SpermatogenesisOnline 1.0

Tag Content
SG ID
SG00004744 
UniProt Accession
Theoretical PI
8.55  
Molecular Weight
32351 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Vdac1 
Gene Synonyms/Alias
Vdac5 
Protein Name
Voltage-dependent anion-selective channel protein 1 
Protein Synonyms/Alias
VDAC-1mVDAC1 Outer mitochondrial membrane protein porin 1; Plasmalemmal porin; Voltage-dependent anion-selective channel protein 5;VDAC-5mVDAC5 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:11;52174362-52202899;1
View in Ensembl genome browser  
Function in Stage
Uncertain 
Function in Cell Type
Uncertain 
Probability (GAS) of Function in Spermatogenesis
0.175250163 
The probability was calculated by GAS algorithm, ranging from 0 to 1. The closer it is to 1, the more possibly it functions in spermatogenesis.
Description
Temporarily unavailable 
Abstract of related literatures
1. Voltage-dependent anion channels (VDACs) are small pore-forming channels found in the mitochondrial outer membrane of all eukaryotes. VDACs conduct adenine nucleotides and are the binding sites for several cytosolic enzymes, including the isoforms of hexokinase and glycerol kinase. VDAC binding is developmentally and metabolically regulated and allows the kinases preferential access to mitochondrial ATP. Two human VDAC cDNAs have recently been identified, and a total of four VDAC loci have been mapped. Here, the isolation of two mouse VDAC cDNAs (VDAC5 and VDAC6) is described. By Northern analysis the two mouse VDAC isoforms show nearly identical expression patterns, with high levels of expression detected in heart, kidney, brain, and skeletal muscle and lesser levels of expression in all other tissues examined. The only exception is the lack of expression of VDAC5 in testes, whereas VDAC6 expression is highest in this tissue. VDAC6 appears to be encoded by more than one transcript. The mouse VDAC5 gene was mapped using an interspecies DNA mapping panel to the proximal region of chromosome 11, and the mouse VDAC6 gene was mapped using a panel to the proximal region of chromosome 14. PMID: [8660977] 

2. Voltage-dependent anion channels (VDACs) are pore-forming proteins (porins) that form the major pathway for movement of adenine nucleotides through the outer mitochondrial membrane. Electrophysiological studies indicate that VDAC-like channel activity is also prevalent in the cell membranes of many mammalian cells. However, the multitopological localization of porins outside the mitochondrion has remained an extremely controversial issue. Herein, we show that usage of two alternative first exons of the murine VDAC-1 gene leads to expression of two porins differing within their N termini. One porin (plasmalemmal VDAC-1) harboring a hydrophobic leader peptide is primarily targeted through the Golgi apparatus to the cell membrane. In contrast, the second isoform lacking the N-terminal leader (mitochondrial VDAC-1) is translocated more efficiently into the outer mitochondrial membrane. Thus, our data provide unique genetic evidence in favor of a multitopological localization of a mitochondrial porin. PMID: [10716730] 

3. This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development. PMID: [16141072] 

4. The mouse (Mus musculus) is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier MGSCv3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes). In addition, we identified 439 long, non-protein-coding RNAs with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not. PMID: [19468303] 

5. The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline. PMID: [15489334] 

6. Extracellular ATP regulates several elements of the mucus clearance process important for pulmonary host defense. However, the mechanisms mediating ATP release onto airway surfaces remain unknown. Mitochondrial voltage-dependent anion channels (mt-VDACs) translocate a variety of metabolites, including ATP and ADP, across the mitochondrial outer membrane, and a plasmalemmal splice variant (pl-VDAC-1) has been proposed to mediate ATP translocation across the plasma membrane. We tested the involvement of VDAC-1 in ATP release in a series of studies in murine cells. First, the full-length coding sequence was cloned from a mouse airway epithelial cell line (MTE7b-) and transfected into NIH 3T3 cells, and pl-VDAC-1-transfected cells exhibited higher rates of ATP release in response to medium change compared with mock-transfected cells. Second, ATP release was compared in cells isolated from VDAC-1 knockout [VDAC-1 (-/-)] and wild-type (WT) mice. Fibroblasts from VDAC-1 (-/-) mice released less ATP than WT mice in response to a medium change. Well-differentiated cultures from nasal and tracheal epithelia of VDAC-1 (-/-) mice exhibited less ATP release in response to luminal hypotonic challenge than WT mice. Confocal microscopy studies revealed that cell volume acutely increased in airway epithelia from both VDAC-1 (-/-) and WT mice after luminal hypotonic challenge, but VDAC-1 (-/-) cells exhibited a slower regulatory volume decrease (RVD) than WT cells. Addition of ATP or apyrase to the luminal surface of VDAC-1 (-/-) or WT cultures with hypotonic challenge produced similar initial cell height responses and RVD kinetics in both cell types, suggesting that involvement of VDAC-1 in RVD is through ATP release. Taken together, these studies suggest that VDAC-1, directly or indirectly, contributes to ATP release from murine cells. However, the observation that VDAC-1 knockout cells released a significant amount of ATP suggests that other molecules also play a role in this function. PMID: [15477379] 

