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{{Infobox_gene}}
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'''26S protease regulatory subunit S10B''', also known as '''26S proteasome AAA-ATPase subunit Rpt4''',is an [[enzyme]] that in humans is encoded by the ''PSMC6'' [[gene]].<ref name="pmid8674546">{{cite journal | vauthors = Fujiwara T, Watanabe TK, Tanaka K, Slaughter CA, DeMartino GN | title = cDNA cloning of p42, a shared subunit of two proteasome regulatory proteins, reveals a novel member of the AAA protein family | journal = FEBS Letters | volume = 387 | issue = 2–3 | pages = 184–8 | date = Jun 1996 | pmid = 8674546 | pmc =  | doi = 10.1016/0014-5793(96)00489-9 }}</ref><ref name="pmid9473509">{{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 = Biochemical and Biophysical Research Communications | volume = 243 | issue = 1 | pages = 229–32 | date = Feb 1998 | pmid = 9473509 | pmc =  | doi = 10.1006/bbrc.1997.7892 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PSMC6 proteasome (prosome, macropain) 26S subunit, ATPase, 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5706| accessdate = }}</ref> This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex<ref name = "Gu_2014">{{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 }}</ref> Six 26S proteasome AAA-ATPase subunits ([[PSMC2|Rpt1]], [[PSMC1|Rpt2]], [[PSMC4|Rpt3]], Rpt4 (this protein), [[PSMC3|Rpt5]], and [[PSMC5|Rpt6]])  together with four non-ATPase subunits ([[PSMD2|Rpn1]], [[PSMD1|Rpn2]], [[PSMD4|Rpn10]], and [[ADRM1|Rpn13]]) form the base sub complex of 19S regulatory particle for [[proteasome]] complex.<ref name = "Gu_2014"/>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Gene ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Proteasome (prosome, macropain) 26S subunit, ATPase, 6
| HGNCid = 9553
| Symbol = PSMC6
| AltSymbols =; CADP44; MGC12520; P44; SUG2; p42
| OMIM = 602708
| ECnumber = 
| Homologene = 2099
| MGIid = 1914339
| GeneAtlas_image1 = PBB_GE_PSMC6_201699_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}} {{GNF_GO|id=GO:0016887 |text = ATPase activity}} {{GNF_GO|id=GO:0030674 |text = protein binding, bridging}}
| Component = {{GNF_GO|id=GO:0000502 |text = proteasome complex (sensu Eukaryota)}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005829 |text = cytosol}}
| Process = {{GNF_GO|id=GO:0006511 |text = ubiquitin-dependent protein catabolic process}} {{GNF_GO|id=GO:0030163 |text = protein catabolic process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5706
    | Hs_Ensembl = ENSG00000100519
    | Hs_RefseqProtein = NP_002797
    | Hs_RefseqmRNA = NM_002806
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 14
    | Hs_GenLoc_start = 52243668
    | Hs_GenLoc_end = 52264463
    | Hs_Uniprot = P62333
    | Mm_EntrezGene = 67089
    | Mm_Ensembl = ENSMUSG00000021832
    | Mm_RefseqmRNA = NM_025959
    | Mm_RefseqProtein = NP_080235
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 14
    | Mm_GenLoc_start = 44251722
    | Mm_GenLoc_end = 44271565
    | Mm_Uniprot = Q14AQ1
  }}
}}
'''Proteasome (prosome, macropain) 26S subunit, ATPase, 6''', also known as '''PSMC6''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PSMC6 proteasome (prosome, macropain) 26S subunit, ATPase, 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5706| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
The gene ''PSMC6'' encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. Pseudogenes have been identified on chromosomes 8 and 12.<ref name="entrez"/> The human gene ''PSMC6''  has 15 exons and locates at chromosome band 14q22.1.
{{PBB_Summary
 
| section_title =  
== Protein ==
| summary_text = 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 one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. Pseudogenes have been identified on chromosomes 8 and 12.<ref name="entrez">{{cite web | title = Entrez Gene: PSMC6 proteasome (prosome, macropain) 26S subunit, ATPase, 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5706| accessdate = }}</ref>
 
