PSMC2

PSMC2
Identifiers
Aliases	PSMC2 , MSS1, Nbla10058, S7, proteasome 26S subunit, ATPase 2, RPT1
External IDs	OMIM: 154365; MGI: 109555; HomoloGene: 2096; GeneCards: PSMC2; OMA:PSMC2 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7q22.1 Start 103,328,570 bp [1] End 103,370,346 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5 A3|5 9.97 cM Start 21,990,281 bp [2] End 22,008,785 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm visceral pleura palpebral conjunctiva parietal pleura tibia trabecular bone oral cavity thoracic diaphragm right ventricle germinal epithelium Top expressed in facial motor nucleus primitive streak motor neuron superior cervical ganglion medullary collecting duct seminiferous tubule ureter fossa hair follicle barrel cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding ATPase activity protein binding TBP-class protein binding ATP binding hydrolase activity proteasome-activating activity Cellular component nuclear proteasome complex proteasome regulatory particle, base subcomplex membrane proteasome accessory complex nucleoplasm cytosolic proteasome complex proteasome complex nucleus extracellular region cytoplasm cytosol secretory granule lumen ficolin-1-rich granule lumen P-body cytoplasmic ribonucleoprotein granule dendritic spine Biological process positive regulation of RNA polymerase II transcription preinitiation complex assembly regulation of cellular amino acid metabolic process antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent ubiquitin-dependent protein catabolic process regulation of mRNA stability positive regulation of canonical Wnt signaling pathway protein polyubiquitination stimulatory C-type lectin receptor signaling pathway tumor necrosis factor-mediated signaling pathway MAPK cascade Fc-epsilon receptor signaling pathway protein catabolic process NIK/NF-kappaB signaling osteoblast differentiation ubiquitin-dependent ERAD pathway anaphase-promoting complex-dependent catabolic process T cell receptor signaling pathway negative regulation of canonical Wnt signaling pathway proteasome-mediated ubiquitin-dependent protein catabolic process Wnt signaling pathway, planar cell polarity pathway viral process positive regulation of proteasomal protein catabolic process negative regulation of G2/M transition of mitotic cell cycle protein deubiquitination SCF-dependent proteasomal ubiquitin-dependent protein catabolic process neutrophil degranulation transmembrane transport regulation of transcription from RNA polymerase II promoter in response to hypoxia post-translational protein modification regulation of hematopoietic stem cell differentiation interleukin-1-mediated signaling pathway regulation of mitotic cell cycle phase transition Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5701 19181 Ensembl ENSG00000161057 ENSMUSG00000028932 UniProt P35998 P46471 Q8BVQ9 RefSeq (mRNA) NM_001204453 NM_002803 NM_011188 NM_001368661 RefSeq (protein) NP_001191382 NP_002794 NP_035318 NP_001355590 Location (UCSC) Chr 7: 103.33 – 103.37 Mb Chr 5: 21.99 – 22.01 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

26S protease regulatory subunit 7, also known as 26S proteasome AAA-ATPase subunit Rpt1, is an enzyme that in humans is encoded by the PSMC2 gene ^{[5] [6] [7]} This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex. ^[8] Six 26S proteasome AAA-ATPase subunits (Rpt1 (this protein), Rpt2, Rpt3, Rpt4, Rpt5, and Rpt6) together with four non-ATPase subunits (Rpn1, Rpn2, Rpn10, and Rpn13) form the base sub complex of 19S regulatory particle for proteasome complex. ^[8]

Gene

The gene PSMC2 encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. This subunit has been shown to interact with several of the basal transcription factors so, in addition to participation in proteasome functions, this subunit may participate in the regulation of transcription. This subunit may also compete with PSMC3 for binding to the HIV tat protein to regulate the interaction between the viral protein and the transcription complex. ^[7] The human PSMC2 gene has 13 exons and locates at chromosome band 7q22.1-q22.3.

Protein

The human protein 26S protease regulatory subunit 7 is 48.6kDa in size and composed of 433 amino acids. The calculated theoretical pI of this protein is 526S protease regulatory subunit 5.71. One expression isoform is generated by alternative splicing, in which 1–137 of the amino acid sequence is missing. ^[9]

