figf;
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-141.
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].
RC STRAIN=Sprague-Dawley;
RA Yamada Y., Hirata Y., Nezu J., Shimane M.;
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Growth factor active in angiogenesis, lymphangiogenesis and
CC endothelial cell growth, stimulating their proliferation and migration
CC and also has effects on the permeability of blood vessels. May function
CC in the formation 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 VEGFR-3 (Flt4) receptor (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; non-covalent and antiparallel. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the spleen, kidney, lung,
CC tongue, ovary and mammary gland. {ECO:0000269|PubMed:11683876}.
CC -!- PTM: Undergoes a complex proteolytic maturation which generates a
CC variety of processed secreted forms with increased activity toward
CC VEGFR-3 and VEGFR-2. VEGF-D first form an antiparallel homodimer linked
CC by disulfide bonds before secretion. The fully processed VEGF-D is
CC 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-D
CC induced activation of VEGFR-3.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY032728; AAK96008.1; -; mRNA.
DR EMBL; AF014827; AAB66557.1; -; mRNA.
DR RefSeq; NP_113949.1; NM_031761.1.
DR AlphaFoldDB; O35251; -.
DR SMR; O35251; -.
DR STRING; 10116.ENSRNOP00000058883; -.
DR GlyGen; O35251; 3 sites.
DR jPOST; O35251; -.
DR PaxDb; O35251; -.
DR GeneID; 360457; -.
DR KEGG; rno:360457; -.
DR UCSC; RGD:620695; rat.
DR CTD; 2277; -.
DR RGD; 620695; Vegfd.
DR eggNOG; ENOG502QVIH; Eukaryota.
DR InParanoid; O35251; -.
DR OrthoDB; 1364454at2759; -.
DR PRO; PR:O35251; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0043185; F:vascular endothelial growth factor receptor 3 binding; ISO:RGD.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IMP:RGD.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; ISO:RGD.
DR GO; GO:0050930; P:induction of positive chemotaxis; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; TAS:RGD.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:RGD.
DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; ISO:RGD.
DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; IMP:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; IEP:RGD.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:RGD.
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; 1.
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..21
FT /evidence="ECO:0000255"
FT PROPEP 22..93
FT /evidence="ECO:0000255"
FT /id="PRO_0000023414"
FT CHAIN 94..210
FT /note="Vascular endothelial growth factor D"
FT /id="PRO_0000023415"
FT PROPEP 211..326
FT /evidence="ECO:0000255"
FT /id="PRO_0000023416"
FT REPEAT 227..242
FT /note="1; approximate"
FT REPEAT 263..278
FT /note="2"
FT REPEAT 282..298
FT /note="3"
FT REPEAT 306..317
FT /note="4; truncated"
FT REGION 227..317
FT /note="4 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 116..158
FT /evidence="ECO:0000250"
FT DISULFID 141
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 147..194
FT /evidence="ECO:0000250"
FT DISULFID 150
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 151..196
FT /evidence="ECO:0000250"
FT MUTAGEN 141
FT /note="C->S: Inhibits ability to activate VEGFR-2 and
FT VEGFR-3."
FT /evidence="ECO:0000269|PubMed:11683876"
FT CONFLICT 24
FT /note="I -> S (in Ref. 1; AAK96008)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="L -> F (in Ref. 1; AAK96008)"
FT /evidence="ECO:0000305"
FT CONFLICT 54
FT /note="T -> S (in Ref. 1; AAK96008)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 326 AA; 37113 MW; 1261AFA373596C00 CRC64;
MYGEWAAVNI LMMSYVYLVQ GFSIEHRAVK DVSLERSSRS VLERSEQQIR AASTLEELLQ
VAHSEDWKLW RCRLKLKSLA NVDSRSTSHR STRFAATFYD TETLKVIDEE WQRTQCSPRE
TCVEVASELG KTTNTFFKPP CVNVFRCGGC CNEESVMCMN TSTSYISKQL FEISVPLTSV
PELVPVKIAN HTGCKCLPTG PRHPYSIIRR SIQIPEEDQC PHSKKLCPVD MLWDNTKCKC
VLQDENPLPG TEDHSYLQEP ALCGPHMMFD EDRCECVCKA PCPGDLIQHP ENCSCFECKE
SLESCCQKHK MFHPDTCRSM VFSLSP
