SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00001078 
UniProt Accession
Theoretical PI
7.97  
Molecular Weight
21914 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Vegfb 
Gene Synonyms/Alias
Vrf 
Protein Name
Vascular endothelial growth factor B 
Protein Synonyms/Alias
VEGF-B VEGF-related factor;VRFFlags: Precursor 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:19;7056963-7062141;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Temporarily unavailable 
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 for endothelial cells. VEGF-B167 bindsheparin and neuropilin-1 whereas the binding to neuropilin-1 ofVEGF-B186 is regulated by proteolysis. VEGF-B seems to be requiredfor normal heart function in adult but is not required for properdevelopment of the cardiovascular system either during developmentor for angiogenesis in adults. 
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Subcellular Location
Secreted. Note=Secreted but remainsassociated to cells or to the extracellular matrix unless releasedby heparin. 
Tissue Specificity
Abundantly expressed in heart, brain, kidneyand skeletal muscle. 
Gene Ontology
GO IDGO termEvidence
GO:0005576 C:extracellular region IDA:MGI.
GO:0005615 C:extracellular space IEA:Compara.
GO:0005622 C:intracellular IDA:MGI.
GO:0016020 C:membrane IEA:InterPro.
GO:0042056 F:chemoattractant activity IEA:Compara.
GO:0008201 F:heparin binding IEA:UniProtKB-KW.
GO:0001525 P:angiogenesis IEA:UniProtKB-KW.
GO:0006916 P:anti-apoptosis IEA:Compara.
GO:0060048 P:cardiac muscle contraction IMP:MGI.
GO:0030154 P:cell differentiation IEA:UniProtKB-KW.
GO:0060976 P:coronary vasculature development IMP:MGI.
GO:0050930 P:induction of positive chemotaxis IEA:Compara.
GO:0010629 P:negative regulation of gene expression IEA:Compara.
GO:0043524 P:negative regulation of neuron apoptotic process IEA:Compara.
GO:0051781 P:positive regulation of cell division IEA:UniProtKB-KW.
GO:0001938 P:positive regulation of endothelial cell proliferation IEA:Compara.
GO:0070374 P:positive regulation of ERK1 and ERK2 cascade IEA:Compara.
GO:0060754 P:positive regulation of mast cell chemotaxis IEA:Compara.
GO:0050731 P:positive regulation of peptidyl-tyrosine phosphorylation IEA:Compara.
GO:0051897 P:positive regulation of protein kinase B signaling cascade IEA:Compara.
GO:0030949 P:positive regulation of vascular endothelial growth factor receptor signaling pathway IEA:Compara.
GO:0035470 P:positive regulation of vascular wound healing IEA:Compara.
GO:0006493 P:protein O-linked glycosylation 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     21       Potential.
CHAIN        22    207       Vascular endothelial growth factor B.
                             /FTId=PRO_0000023399.
DISULFID     47     89       By similarity.
DISULFID     72     72       Interchain (By similarity).
DISULFID     78    122       By similarity.
DISULFID     81     81       Interchain (By similarity).
DISULFID     82    124       By similarity.
VAR_SEQ     137    207       RVAIPHHRPQPRSVPGWDSTPGASSPADIIHPTPAPGSSAR
                             LAPSAVNALTPGPAAAAADAAASSIAKGGA -> SPRILCP
                             PCTQRRQRPDPRTCRCRCRRRRFLHCQGRGLELNPDTCRCR
                             KPRK (in isoform VEGF-B167).
                             /FTId=VSP_004641.
CONFLICT     69     69       V -> A (in Ref. 4; BAE28405).
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Nucleotide Sequence
Length: 1236 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 207 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
Itgb1MINT 
Poldip2String 
Poldip2String 
Other Protein-Protein interaction resources
String database  
View Microarray data
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