Complex assembly

26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin-like activities. These proteolytic active sites located in the inner side of a chamber formed by 4 stacked rings of 20S subunits, preventing random protein-enzyme encounter and uncontrolled protein degradation. The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, open the gate of 20S core particle, and guide the substrate into the proteolytic chamber. To meet such functional complexity, 19S regulatory particle contains at least 18 constitutive subunits. These subunits can be categorized into two classes based on the ATP dependence of subunits, ATP-dependent subunits and ATP-independent subunits. According to the protein interaction and topological characteristics of this multisubunit complex, the 19S regulatory particle is composed of a base and a lid subcomplex. The base consists of a ring of six AAA ATPases (Subunit Rpt1–6, systematic nomenclature) and four non-ATPase subunits (Rpn1, Rpn2, Rpn10, and Rpn13). Thus, 26S protease regulatory subunit 4 (Rpt2) is an essential component of forming the base subcomplex of 19S regulatory particle. For the assembly of 19S base sub complex, four sets of pivotal assembly chaperons (Hsm3/S5b, Nas2/P27, Nas6/P28, and Rpn14/PAAF1, nomenclature in yeast/mammals) were identified by four groups independently. ^{[10] [11] [12] [13] [14] [15]} These 19S regulatory particle base-dedicated chaperons all binds to individual ATPase subunits through the C-terminal regions. For example, Hsm3/S5b binds to the subunit Rpt1 (this protein) and Rpt2, Nas2/p27 to Rpt5, Nas6/p28 to Rpt3, and Rpn14/PAAAF1 to Rpt6, respectively. Subsequently, three intermediate assembly modules are formed as following, the Nas6/p28-Rpt3-Rpt6-Rpn14/PAAF1 module, the Nas2/p27-Rpt4-Rpt5 module, and the Hsm3/S5b-Rpt1-Rpt2-Rpn2 module. Eventually, these three modules assemble together to form the heterohexameric ring of 6 Atlases with Rpn1. The final addition of Rpn13 indicates the completion of 19S base sub complex assembly. ^[8]

Function

As the degradation machinery that is responsible for ~70% of intracellular proteolysis, ^[16] proteasome complex (26S proteasome) plays a critical roles in maintaining the homeostasis of cellular proteome. Accordingly, misfolded proteins and damaged protein need to be continuously removed to recycle amino acids for new synthesis; in parallel, some key regulatory proteins fulfill their biological functions via selective degradation; furthermore, proteins are digested into peptides for MHC class I antigen presentation. To meet such complicated demands in biological process via spatial and temporal proteolysis, protein substrates have to be recognized, recruited, and eventually hydrolyzed in a well controlled fashion. Thus, 19S regulatory particle pertains a series of important capabilities to address these functional challenges. To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special degradative tag, the ubiquitinylation. It also have subunits that can bind with nucleotides (e.g., ATPs) in order to facilitate the association between 19S and 20S particles, as well as to cause confirmation changes of alpha subunit C-terminals that form the substrate entrance of 20S complex. The ATPases subunits assemble into a six-membered ring with a sequence of Rpt1–Rpt5–Rpt4–Rpt3–Rpt6–Rpt2, which interacts with the seven-membered alpha ring of 20S core particle and establishes an asymmetric interface between the 19S RP and the 20S CP. ^{[17] [18]} Three C-terminal tails with HbYX motifs of distinct Rpt ATPases insert into pockets between two defined alpha subunits of the CP and regulate the gate opening of the central channels in the CP alpha ring. ^{[19] [20]}

Interactions

PSMC2 has been shown to interact with:

• NDC80, ^[21]
• PSMC1, ^{[22] [23]}
• PSMC4, ^{[23] [24]} and
• PSMD5. ^{[22] [25]}

References

1. GRCh38: Ensembl release 89: ENSG00000161057 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028932 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Tanahashi N, Suzuki M, Fujiwara T, Takahashi E, Shimbara N, Chung CH, Tanaka K (March 1998). "Chromosomal localization and immunological analysis of a family of human 26S proteasomal ATPases". Biochem Biophys Res Commun. 243 (1): 229–32. doi:10.1006/bbrc.1997.7892. PMID   9473509.
6. Shibuya H, Irie K, Ninomiya-Tsuji J, Goebl M, Taniguchi T, Matsumoto K (July 1992). "New human gene encoding a positive modulator of HIV Tat-mediated transactivation". Nature. 357 (6380): 700–2. Bibcode:1992Natur.357..700S. doi:10.1038/357700a0. PMID   1377363. S2CID   4343919.
7. "Entrez Gene: PSMC2 proteasome (prosome, macropain) 26S subunit, ATPase, 2".
8. Gu ZC, Enenkel C (Dec 2014). "Proteasome assembly". Cellular and Molecular Life Sciences. 71 (24): 4729–45. doi:10.1007/s00018-014-1699-8. PMC   11113775 . PMID   25107634. S2CID   15661805.
9. "Uniprot: P35998 - PRS7_HUMAN".
10. Le Tallec B, Barrault MB, Guérois R, Carré T, Peyroche A (Feb 2009). "Hsm3/S5b participates in the assembly pathway of the 19S regulatory particle of the proteasome". Molecular Cell. 33 (3): 389–99. doi: 10.1016/j.molcel.2009.01.010 . PMID   19217412.
11. Funakoshi M, Tomko RJ, Kobayashi H, Hochstrasser M (May 2009). "Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base". Cell. 137 (5): 887–99. doi:10.1016/j.cell.2009.04.061. PMC   2718848 . PMID   19446322.
12. Park S, Roelofs J, Kim W, Robert J, Schmidt M, Gygi SP, Finley D (Jun 2009). "Hexameric assembly of the proteasomal ATPases is templated through their C termini". Nature. 459 (7248): 866–70. Bibcode:2009Natur.459..866P. doi:10.1038/nature08065. PMC   2722381 . PMID   19412160.
13. Roelofs J, Park S, Haas W, Tian G, McAllister FE, Huo Y, Lee BH, Zhang F, Shi Y, Gygi SP, Finley D (Jun 2009). "Chaperone-mediated pathway of proteasome regulatory particle assembly". Nature. 459 (7248): 861–5. Bibcode:2009Natur.459..861R. doi:10.1038/nature08063. PMC   2727592 . PMID   19412159.
14. Saeki Y, Toh-E A, Kudo T, Kawamura H, Tanaka K (May 2009). "Multiple proteasome-interacting proteins assist the assembly of the yeast 19S regulatory particle". Cell. 137 (5): 900–13. doi: 10.1016/j.cell.2009.05.005 . PMID   19446323. S2CID   14151131.
15. Kaneko T, Hamazaki J, Iemura S, Sasaki K, Furuyama K, Natsume T, Tanaka K, Murata S (May 2009). "Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones". Cell. 137 (5): 914–25. doi: 10.1016/j.cell.2009.05.008 . PMID   19490896. S2CID   18551885.
16. Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL (Sep 1994). "Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules". Cell. 78 (5): 761–71. doi:10.1016/s0092-8674(94)90462-6. PMID   8087844. S2CID   22262916.
17. Tian G, Park S, Lee MJ, Huck B, McAllister F, Hill CP, Gygi SP, Finley D (Nov 2011). "An asymmetric interface between the regulatory and core particles of the proteasome". Nature Structural & Molecular Biology. 18 (11): 1259–67. doi:10.1038/nsmb.2147. PMC   3210322 . PMID   22037170.
18. Lander GC, Estrin E, Matyskiela ME, Bashore C, Nogales E, Martin A (Feb 2012). "Complete subunit architecture of the proteasome regulatory particle". Nature. 482 (7384): 186–91. Bibcode:2012Natur.482..186L. doi:10.1038/nature10774. PMC   3285539 . PMID   22237024.
19. Gillette TG, Kumar B, Thompson D, Slaughter CA, DeMartino GN (Nov 2008). "Differential roles of the COOH termini of AAA subunits of PA700 (19 S regulator) in asymmetric assembly and activation of the 26 S proteasome". The Journal of Biological Chemistry. 283 (46): 31813–22. doi: 10.1074/jbc.M805935200 . PMC   2581596 . PMID   18796432.
20. Smith DM, Chang SC, Park S, Finley D, Cheng Y, Goldberg AL (Sep 2007). "Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry". Molecular Cell. 27 (5): 731–44. doi:10.1016/j.molcel.2007.06.033. PMC   2083707 . PMID   17803938.
21. Chen Y, Sharp ZD, Lee WH (September 1997). "HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins". J. Biol. Chem. 272 (38): 24081–7. doi: 10.1074/jbc.272.38.24081 . PMID   9295362.
22. Gorbea C, Taillandier D, Rechsteiner M (January 2000). "Mapping subunit contacts in the regulatory complex of the 26 S proteasome. S2 and S5b form a tetramer with ATPase subunits S4 and S7". J. Biol. Chem. 275 (2): 875–82. doi: 10.1074/jbc.275.2.875 . PMID   10625621.
23. Hartmann-Petersen R, Tanaka K, Hendil KB (February 2001). "Quaternary structure of the ATPase complex of human 26S proteasomes determined by chemical cross-linking". Arch. Biochem. Biophys. 386 (1): 89–94. doi:10.1006/abbi.2000.2178. PMID   11361004.
24. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.
25. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.

