SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00001039 
UniProt Accession
Theoretical PI
9.25  
Molecular Weight
25283 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Vegfa 
Gene Synonyms/Alias
Vegf 
Protein Name
Vascular endothelial growth factor A 
Protein Synonyms/Alias
VEGF-A Vascular permeability factor;VPFFlags: Precursor 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:17;46153942-46169326;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Vascular endothelial growth factor (VEGF) is a key regulator of endothelial growth and permeability. VEGF may play a potential role in regulating the initial stages of the process of spermatogonial proliferation through VEGFR-2 and spermiogenesis through VEGFR-1. 
The information of related literatures
1. E. I. Korpelainen, M. J. Karkkainen, A. Tenhunen, M. Lakso, H. Rauvala, M. Vierula, M. Parvinen and K. Alitalo (1998) Overexpression of VEGF in testis and epididymis causes infertility in transgenic mice. J Cell Biol 143(6): 1705-12. 

Abstract
Vascular endothelial growth factor (VEGF) is a key regulator of endothelial growth and permeability. However, VEGF may also target nonendothelial cells, as VEGF receptors and responsiveness have been detected for example in monocytes, and high concentrations of VEGF have been reported in human semen. In this work we present evidence that overexpression of VEGF in the testis and epididymis of transgenic mice under the mouse mammary tumor virus (MMTV) LTR promoter causes infertility. The testes of the transgenic mice exhibited spermatogenic arrest and increased capillary density. The ductus epididymidis was dilated, containing areas of epithelial hyperplasia. The number of subepithelial capillaries in the epididymis was also increased and these vessels were highly permeable as judged by the detection of extravasated fibrinogen products. Intriguingly, the expression of VEGF receptor-1 (VEGFR-1) was detected in certain spermatogenic cells in addition to vascular endothelium, and both VEGFR-1 and VEGFR-2 were also found in the Leydig cells of the testis. The infertility of the MMTV-VEGF male mice could thus result from VEGF acting on both endothelial and nonendothelial cells of the male genital tract. Taken together, these findings suggest that the VEGF transgene has nonendothelial target cells in the testis and that VEGF may regulate male fertility. PMID: [9852161] 

2. A. Nalbandian, L. Dettin, M. Dym and N. Ravindranath (2003) Expression of vascular endothelial growth factor receptors during male germ cell differentiation in the mouse. Biol Reprod 69(3): 985-94. 

Abstract
Overexpression of vascular endothelial growth factor (VEGF) in the testis of transgenic mice induces infertility, suggesting a potential role for VEGF in the process of spermatogenesis. Spermatogenesis occurs within the confines of the seminiferous tubules, and the seminiferous epithelium lining these tubules consists of Sertoli cells and germ cells in various stages of maturation. We investigated the source of VEGF and VEGF-target cells within the seminiferous tubules of the normal mouse testis. Sections of testes fixed in Bouin solution and embedded in paraffin were subjected to immunofluorescent staining with specific antibodies against VEGF, and its receptors, VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1). Total RNA was extracted from isolated populations of Sertoli cells, type A spermatogonia, pachytene spermatocytes, and spermatids. Primer pairs specific for VEGF and its receptors were designed and reverse-transcriptase polymerase chain reaction (RT-PCR) was performed. Immunofluorescent studies indicated that VEGF is strongly expressed in the cytoplasm of Sertoli cells. VEGFR-1 and VEGFR-2 were not expressed by the Sertoli cell. In contrast, a differential expression of VEGF receptors was observed in germ cells. Although VEGFR-2 was expressed in the cytoplasm of type A spermatogonia, VEGFR-1 was expressed in the acrosomal region of spermatids and spermatozoa. Pachytene spermatocytes did not exhibit any staining. Further, we examined the transcription of VEGF and its receptors by RT-PCR. VEGF was actively transcribed only in Sertoli cells. The transcription of VEGFR-2 was confined to type A spermatogonia. Interestingly, VEGFR-1 was transcribed both in pachytene spermatocytes and round spermatids. The mRNA expression of VEGFR-1 and VEGFR-2 in germ cells was inversely correlated during postnatal development of the mouse testis. Thus, VEGF may play a potential role in regulating the initial stages of the process of spermatogonial proliferation through VEGFR-2 and spermiogenesis through VEGFR-1. PMID: [12773425] 

