Vascular endothelial growth factor B

VEGFB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2C7W, 2VWE, 2XAC
Identifiers
Aliases	VEGFB, VEGFL, VRF, vascular endothelial growth factor B
External IDs	OMIM: 601398; MGI: 106199; HomoloGene: 87131; GeneCards: VEGFB; OMA:VEGFB - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q13.1 Start 64,234,584 bp End 64,239,264 bp
Gene location (Mouse) Chr. Chromosome 19 (mouse) Band 19|19 A Start 6,959,841 bp End 6,965,019 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart right auricle right coronary artery left coronary artery popliteal artery tibial arteries Descending thoracic aorta ascending aorta muscle of thigh muscle layer of sigmoid colon Top expressed in myocardium myocardium of ventricle right ventricle interventricular septum cardiac muscles muscle of thigh extraocular muscle cardiac muscle tissue of left ventricle digastric muscle plantaris muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function heparin binding protein homodimerization activity protein binding protein heterodimerization activity chemoattractant activity growth factor activity vascular endothelial growth factor receptor 1 binding vascular endothelial growth factor receptor 2 binding vascular endothelial growth factor receptor 3 binding vascular endothelial growth factor receptor binding Cellular component membrane intracellular anatomical structure extracellular region platelet alpha granule lumen extracellular space Biological process negative regulation of neuron apoptotic process positive regulation of vascular endothelial growth factor receptor signaling pathway positive regulation of protein kinase B signaling cardiac muscle contraction protein O-linked glycosylation platelet degranulation negative regulation of apoptotic process coronary vasculature development negative regulation of gene expression heart development positive regulation of vascular permeability positive regulation of vascular wound healing positive regulation of ERK1 and ERK2 cascade positive regulation of peptidyl-tyrosine phosphorylation positive regulation of cell division positive chemotaxis response to hypoxia angiogenesis positive regulation of endothelial cell proliferation positive regulation of angiogenesis vascular endothelial growth factor receptor signaling pathway induction of positive chemotaxis positive regulation of mast cell chemotaxis regulation of signaling receptor activity positive regulation of protein phosphorylation sprouting angiogenesis vascular endothelial growth factor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7423 22340 Ensembl ENSG00000173511 ENSMUSG00000024962 UniProt P49765 P49766 RefSeq (mRNA) NM_003377 NM_001243733 NM_001185164 NM_011697 RefSeq (protein) NP_001230662 NP_003368 NP_001172093 NP_035827 Location (UCSC) Chr 11: 64.23 – 64.24 Mb Chr 19: 6.96 – 6.97 Mb PubMed search
Wikidata
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Vascular endothelial growth factor B also known as VEGF-B is a protein that, in humans, is encoded by the VEGF-B gene. VEGF-B is a growth factor that belongs to the vascular endothelial growth factor family, of which VEGF-A is the best-known member.

Function

In contrast to VEGF-A, VEGF-B plays a less pronounced role in the vascular system: Whereas VEGF-A is important for the formation of blood vessels, such as during development or in pathological conditions, VEGF-B seems to play a role only in the maintenance of newly formed blood vessels during pathological conditions. VEGF-B plays also an important role on several types of neurons. It is important for the protection of neurons in the retina and the cerebral cortex during stroke, and of motor neurons during motor neuron diseases such as amyotrophic lateral sclerosis.

VEGF-B exerts its effects via the FLT1 receptor. But the role of co-receptor NRP in VEGF-B-mediated effects is still unclear.

VEGF-B has also been found to control endothelial uptake and transport of fatty acids in heart and skeletal muscle.

Interactions

Vascular endothelial growth factor B has been shown to interact with FLT1, NRP1 and NRP2.

