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 11-NOV-2015, entry version 142. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT vascular 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., RA Eriksson U.; RT "Genomic organization of the mouse and human genes for vascular RT endothelial growth factor B (VEGF-B) and characterization of a second RT 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 RT project: 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 CC heparin and neuropilin-1 whereas the binding to neuropilin-1 of CC VEGF-B186 is regulated by proteolysis. CC -!- SUBUNIT: Homodimer; disulfide-linked. Can also form heterodimer CC with VEGF. {ECO:0000269|PubMed:16616187}. CC -!- SUBCELLULAR LOCATION: Secreted. Note=Secreted but remains CC associated to cells or to the extracellular matrix unless released CC 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}. 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; 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 UniGene; Hs.732095; -. 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 PDBsum; 2C7W; -. DR PDBsum; 2VWE; -. DR PDBsum; 2XAC; -. DR ProteinModelPortal; P49765; -. DR SMR; P49765; 31-129. DR BioGrid; 113266; 13. DR DIP; DIP-6045N; -. DR IntAct; P49765; 2. DR STRING; 9606.ENSP00000311127; -. DR DrugBank; DB08885; Aflibercept. DR BioMuta; VEGFB; -. DR DMDM; 17380554; -. DR PaxDb; P49765; -. DR PRIDE; P49765; -. DR DNASU; 7423; -. DR Ensembl; ENST00000309422; ENSP00000311127; ENSG00000173511. [P49765-1] DR Ensembl; ENST00000426086; ENSP00000401550; ENSG00000173511. [P49765-2] DR GeneID; 7423; -. DR KEGG; hsa:7423; -. DR UCSC; uc001nyw.3; human. [P49765-1] DR UCSC; uc001nyx.3; human. [P49765-2] DR CTD; 7423; -. DR GeneCards; VEGFB; -. DR HGNC; HGNC:12681; VEGFB. DR HPA; CAB025499; -. DR HPA; HPA044361; -. DR MIM; 601398; gene. DR neXtProt; NX_P49765; -. DR PharmGKB; PA37303; -. DR eggNOG; ENOG410II0A; Eukaryota. DR eggNOG; ENOG410ZN1X; LUCA. DR GeneTree; ENSGT00730000110791; -. DR HOGENOM; HOG000230896; -. DR HOVERGEN; HBG000105; -. DR InParanoid; P49765; -. DR KO; K16858; -. DR OMA; LECVPIG; -. DR OrthoDB; EOG74R1S0; -. DR PhylomeDB; P49765; -. DR TreeFam; TF319554; -. 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 ChiTaRS; VEGFB; human. DR EvolutionaryTrace; P49765; -. DR GeneWiki; Vascular_endothelial_growth_factor_B; -. DR GenomeRNAi; 7423; -. DR NextBio; 29076; -. DR PRO; PR:P49765; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; P49765; -. DR CleanEx; HS_VEGFB; -. 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:0008201; F:heparin binding; IEA:UniProtKB-KW. DR GO; GO:0043183; F:vascular endothelial growth factor receptor 1 binding; IPI:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. 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:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0050918; P:positive chemotaxis; IDA:GOC. 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: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:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome. 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; Complete proteome; Disulfide bond; KW Glycoprotein; Growth factor; Heparin-binding; Mitogen; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 207 Vascular endothelial growth factor B. FT /FTId=PRO_0000023398. FT DISULFID 47 89 {ECO:0000269|PubMed:16616187}. FT DISULFID 72 72 Interchain. FT {ECO:0000269|PubMed:16616187}. FT DISULFID 78 122 {ECO:0000269|PubMed:16616187}. FT DISULFID 81 81 Interchain. FT {ECO:0000269|PubMed:16616187}. FT DISULFID 82 124 {ECO:0000269|PubMed:16616187}. FT VAR_SEQ 137 188 RAATPHHRPQPRSVPGWDSAPGAPSPADITHPTPAPGPSAH FT AAPSTTSALTP -> SPRPLCPRCTQHHQRPDPRTCRCRCR FT RRSFLRCQGRGLELNPDTCRCRKLRR (in isoform FT VEGF-B167). {ECO:0000303|PubMed:8637916, FT ECO:0000303|PubMed:8919691}. FT /FTId=VSP_004639. FT VAR_SEQ 189 207 Missing (in isoform VEGF-B167). FT {ECO:0000303|PubMed:8637916, FT ECO:0000303|PubMed:8919691}. FT /FTId=VSP_004640. FT TURN 33 35 {ECO:0000244|PDB:2XAC}. FT HELIX 38 45 {ECO:0000244|PDB:2C7W}. FT STRAND 46 55 {ECO:0000244|PDB:2C7W}. FT TURN 58 60 {ECO:0000244|PDB:2XAC}. FT STRAND 61 64 {ECO:0000244|PDB:2XAC}. FT STRAND 66 81 {ECO:0000244|PDB:2C7W}. FT STRAND 83 86 {ECO:0000244|PDB:2C7W}. FT STRAND 88 105 {ECO:0000244|PDB:2C7W}. FT STRAND 108 125 {ECO:0000244|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 //