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Protein

Vascular endothelial growth factor A

Gene

Vegfa

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. May play a role in increasing vascular permeability during lactation, when increased transport of molecules from the blood is required for efficient milk protein synthesis.1 Publication

GO - Molecular functioni

  • chemoattractant activity Source: RGD
  • growth factor activity Source: RGD
  • growth factor binding Source: RGD
  • heparin binding Source: UniProtKB-KW
  • protein homodimerization activity Source: RGD
  • vascular endothelial growth factor receptor 2 binding Source: RGD
  • vascular endothelial growth factor receptor binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • angiogenesis Source: RGD
  • angiogenesis involved in coronary vascular morphogenesis Source: RGD
  • blood vessel remodeling Source: RGD
  • cell chemotaxis Source: RGD
  • cell differentiation Source: UniProtKB-KW
  • cellular response to dexamethasone stimulus Source: RGD
  • cellular response to drug Source: RGD
  • cellular response to fibroblast growth factor stimulus Source: RGD
  • female pregnancy Source: RGD
  • hyaluronan metabolic process Source: RGD
  • lung alveolus development Source: RGD
  • mRNA stabilization Source: RGD
  • negative regulation of bone resorption Source: RGD
  • negative regulation of neuron death Source: RGD
  • negative regulation of programmed cell death Source: RGD
  • nervous system development Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of endothelial cell migration Source: UniProtKB
  • positive regulation of endothelial cell proliferation Source: UniProtKB
  • positive regulation of focal adhesion assembly Source: UniProtKB
  • positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of protein complex assembly Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of signal transduction Source: RGD
  • positive regulation of smooth muscle cell proliferation Source: RGD
  • positive regulation of transcription from RNA polymerase II promoter Source: RGD
  • positive regulation of vascular permeability Source: RGD
  • response to cold Source: RGD
  • response to dexamethasone Source: RGD
  • response to estradiol Source: RGD
  • response to folic acid Source: RGD
  • response to hypoxia Source: RGD
  • response to oxygen levels Source: RGD
  • response to progesterone Source: RGD
  • response to vitamin A Source: RGD
  • T-helper 1 type immune response Source: RGD
  • tube formation Source: UniProtKB
  • vascular endothelial growth factor receptor signaling pathway Source: RGD
  • wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Angiogenesis, Differentiation

Keywords - Ligandi

Heparin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Vascular endothelial growth factor A
Short name:
VEGF-A
Alternative name(s):
Vascular permeability factor
Short name:
VPF
Gene namesi
Name:Vegfa
Synonyms:Vegf
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi619991. Vegfa.

Subcellular locationi

  • Secreted By similarity

  • Note: VEGF-A120 is acidic and freely secreted. VEGF-A164 is more basic, has heparin-binding properties and, although a signicant proportion remains cell-associated, most is freely secreted. VEGF-A188 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix, although it may be released as a soluble form by heparin, heparinase or plasmin (By similarity).By similarity

GO - Cellular componenti

  • basement membrane Source: RGD
  • extracellular space Source: RGD
  • membrane Source: InterPro
  • membrane-bounded vesicle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 26262 PublicationsAdd
BLAST
Chaini27 – 214188Vascular endothelial growth factor APRO_0000023390Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi51 ↔ 93By similarity
Disulfide bondi76 – 76InterchainBy similarity
Disulfide bondi82 ↔ 127By similarity
Disulfide bondi85 – 85InterchainBy similarity
Disulfide bondi86 ↔ 129By similarity
Glycosylationi100 – 1001N-linked (GlcNAc...)

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP16612.
PRIDEiP16612.

PTM databases

PhosphoSiteiP16612.

Expressioni

Tissue specificityi

Expressed in the pituitary, in brain, in particularly in supraoptic and paraventricular nuclei and the choroid plexus. Also found abundantly in the corpus luteum of the ovary and in kidney glomeruli. Expressed in the ductal epithelial cells of post-pubertal mammary glands. Expressed in the ductal and alveolar epithelial cells throughout the whole period of gestational evolution, lactation and involution.1 Publication

Developmental stagei

Increases during pregnancy (5.0-fold increase on day 12 with a subsequent decrease on day 18) and during lactation (18.5-fold increase on day 7). Levels appear to be minimally altered during involution.1 Publication

Gene expression databases

GenevisibleiP16612. RN.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Also found as heterodimer with PGF.

