| 词条 | PSMC5 |
| 释义 |
GeneThe gene PSMC5 encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. In addition to participation in proteasome functions, this subunit may participate in transcriptional regulation since it has been shown to interact with the thyroid hormone receptor and retinoid X receptor-alpha.[3] The human PSMC5 gene has 13 exons and locates at chromosome band 17q23.3. ProteinThe human protein 26S protease regulatory subunit 8 is 45.6kDa in size and composed of 406 amino acids. The calculated theoretical pI of this protein is 8.23.[5] Complex assembly26S 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 substate 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.[6][7][8][9][10][11] 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 and Rpt2 (this protein), Nas2/p27 to Rpt5, Nas6/p28 to Rpt3, and Rpn14/PAAAF1 to Rpt6 (this protein), 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.[4] FunctionAs the degradation machinery that is responsible for ~70% of intracellular proteolysis,[12] 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 substate 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 eastablishs an asymmetric interface between the 19S RP and the 20S CP.[13][14] 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.[15][16] Evidence showed that ATPase subunit Rpt5, along with other ubuiqintinated 19S proteasome subunits (Rpn13, Rpn10) and the deubiquitinating enzyme Uch37, can be ubiquitinated in situ by proteasome-associating ubiquitination enzymes. Ubiquitination of proteasome subunits can regulates proteasomal activity in response to the alteration of cellular ubiquitination levels.[17] InteractionsPSMC5 has been shown to interact with:
References1. ^{{cite journal | vauthors = Tanahashi N, Suzuki M, Fujiwara T, Takahashi E, Shimbara N, Chung CH, Tanaka K | title = Chromosomal localization and immunological analysis of a family of human 26S proteasomal ATPases | journal = Biochem Biophys Res Commun | volume = 243 | issue = 1 | pages = 229–32 | date = March 1998 | pmid = 9473509 | pmc = | doi = 10.1006/bbrc.1997.7892 }} 2. ^{{cite journal | vauthors = Hoyle J, Tan KH, Fisher EM | title = Localization of genes encoding two human one-domain members of the AAA family: PSMC5 (the thyroid hormone receptor-interacting protein, TRIP1) and PSMC3 (the Tat-binding protein, TBP1) | journal = Hum Genet | volume = 99 | issue = 2 | pages = 285–8 | date = March 1997 | pmid = 9048938 | pmc = | doi = 10.1007/s004390050356 }} 3. ^1 {{cite web | title = Entrez Gene: PSMC5 proteasome (prosome, macropain) 26S subunit, ATPase, 5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5705| accessdate = }} 4. ^1 2 {{cite journal | vauthors = Gu ZC, Enenkel C | title = Proteasome assembly | journal = Cellular and Molecular Life Sciences | volume = 71 | issue = 24 | pages = 4729–45 | date = Dec 2014 | pmid = 25107634 | doi = 10.1007/s00018-014-1699-8 }} 5. ^{{cite web|title=Uniprot: P62195 - PRS8_HUMAN|url=https://www.uniprot.org/uniprot/P62195}} 6. ^{{cite journal | vauthors = Le Tallec B, Barrault MB, Guérois R, Carré T, Peyroche A | title = Hsm3/S5b participates in the assembly pathway of the 19S regulatory particle of the proteasome | journal = Molecular Cell | volume = 33 | issue = 3 | pages = 389–99 | date = Feb 2009 | pmid = 19217412 | doi = 10.1016/j.molcel.2009.01.010 }} 7. ^{{cite journal | vauthors = Funakoshi M, Tomko RJ, Kobayashi H, Hochstrasser M | title = Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base | journal = Cell | volume = 137 | issue = 5 | pages = 887–99 | date = May 2009 | pmid = 19446322 | pmc = 2718848 | doi = 10.1016/j.cell.2009.04.061 }} 8. ^{{cite journal | vauthors = Park S, Roelofs J, Kim W, Robert J, Schmidt M, Gygi SP, Finley D | title = Hexameric assembly of the proteasomal ATPases is templated through their C termini | journal = Nature | volume = 459 | issue = 7248 | pages = 866–70 | date = Jun 2009 | pmid = 19412160 | pmc = 2722381 | doi = 10.1038/nature08065 | bibcode = 2009Natur.459..866P }} 9. ^{{cite journal | vauthors = Roelofs J, Park S, Haas W, Tian G, McAllister FE, Huo Y, Lee BH, Zhang F, Shi Y, Gygi SP, Finley D | title = Chaperone-mediated pathway of proteasome regulatory particle assembly | journal = Nature | volume = 459 | issue = 7248 | pages = 861–5 | date = Jun 2009 | pmid = 19412159 | pmc = 2727592 | doi = 10.1038/nature08063 | bibcode = 2009Natur.459..861R }} 10. ^{{cite journal | vauthors = Saeki Y, Toh-E A, Kudo T, Kawamura H, Tanaka K | title = Multiple