VEGFB_HUMAN
ID VEGFB_HUMAN Reviewed; 207 AA.
AC P49765; Q16528;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Vascular endothelial growth factor B;
DE Short=VEGF-B;
DE AltName: Full=VEGF-related factor;
DE Short=VRF;
DE Flags: Precursor;
GN Name=VEGFB; Synonyms=VRF;
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] (ISOFORMS VEGF-B186 AND VEGF-B167).
RC TISSUE=Fetal brain;
RX PubMed=8919691; DOI=10.1101/gr.6.2.124;
RA Grimmond S., Lagercrantz J., Drinkwater C., Silins G., Townson S.,
RA Pollock P., Gotley D., Carson E., Rakar S., Nordenskjoeld M., Ward L.,
RA Hayward N.K., Weber G.;
RT "Cloning and characterization of a novel human gene related to vascular
RT endothelial growth factor.";
RL Genome Res. 6:124-131(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF-B186).
RC TISSUE=Fibrosarcoma;
RX PubMed=8702615; DOI=10.1074/jbc.271.32.19310;
RA Olofsson B., Pajusola K., von Euler G., Chilov D., Alitalo K., Eriksson U.;
RT "Genomic organization of the mouse and human genes for vascular endothelial
RT growth factor B (VEGF-B) and characterization of a second splice isoform.";
RL J. Biol. Chem. 271:19310-19317(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF-B167).
RX PubMed=8637916; DOI=10.1073/pnas.93.6.2576;
RA Olofsson B., Pajusola K., Kaipainen A., von Euler G., Joukov V.,
RA Saksela O., Orpana A., Pettersson R.F., Alitalo K., Eriksson U.;
RT "Vascular endothelial growth factor B, a novel growth factor for
RT endothelial cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2576-2581(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM VEGF-B186).
RC TISSUE=Tonsil;
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 X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 31-129, DISULFIDE BONDS, AND
RP SUBUNIT.
RX PubMed=16616187; DOI=10.1016/j.jmb.2006.03.002;
RA Iyer S., Scotney P.D., Nash A.D., Ravi Acharya K.;
RT "Crystal structure of human vascular endothelial growth factor-B:
RT identification of amino acids important for receptor binding.";
RL J. Mol. Biol. 359:76-85(2006).
CC -!- FUNCTION: Growth factor for endothelial cells. VEGF-B167 binds heparin
CC and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is
CC regulated by proteolysis.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Can also form heterodimer with
CC VEGF. {ECO:0000269|PubMed:16616187}.
CC -!- INTERACTION:
CC P49765; Q53G59: KLHL12; NbExp=3; IntAct=EBI-2799898, EBI-740929;
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Secreted but remains associated to
CC cells or to the extracellular matrix unless released by heparin.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=VEGF-B186;
CC IsoId=P49765-1; Sequence=Displayed;
CC Name=VEGF-B167;
CC IsoId=P49765-2; Sequence=VSP_004639, VSP_004640;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues except liver. Highest
CC levels found in heart, skeletal muscle and pancreas.
CC -!- PTM: VEGF-B186 is O-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; U43368; AAA91462.1; -; mRNA.
DR EMBL; U43369; AAA91463.1; -; mRNA.
DR EMBL; U52819; AAC50721.1; -; mRNA.
DR EMBL; U48801; AAB06274.1; -; mRNA.
DR EMBL; BC008818; AAH08818.1; -; mRNA.
DR CCDS; CCDS58144.1; -. [P49765-2]
DR CCDS; CCDS8062.1; -. [P49765-1]
DR RefSeq; NP_001230662.1; NM_001243733.1. [P49765-2]
DR RefSeq; NP_003368.1; NM_003377.4. [P49765-1]
DR PDB; 2C7W; X-ray; 2.48 A; A/B=31-129.
DR PDB; 2VWE; X-ray; 3.40 A; A/B=22-196.
DR PDB; 2XAC; X-ray; 2.71 A; A/B=31-129.
DR PDB; 6TKK; X-ray; 1.06 A; B=144-148.
DR PDBsum; 2C7W; -.
DR PDBsum; 2VWE; -.
DR PDBsum; 2XAC; -.
DR PDBsum; 6TKK; -.
DR AlphaFoldDB; P49765; -.
DR SMR; P49765; -.
DR BioGRID; 113266; 36.
DR DIP; DIP-6045N; -.
DR IntAct; P49765; 8.
DR STRING; 9606.ENSP00000311127; -.
DR ChEMBL; CHEMBL3580488; -.
DR DrugBank; DB08885; Aflibercept.
DR DrugCentral; P49765; -.
DR GlyGen; P49765; 1 site, 1 O-linked glycan (1 site).
DR PhosphoSitePlus; P49765; -.
DR BioMuta; VEGFB; -.
DR DMDM; 17380554; -.
DR MassIVE; P49765; -.
DR PaxDb; P49765; -.
DR PeptideAtlas; P49765; -.
DR PRIDE; P49765; -.
DR ProteomicsDB; 56103; -. [P49765-1]
DR ProteomicsDB; 56104; -. [P49765-2]
DR ABCD; P49765; 1 sequenced antibody.