References

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000173511 – Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024962 – Ensembl, May 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ "Entrez Gene: VEGFB vascular endothelial growth factor B".
6. ^ Zhang F, Tang Z, Hou X, Lennartsson J, Li Y, Koch AW, et al. (April 2009). "VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis". Proceedings of the National Academy of Sciences of the United States of America. 106 (15): 6152–6157. Bibcode:2009PNAS..106.6152Z. doi:10.1073/pnas.0813061106. PMC 2669337. PMID 19369214.
7. ^ Li Y, Zhang F, Nagai N, Tang Z, Zhang S, Scotney P, et al. (March 2008). "VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats". The Journal of Clinical Investigation. 118 (3): 913–923. doi:10.1172/JCI33673. PMC 2230661. PMID 18259607.
8. ^ Sun Y, Jin K, Childs JT, Xie L, Mao XO, Greenberg DA (October 2004). "Increased severity of cerebral ischemic injury in vascular endothelial growth factor-B-deficient mice". Journal of Cerebral Blood Flow and Metabolism. 24 (10): 1146–1152. doi:10.1097/01.wcb.0000134477.38980.38. PMID 15529014.
9. ^ Poesen K, Lambrechts D, Van Damme P, Dhondt J, Bender F, Frank N, et al. (October 2008). "Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration". The Journal of Neuroscience. 28 (42): 10451–10459. doi:10.1523/JNEUROSCI.1092-08.2008. PMC 6671326. PMID 18923022.
10. ^ Yamazaki Y, Morita T (November 2006). "Molecular and functional diversity of vascular endothelial growth factors". Molecular Diversity. 10 (4): 515–527. doi:10.1007/s11030-006-9027-3. PMID 16972015. S2CID 28692204.
11. ^ Mallick R, Ylä-Herttuala S (December 2022). "Therapeutic Potential of VEGF-B in Coronary Heart Disease and Heart Failure: Dream or Vision?". Cells. 11 (24): 4134. doi:10.3390/cells11244134. PMC 9776740. PMID 36552897.
12. ^ Muoio DM (July 2010). "Metabolism and vascular fatty acid transport". The New England Journal of Medicine. 363 (3): 291–293. doi:10.1056/NEJMcibr1005397. PMID 20647206.
13. ^ Hagberg CE, Mehlem A, Falkevall A, Muhl L, Fam BC, Ortsäter H, et al. (October 2012). "Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes". Nature. 490 (7420): 426–430. Bibcode:2012Natur.490..426H. doi:10.1038/nature11464. PMID 23023133. S2CID 4315297.
14. ^ Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, et al. (September 1998). "Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11709–11714. Bibcode:1998PNAS...9511709O. doi:10.1073/pnas.95.20.11709. PMC 21705. PMID 9751730.
15. ^ Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, et al. (July 1999). "Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1". The Journal of Biological Chemistry. 274 (30): 21217–21222. doi:10.1074/jbc.274.30.21217. PMID 10409677.
16. ^ Mallick R, Ylä-Herttuala S (December 2022). "Therapeutic Potential of VEGF-B in Coronary Heart Disease and Heart Failure: Dream or Vision?". Cells. 11 (24): 4134. doi:10.3390/cells11244134. PMC 9776740. PMID 36552897.
17. ^ Mallick R, Gurzeler E, Toivanen PI, Nieminen T, Ylä-Herttuala S (2022-08-04). "Novel Designed Proteolytically Resistant VEGF-B186R127S Promotes Angiogenesis in Mouse Heart by Recruiting Endothelial Progenitor Cells". Frontiers in Bioengineering and Biotechnology. 10: 907538. doi:10.3389/fbioe.2022.907538. PMC 9385986. PMID 35992336.