7. Acetylation of proteins on lysine residues is a dynamic posttranslational modification that is known to play a key role in regulating transcription and other DNA-dependent nuclear processes. However, the extent of this modification in diverse cellular proteins remains largely unknown, presenting a major bottleneck for lysine-acetylation biology. Here we report the first proteomic survey of this modification, identifying 388 acetylation sites in 195 proteins among proteins derived from HeLa cells and mouse liver mitochondria. In addition to regulators of chromatin-based cellular processes, nonnuclear localized proteins with diverse functions were identified. Most strikingly, acetyllysine was found in more than 20% of mitochondrial proteins, including many longevity regulators and metabolism enzymes. Our study reveals previously unappreciated roles for lysine acetylation in the regulation of diverse cellular pathways outside of the nucleus. The combined data sets offer a rich source for further characterization of the contribution of this modification to cellular physiology and human diseases. PMID: [16916647] 

8. Metazoans employ reversible tyrosine phosphorylation to regulate innumerable biological processes. Thus, the large-scale identification of tyrosine phosphorylation sites from primary tissues is an essential step toward a molecular systems understanding of dynamic regulation in vivo. The relative paucity of phosphotyrosine has greatly limited its identification in large-scale phosphoproteomic experiments. However, using antiphosphotyrosine peptide immunoprecipitations, we report the largest study to date of tyrosine phosphorylation sites from primary tissue, identifying 414 unique tyrosine phosphorylation sites from murine brain. To measure the conservation of phosphorylated tyrosines and their surrounding residues, we constructed a computational pipeline and identified patterns of conservation within the signature of phosphotyrosine. PMID: [18034455] 

9. Activity-dependent protein phosphorylation is a highly dynamic yet tightly regulated process essential for cellular signaling. Although recognized as critical for neuronal functions, the extent and stoichiometry of phosphorylation in brain cells remain undetermined. In this study, we resolved activity-dependent changes in phosphorylation stoichiometry at specific sites in distinct subcellular compartments of brain cells. Following highly sensitive phosphopeptide enrichment using immobilized metal affinity chromatography and mass spectrometry, we isolated and identified 974 unique phosphorylation sites on 499 proteins, many of which are novel. To further explore the significance of specific phosphorylation sites, we used isobaric peptide labels and determined the absolute quantity of both phosphorylated and non-phosphorylated peptides of candidate phosphoproteins and estimated phosphorylation stoichiometry. The analyses of phosphorylation dynamics using differentially stimulated synaptic terminal preparations revealed activity-dependent changes in phosphorylation stoichiometry of target proteins. Using this method, we were able to differentiate between distinct isoforms of Ca2+/calmodulin-dependent protein kinase (CaMKII) and identify a novel activity-regulated phosphorylation site on the glutamate receptor subunit GluR1. Together these data illustrate that mass spectrometry-based methods can be used to determine activity-dependent changes in phosphorylation stoichiometry on candidate phosphopeptides following large scale phosphoproteome analysis of brain tissue. PMID: [17114649] 

10. IMAC in combination with mass spectrometry is a promising approach for global analysis of protein phosphorylation. Nevertheless this approach suffers from two shortcomings: inadequate efficiency of IMAC and poor fragmentation of phosphopeptides in the mass spectrometer. Here we report optimization of the IMAC procedure using (32)P-labeled tryptic peptides and development of MS/MS/MS (MS3) for identifying phosphopeptide sequences and phosphorylation sites. The improved IMAC method allowed recovery of phosphorylated tryptic peptides up to approximately 77% with only minor retention of unphosphorylated peptides. MS3 led to efficient fragmentation of the peptide backbone in phosphopeptides for sequence assignment. Proteomics of mitochondrial phosphoproteins using the resulting IMAC protocol and MS3 revealed 84 phosphorylation sites in 62 proteins, most of which have not been reported before. These results revealed diverse phosphorylation pathways involved in the regulation of mitochondrial functions. Integration of the optimized batchwise IMAC protocol with MS3 offers a relatively simple and more efficient approach for proteomics of protein phosphorylation. PMID: [17208939] 

11. The voltage-dependent anion channel (VDAC) constitutes the major pathway for the entry and exit of metabolites across the outer membrane of the mitochondria and can serve as a scaffold for molecules that modulate the organelle. We report the crystal structure of a beta-barrel eukaryotic membrane protein, the murine VDAC1 (mVDAC1) at 2.3 A resolution, revealing a high-resolution image of its architecture formed by 19 beta-strands. Unlike the recent NMR structure of human VDAC1, the position of the voltage-sensing N-terminal segment is clearly resolved. The alpha-helix of the N-terminal segment is oriented against the interior wall, causing a partial narrowing at the center of the pore. This segment is ideally positioned to regulate the conductance of ions and metabolites passing through the VDAC pore. PMID: [18988731] 

