SpermatogenesisOnline 1.0

Tag Content
SG ID
SG00002561 
UniProt Accession
Theoretical PI
5.28  
Molecular Weight
178932 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Peg3 
Gene Synonyms/Alias
Kiaa0287, Pw1 
Protein Name
Paternally-expressed gene 3 protein 
Protein Synonyms/Alias
ASF-1; 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:7;6656603-6683132;-1
View in Ensembl genome browser  
Function in Stage
Uncertain 
Function in Cell Type
Uncertain 
Probability (GAS) of Function in Spermatogenesis
0.106954451 
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. Genetic and embryological studies in the mouse demonstrated functional differences between parental chromosomes during development. This is due to imprinted genes whose expression is dependent on their parental origin. In a recent systematic screen for imprinted genes, we detected Peg3 (paternally expressed gene 3). Peg3 is not expressed in parthenogenones. In interspecific hybrids, only the paternal copy of the gene is expressed in the embryos, individual tissues examined in d9.5-13.5 embryos, neonates and adults. Peg3 mRNA is a 9 kb transcript encoding an unusual zinc finger protein with eleven widely spaced C2H2 type motifs and two groups of amino acid repeats. Peg3 is expressed in early somites, branchial arches and other mesodermal tissues, as well as in the hypothalamus. Peg3 maps to the proximal region of chromosome 7. Consistent with our findings, maternal duplication of the proximal chromosome 7 causes neonatal lethality. This region is syntenic with human chromosome 19q13.1-13.3 (refs 10,11), where the genes for myotonic dystrophy and a putative tumour suppressor gene are located. PMID: [8563758] 

2.

BACKGROUND:

Mouse imprinted gene Peg3 encodes a large C2H2 type zinc finger protein with unique characteristics. Peg3 knockout mice were found to show an impairment in maternal behaviour of the adult female. Mouse Peg3 is located on the proximal region of chromosome 7 which is syntenic to the long arm of human chromosome 19. It has been reported that a loss of heterozygosity (LOH) of chromosome 19q occurs frequently in several glioma types. PMID: [11260267] 

3. We have accumulated information of the coding sequences of uncharacterized human genes, which are known as KIAA genes, and the number of these genes exceeds 2000 at present. As an extension of this sequencing project, we recently have begun to accumulate mouse KIAA-homologous cDNAs, because it would be useful to prepare a set of human and mouse homologous cDNA pairs for further functional analysis of the KIAA genes. We herein present the entire sequences of 400 mouse KIAA cDNA clones and 4 novel cDNA clones which were incidentally identified during this project. Most of clones entirely sequenced in this study were selected by computer-assisted analysis of terminal sequences of the cDNAs. The average size of the 404 cDNA sequences reached 5.3 kb and that of the deduced amino acid sequences from these cDNAs was 868 amino acid residues. The results of sequence analyses of these clones showed that single mouse KIAA cDNAs bridged two different human KIAA cDNAs in some cases, which indicated that these two human KIAA cDNAs were derived from single genes although they had been supposed to originate from different genes. Furthermore, we successfully mapped all the mouse KIAA cDNAs along the genome using a recently published mouse genome draft sequence. PMID: [12693553] 

4. 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] 

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. Peg3 is the first imprinted gene to be identified on mouse proximal chromosome 7; the human PEG3 homologue is on chromosome 19q13.4. Peg3 encodes a C(2)H(2)-type zinc finger protein that is expressed only from the paternal allele in embryos and adult brain. The gene has been shown to regulate maternal behavior and offspring growth and has been implicated in the TNF-NFkappaB signal pathway. Here we show that Peg3 consists of nine exons spanning 26 kb. The 5' region of the gene contains a region rich in repeated sequences and a CpG island. Analysis of expressed sequence tags revealed a transcript present upstream of the island and on the strand opposite to Peg3. These structural features and DNA sequences are conserved in mouse and human. The 5' region of Peg3 is preferentially methylated on the inactive maternal allele, as shown by comparing embryos with paternal (PatDp. prox7) and maternal (MatDp.prox7) duplication of proximal chromosome 7. Recently, a new maternally expressed Zim1 gene located downstream of Peg3 was identified, which suggested that another imprinted cluster is present on proximal chromosome 7. PMID: [10704281] 