Further reading

• Coux O, Tanaka K, Goldberg AL (1996). "Structure and functions of the 20S and 26S proteasomes". Annu. Rev. Biochem. 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID   8811196.
• Goff SP (2003). "Death by deamination: a novel host restriction system for HIV-1". Cell. 114 (3): 281–3. doi: 10.1016/S0092-8674(03)00602-0 . PMID   12914693. S2CID   16340355.
• Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID   1602151.
• Nacken W, Kingsman AJ, Kingsman SM, Sablitzky F, Sorg C (1995). "A homologue of the human MSS1 gene, a positive modulator of HIV-1 gene expression, is massively expressed in Xenopus oocytes". Biochim. Biophys. Acta. 1261 (2): 293–5. doi:10.1016/0167-4781(95)00022-9. PMID   7711076.
• Ghislain M, Udvardy A, Mann C (1993). "S. cerevisiae 26S protease mutants arrest cell division in G2/metaphase". Nature. 366 (6453): 358–62. Bibcode:1993Natur.366..358G. doi:10.1038/366358a0. PMID   8247132. S2CID   2168133.
• Dubiel W, Ferrell K, Rechsteiner M (1993). "Peptide sequencing identifies MSS1, a modulator of HIV Tat-mediated transactivation, as subunit 7 of the 26 S protease". FEBS Lett. 323 (3): 276–8. Bibcode:1993FEBSL.323..276D. doi:10.1016/0014-5793(93)81356-5. PMID   8500623. S2CID   26726988.
• Seeger M, Ferrell K, Frank R, Dubiel W (1997). "HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation". J. Biol. Chem. 272 (13): 8145–8. doi: 10.1074/jbc.272.13.8145 . PMID   9079628.
• Chen Y, Sharp ZD, Lee WH (1997). "HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins". J. Biol. Chem. 272 (38): 24081–7. doi: 10.1074/jbc.272.38.24081 . PMID   9295362.
• Madani N, Kabat D (1998). "An Endogenous Inhibitor of Human Immunodeficiency Virus in Human Lymphocytes Is Overcome by the Viral Vif Protein". J. Virol. 72 (12): 10251–5. doi:10.1128/JVI.72.12.10251-10255.1998. PMC   110608 . PMID   9811770.
• Simon JH, Gaddis NC, Fouchier RA, Malim MH (1998). "Evidence for a newly discovered cellular anti-HIV-1 phenotype". Nat. Med. 4 (12): 1397–400. doi:10.1038/3987. PMID   9846577. S2CID   25235070.
• Zheng L, Chen Y, Lee WH (1999). "Hec1p, an Evolutionarily Conserved Coiled-Coil Protein, Modulates Chromosome Segregation through Interaction with SMC Proteins". Mol. Cell. Biol. 19 (8): 5417–28. doi:10.1128/mcb.19.8.5417. PMC   84384 . PMID   10409732.
• Gorbea C, Taillandier D, Rechsteiner M (2000). "Mapping subunit contacts in the regulatory complex of the 26 S proteasome. S2 and S5b form a tetramer with ATPase subunits S4 and S7". J. Biol. Chem. 275 (2): 875–82. doi: 10.1074/jbc.275.2.875 . PMID   10625621.
• Mulder LC, Muesing MA (2000). "Degradation of HIV-1 integrase by the N-end rule pathway". J. Biol. Chem. 275 (38): 29749–53. doi: 10.1074/jbc.M004670200 . PMID   10893419.
• Hwang J, Fauzi H, Fukuda K, Sekiya S, Kakiuchi N, Shimotohno K, Taira K, Kusakabe I, Nishikawa S (2001). "The RNA aptamer-binding site of hepatitis C virus NS3 protease". Biochem. Biophys. Res. Commun. 279 (2): 557–62. doi:10.1006/bbrc.2000.4007. PMID   11118325.
• Yanagi S, Shimbara N, Tamura Ta (2001). "Tissue and cell distribution of a mammalian proteasomal ATPase, MSS1, and its complex formation with the basal transcription factors". Biochem. Biophys. Res. Commun. 279 (2): 568–73. doi:10.1006/bbrc.2000.3969. PMID   11118327.
• Hartmann-Petersen R, Tanaka K, Hendil KB (2001). "Quaternary structure of the ATPase complex of human 26S proteasomes determined by chemical cross-linking". Arch. Biochem. Biophys. 386 (1): 89–94. doi:10.1006/abbi.2000.2178. PMID   11361004.
• Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002). "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein". Nature. 418 (6898): 646–50. Bibcode:2002Natur.418..646S. doi:10.1038/nature00939. PMID   12167863. S2CID   4403228.