VGFAA_DANRE
ID VGFAA_DANRE Reviewed; 188 AA.
AC O73682; B3DG34; O73822;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Vascular endothelial growth factor A-A;
DE Short=VEGF-A-A;
DE Flags: Precursor;
GN Name=vegfaa; Synonyms=vegf, vegfa;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:AAC41274.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF165), AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo {ECO:0000269|PubMed:9545518};
RX PubMed=9545518; DOI=10.1016/s0167-4781(97)00233-9;
RA Liang D., Xu X., Chin A.J., Balasubramaniyan N.V., Teo M.A.L., Lam T.J.,
RA Weinberg E.S., Ge R.;
RT "Cloning and characterization of vascular endothelial growth factor (VEGF)
RT from zebrafish, Danio rerio.";
RL Biochim. Biophys. Acta 1397:14-20(1998).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF121), FUNCTION, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Embryo {ECO:0000269|PubMed:11578859};
RX PubMed=11578859; DOI=10.1016/s0925-4773(01)00468-3;
RA Liang D., Chang J.R., Chin A.J., Smith A., Kelly C., Weinberg E.S., Ge R.;
RT "The role of vascular endothelial growth factor (VEGF) in vasculogenesis,
RT angiogenesis, and hematopoiesis in zebrafish development.";
RL Mech. Dev. 108:29-43(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM VEGF165).
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KDR AND KDRL.
RX PubMed=17698971; DOI=10.1182/blood-2006-04-016378;
RA Bahary N., Goishi K., Stuckenholz C., Weber G., Leblanc J., Schafer C.A.,
RA Berman S.S., Klagsbrun M., Zon L.I.;
RT "Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase
RT family mediate vascular development in the zebrafish.";
RL Blood 110:3627-3636(2007).
CC -!- FUNCTION: Growth factor active in angiogenesis, vasculogenesis and
CC endothelial cell growth. Induces endothelial cell proliferation,
CC promotes cell migration, inhibits apoptosis, and induces
CC permeabilization of blood vessels. Acts both upstream of kdr and tie1
CC to stimulate endothelial cell differentiation, and upstream of gata1 to
CC stimulate hematopoietic cell differentiation.
CC {ECO:0000250|UniProtKB:P15692, ECO:0000269|PubMed:11578859,
CC ECO:0000269|PubMed:17698971}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Isoform VEGF165
CC binds kdr and kdrl. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17698971}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=VEGF165 {ECO:0000269|PubMed:9545518};
CC IsoId=O73682-1; Sequence=Displayed;
CC Name=VEGF121 {ECO:0000269|PubMed:11578859};
CC IsoId=O73682-2; Sequence=VSP_050737;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in regions associated with
CC active vascularization. From 15-16 hours post-fertilization (hpf),
CC expressed in the anterior forebrain, the mesoderm underlying and
CC lateral to the anterior hindbrain, the mesoderm underlying and lateral
CC to the posterior hindbrain, and in the ventral medial portions of the
CC somites. By 30-36 hpf, expression in the somites is decreased, while
CC strong expression is observed in the region of the developing glomeruli
CC and in the anterior portion of the pronephric ducts, the pharyngeal
CC arches, and the brain. By 72 hpf, expression remains only in the
CC pronephros region.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Present
CC throughout embryonic development, and in adults.
CC {ECO:0000269|PubMed:11578859, ECO:0000269|PubMed:9545518}.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; AF016244; AAC41274.1; -; mRNA.
DR EMBL; AF059661; AAC14713.1; -; mRNA.
DR EMBL; BC162258; AAI62258.1; -; mRNA.
DR EMBL; BC162588; AAI62588.1; -; mRNA.
DR RefSeq; NP_001103819.2; NM_001110349.2. [O73682-2]
DR RefSeq; NP_571483.1; NM_131408.3. [O73682-1]
DR AlphaFoldDB; O73682; -.
DR SMR; O73682; -.
DR STRING; 7955.ENSDARP00000110575; -.
DR PaxDb; O73682; -.
DR Ensembl; ENSDART00000167719; ENSDARP00000133415; ENSDARG00000103542. [O73682-1]
DR GeneID; 30682; -.
DR KEGG; dre:30682; -.
DR CTD; 30682; -.
DR ZFIN; ZDB-GENE-990415-273; vegfaa.
DR eggNOG; ENOG502QVI8; Eukaryota.
DR GeneTree; ENSGT00940000157284; -.
DR HOGENOM; CLU_042996_2_0_1; -.
DR InParanoid; O73682; -.
DR OMA; AMECVPT; -.
DR OrthoDB; 1364454at2759; -.
DR PhylomeDB; O73682; -.
DR TreeFam; TF319554; -.