7. The cellular and molecular processes leading to the establishment of the skeletal muscle lineage in the vertebrate are not well understood. The MyoD-related family of myogenic regulatory factors (MRFs) are expressed during somitogenesis although cells with myogenic capacity are present prior to gastrulation. We propose that regulatory genes exist that guide the skeletal muscle lineage during early development. In an effort to identify these regulatory genes, we performed a differential screening to isolate transcripts that are present in myogenic cells and in the embryo prior to MRF expression but absent in nonmyogenic fibroblasts. We report here the identification of Pw1. The Pw1 transcript is approximately 8.5 kb long and encodes a large protein containing 12 widespread C2H2 zinc fingers and 3 motifs containing periodic prolines and acidic residues. Consistent with the possibility that Pw1 is a transcription factor, we observe nuclear localization of the protein. Pw1 is strongly expressed upon gastrulation and subsequently becomes restricted to skeletal muscle and subregions of the central nervous system. Pw1 is initially expressed in all mesodermal cells early in development; however, its maintained expression in adult differentiated muscle suggests a specific role in the skeletal muscle lineage. Pw1 expression is cell cycle specific with levels highest during late M-phase. The gene is intronless which may facilitate transcription during cell division. At present, the precise function of Pw1 is not understood; however, we note that Pw1 maps to the proximal region of chromosome 7 near the axial segmentation mutant pudgy which shows severe perturbation of axial skeletal and muscle structures. PMID: [8806818] 

8. Tumor necrosis factor (TNF) mediates a variety of biological activities including cell proliferation, differentiation and programmed cell death. The specific response to TNF depends upon cell type and reflects the presence of specific regulatory proteins that participate in the TNF response pathway. TNF signal transduction is mediated by TRAF2 which binds the TNF Receptor2 (TNFR2) and activates NFkappaB. We previously identified a gene Pw1, which encodes a large zinc-finger containing protein. We have determined that Pw1 is identical to Peg3, a paternally expressed gene of unknown function (and will therefore be referred to as Peg3 throughout this text). We report here that Peg3 associates specifically with TRAF2 but not with other TRAF family members. Peg3 expression activates NFkappaB via IkappaB-NFkappaB dissociation and acts synergistically with TRAF2. Transfection of a truncated Peg3 containing the TRAF2 interaction site, abolishes NFkappaB activation by TRAF2 and/or TNF. We conclude that Peg3 is a regulator of the TNF response. These data reveal the involvement of an imprinted gene in this pathway. PMID: [9500555] 

9. Imprinted genes display parent-of-origin-dependent monoallelic expression that apparently regulates complex mammalian traits, including growth and behavior. The Peg3 gene is expressed in embryos and the adult brain from the paternal allele only. A mutation in the Peg3 gene resulted in growth retardation, as well as a striking impairment of maternal behavior that frequently resulted in death of the offspring. This result may be partly due to defective neuronal connectivity, as well as reduced oxytocin neurons in the hypothalamus, because mutant mothers were deficient in milk ejection. This study provides further insights on the evolution of epigenetic regulation of imprinted gene dosage in modulating mammalian growth and behavior. PMID: [10195900] 

10. Induction of wild-type p53 in mouse fibroblasts causes cell cycle arrest at the G(1) phase, whereas coexpression of p53 and the protooncogene c-myc induces apoptosis. Although p53 transcriptional activity generally is required for both pathways, the molecular components mediating p53-dependent apoptosis are not well understood. To identify factors that could mediate p53-induced cell death, we used a comparative RNA differential display procedure. We have identified Pw1/Peg3 as a gene product induced during p53/c-myc-mediated apoptosis. Pw1/Peg3 is not induced during p53-mediated G(1) growth arrest nor by c-myc alone. Although it is not clear whether the induction of Pw1/Peg3 depends on p53 activity, we show that Pw1/Peg3 interacts with a p53-inducible gene product Siah1a. We demonstrate that coexpression of Pw1/Peg3 with Siah1a induces apoptosis independently of p53 whereas expression of Pw1/Peg3 or Siah1a separately has no effect on cell death. These data suggest that Siah1a and Pw1/Peg3 cooperate in the p53-mediated cell death pathway. Furthermore, we show that inhibiting Pw1/Peg3 activity blocks p53-induced apoptosis. The observation that Pw1/Peg3 is necessary for the p53 apoptotic response suggests a pivotal role for this gene in determining cell death versus survival. PMID: [10681424] 

