P49765 (VEGFB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vascular endothelial growth factor B
Short name=VEGF-B

Alternative name(s):
VEGF-related factor
Short name=VRF

Gene names

Name:	VEGFB
Synonyms:	VRF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	207 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Homodimer; disulfide-linked. Can also form heterodimer with VEGF. Ref.5
Subcellular location	Secreted. Note: Secreted but remains associated to cells or to the extracellular matrix unless released by heparin.
Tissue specificity	Expressed in all tissues except liver. Highest levels found in heart, skeletal muscle and pancreas.
Post-translational modification	VEGF-B186 is O-glycosylated By similarity.
Sequence similarities	Belongs to the PDGF/VEGF growth factor family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Ligand	Heparin-binding
Molecular function	Growth factor Mitogen
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from direct assay. Source: UniProtKB induction of positive chemotaxis Inferred from direct assay. Source: UniProtKB negative regulation of gene expression Inferred from direct assay. Source: UniProtKB negative regulation of neuron apoptosis Inferred from direct assay. Source: UniProtKB platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome positive regulation of ERK1 and ERK2 cascade Inferred from direct assay. Source: UniProtKB positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of endothelial cell proliferation Inferred from direct assay Ref.3. Source: UniProtKB positive regulation of mast cell chemotaxis Inferred from direct assay. Source: UniProtKB positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from direct assay. Source: UniProtKB positive regulation of vascular endothelial growth factor receptor signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of vascular wound healing Inferred from direct assay. Source: UniProtKB vascular endothelial growth factor receptor signaling pathway Traceable author statement. Source: Reactome
Cellular component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from direct assay Ref.3. Source: UniProtKB membrane Inferred from electronic annotation. Source: InterPro platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular function	chemoattractant activity Inferred from direct assay. Source: UniProtKB growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW heparin binding Inferred from electronic annotation. Source: UniProtKB-KW vascular endothelial growth factor receptor 1 binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform VEGF-B186 (identifier: P49765-1)

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.

Isoform VEGF-B167 (identifier: P49765-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 207

186

Vascular endothelial growth factor B

PRO_0000023398

Amino acid modifications

Disulfide bond

47 ↔ 89

Ref.5

Disulfide bond

72

Interchain Ref.5

Disulfide bond

78 ↔ 122

Ref.5

Disulfide bond

81

Interchain Ref.5

Disulfide bond

82 ↔ 124

Ref.5

Natural variations

Alternative sequence

137 – 188

52

RAATP…SALTP → SPRPLCPRCTQHHQRPDPRT CRCRCRRRSFLRCQGRGLEL NPDTCRCRKLRR in isoform VEGF-B167.

VSP_004639

Alternative sequence

189 – 207

19

Missing in isoform VEGF-B167.

VSP_004640

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

207

Helix Strand Turn

Details...

Helix

38 – 45

8

Beta strand

50 – 55

6

Beta strand

66 – 77

12

Beta strand

88 – 91

4

Beta strand

95 – 99

5

Beta strand

102 – 105

4

Beta strand

108 – 110

3

Beta strand

114 – 118

5

Beta strand

122 – 125

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform VEGF-B186 [UniParc]. Last modified November 16, 2001. Version 2. Checksum: EDE4B1C0DFDAD6BC	FASTA	207	21,602
	10 20 30 40 50 60 MSPLLRRLLL AALLQLAPAQ APVSQPDAPG HQRKVVSWID VYTRATCQPR EVVVPLTVEL 70 80 90 100 110 120 MGTVAKQLVP SCVTVQRCGG CCPDDGLECV PTGQHQVRMQ ILMIRYPSSQ LGEMSLEEHS 130 140 150 160 170 180 QCECRPKKKD SAVKPDRAAT PHHRPQPRSV PGWDSAPGAP SPADITHPTP APGPSAHAAP 190 200 STTSALTPGP AAAAADAAAS SVAKGGA
	Isoform VEGF-B167 [UniParc]. Checksum: F04654D5A3727194	FASTA	188	21,261
	10 20 30 40 50 60 MSPLLRRLLL AALLQLAPAQ APVSQPDAPG HQRKVVSWID VYTRATCQPR EVVVPLTVEL 70 80 90 100 110 120 MGTVAKQLVP SCVTVQRCGG CCPDDGLECV PTGQHQVRMQ ILMIRYPSSQ LGEMSLEEHS 130 140 150 160 170 180 QCECRPKKKD SAVKPDSPRP LCPRCTQHHQ RPDPRTCRCR CRRRSFLRCQ GRGLELNPDT CRCRKLRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 8919691] [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: 8702615] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF-B186). Tissue: Fibrosarcoma.
[3]	"Vascular endothelial growth factor B, a novel growth factor for endothelial cells." Olofsson B., Pajusola K., Kaipainen A., von Euler G., Joukov V., Saksela O., Orpana A., Pettersson R.F., Alitalo K., Eriksson U. Proc. Natl. Acad. Sci. U.S.A. 93:2576-2581(1996) [PubMed: 8637916] [Abstract] 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: 15489334] [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: 16616187] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 31-129, DISULFIDE BONDS, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00028075.
IPI00219686.

RefSeq

NP_001230662.1. NM_001243733.1.
NP_003368.1. NM_003377.4.

UniGene

Hs.78781.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C7W	X-ray	2.48	A/B	31-129	[»]
2VWE	X-ray	3.40	A/B	22-136	[»]
2XAC	X-ray	2.71	A/B	31-129	[»]

ProteinModelPortal

P49765.

SMR

P49765. Positions 31-129.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6045N.

IntAct

P49765. 1 interaction.

STRING

P49765.

Polymorphism databases

DMDM

17380554.

Proteomic databases

PRIDE

P49765.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309422; ENSP00000311127; ENSG00000173511.

GeneID

7423.

KEGG

hsa:7423.

UCSC

uc001nyw.1. human.
uc001nyx.1. human.

Organism-specific databases

CTD

7423.

GeneCards

GC11P064002.

H-InvDB

HIX0201663.

HGNC

HGNC:12681. VEGFB.

HPA

CAB025499.

MIM

601398. gene.

neXtProt

NX_P49765.

PharmGKB

PA37303.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07990.

HOGENOM

HBG444674.

HOVERGEN

HBG000105.

InParanoid

P49765.

OMA

PADITHP.

PhylomeDB

P49765.

Enzyme and pathway databases

Pathway_Interaction_DB

vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P49765.

Bgee

P49765.

CleanEx

HS_VEGFB.

Genevestigator

P49765.

GermOnline

ENSG00000173511. Homo sapiens.

Family and domain databases

InterPro

IPR000072. PD_growth_factor.
IPR023581. PD_growth_factor_CS.
[Graphical view]

KO

K05448.

Pfam

PF00341. PDGF. 1 hit.
[Graphical view]

SMART

SM00141. PDGF. 1 hit.
[Graphical view]

PROSITE

PS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

29076.

SOURCE

Search...

Entry information

Entry name

VEGFB_HUMAN

Accession

Primary (citable) accession number: P49765
Secondary accession number(s): Q16528

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 16, 2001
Last modified:	January 25, 2012
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.