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Figures for illustrating the function of this protein/gene
Ref: E. I. Korpelainen, M. J. Karkkainen, A. Tenhunen, M. Lakso, H. Rauvala, M. Vierula, M. Parvinen and K. Alitalo (1998) Overexpression of VEGF in testis and epididymis causes infertility in transgenic mice. J Cell Biol 143(6): 1705-12. PMID: [9852161]
Ref: E. I. Korpelainen, M. J. Karkkainen, A. Tenhunen, M. Lakso, H. Rauvala, M. Vierula, M. Parvinen and K. Alitalo (1998) Overexpression of VEGF in testis and epididymis causes infertility in transgenic mice. J Cell Biol 143(6): 1705-12. PMID: [9852161]
Ref: E. I. Korpelainen, M. J. Karkkainen, A. Tenhunen, M. Lakso, H. Rauvala, M. Vierula, M. Parvinen and K. Alitalo (1998) Overexpression of VEGF in testis and epididymis causes infertility in transgenic mice. J Cell Biol 143(6): 1705-12. PMID: [9852161]
Ref: A. Nalbandian, L. Dettin, M. Dym and N. Ravindranath (2003) Expression of vascular endothelial growth factor receptors during male germ cell differentiation in the mouse. Biol Reprod 69(3): 985-94. PMID: [12773425]
Ref: A. Nalbandian, L. Dettin, M. Dym and N. Ravindranath (2003) Expression of vascular endothelial growth factor receptors during male germ cell differentiation in the mouse. Biol Reprod 69(3): 985-94. PMID: [12773425]
Ref: A. Nalbandian, L. Dettin, M. Dym and N. Ravindranath (2003) Expression of vascular endothelial growth factor receptors during male germ cell differentiation in the mouse. Biol Reprod 69(3): 985-94. PMID: [12773425]
Function
Growth factor active in angiogenesis, vasculogenesis andendothelial cell growth. Induces endothelial cell proliferation,promotes cell migration, inhibits apoptosis and inducespermeabilization of blood vessels. Binds to the FLT1/VEGFR1 andKDR/VEGFR2 receptors, heparan sulfate and heparin. May play a rolein increasing vascular permeability during lactation, whenincreased transport of molecules from the blood is required forefficient milk protein synthesis (By similarity). 
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Subcellular Location
Isoform VEGF-3: Cell membrane; Peripheralmembrane protein. Note=Remains cell-surface associated unlessreleased by heparin. 
Tissue Specificity
In developing embryos, expressed mainly in thechoroid plexus, paraventricular neuroepithelium, placenta andkidney glomeruli. Also found in bronchial epithelium, adrenalgland and in seminiferous tubules of testis. High expression ofVEGF continues in kidney glomeruli and choroid plexus in adults. 
Gene Ontology
GO IDGO termEvidence
GO:0009986 C:cell surface ISS:UniProtKB.
GO:0005615 C:extracellular space IDA:MGI.
GO:0005886 C:plasma membrane IEA:UniProtKB-SubCell.
GO:0030141 C:secretory granule ISS:UniProtKB.
GO:0043498 F:cell surface binding ISS:UniProtKB.
GO:0042056 F:chemoattractant activity ISS:UniProtKB.
GO:0008201 F:heparin binding ISS:UniProtKB.
GO:0032147 P:activation of protein kinase activity ISS:UniProtKB.
GO:0006916 P:anti-apoptosis IMP:MGI.
GO:0048844 P:artery morphogenesis IMP:MGI.
GO:0007610 P:behavior IMP:MGI.
GO:0048593 P:camera-type eye morphogenesis IMP:MGI.
GO:0048739 P:cardiac muscle fiber development IMP:MGI.
GO:0060948 P:cardiac vascular smooth muscle cell development IMP:BHF-UCL.
GO:0048469 P:cell maturation IMP:MGI.
GO:0002042 P:cell migration involved in sprouting angiogenesis ISS:UniProtKB.
GO:0008283 P:cell proliferation IMP:MGI.
GO:0071456 P:cellular response to hypoxia ISS:UniProtKB.
GO:0060982 P:coronary artery morphogenesis IMP:BHF-UCL.
GO:0003169 P:coronary vein morphogenesis IMP:BHF-UCL.
GO:0071542 P:dopaminergic neuron differentiation IGI:MGI.
GO:0035767 P:endothelial cell chemotaxis ISS:UniProtKB.
GO:0030855 P:epithelial cell differentiation IMP:MGI.
GO:0042462 P:eye photoreceptor cell development IMP:MGI.
GO:0040007 P:growth IMP:MGI.
GO:0003007 P:heart morphogenesis IMP:MGI.
GO:0001701 P:in utero embryonic development IMP:MGI.
GO:0001822 P:kidney development IMP:MGI.
GO:0007595 P:lactation IMP:MGI.
GO:0030324 P:lung development IDA:MGI.
GO:0001945 P:lymph vessel development IMP:BHF-UCL.
GO:0030225 P:macrophage differentiation ISS:UniProtKB.
GO:0060749 P:mammary gland alveolus development IMP:MGI.
GO:0007498 P:mesoderm development IMP:MGI.
GO:0030224 P:monocyte differentiation ISS:UniProtKB.
GO:0003151 P:outflow tract morphogenesis IMP:BHF-UCL.
GO:0001541 P:ovarian follicle development IMP:MGI.
GO:0001569 P:patterning of blood vessels IMP:MGI.
GO:0090190 P:positive regulation of branching involved in ureteric bud morphogenesis IDA:UniProtKB.
GO:0051781 P:positive regulation of cell division IEA:UniProtKB-KW.
GO:0090050 P:positive regulation of cell migration involved in sprouting angiogenesis ISS:UniProtKB.
