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Protein

Vascular endothelial growth factor B

Gene

VEGFB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis.

GO - Molecular functioni

  • chemoattractant activity Source: UniProtKB
  • heparin binding Source: UniProtKB-KW
  • vascular endothelial growth factor receptor 1 binding Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: Ensembl
  • blood coagulation Source: Reactome
  • cardiac muscle contraction Source: Ensembl
  • coronary vasculature development Source: Ensembl
  • induction of positive chemotaxis Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • platelet activation Source: Reactome
  • platelet degranulation Source: Reactome
  • positive chemotaxis Source: GOC
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of endothelial cell proliferation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of mast cell chemotaxis Source: UniProtKB
  • positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of vascular wound healing Source: UniProtKB
  • protein O-linked glycosylation Source: Ensembl
  • response to drug Source: Ensembl
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Mitogen

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiREACT_12380. VEGF ligand-receptor interactions.
REACT_12583. VEGF binds to VEGFR leading to receptor dimerization.
REACT_318. Platelet degranulation.
SignaLinkiP49765.

Names & Taxonomyi

Protein namesi
Recommended name:
Vascular endothelial growth factor B
Short name:
VEGF-B
Alternative name(s):
VEGF-related factor
Short name:
VRF
Gene namesi
Name:VEGFB
Synonyms:VRF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:12681. VEGFB.

Subcellular locationi

  • Secreted

  • Note: Secreted but remains associated to cells or to the extracellular matrix unless released by heparin.

GO - Cellular componenti

  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • membrane Source: InterPro
  • platelet alpha granule lumen Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37303.

Chemistry

DrugBankiDB08885. Aflibercept.

Polymorphism and mutation databases

BioMutaiVEGFB.
DMDMi17380554.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 207186Vascular endothelial growth factor BPRO_0000023398Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi47 ↔ 891 Publication
Disulfide bondi72 – 72Interchain1 Publication
Disulfide bondi78 ↔ 1221 Publication
Disulfide bondi81 – 81Interchain1 Publication
Disulfide bondi82 ↔ 1241 Publication

Post-translational modificationi

VEGF-B186 is O-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP49765.
PRIDEiP49765.

Expressioni

Tissue specificityi

Expressed in all tissues except liver. Highest levels found in heart, skeletal muscle and pancreas.

Gene expression databases

BgeeiP49765.
CleanExiHS_VEGFB.
ExpressionAtlasiP49765. baseline and differential.
GenevestigatoriP49765.

Organism-specific databases

HPAiCAB025499.
HPA044361.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Can also form heterodimer with VEGF.1 Publication

Protein-protein interaction databases

BioGridi113266. 8 interactions.
DIPiDIP-6045N.
IntActiP49765. 2 interactions.
STRINGi9606.ENSP00000311127.

Structurei

Secondary structure

1
207
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni33 – 353Combined sources
Helixi38 – 458Combined sources
Beta strandi46 – 5510Combined sources
Turni58 – 603Combined sources
Beta strandi61 – 644Combined sources
Beta strandi66 – 8116Combined sources
Beta strandi83 – 864Combined sources
Beta strandi88 – 10518Combined sources
Beta strandi108 – 12518Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2C7WX-ray2.48A/B31-129[»]
2VWEX-ray3.40A/B22-196[»]
2XACX-ray2.71A/B31-129[»]
ProteinModelPortaliP49765.
SMRiP49765. Positions 31-129.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49765.

Family & Domainsi

Sequence similaritiesi

Belongs to the PDGF/VEGF growth factor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG77417.
GeneTreeiENSGT00730000110791.
HOGENOMiHOG000230896.
HOVERGENiHBG000105.
InParanoidiP49765.
KOiK16858.
OMAiASTPHHR.
OrthoDBiEOG74R1S0.
PhylomeDBiP49765.
TreeFamiTF319554.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamiPF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.

Isoform VEGF-B186 (identifier: P49765-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSPLLRRLLL AALLQLAPAQ APVSQPDAPG HQRKVVSWID VYTRATCQPR
60 70 80 90 100
EVVVPLTVEL MGTVAKQLVP SCVTVQRCGG CCPDDGLECV PTGQHQVRMQ
110 120 130 140 150
ILMIRYPSSQ LGEMSLEEHS QCECRPKKKD SAVKPDRAAT PHHRPQPRSV
160 170 180 190 200
PGWDSAPGAP SPADITHPTP APGPSAHAAP STTSALTPGP AAAAADAAAS

SVAKGGA
Length:207
Mass (Da):21,602
Last modified:November 16, 2001 - v2
Checksum:iEDE4B1C0DFDAD6BC
GO
Isoform VEGF-B167 (identifier: P49765-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     137-188: RAATPHHRPQ...APSTTSALTP → SPRPLCPRCT...DTCRCRKLRR
     189-207: Missing.