proteasome-interacting proteins assist the assembly of the yeast 19S regulatory particle | journal = Cell | volume = 137 | issue = 5 | pages = 900–13 | date = May 2009 | pmid = 19446323 | doi = 10.1016/j.cell.2009.05.005 }} 11. ^{{cite journal | vauthors = Kaneko T, Hamazaki J, Iemura S, Sasaki K, Furuyama K, Natsume T, Tanaka K, Murata S | title = Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones | journal = Cell | volume = 137 | issue = 5 | pages = 914–25 | date = May 2009 | pmid = 19490896 | doi = 10.1016/j.cell.2009.05.008 }} 12. ^{{cite journal | vauthors = Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL | title = Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules | journal = Cell | volume = 78 | issue = 5 | pages = 761–71 | date = Sep 1994 | pmid = 8087844 | doi=10.1016/s0092-8674(94)90462-6}} 13. ^{{cite journal | vauthors = Tian G, Park S, Lee MJ, Huck B, McAllister F, Hill CP, Gygi SP, Finley D | title = An asymmetric interface between the regulatory and core particles of the proteasome | journal = Nature Structural & Molecular Biology | volume = 18 | issue = 11 | pages = 1259–67 | date = Nov 2011 | pmid = 22037170 | pmc = 3210322 | doi = 10.1038/nsmb.2147 }} 14. ^{{cite journal | vauthors = Lander GC, Estrin E, Matyskiela ME, Bashore C, Nogales E, Martin A | title = Complete subunit architecture of the proteasome regulatory particle | journal = Nature | volume = 482 | issue = 7384 | pages = 186–91 | date = Feb 2012 | pmid = 22237024 | pmc = 3285539 | doi = 10.1038/nature10774 | bibcode = 2012Natur.482..186L }} 15. ^{{cite journal | vauthors = Gillette TG, Kumar B, Thompson D, Slaughter CA, DeMartino GN | title = Differential roles of the COOH termini of AAA subunits of PA700 (19 S regulator) in asymmetric assembly and activation of the 26 S proteasome | journal = The Journal of Biological Chemistry | volume = 283 | issue = 46 | pages = 31813–31822 | date = Nov 2008 | pmid = 18796432 | pmc = 2581596 | doi = 10.1074/jbc.M805935200 }} 16. ^{{cite journal | vauthors = Smith DM, Chang SC, Park S, Finley D, Cheng Y, Goldberg AL | title = Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry | journal = Molecular Cell | volume = 27 | issue = 5 | pages = 731–744 | date = Sep 2007 | pmid = 17803938 | pmc = 2083707 | doi = 10.1016/j.molcel.2007.06.033 }} 17. ^{{cite journal | vauthors = Jacobson AD, MacFadden A, Wu Z, Peng J, Liu CW | title = Autoregulation of the 26S proteasome by in situ ubiquitination | journal = Molecular Biology of the Cell | volume = 25 | issue = 12 | pages = 1824–35 | date = Jun 2014 | pmid = 24743594 | pmc = 4055262 | doi = 10.1091/mbc.E13-10-0585 }} 18. ^{{cite journal | vauthors = Ishizuka T, Satoh T, Monden T, Shibusawa N, Hashida T, Yamada M, Mori M | title = Human immunodeficiency virus type 1 Tat binding protein-1 is a transcriptional coactivator specific for TR | journal = Mol. Endocrinol. | volume = 15 | issue = 8 | pages = 1329–43 | date = August 2001 | pmid = 11463857 | doi = 10.1210/mend.15.8.0680 }} 19. ^{{cite journal | vauthors = 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 | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | bibcode = 2005Natur.437.1173R }} 20. ^{{cite journal | vauthors = 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 | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Mol. Syst. Biol. | volume = 3 | issue = | pages = 89 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 | year = 2007 }} 21. ^{{cite journal | vauthors = Su K, Yang X, Roos MD, Paterson AJ, Kudlow JE | title = Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1 | journal = Biochem. J. | volume = 348 Pt 2 | issue = 2| pages = 281–9 | date = June 2000 | pmid = 10816420 | pmc = 1221064 | doi = 10.1042/0264-6021:3480281| series = 348 }} 22. ^{{cite journal | vauthors = Wang YT, Chuang JY, Shen MR, Yang WB, Chang WC, Hung JJ | title = Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process | journal = J. Mol. Biol. | volume = 380 | issue = 5 | pages = 869–85 | date = July 2008 | pmid = 18572193 | doi = 10.1016/j.jmb.2008.05.043 }} 23. ^{{cite journal | vauthors = Weeda G, Rossignol M, Fraser RA, Winkler GS, Vermeulen W, van 't Veer LJ, Ma L, Hoeijmakers JH, Egly JM | title = The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor | journal = Nucleic Acids Res. | volume = 25 | issue = 12 | pages = 2274–83 | date = June 1997 | pmid = 9173976 | pmc = 146752 | doi = 10.1093/nar/25.12.2274}} Further reading{{refbegin|33em}}
|
| 随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。