11. Genomic imprinting is the phenomenon whereby mono-allelic expression of certain genes occurs depending on their parental origin. The observation that imprinting only occurs in placental mammals has led to the suggestion that it may play a role in this form of reproduction. In the present study we have investigated the pattern of expression of the human PEG3 gene in the early to term placenta, as well as the uterus and ovary, using RT-PCR, northern blot and in situ hybridization. A comparison is made with the expression of Peg3 in the mouse by histochemical staining in betageo knock out mice. We have demonstrated high levels of PEG3 in the human placenta and have localized the signal to the layer of villous cytotrophoblast cells. In contrast, the pattern of expression of Peg3 in the mouse placenta is less restricted, the message being present in all trophoblast populations. Thus, expression of PEG3/Peg3 in the human and mouse placenta is not directly comparable. We have also detected PEG3 message in the ovarian stroma. We have sequenced the human PEG3 gene from exon 3 to exon 9. By utilizing a polymorphism detected in exon 9, we have established that only the paternal allele is expressed in human placenta. Human PEG3 is therefore maternally imprinted as in mouse. PMID: [11331620] 

12. Neuronal cell death after DNA damage requires p53 and Bax, but the mechanism by which p53 activation leads to Bax translocation and cell death in neurons is not known. We report here that Peg3/Pw1 is up-regulated after DNA damage in cortical neurons in a p53-dependent manner. Overexpression of Peg3/Pw1 leads to decreased neuronal viability. The deleterious effect of Peg3/Pw1 on neuronal survival is abrogated by deletion of either p53 or Bax, indicating an essential role for both in Peg3/Pw1-mediated neuronal death. Moreover, overexpression of a Peg3/Pw1 dominant negative protein inhibits Bax translocation and neuronal cell death after DNA damage. These findings implicate Peg3/Pw1 as a mediator between p53 and Bax in a neuronal cell death pathway activated by DNA damage. PMID: [11943780] 

