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Gene Symbol |
OAZ3 |
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Aliases |
AZ3, OAZ-t, TISP15 |
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Entrez Gene ID |
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Gene Name |
Ornithine decarboxylase antizyme 3 |
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Chromosomal Location |
1q21.3 |
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HGNC ID |
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Summary |
The protein encoded by this gene belongs to the ornithine decarboxylase antizyme family, which plays a role in cell growth and proliferation by regulating intracellular polyamine levels. Expression of antizymes requires +1 ribosomal frameshifting, which is enhanced by high levels of polyamines. Antizymes in turn bind to and inhibit ornithine decarboxylase (ODC), the key enzyme in polyamine biosynthesis; thus, completing the auto-regulatory circuit. This gene encodes antizyme 3, the third member of the antizyme family. Like antizymes 1 and 2, antizyme 3 inhibits ODC activity and polyamine uptake; however, it does not stimulate ODC degradation. Also, while antizymes 1 and 2 have broad tissue distribution, expression of antizyme 3 is restricted to haploid germ cells in testis, suggesting a distinct role for this antizyme in spermiogenesis. Antizyme 3 gene knockout studies showed that homozygous mutant male mice were infertile, and indicated the likely role of this antizyme in the formation of a rigid connection between the sperm head and tail during spermatogenesis. Alternatively spliced transcript variants encoding different isoforms, including one resulting from the use of non-AUG (CUG) translation initiation codon, have been found for this gene. [provided by RefSeq, Dec 2014]
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e!Ensembl
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| Protein Information |
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Protein Name |
Ornithine decarboxylase antizyme 3, ODC-Az 3, antizyme 3, testicular secretory protein Li 31 |
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Function |
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Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimers. Does not target the ODC monomers for degradation, which allows a protein synthesis-independent restoration of ODC activity (PubMed:17900240). Stabilizes AZIN2 by interfering with its ubiquitination. Involved in the translocation of AZNI2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol. Probably plays a key role in spermatogenesis by regulating the intracellular concentration of polyamines in haploid germ cells (By similarity). |
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UniProt |
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Pfam |
| Pfam Accession |
Pfam ID |
| PF02100 |
ODC_AZ |
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Interactions |
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| STRING |
MINT |
IntAct |
| ENSP00000360493 |
Q13950 |
Q13950 |
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View interactions
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Associated Diseases
| Disease group | Disease Name | References |
| Digestive System Diseases |
| Gastrointestinal Diseases |
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| Endocrine System Diseases |
| PCOS |
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| Neoplasms |
| Genital Neoplasms, Male |
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| Breast Cancer |
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| Nutritional and Metabolic Diseases |
| Obesity |
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| Reproductive disorders |
| Male infertility |
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| Infertility |
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| Teratozoospermia |
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References |
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| Wei Lina, Xin Chunlei, Wang Wenjuan, Hao Cuifang |
| Department of Reproductive Medical, The Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, PR China; Department of Reproductive Medical, Jining No. 1 People's Hospital, Jining, Shandong 272011, PR China.| Department of Hematology, Jining No. 1 People's Hospital, Jining, Shandong 272011, PR China.| Department of Reproductive Medical, The Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, PR China.| Department of Reproductive Medical, The Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, PR China. Electronic address: cuifang-hao@163.com. |
| Gene. 2018 Jun 30;661:85-94. doi: 10.1016/j.gene.2018.03.079. Epub 2018 Mar 28. |
Abstract
PURPOSE: This study aimed to screen key genes and pathways involved in obese polycystic ovary syndrome (PCOS), and predict drugs for treatment of obese PCOS via bioinformatics approaches. METHODS: Microarray dataset GSE10946 were downloaded from the Gene Expression Omnibus database, including 7 cumulus cell samples from obese PCOS patients and 6 lean control samples. Differentially expressed genes (DEGs) between obese PCOS and controls were obtained using Bayesian test after data preprocessing, followed by functional enrichment analyses for DEGs. Besides, protein-protein interaction (PPI) network and sub-network analyses were performed. Furthermore, drug prediction was carried out based on the DEGs. RESULTS: A total of 793 DEGs were identified in PCOS compared with control, including 352 up-regulated and 441 down-regulated DEGs. Specifically, upregulated RNA polymerase I subunit B (POLR1B), DNA polymerase epsilon 3, accessory subunit (POLE3), and DNA polymerase delta 3, accessory subunit (POLD3) were enriched in pathway of pyrimidine metabolism associated with obesity and PCOS, and 5-hydroxytryptamine receptor 2C (HTR2C) was enriched calcium signaling pathway. Additionally, 10 significant potential drugs, such as spironolactone targeting androgen receptor (AR), trimipramine targeting adrenoceptor beta 2 (ADRB2), and L-ornithine targeting ornithine decarboxylase antizyme 3 (OAZ3), were obtained. CONCLUSIONS: In conclusion, POLR1B, POLE3, POLD3, and HTR2C might play important roles in obese PCOS via involvement of pyrimidine metabolism and calcium signaling pathway. Moreover, AR, ADRB2, and OAZ3 might be targets of spironolactone, trimipramine, and L-ornithine in the treatment of obese PCOS. |
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| © 2019, Biomedical Informatics Centre, NIRRH |
National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai-400 012
Tel: 91-22-24192104, Fax No: 91-22-24139412
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