ID VEGFD_MOUSE Reviewed; 358 AA. AC P97946; A2AIH3; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 02-SEP-2026, entry version 183. DE RecName: Full=Vascular endothelial growth factor D {ECO:0000312|MGI:MGI:108037}; DE Short=VEGF-D; DE AltName: Full=c-Fos-induced growth factor; DE Short=FIGF; DE Flags: Precursor; GN Name=Vegfd {ECO:0000312|MGI:MGI:108037}; Synonyms=Figf; 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]. RC STRAIN=C57BL/6J; TISSUE=Fibroblast; RX PubMed=8876195; DOI=10.1073/pnas.93.21.11675; RA Orlandini M., Marconcini L., Ferruzzi R., Oliviero S.; RT "Identification of a c-fos-induced gene that is related to the platelet- RT derived growth factor/vascular endothelial growth factor family."; RL Proc. Natl. Acad. Sci. U.S.A. 93:11675-11680(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lung; RX PubMed=9205122; DOI=10.1006/geno.1997.4774; RA Yamada Y., Nezu J., Shimane M., Hirata Y.; RT "Molecular cloning of a novel vascular endothelial growth factor, VEGF-D."; RL Genomics 42:483-488(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Bone, and Limb; 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 [5] RP DEVELOPMENTAL STAGE. RX PubMed=9622638; DOI=10.1016/s0925-4773(98)00049-5; RA Avantaggiato V., Orlandini M., Acampora D., Oliviero S., Simeone A.; RT "Embryonic expression pattern of the murine figf gene, a growth factor RT belonging to platelet-derived growth factor/vascular endothelial growth RT factor family."; RL Mech. Dev. 73:221-224(1998). RN [6] RP RECEPTOR SPECIFICITY. RX PubMed=11279005; DOI=10.1074/jbc.m100097200; RA Baldwin M.E., Catimel B., Nice E.C., Roufail S., Hall N.E., Stenvers K.L., RA Karkkainen M.J., Alitalo K., Stacker S.A., Achen M.G.; RT "The specificity of receptor binding by vascular endothelial growth factor- RT d is different in mouse and man."; RL J. Biol. Chem. 276:19166-19171(2001). 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. CC -!- SUBUNIT: Homodimer; non-covalent and antiparallel. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Highly expressed in fetal and adult lung. CC -!- DEVELOPMENTAL STAGE: Expressed in a dynamic pattern in several body CC structures and organs of the embryo such as limb buds, acoustic CC ganglion, teeth, heart, anterior pituitary as well as lung and kidney CC mesenchyme, liver, derma, and periosteum of the vertebral column. CC {ECO:0000269|PubMed:9622638}. CC -!- INDUCTION: By the transcription factor c-fos. 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 -!- 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; X99572; CAA67892.1; -; mRNA. DR EMBL; D89628; BAA14002.1; -; mRNA. DR EMBL; AL732475; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC080770; AAH80770.1; -; mRNA. DR CCDS; CCDS30521.1; -. DR RefSeq; NP_001295418.1; NM_001308489.2. DR RefSeq; NP_034346.1; NM_010216.3. DR AlphaFoldDB; P97946; -. DR SMR; P97946; -. DR BioGRID; 199673; 3. DR FunCoup; P97946; 1377. DR STRING; 10090.ENSMUSP00000033751; -. DR GlyCosmos; P97946; 3 sites, No reported glycans. DR GlyGen; P97946; 3 sites. DR iPTMnet; P97946; -. DR PhosphoSitePlus; P97946; -. DR PaxDb; 10090-ENSMUSP00000033751; -. DR PeptideAtlas; P97946; -. DR ProteomicsDB; 298278; -. DR Pumba; P97946; -. DR Antibodypedia; 8816; 685 antibodies from 42 providers. DR DNASU; 14205; -. DR Ensembl; ENSMUST00000033751.8; ENSMUSP00000033751.8; ENSMUSG00000031380.11. DR GeneID; 14205; -. DR KEGG; mmu:14205; -. DR UCSC; uc009uvm.1; mouse. DR AGR; MGI:108037; -. DR CTD; 2277; -. DR MGI; MGI:108037; Vegfd. DR VEuPathDB; HostDB:ENSMUSG00000031380; -. DR eggNOG; ENOG502QVIH; Eukaryota. DR GeneTree; ENSGT00940000159726; -. DR HOGENOM; CLU_061712_0_0_1; -. DR InParanoid; P97946; -. DR OMA; IDMLWDN; -. DR OrthoDB; 198735at2759; -. DR PhylomeDB; P97946; -. 