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Function
Forms a channel through the mitochondrial outer membraneand also the plasma membrane. The channel at the outermitochondrial membrane allows diffusion of small hydrophilicmolecules; in the plasma membrane it is involved in cell volumeregulation and apoptosis. It adopts an open conformation at low orzero membrane potential and a closed conformation at potentialsabove 30-40 mV. The open state has a weak anion selectivitywhereas the closed state is cation-selective. May participate inthe formation of the permeability transition pore complex (PTPC)responsible for the release of mitochondrial products thattriggers apoptosis. 
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Subcellular Location
Isoform Pl-VDAC1: Cell membrane; Multi-passmembrane protein. 
Tissue Specificity
High levels of expression detected in heart,kidney, brain, and skeletal muscle. Not expressed in testis. 
Gene Ontology
GO IDGO termEvidence
GO:0005743 C:mitochondrial inner membrane IDA:MGI.
GO:0042645 C:mitochondrial nucleoid IEA:Compara.
GO:0005741 C:mitochondrial outer membrane ISO:MGI.
GO:0005886 C:plasma membrane IEA:UniProtKB-SubCell.
GO:0046930 C:pore complex IEA:UniProtKB-KW.
GO:0000166 F:nucleotide binding IEA:UniProtKB-KW.
GO:0015288 F:porin activity IEA:UniProtKB-KW.
GO:0008308 F:voltage-gated anion channel activity IDA:UniProtKB.
GO:0006915 P:apoptotic process IEA:UniProtKB-KW.
GO:0001662 P:behavioral fear response IMP:MGI.
GO:0007612 P:learning IMP:MGI.
GO:0007270 P:neuron-neuron synaptic transmission IMP:MGI.
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Interpro
IPR001925;    Porin_Euk.
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Pfam
PF01459;    Porin_3;    1.
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SMART
PROSITE
PS00558;    EUKARYOTIC_PORIN;    1.
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PRINTS
PR00185;    EUKARYTPORIN.;   
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Created Date
18-Oct-2012 
Record Type
GAS predicted 
Sequence Annotation
CHAIN         1    296       Voltage-dependent anion-selective channel
                             protein 1.
                             /FTId=PRO_0000050500.
TRANSMEM     39     46       Beta stranded.
TRANSMEM     52     61       Beta stranded.
TRANSMEM     67     77       Beta stranded.
TRANSMEM     82     89       Beta stranded.
TRANSMEM     93    101       Beta stranded.
TRANSMEM    108    117       Beta stranded.
TRANSMEM    123    132       Beta stranded.
TRANSMEM    136    145       Beta stranded.
TRANSMEM    149    158       Beta stranded.
TRANSMEM    162    171       Beta stranded.
TRANSMEM    178    188       Beta stranded.
TRANSMEM    191    198       Beta stranded.
TRANSMEM    202    211       Beta stranded.
TRANSMEM    215    223       Beta stranded.
TRANSMEM    230    239       Beta stranded.
TRANSMEM    244    251       Beta stranded.
TRANSMEM    255    264       Beta stranded.
TRANSMEM    268    276       Beta stranded.
TRANSMEM    286    296       Beta stranded.
NP_BIND     255    257       NAD (By similarity).
NP_BIND     273    277       NAD (By similarity).
SITE         86     86       Involved in hexokinase binding (By
                             similarity).
MOD_RES      14     14       N-acetylmethionine; in isoform Mt-VDAC1
                             (By similarity).
MOD_RES      26     26       Phosphoserine (By similarity).
MOD_RES      33     33       N6-acetyllysine.
MOD_RES      41     41       N6-acetyllysine.
MOD_RES      74     74       N6-acetyllysine.
MOD_RES      80     80       Phosphotyrosine.
MOD_RES     114    114       Phosphoserine (By similarity).
MOD_RES     117    117       Phosphoserine.
MOD_RES     120    120       Phosphothreonine (By similarity).
MOD_RES     150    150       Phosphoserine (By similarity).
MOD_RES     208    208       Phosphotyrosine.
MOD_RES     237    237       N6-acetyllysine.
MOD_RES     279    279       N6-acetyllysine (By similarity).
VAR_SEQ       1     13       Missing (in isoform Mt-VDAC1).
                             /FTId=VSP_005075.
HELIX        20     22
HELIX        25     32
STRAND       39     45
STRAND       49     61
TURN         62     64
STRAND       67     77
TURN         78     81
STRAND       82     89
STRAND       94    105
STRAND      108    116
TURN        118    120
STRAND      123    133
STRAND      136    144
STRAND      150    159
STRAND      162    171
TURN        172    175
STRAND      176    187
STRAND      189    198
TURN        199    201
STRAND      202    210
STRAND      212    224
STRAND      227    238
STRAND      241    251
STRAND      254    265
STRAND      268    279
TURN        281    283
STRAND      287    295
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Nucleotide Sequence
Length: 1767 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 296 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
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YwhabIntAct 
Dlg4IntAct 
Kcnma1IntAct 
PrkceIntAct 
Grin2bIntAct 
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