Show »
Length:188
Mass (Da):21,261
Checksum:iF04654D5A3727194
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei137 – 18852RAATP…SALTP → SPRPLCPRCTQHHQRPDPRT CRCRCRRRSFLRCQGRGLEL NPDTCRCRKLRR in isoform VEGF-B167. 2 PublicationsVSP_004639Add
BLAST
Alternative sequencei189 – 20719Missing in isoform VEGF-B167. 2 PublicationsVSP_004640Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43368 mRNA. Translation: AAA91462.1.
U43369 mRNA. Translation: AAA91463.1.
U52819 mRNA. Translation: AAC50721.1.
U48801 mRNA. Translation: AAB06274.1.
BC008818 mRNA. Translation: AAH08818.1.
CCDSiCCDS58144.1. [P49765-2]
CCDS8062.1. [P49765-1]
RefSeqiNP_001230662.1. NM_001243733.1. [P49765-2]
NP_003368.1. NM_003377.4. [P49765-1]
UniGeneiHs.732095.

Genome annotation databases

EnsembliENST00000309422; ENSP00000311127; ENSG00000173511. [P49765-1]
ENST00000426086; ENSP00000401550; ENSG00000173511. [P49765-2]
GeneIDi7423.
KEGGihsa:7423.
UCSCiuc001nyw.3. human. [P49765-1]
uc001nyx.3. human. [P49765-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43368 mRNA. Translation: AAA91462.1.
U43369 mRNA. Translation: AAA91463.1.
U52819 mRNA. Translation: AAC50721.1.
U48801 mRNA. Translation: AAB06274.1.
BC008818 mRNA. Translation: AAH08818.1.
CCDSiCCDS58144.1. [P49765-2]
CCDS8062.1. [P49765-1]
RefSeqiNP_001230662.1. NM_001243733.1. [P49765-2]
NP_003368.1. NM_003377.4. [P49765-1]
UniGeneiHs.732095.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2C7WX-ray2.48A/B31-129[»]
2VWEX-ray3.40A/B22-196[»]
2XACX-ray2.71A/B31-129[»]
ProteinModelPortaliP49765.
SMRiP49765. Positions 31-129.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113266. 8 interactions.
DIPiDIP-6045N.
IntActiP49765. 2 interactions.
STRINGi9606.ENSP00000311127.

Chemistry

DrugBankiDB08885. Aflibercept.

Polymorphism and mutation databases

BioMutaiVEGFB.
DMDMi17380554.

Proteomic databases

PaxDbiP49765.
PRIDEiP49765.

Protocols and materials databases

DNASUi7423.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309422; ENSP00000311127; ENSG00000173511. [P49765-1]
ENST00000426086; ENSP00000401550; ENSG00000173511. [P49765-2]
GeneIDi7423.
KEGGihsa:7423.
UCSCiuc001nyw.3. human. [P49765-1]
uc001nyx.3. human. [P49765-2]

Organism-specific databases

CTDi7423.
GeneCardsiGC11P064002.
HGNCiHGNC:12681. VEGFB.
HPAiCAB025499.
HPA044361.
MIMi601398. gene.
neXtProtiNX_P49765.
PharmGKBiPA37303.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG77417.
GeneTreeiENSGT00730000110791.
HOGENOMiHOG000230896.
HOVERGENiHBG000105.
InParanoidiP49765.
KOiK16858.
OMAiASTPHHR.
OrthoDBiEOG74R1S0.
PhylomeDBiP49765.
TreeFamiTF319554.

Enzyme and pathway databases

ReactomeiREACT_12380. VEGF ligand-receptor interactions.
REACT_12583. VEGF binds to VEGFR leading to receptor dimerization.
REACT_318. Platelet degranulation.
SignaLinkiP49765.

Miscellaneous databases

ChiTaRSiVEGFB. human.
EvolutionaryTraceiP49765.
GeneWikiiVascular_endothelial_growth_factor_B.
GenomeRNAii7423.
NextBioi29076.
PROiP49765.
SOURCEiSearch...

Gene expression databases

BgeeiP49765.
CleanExiHS_VEGFB.
ExpressionAtlasiP49765. baseline and differential.
GenevestigatoriP49765.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamiPF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of a novel human gene related to vascular endothelial growth factor."
    Grimmond S., Lagercrantz J., Drinkwater C., Silins G., Townson S., Pollock P., Gotley D., Carson E., Rakar S., Nordenskjoeld M., Ward L., Hayward N.K., Weber G.
    Genome Res. 6:124-131(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS VEGF-B186 AND VEGF-B167).
    Tissue: Fetal brain.
  2. "Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform."
    Olofsson B., Pajusola K., von Euler G., Chilov D., Alitalo K., Eriksson U.
    J. Biol. Chem. 271:19310-19317(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF-B186).
    Tissue: Fibrosarcoma.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF-B167).
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM VEGF-B186).
    Tissue: Tonsil.
  5. "Crystal structure of human vascular endothelial growth factor-B: identification of amino acids important for receptor binding."
    Iyer S., Scotney P.D., Nash A.D., Ravi Acharya K.
    J. Mol. Biol. 359:76-85(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 31-129, DISULFIDE BONDS, SUBUNIT.

Entry informationi

Entry nameiVEGFB_HUMAN
AccessioniPrimary (citable) accession number: P49765
Secondary accession number(s): Q16528
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 16, 2001
Last modified: April 29, 2015
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.