GO - Molecular functioni

  • growth factor activity Source: RGD
  • growth factor binding Source: RGD
  • protein homodimerization activity Source: RGD
  • vascular endothelial growth factor receptor 2 binding Source: RGD
  • vascular endothelial growth factor receptor binding Source: RGD

Protein-protein interaction databases

BioGridi249830. 1 interaction.
STRINGi10116.ENSRNOP00000026637.

Structurei

3D structure databases

ProteinModelPortaliP16612.
SMRiP16612. Positions 37-134, 166-214.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the PDGF/VEGF growth factor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IGCM. Eukaryota.
ENOG410ZWYU. LUCA.
HOGENOMiHOG000072704.
HOVERGENiHBG000105.
InParanoidiP16612.
KOiK05448.
PhylomeDBiP16612.

Family and domain databases

Gene3Di2.10.160.10. 1 hit.
2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
IPR027928. VEGF_C.
[Graphical view]
PfamiPF00341. PDGF. 1 hit.
PF14554. VEGF_C. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
SSF57593. SSF57593. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.

Isoform VEGF-A188 (identifier: P16612-1) [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
MNFLLSWVHW TLALLLYLHH AKWSQAAPTT EGEQKAHEVV KFMDVYQRSY
60 70 80 90 100
CRPIETLVDI FQEYPDEIEY IFKPSCVPLM RCAGCCNDEA LECVPTSESN
110 120 130 140 150
VTMQIMRIKP HQSQHIGEMS FLQHSRCECR PKKDRTKPEK KSVRGKGKGQ
160 170 180 190 200
KRKRKKSRFK SWSVHCEPCS ERRKHLFVQD PQTCKCSCKN TDSRCKARQL
210
ELNERTCRCD KPRR
Length:214
Mass (Da):25,239
Last modified:November 16, 2001 - v2
Checksum:i60FBB876F5304946
GO
Isoform VEGF-A164 (identifier: P16612-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     140-140: K → N
     141-164: Missing.

Show »
Length:190
Mass (Da):22,396
Checksum:i589374010441F377
GO
Isoform VEGF-A144 (identifier: P16612-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     165-208: Missing.

Show »
Length:170
Mass (Da):20,018
Checksum:iB371BF4A67E3231B
GO
Isoform VEGF-A120 (identifier: P16612-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     141-208: Missing.

Show »
Length:146
Mass (Da):17,189
Checksum:i8DC2979C38FCF1A0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti101 – 1011V → A in AAF19212 (PubMed:11163598).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei140 – 1401K → N in isoform VEGF-A164. 3 PublicationsVSP_004629
Alternative sequencei141 – 20868Missing in isoform VEGF-A120. 1 PublicationVSP_004631Add
BLAST
Alternative sequencei141 – 16424Missing in isoform VEGF-A164. 3 PublicationsVSP_004630Add
BLAST
Alternative sequencei165 – 20844Missing in isoform VEGF-A144. 1 PublicationVSP_004632Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32167 mRNA. Translation: AAA41211.1.
AF215725 mRNA. Translation: AAF19211.1.
AF215726 mRNA. Translation: AAF19212.1.
AF222779 mRNA. Translation: AAF25958.1.
AY033506 mRNA. Translation: AAL07526.1.
AY033508 mRNA. Translation: AAL07528.1.
PIRiA35987.
RefSeqiNP_001103804.1. NM_001110334.2.
NP_001274036.1. NM_001287107.1. [P16612-1]
NP_001274037.1. NM_001287108.1. [P16612-2]
NP_001274039.1. NM_001287110.1. [P16612-4]
NP_001274040.1. NM_001287111.1.
NP_001274041.1. NM_001287112.1. [P16612-3]
NP_001274043.1. NM_001287114.1.
NP_114024.2. NM_031836.3.
UniGeneiRn.1923.