DR Reactome; R-DRE-114608; Platelet degranulation.
DR Reactome; R-DRE-194313; VEGF ligand-receptor interactions.
DR Reactome; R-DRE-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR SignaLink; O73682; -.
DR PRO; PR:O73682; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 16.
DR Bgee; ENSDARG00000103542; Expressed in mid cerebral vein and 36 other tissues.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0042056; F:chemoattractant activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IMP:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IEA:InterPro.
DR GO; GO:0043183; F:vascular endothelial growth factor receptor 1 binding; IBA:GO_Central.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0007202; P:activation of phospholipase C activity; IDA:ZFIN.
DR GO; GO:0035479; P:angioblast cell migration from lateral mesoderm to midline; IMP:ZFIN.
DR GO; GO:0001525; P:angiogenesis; IDA:ZFIN.
DR GO; GO:0048844; P:artery morphogenesis; IMP:ZFIN.
DR GO; GO:0001568; P:blood vessel development; IMP:ZFIN.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IDA:ZFIN.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:ZFIN.
DR GO; GO:0003319; P:cardioblast migration to the midline involved in heart rudiment formation; IMP:ZFIN.
DR GO; GO:0022009; P:central nervous system vasculogenesis; IMP:ZFIN.
DR GO; GO:0035907; P:dorsal aorta development; IMP:ZFIN.
DR GO; GO:0003262; P:endocardial progenitor cell migration to the midline involved in heart field formation; IGI:ZFIN.
DR GO; GO:0030097; P:hemopoiesis; IDA:ZFIN.
DR GO; GO:0050930; P:induction of positive chemotaxis; IBA:GO_Central.
DR GO; GO:0008045; P:motor neuron axon guidance; IGI:ZFIN.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:ZFIN.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; IBA:GO_Central.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0048793; P:pronephros development; IMP:ZFIN.
DR GO; GO:0043491; P:protein kinase B signaling; IDA:ZFIN.
DR GO; GO:0035477; P:regulation of angioblast cell migration involved in selective angioblast sprouting; IMP:ZFIN.
DR GO; GO:0008016; P:regulation of heart contraction; IMP:ZFIN.
DR GO; GO:1901342; P:regulation of vasculature development; IGI:ZFIN.
DR GO; GO:0009749; P:response to glucose; IDA:ZFIN.
DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:ZFIN.
DR GO; GO:0030878; P:thyroid gland development; IMP:ZFIN.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IGI:ZFIN.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IBA:GO_Central.
DR GO; GO:0001944; P:vasculature development; IMP:ZFIN.
DR GO; GO:0001570; P:vasculogenesis; IDA:ZFIN.
DR GO; GO:0060841; P:venous blood vessel development; IMP:ZFIN.
DR CDD; cd00135; PDGF; 1.
DR Gene3D; 2.10.160.10; -; 1.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR023581; PD_growth_factor_CS.
DR InterPro; IPR000072; PDGF/VEGF_dom.
DR InterPro; IPR027928; VEGF_C.
DR InterPro; IPR036841; VEGF_C_sf.
DR Pfam; PF00341; PDGF; 1.
DR Pfam; PF14554; VEGF_C; 1.
DR SMART; SM00141; PDGF; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR SUPFAM; SSF57593; SSF57593; 1.
DR PROSITE; PS00249; PDGF_1; 1.
DR PROSITE; PS50278; PDGF_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Angiogenesis; Developmental protein; Differentiation;
KW Disulfide bond; Glycoprotein; Growth factor; Mitogen; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..188
FT /note="Vascular endothelial growth factor A-A"
FT /id="PRO_0000023394"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 49..91
FT /evidence="ECO:0000250|UniProtKB:P15692"
FT DISULFID 74
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P15692"
FT DISULFID 80..125
FT /evidence="ECO:0000250|UniProtKB:P15692"
FT DISULFID 83
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P15692"
FT DISULFID 84..127
FT /evidence="ECO:0000250|UniProtKB:P15692"
FT VAR_SEQ 139..182
FT /note="Missing (in isoform VEGF121)"
FT /evidence="ECO:0000303|PubMed:11578859"
FT /id="VSP_050737"
SQ SEQUENCE 188 AA; 21756 MW; FD203334EF365D1E CRC64;
MNLVVYLIQL FLAALLHLSA VKAAHIPKEG GKSKNDVIPF MDVYKKSACK TRELLVDIIQ
EYPDEIEHTY IPSCVVLMRC AGCCNDEALE CVPTETRNVT MEVLRVKQRV SQHNFQLSFT
EHTKCECRPK AEVKAKKENH CEPCSERRKR LYVQDPLTCK CSCKFTQMQC KSRQLELNER
TCRCEKPR