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Function
Induces apoptosis in cooperation with SIAH1A. Acts as amediator between p53/TP53 and BAX in a neuronal death pathway thatis activated by DNA damage. Acts synergistically with TRAF2 andinhibits TNF induced apoptosis through activation of NF-kappa-B.Plays a role in regulating maternal behavior and offspring growth. 
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Subcellular Location
Nucleus. Cytoplasm. 
Tissue Specificity
Brain, glial cells, neurons, skeletal muscle,uterus and placenta. In the placenta it found in all trophoblastcells. 
Gene Ontology
GO IDGO termEvidence
GO:0005737 C:cytoplasm IEA:UniProtKB-SubCell.
GO:0005634 C:nucleus IEA:UniProtKB-SubCell.
GO:0003676 F:nucleic acid binding IEA:InterPro.
GO:0008270 F:zinc ion binding IEA:InterPro.
GO:0006915 P:apoptotic process IEA:UniProtKB-KW.
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Interpro
IPR007087;    Znf_C2H2.
IPR015880;    Znf_C2H2-like.
IPR013087;    Znf_C2H2/integrase_DNA-bd.
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Pfam
PF00096;    zf-C2H2;    4.
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SMART
SM00355;    ZnF_C2H2;    12.
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PROSITE
PS00028;    ZINC_FINGER_C2H2_1;    11.
PS50157;    ZINC_FINGER_C2H2_2;    12.
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PRINTS
Created Date
18-Oct-2012 
Record Type
GAS predicted 
Sequence Annotation
CHAIN         1   1571       Paternally-expressed gene 3 protein.
                             /FTId=PRO_0000249229.
REPEAT      942    946       1-1.
REPEAT      967    971       1-2.
REPEAT      987    991       2-1.
REPEAT      992    996       1-3.
REPEAT      997   1001       2-2.
REPEAT     1002   1006       1-4.
REPEAT     1007   1011       2-3.
REPEAT     1012   1016       1-5.
REPEAT     1017   1021       1-6.
REPEAT     1022   1026       1-7.
REPEAT     1027   1031       1-8.
REPEAT     1032   1036       1-9.
REPEAT     1047   1051       1-10.
ZN_FING     325    347       C2H2-type 1.
ZN_FING     378    400       C2H2-type 2.
ZN_FING     436    458       C2H2-type 3.
ZN_FING     520    542       C2H2-type 4.
ZN_FING     850    872       C2H2-type 5.
ZN_FING    1091   1113       C2H2-type 6.
ZN_FING    1147   1169       C2H2-type 7.
ZN_FING    1209   1231       C2H2-type 8.
ZN_FING    1266   1289       C2H2-type 9.
ZN_FING    1317   1339       C2H2-type 10; degenerate.
ZN_FING    1488   1510       C2H2-type 11.
ZN_FING    1547   1569       C2H2-type 12.
REGION      199    265       10 X 5 AA repeat of P-H-X-X-E.
REGION      199    265       3 X 5 AA repeat of P-H-D-D-K.
COMPBIAS    228    231       Poly-Ser.
COMPBIAS    695    698       Poly-Ser.
COMPBIAS    771    774       Poly-Ser.
VAR_SEQ     989   1048       Missing (in isoform 2).
                             /FTId=VSP_020375.
VAR_SEQ    1202   1254       PAVSGSAIRCRQCGQGFIHSSALNEHMRQHRDNEIMEQSEL
                             SDEIFIQGLALT -> ASSLPNSSGTTTPKFTRMSPMSMGP
                             PTPMPPFSPSPSGSTSHCTNAKIAASPS (in isoform
                             2).
                             /FTId=VSP_020376.
VAR_SEQ    1255   1571       Missing (in isoform 2).
                             /FTId=VSP_020377.
CONFLICT      5      5       E -> G (in Ref. 1 and 2).
CONFLICT    156    156       T -> A (in Ref. 1; AAB96922).
CONFLICT    321    321       G -> W (in Ref. 2; BAB85589).
CONFLICT    351    351       N -> T (in Ref. 6).
CONFLICT    370    371       KG -> RS (in Ref. 1 and 2).
CONFLICT    382    382       E -> V (in Ref. 2; BAB85589).
CONFLICT    403    403       E -> R (in Ref. 7).
CONFLICT    567    568       Missing (in Ref. 7).
CONFLICT    570    570       K -> E (in Ref. 2; BAB85589).
CONFLICT    608    608       R -> G (in Ref. 2; BAB85589).
CONFLICT    614    614       F -> S (in Ref. 2; BAB85589).
CONFLICT    645    645       K -> E (in Ref. 2; BAB85589).
CONFLICT    648    648       F -> L (in Ref. 1; AAB96922).
CONFLICT    660    660       Y -> C (in Ref. 1; AAB96922).
CONFLICT    669    669       G -> A (in Ref. 7).
CONFLICT    712    712       E -> K (in Ref. 7).
CONFLICT    736    737       ND -> MN (in Ref. 2; BAB85589).
CONFLICT    856    856       G -> R (in Ref. 7).
CONFLICT    979    979       D -> V (in Ref. 1; AAB96922).
CONFLICT   1011   1011       K -> E (in Ref. 7).
CONFLICT   1051   1051       E -> Q (in Ref. 5; AAH89344).
CONFLICT   1123   1123       E -> G (in Ref. 7).
CONFLICT   1171   1171       Missing (in Ref. 3; BAC65520).
CONFLICT   1181   1181       D -> Y (in Ref. 1 and 2).
CONFLICT   1401   1401       N -> I (in Ref. 1 and 2).
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Nucleotide Sequence
Length: 5560 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 1571 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
Other Protein-Protein interaction resources
String database  
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