Genome annotation databases

GeneIDi83785.
KEGGirno:83785.
UCSCiRGD:619991. rat. [P16612-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32167 mRNA. Translation: AAA41211.1.
AF215725 mRNA. Translation: AAF19211.1.
AF215726 mRNA. Translation: AAF19212.1.
AF222779 mRNA. Translation: AAF25958.1.
AY033506 mRNA. Translation: AAL07526.1.
AY033508 mRNA. Translation: AAL07528.1.
PIRiA35987.
RefSeqiNP_001103804.1. NM_001110334.2.
NP_001274036.1. NM_001287107.1. [P16612-1]
NP_001274037.1. NM_001287108.1. [P16612-2]
NP_001274039.1. NM_001287110.1. [P16612-4]
NP_001274040.1. NM_001287111.1.
NP_001274041.1. NM_001287112.1. [P16612-3]
NP_001274043.1. NM_001287114.1.
NP_114024.2. NM_031836.3.
UniGeneiRn.1923.

3D structure databases

ProteinModelPortaliP16612.
SMRiP16612. Positions 37-134, 166-214.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249830. 1 interaction.
STRINGi10116.ENSRNOP00000026637.

PTM databases

PhosphoSiteiP16612.

Proteomic databases

PaxDbiP16612.
PRIDEiP16612.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi83785.
KEGGirno:83785.
UCSCiRGD:619991. rat. [P16612-1]

Organism-specific databases

CTDi7422.
RGDi619991. Vegfa.

Phylogenomic databases

eggNOGiENOG410IGCM. Eukaryota.
ENOG410ZWYU. LUCA.
HOGENOMiHOG000072704.
HOVERGENiHBG000105.
InParanoidiP16612.
KOiK05448.
PhylomeDBiP16612.

Miscellaneous databases

PROiP16612.

Gene expression databases

GenevisibleiP16612. RN.

Family and domain databases

Gene3Di2.10.160.10. 1 hit.
2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
IPR027928. VEGF_C.
[Graphical view]
PfamiPF00341. PDGF. 1 hit.
PF14554. VEGF_C. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
SSF57593. SSF57593. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor."
    Conn G., Bayne M.L., Soderman D.D., Kwok P.W., Sullivan K.A., Palisi T.M., Hope D.A., Thomas K.A.
    Proc. Natl. Acad. Sci. U.S.A. 87:2628-2633(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF-A164), PROTEIN SEQUENCE OF 27-190.
  2. "Developmental expression of vascular endothelial growth factor in the masseter muscle of rats."
    Ishii H., Oota I., Takuma T., Inomata K.
    Arch. Oral Biol. 46:77-82(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS VEGF-A188; VEGF-A164; VEGF-A144 AND VEGF-A120).
  3. "Cloning of multiple VEGF splice variants from hypoxic neonatal rat cardiomyocytes."
    Marion S., Lee T.-C.
    Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS VEGF-A164 AND VEGF-A188).
    Strain: Sprague-Dawley.
  4. "Purification and characterization of a naturally occurring vascular endothelial growth factor.placenta growth factor heterodimer."
    DiSalvo J., Bayne M.L., Conn G., Kwok P.W., Trivedi P.G., Soderman D.D., Palisi T.M., Sullivan K.A., Thomas K.A.
    J. Biol. Chem. 270:7717-7723(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 27-40, HETERODIMERIZATION WITH PGF.
    Tissue: Glial tumor.
  5. "Regulation of VEGF and VEGF receptor expression in the rodent mammary gland during pregnancy, lactation, and involution."
    Pepper M.S., Baetens D., Mandriota S.J., Di Sanza C., Oikemus S., Lane T.F., Soriano J.V., Montesano R., Iruela-Arispe M.L.
    Dev. Dyn. 218:507-524(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiVEGFA_RAT
AccessioniPrimary (citable) accession number: P16612
Secondary accession number(s): Q541S6
, Q91ZE1, Q9JKX7, Q9QXG6, Q9QXG7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 16, 2001
Last modified: July 6, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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 one 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.