GO:0038091 P:positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway ISS:UniProtKB.
GO:0032793 P:positive regulation of CREB transcription factor activity ISS:UniProtKB.
GO:2001028 P:positive regulation of endothelial cell chemotaxis ISS:UniProtKB.
GO:0001938 P:positive regulation of endothelial cell proliferation IDA:MGI.
GO:0051894 P:positive regulation of focal adhesion assembly ISS:UniProtKB.
GO:0043406 P:positive regulation of MAP kinase activity ISS:UniProtKB.
GO:0002053 P:positive regulation of mesenchymal cell proliferation IDA:MGI.
GO:0002052 P:positive regulation of neuroblast proliferation IGI:MGI.
GO:0033138 P:positive regulation of peptidyl-serine phosphorylation ISS:UniProtKB.
GO:1900086 P:positive regulation of peptidyl-tyrosine autophosphorylation ISS:UniProtKB.
GO:0050927 P:positive regulation of positive chemotaxis ISS:UniProtKB.
GO:0031334 P:positive regulation of protein complex assembly ISS:UniProtKB.
GO:0090037 P:positive regulation of protein kinase C signaling cascade ISS:UniProtKB.
GO:0002092 P:positive regulation of receptor internalization ISS:UniProtKB.
GO:0045944 P:positive regulation of transcription from RNA polymerase II promoter IMP:BHF-UCL.
GO:0030949 P:positive regulation of vascular endothelial growth factor receptor signaling pathway ISS:UniProtKB.
GO:0043117 P:positive regulation of vascular permeability IDA:MGI.
GO:0031077 P:post-embryonic camera-type eye development IMP:MGI.
GO:0060319 P:primitive erythrocyte differentiation IMP:MGI.
GO:0008360 P:regulation of cell shape ISS:UniProtKB.
GO:0043129 P:surfactant homeostasis IMP:MGI.
GO:0048010 P:vascular endothelial growth factor receptor signaling pathway IDA:MGI.
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Interpro
IPR000072;    PD_growth_factor.
IPR023581;    PD_growth_factor_CS.
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Pfam
PF00341;    PDGF;    1.
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SMART
SM00141;    PDGF;    1.
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PROSITE
PS00249;    PDGF_1;    1.
PS50278;    PDGF_2;    1.
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PRINTS
Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
SIGNAL        1     26       By similarity.
CHAIN        27    214       Vascular endothelial growth factor A.
                             /FTId=PRO_0000023388.
MOD_RES     146    146       N6-acetyllysine (By similarity).
MOD_RES     148    148       N6-acetyllysine (By similarity).
MOD_RES     151    151       N6-acetyllysine (By similarity).
CARBOHYD    100    100       N-linked (GlcNAc...) (Probable).
DISULFID     51     93       By similarity.
DISULFID     76     76       Interchain (By similarity).
DISULFID     82    127       By similarity.
DISULFID     85     85       Interchain (By similarity).
DISULFID     86    129       By similarity.
VAR_SEQ       1      1       M -> MTDRQTDTAPSPSAHLLAGGLPTVDAAASREEPKPA
                             PGGGVEGVGARGIARKLFVQLLGSSRSVVAVVCAAGDKPIG
                             AGRSASSGLEKPGPEKRGEEEKEEERGPQWALGSQEPSSWT
                             GEAAVCADSAPAARAPQAPARASVPEGRGARQGAQESGLPR
                             SPSRRGSASRAGPGRASETM (in isoform L-VEGF-
                             1).
                             /FTId=VSP_038746.
VAR_SEQ     105    141       IMRIKPHQSQHIGEMSFLQHSRCECRPKKDRTKPEKK ->
                             VGTCGTGDGAGAGGGRRTVVQGGALEGCLGLCLGNFW (in
                             isoform VEGF-4).
                             /FTId=VSP_016418.
VAR_SEQ     105    128       IMRIKPHQSQHIGEMSFLQHSRCE -> VGTCGTGDGAGAG
                             GAGGQWYKEGH (in isoform VEGF-5).
                             /FTId=VSP_016419.
VAR_SEQ     129    214       Missing (in isoform VEGF-5).
                             /FTId=VSP_016420.
VAR_SEQ     140    140       K -> N (in isoform VEGF-1 and isoform L-
                             VEGF-1).
                             /FTId=VSP_004626.
VAR_SEQ     141    208       Missing (in isoform VEGF-2).
                             /FTId=VSP_004628.
VAR_SEQ     141    164       Missing (in isoform VEGF-1 and isoform L-
                             VEGF-1).
                             /FTId=VSP_004627.
VAR_SEQ     142    214       Missing (in isoform VEGF-4).
                             /FTId=VSP_016421.
CONFLICT     61     61       F -> I (in Ref. 3; AAC05442).
CONFLICT    117    118       GE -> ER (in Ref. 2; AAA40547).
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Nucleotide Sequence
Length: 661 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 214 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
Grin2bIntAct 
Ep300IntAct 
KdrIntAct 
Other Protein-Protein interaction resources
String database  
View Microarray data
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