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; 14205; 3 hits in 77 CRISPR screens. DR PRO; PR:P97946; -. DR Proteomes; UP000000589; Chromosome X. DR RNAct; P97946; protein. DR Bgee; ENSMUSG00000031380; Expressed in left lung lobe and 187 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; IDA:MGI. DR GO; GO:0016020; C:membrane; IEA:InterPro. DR GO; GO:0042056; F:chemoattractant activity; ISO:GO_Central. DR GO; GO:0008083; F:growth factor activity; IDA:MGI. DR GO; GO:0042802; F:identical protein binding; IPI:MGI. DR GO; GO:0043185; F:vascular endothelial growth factor receptor 3 binding; IDA:MGI. DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; ISO:GO_Central. DR GO; GO:0008283; P:cell population proliferation; IDA:MGI. DR GO; GO:0071542; P:dopaminergic neuron differentiation; IDA:ParkinsonsUK-UCL. DR GO; GO:0050930; P:induction of positive chemotaxis; ISO:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:GO_Central. DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; ISO:GO_Central. DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; ISO:GO_Central. DR GO; GO:0009617; P:response to bacterium; IEP:MGI. DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central. DR GO; GO:0002040; P:sprouting angiogenesis; IBA:GO_Central. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IGI:MGI. DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IBA:GO_Central. DR CDD; cd00135; PDGF; 1. DR FunFam; 2.10.90.10:FF:000021; vascular endothelial growth factor D; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 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 InterPro; IPR050507; PDGF/VEGF_growth_factor. DR PANTHER; PTHR12025; VASCULAR ENDOTHELIAL GROWTH FACTOR; 1. DR PANTHER; PTHR12025:SF11; VASCULAR ENDOTHELIAL GROWTH FACTOR D; 1. DR Pfam; PF03128; CXCXC; 1. DR Pfam; PF00341; PDGF; 1. DR SMART; SM00141; PDGF; 1. DR SUPFAM; SSF57501; Cystine-knot cytokines; 1. DR PROSITE; PS00249; PDGF_1; 1. DR PROSITE; PS50278; PDGF_2; 1. PE 2: Evidence at transcript 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_0000023411" FT CHAIN 94..210 FT /note="Vascular endothelial growth factor D" FT /id="PRO_0000023412" FT PROPEP 211..358 FT /evidence="ECO:0000255" FT /id="PRO_0000023413" 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..323 FT /note="4" FT REGION 227..323 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" SQ SEQUENCE 358 AA; 40909 MW; 6636B17FBF07037C CRC64; MYGEWGMGNI LMMFHVYLVQ GFRSEHGPVK DFSFERSSRS MLERSEQQIR AASSLEELLQ IAHSEDWKLW RCRLKLKSLA SMDSRSASHR STRFAATFYD TETLKVIDEE WQRTQCSPRE TCVEVASELG KTTNTFFKPP CVNVFRCGGC CNEEGVMCMN TSTSYISKQL FEISVPLTSV PELVPVKIAN HTGCKCLPTG PRHPYSIIRR SIQTPEEDEC PHSKKLCPID MLWDNTKCKC VLQDETPLPG TEDHSYLQEP TLCGPHMTFD EDRCECVCKA PCPGDLIQHP ENCSCFECKE SLESCCQKHK IFHPDTCSCE DRCPFHTRTC ASRKPACGKH WRFPKETRAQ GLYSQENP //