Further reading

• Poesen K, Lambrechts D, Van Damme P, Dhondt J, Bender F, Frank N, et al. (October 2008). "Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration". The Journal of Neuroscience. 28 (42): 10451–10459. doi:10.1523/JNEUROSCI.1092-08.2008. PMC 6671326. PMID 18923022.
• Joukov V, Kaipainen A, Jeltsch M, Pajusola K, Olofsson B, Kumar V, et al. (November 1997). "Vascular endothelial growth factors VEGF-B and VEGF-C". Journal of Cellular Physiology. 173 (2): 211–215. doi:10.1002/(SICI)1097-4652(199711)173:2<211::AID-JCP23>3.0.CO;2-H. PMID 9365524. S2CID 2930599.
• Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, et al. (March 1996). "Vascular endothelial growth factor B, a novel growth factor for endothelial cells". Proceedings of the National Academy of Sciences of the United States of America. 93 (6): 2576–2581. Bibcode:1996PNAS...93.2576O. doi:10.1073/pnas.93.6.2576. PMC 39839. PMID 8637916.
• Olofsson B, Pajusola K, von Euler G, Chilov D, Alitalo K, Eriksson U (August 1996). "Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform". The Journal of Biological Chemistry. 271 (32): 19310–19317. doi:10.1074/jbc.271.32.19310. PMID 8702615.
• Grimmond S, Lagercrantz J, Drinkwater C, Silins G, Townson S, Pollock P, et al. (February 1996). "Cloning and characterization of a novel human gene related to vascular endothelial growth factor". Genome Research. 6 (2): 124–131. doi:10.1101/gr.6.2.124. PMID 8919691.
• Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, et al. (September 1998). "Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11709–11714. Bibcode:1998PNAS...9511709O. doi:10.1073/pnas.95.20.11709. PMC 21705. PMID 9751730.
• Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, et al. (July 1999). "Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1". The Journal of Biological Chemistry. 274 (30): 21217–21222. doi:10.1074/jbc.274.30.21217. PMID 10409677.
• Ikuta T, Ariga H, Matsumoto K (November 2000). "Extracellular matrix tenascin-X in combination with vascular endothelial growth factor B enhances endothelial cell proliferation". Genes to Cells. 5 (11): 913–927. doi:10.1046/j.1365-2443.2000.00376.x. PMID 11122379. S2CID 41366972.
• Qi JH, Ebrahem Q, Moore N, Murphy G, Claesson-Welsh L, Bond M, et al. (April 2003). "A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2". Nature Medicine. 9 (4): 407–415. doi:10.1038/nm846. PMID 12652295. S2CID 12563403.
• Trompezinski S, Berthier-Vergnes O, Denis A, Schmitt D, Viac J (February 2004). "Comparative expression of vascular endothelial growth factor family members, VEGF-B, -C and -D, by normal human keratinocytes and fibroblasts". Experimental Dermatology. 13 (2): 98–105. doi:10.1111/j.0906-6705.2004.00137.x. PMID 15009103. S2CID 13040175.
• Timoshenko AV, Chakraborty C, Wagner GF, Lala PK (April 2006). "COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer". British Journal of Cancer. 94 (8): 1154–1163. doi:10.1038/sj.bjc.6603067. PMC 2361247. PMID 16570043.
• Iyer S, Scotney PD, Nash AD, Ravi Acharya K (May 2006). "Crystal structure of human vascular endothelial growth factor-B: identification of amino acids important for receptor binding". Journal of Molecular Biology. 359 (1): 76–85. doi:10.1016/j.jmb.2006.03.002. PMID 16616187.
• Yamada E, Yamazaki K, Takano K, Obara T, Sato K (June 2006). "Iodide inhibits vascular endothelial growth factor-A expression in cultured human thyroid follicles: a microarray search for effects of thyrotropin and iodide on angiogenesis factors". Thyroid. 16 (6): 545–554. doi:10.1089/thy.2006.16.545. PMID 16839256.
• de Paulis A, Prevete N, Fiorentino I, Rossi FW, Staibano S, Montuori N, et al. (November 2006). "Expression and functions of the vascular endothelial growth factors and their receptors in human basophils". Journal of Immunology. 177 (10): 7322–7331. doi:10.4049/jimmunol.177.10.7322. PMID 17082651.

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Vascular endothelial growth factor B

v t e PDB gallery
2c7w: CRYSTAL STRUCTURE OF HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR-B: IDENTIFICATION OF AMINO ACIDS IMPORTANT FOR ANGIOGENINC ACTIVITY

v t e Growth factors
Fibroblast	FGF receptor ligands: FGF1/FGF2/FGF5 FGF3/FGF4/FGF6 KGF FGF7/FGF10/FGF22 FGF8/FGF17/FGF18 FGF9/FGF16/FGF20 FGF homologous factors: FGF11(FHF3) FGF12(FHF1) FGF13(FHF2) FGF14(FHF4) hormone-like: FGF15/19 FGF15 FGF19 FGF21 FGF23
EGF-like domain	TGFα EGF HB-EGF
TGFβ pathway	TGFβ TGFβ1 TGFβ2 TGFβ3
Insulin/IGF/ Relaxin family	Insulin and Insulin-like growth factor IGF1 IGF2 Relaxin family peptide hormones INSL3 INSL4 INSL5 INSL6 Relaxin 1 2 3
Platelet-derived	PDGFA PDGFB PDGFC PDGFD
Vascular endothelial	VEGF-A VEGF-B VEGF-C VEGF-D PGF
Other	Nerve Hepatocyte