DR Antibodypedia; 15308; 707 antibodies from 36 providers.
DR DNASU; 7423; -.
DR Ensembl; ENST00000309422.7; ENSP00000311127.2; ENSG00000173511.10. [P49765-1]
DR Ensembl; ENST00000426086.3; ENSP00000401550.2; ENSG00000173511.10. [P49765-2]
DR GeneID; 7423; -.
DR KEGG; hsa:7423; -.
DR MANE-Select; ENST00000309422.7; ENSP00000311127.2; NM_003377.5; NP_003368.1.
DR UCSC; uc001nyx.4; human. [P49765-1]
DR CTD; 7423; -.
DR DisGeNET; 7423; -.
DR GeneCards; VEGFB; -.
DR HGNC; HGNC:12681; VEGFB.
DR HPA; ENSG00000173511; Low tissue specificity.
DR MIM; 601398; gene.
DR neXtProt; NX_P49765; -.
DR OpenTargets; ENSG00000173511; -.
DR PharmGKB; PA37303; -.
DR VEuPathDB; HostDB:ENSG00000173511; -.
DR eggNOG; ENOG502SU5Y; Eukaryota.
DR GeneTree; ENSGT00940000161844; -.
DR HOGENOM; CLU_1331530_0_0_1; -.
DR InParanoid; P49765; -.
DR OMA; PRCTQRH; -.
DR PhylomeDB; P49765; -.
DR TreeFam; TF319554; -.
DR PathwayCommons; P49765; -.
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; P49765; -.
DR SIGNOR; P49765; -.
DR BioGRID-ORCS; 7423; 12 hits in 1075 CRISPR screens.
DR ChiTaRS; VEGFB; human.
DR EvolutionaryTrace; P49765; -.
DR GeneWiki; Vascular_endothelial_growth_factor_B; -.
DR GenomeRNAi; 7423; -.
DR Pharos; P49765; Tclin.
DR PRO; PR:P49765; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P49765; protein.
DR Bgee; ENSG00000173511; Expressed in apex of heart and 161 other tissues.
DR ExpressionAtlas; P49765; baseline and differential.
DR Genevisible; P49765; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
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:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0043183; F:vascular endothelial growth factor receptor 1 binding; IPI:UniProtKB.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl.
DR GO; GO:0060976; P:coronary vasculature development; IEA:Ensembl.
DR GO; GO:0050930; P:induction of positive chemotaxis; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IBA:GO_Central.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0035470; P:positive regulation of vascular wound healing; IDA:UniProtKB.
DR GO; GO:0006493; P:protein O-linked glycosylation; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IBA:GO_Central.
DR CDD; cd00135; PDGF; 1.
DR DisProt; DP02417; -.
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 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; Alternative splicing; Disulfide bond; Glycoprotein;
KW Growth factor; Heparin-binding; Mitogen; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..207
FT /note="Vascular endothelial growth factor B"
FT /id="PRO_0000023398"
FT REGION 122..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..143
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 47..89
FT /evidence="ECO:0000269|PubMed:16616187"
FT DISULFID 72
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:16616187"
FT DISULFID 78..122
FT /evidence="ECO:0000269|PubMed:16616187"
FT DISULFID 81
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:16616187"
FT DISULFID 82..124
FT /evidence="ECO:0000269|PubMed:16616187"
FT VAR_SEQ 137..188
FT /note="RAATPHHRPQPRSVPGWDSAPGAPSPADITHPTPAPGPSAHAAPSTTSALTP
FT -> SPRPLCPRCTQHHQRPDPRTCRCRCRRRSFLRCQGRGLELNPDTCRCRKLRR (in
FT isoform VEGF-B167)"
FT /evidence="ECO:0000303|PubMed:8637916,
FT ECO:0000303|PubMed:8919691"
FT /id="VSP_004639"
FT VAR_SEQ 189..207
FT /note="Missing (in isoform VEGF-B167)"
FT /evidence="ECO:0000303|PubMed:8637916,
FT ECO:0000303|PubMed:8919691"
FT /id="VSP_004640"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:2XAC"
FT HELIX 38..45
FT /evidence="ECO:0007829|PDB:2C7W"
FT STRAND 46..55
FT /evidence="ECO:0007829|PDB:2C7W"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:2XAC"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:2XAC"
FT STRAND 66..81
FT /evidence="ECO:0007829|PDB:2C7W"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:2C7W"
FT STRAND 88..105
FT /evidence="ECO:0007829|PDB:2C7W"
FT STRAND 108..125
FT /evidence="ECO:0007829|PDB:2C7W"
SQ SEQUENCE 207 AA; 21602 MW; EDE4B1C0DFDAD6BC CRC64;
MSPLLRRLLL AALLQLAPAQ APVSQPDAPG HQRKVVSWID VYTRATCQPR EVVVPLTVEL
MGTVAKQLVP SCVTVQRCGG CCPDDGLECV PTGQHQVRMQ ILMIRYPSSQ LGEMSLEEHS
QCECRPKKKD SAVKPDRAAT PHHRPQPRSV PGWDSAPGAP SPADITHPTP APGPSAHAAP
STTSALTPGP AAAAADAAAS SVAKGGA
