PSMD9
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| Location (UCSC) | Chr 12: 121.89 – 121.92 Mb | Chr 5: 123.31 – 123.39 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
26S proteasome non-ATPase regulatory subunit 9 is an enzyme that in humans is encoded by the PSMD9 gene.[5][6]
Function
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator.[6]
Clinical significance
The proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future.
The proteasomes form a pivotal component for the
Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including
Gene expression levels of the proteasomal subunits (
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000110801 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029440 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 9653651.
- ^ a b "Entrez Gene: PSMD9 proteasome (prosome, macropain) 26S subunit, non-ATPase, 9".
- PMID 24457024.
- PMID 9383453.
- S2CID 14103185.
- PMID 25324717.
- PMID 24380730.
- PMID 25133688.
- PMID 25651176.
- ^ PMID 10723801.
- PMID 25560147.
- PMID 10899438.
- ^ S2CID 2211658.
- ^ S2CID 22396490.
- S2CID 28190967.
- S2CID 5780576.
- PMID 12792671.
- PMID 23220331.
- PMID 20159828.
- S2CID 7073263.
- PMID 12654543.
- S2CID 26973319.
- PMID 12375310.
- PMID 25157275.
- PMID 22818443.
Further reading
- Coux O, Tanaka K, Goldberg AL (1996). "Structure and functions of the 20S and 26S proteasomes". Annual Review of Biochemistry. 65 (1): 801–47. PMID 8811196.
- Goff SP (Aug 2003). "Death by deamination: a novel host restriction system for HIV-1". Cell. 114 (3): 281–3. S2CID 16340355.
- Seeger M, Ferrell K, Frank R, Dubiel W (Mar 1997). "HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation". The Journal of Biological Chemistry. 272 (13): 8145–8. PMID 9079628.
- Madani N, Kabat D (Dec 1998). "An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein". Journal of Virology. 72 (12): 10251–5. PMID 9811770.
- Simon JH, Gaddis NC, Fouchier RA, Malim MH (Dec 1998). "Evidence for a newly discovered cellular anti-HIV-1 phenotype". Nature Medicine. 4 (12): 1397–400. S2CID 25235070.
- Thomas MK, Yao KM, Tenser MS, Wong GG, Habener JF (Dec 1999). "Bridge-1, a novel PDZ-domain coactivator of E2A-mediated regulation of insulin gene transcription". Molecular and Cellular Biology. 19 (12): 8492–504. PMID 10567574.
- Tanahashi N, Murakami Y, Minami Y, Shimbara N, Hendil KB, Tanaka K (May 2000). "Hybrid proteasomes. Induction by interferon-gamma and contribution to ATP-dependent proteolysis". The Journal of Biological Chemistry. 275 (19): 14336–45. PMID 10799514.
- Mulder LC, Muesing MA (Sep 2000). "Degradation of HIV-1 integrase by the N-end rule pathway". The Journal of Biological Chemistry. 275 (38): 29749–53. PMID 10893419.
- Ciarallo S, Subramaniam V, Hung W, Lee JH, Kotchetkov R, Sandhu C, Milic A, Slingerland JM (May 2002). "Altered p27(Kip1) phosphorylation, localization, and function in human epithelial cells resistant to transforming growth factor beta-mediated G(1) arrest". Molecular and Cellular Biology. 22 (9): 2993–3002. PMID 11940657.
- Sheehy AM, Gaddis NC, Choi JD, Malim MH (Aug 2002). "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein". Nature. 418 (6898): 646–50. S2CID 4403228.
- Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, Henke W, Sijts AJ, Kloetzel PM, Dubiel W (Nov 2002). "The RTP site shared by the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen processing". Journal of Molecular Biology. 323 (4): 771–82. PMID 12419264.
- Gaddis NC, Chertova E, Sheehy AM, Henderson LE, Malim MH (May 2003). "Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions". Journal of Virology. 77 (10): 5810–20. PMID 12719574.
- Lecossier D, Bouchonnet F, Clavel F, Hance AJ (May 2003). "Hypermutation of HIV-1 DNA in the absence of the Vif protein". Science. 300 (5622): 1112. S2CID 20591673.
- Hedberg Y, Ljungberg B, Roos G, Landberg G (May 2003). "Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray". British Journal of Cancer. 88 (9): 1417–23. PMID 12778072.
- Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L (Jul 2003). "The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA". Nature. 424 (6944): 94–8. PMID 12808465.
- Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D (Jul 2003). "Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts". Nature. 424 (6944): 99–103. S2CID 4347374.
- Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH (Jun 2003). "DNA deamination mediates innate immunity to retroviral infection". Cell. 113 (6): 803–9. S2CID 544971.