v t e Growth factor receptor modulators
Angiopoietin	Agonists: Angiopoietin 1 Angiopoietin 4 Antagonists: Angiopoietin 2 Angiopoietin 3 Kinase inhibitors: Altiratinib CE-245677 Rebastinib Antibodies: Evinacumab (against angiopoietin 3) Nesvacumab (against angiopoietin 2)
CNTF	Agonists: Axokine CNTF Dapiclermin
EGF (ErbB)	EGF (ErbB1/HER1) Agonists: Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors: Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies: Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab ErbB2/HER2 Agonists: Unknown/none Antibodies: Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors: Afatinib Lapatinib Mubritinib Neratinib Tucatinib ErbB3/HER3 Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C)) Antibodies: Duligotumab Patritumab Seribantumab ErbB4/HER4 Agonists: Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))
FGF	FGFR1 Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20) Repifermin Selpercatinib Trafermin Velafermin FGFR2 Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22) Palifermin Repifermin Selpercatinib Sprifermin Trafermin Antibodies: Aprutumab Aprutumab ixadotin Kinase inhibitors: Infigratinib FGFR3 Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 8, 9, 18, 23) Selpercatinib Sprifermin Trafermin Antibodies: Burosumab (against FGF23) FGFR4 Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 6, 8, 9, 19) Trafermin Unsorted Agonists: FGF15/19
HGF (c-Met)	Agonists: Fosgonimeton Hepatocyte growth factor Potentiators: Dihexa (PNB-0408) Kinase inhibitors: Altiratinib AM7 AMG-458 Amuvatinib BMS-777607 Cabozantinib Capmatinib Crizotinib Foretinib Golvatinib INCB28060 JNJ-38877605 K252a MK-2461 PF-04217903 PF-2341066 PHA-665752 SU-11274 Tivantinib Volitinib Antibodies: Emibetuzumab Ficlatuzumab Flanvotumab Onartuzumab Rilotumumab Telisotuzumab Telisotuzumab vedotin
IGF	IGF-1 Agonists: des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors: BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies: AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2) IGF-2 Agonists: Insulin-like growth factor-2 (somatomedin A) Antibodies: Dusigitumab Xentuzumab (against IGF-1 and IGF-2) Others Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7) Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) Trofinetide
LNGF (p75NTR)	Agonists: BDNF BNN-20 BNN-27 Cenegermin DHEA DHEA-S NGF NT-3 NT-4 Antagonists: ALE-0540 Dexamethasone EVT-901 (SAR-127963) Testosterone Antibodies: Against NGF: ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers: Against NGF: RBM-004 Decoy receptors: LEVI-04 (p75NTR-Fc)
PDGF	Agonists: Becaplermin Platelet-derived growth factor (A, B, C, D) Kinase inhibitors: Agerafenib Avapritinib Axitinib Crenolanib Imatinib Lenvatinib Masitinib Motesanib Nintedanib Pazopanib Radotinib Quizartinib Ripretinib Sunitinib Sorafenib Toceranib Antibodies: Olaratumab Ramucirumab Tovetumab
RET (GFL)	GFRα1 Agonists: Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors: Vandetanib GFRα2 Agonists: Neurturin (NRTN) Kinase inhibitors: Vandetanib GFRα3 Agonists: Artemin (ARTN) Kinase inhibitors: Vandetanib GFRα4 Agonists: Persephin (PSPN) Kinase inhibitors: Vandetanib Unsorted Kinase inhibitors: Agerafenib
SCF (c-Kit)	Agonists: Ancestim Stem cell factor Kinase inhibitors: Agerafenib Axitinib Dasatinib Imatinib Masitinib Nilotinib Pazopanib Quizartinib Sorafenib Sunitinib Toceranib
TGFβ	See here instead.
Trk	TrkA Agonists: Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists: ALE-0540 Dexamethasone FX007 Testosterone Negative allosteric modulators: VM-902A Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers: Against NGF: RBM-004 Decoy receptors: ReN-1820 (TrkAd5) TrkB Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 Antagonists: ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands: DHEA Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486 TrkC Agonists: BNN-20 DHEA NT-3 Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486
VEGF	Agonists: Placental growth factor (PGF) Ripretinib Telbermin VEGF (A, B, C, D (FIGF)) Allosteric modulators: Cyclotraxin B Kinase inhibitors: Agerafenib Altiratinib Axitinib Cabozantinib Cediranib Fruquintinib Lapatinib Lenvatinib Motesanib Nintedanib Pazopanib Pegaptanib Rebastinib Regorafenib Semaxanib Sorafenib Sunitinib Toceranib Tivozanib Vandetanib WHI-P 154 Antibodies: Alacizumab pegol Bevacizumab Icrucumab Ramucirumab Ranibizumab Decoy receptors: Aflibercept
Others	Additional growth factors: Adrenomedullin Colony-stimulating factors (see here instead) Connective tissue growth factor (CTGF) Ephrins (A1, A2, A3, A4, A5, B1, B2, B3) Erythropoietin (see here instead) Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF) Glia maturation factor (GMF) Hepatoma-derived growth factor (HDGF) Interleukins/T-cell growth factors (see here instead) Leukemia inhibitory factor (LIF) Macrophage-stimulating protein (MSP; HLP, HGFLP) Midkine (NEGF2) Migration-stimulating factor (MSF; PRG4) Oncomodulin Pituitary adenylate cyclase-activating peptide (PACAP) Pleiotrophin Renalase Thrombopoietin (see here instead) Wnt signaling proteins Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)