}}
The human protein 26S protease regulatory subunit S10B is 44kDa in size and composed of 389 amino acids. The calculated theoretical pI of this protein is 7.09.<ref>{{cite web|title=Uniprot: P62333 - PRS10_HUMAN|url=http://www.uniprot.org/uniprot/P62333}}</ref>
 
== 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 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 ([[PSMD2|Rpn1]], [[PSMD1|Rpn2]], [[PSMD4|Rpn10]], and [[ARDM1|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.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref> 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 [[PSMC2|Rpt1]] and Rpt2 (this protein), Nas2/p27 to [[PSMC3|Rpt5]], Nas6/p28 to [[PSMC4|Rpt3]], and Rpn14/PAAAF1 to [[PSMC5|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 [[ADRM1|Rpn13]] indicates the completion of 19S base sub complex assembly.<ref name = "Gu_2014"/>
 
== Function ==
 
As the degradation machinery that is responsible for ~70% of intracellular proteolysis,<ref>{{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}}</ref> 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.<ref>{{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 }}</ref><ref>{{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 }}</ref> 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.<ref>{{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 }}</ref><ref>{{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 }}</ref> Evidence showed that ATPase subunit Rpt5, along with other ubuiqintinated 19S proteasome subunits ([[ADRM1|Rpn13]], [[PSMD4|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.<ref>{{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 }}</ref>


==References==
==References==
{{reflist|2}}
{{reflist|33em}}
==Further reading==
 
{{refbegin | 2}}
== Further reading ==
{{PBB_Further_reading
{{refbegin|33em}}
| citations =
* {{cite journal | vauthors = Coux O, Tanaka K, Goldberg AL | title = Structure and functions of the 20S and 26S proteasomes | journal = Annual Review of Biochemistry | volume = 65 | issue =  | pages = 801–47 | year = 1996 | pmid = 8811196 | doi = 10.1146/annurev.bi.65.070196.004101 }}
*{{cite journal | author=Coux O, Tanaka K, Goldberg AL |title=Structure and functions of the 20S and 26S proteasomes. |journal=Annu. Rev. Biochem. |volume=65 |issue=  |pages= 801-47 |year= 1996 |pmid= 8811196 |doi= 10.1146/annurev.bi.65.070196.004101 }}
* {{cite journal | vauthors = Hastings R, Walker G, Eyheralde I, Dawson S, Billett M, Mayer RJ | title = Activator complexes containing the proteasomal regulatory ATPases S10b (SUG2) and S6 (TBP1) in different tissues and organisms | journal = Molecular Biology Reports | volume = 26 | issue = 1–2 | pages = 35–8 | date = Apr 1999 | pmid = 10363644 | doi = 10.1023/A:1006903903534 }}
*{{cite journal | author=Hastings R, Walker G, Eyheralde I, ''et al.'' |title=Activator complexes containing the proteasomal regulatory ATPases S10b (SUG2) and S6 (TBP1) in different tissues and organisms. |journal=Mol. Biol. Rep. |volume=26 |issue= 1-2 |pages= 35-8 |year= 1999 |pmid= 10363644 |doi= }}
* {{cite journal | vauthors = Goff SP | title = Death by deamination: a novel host restriction system for HIV-1 | journal = Cell | volume = 114 | issue = 3 | pages = 281–3 | date = Aug 2003 | pmid = 12914693 | doi = 10.1016/S0092-8674(03)00602-0 }}
*{{cite journal | author=Goff SP |title=Death by deamination: a novel host restriction system for HIV-1. |journal=Cell |volume=114 |issue= 3 |pages= 281-3 |year= 2003 |pmid= 12914693 |doi= }}
* {{cite journal | vauthors = DeMartino GN, Proske RJ, Moomaw CR, Strong AA, Song X, Hisamatsu H, Tanaka K, Slaughter CA | title = Identification, purification, and characterization of a PA700-dependent activator of the proteasome | journal = The Journal of Biological Chemistry | volume = 271 | issue = 6 | pages = 3112–8 | date = Feb 1996 | pmid = 8621709 | doi = 10.1074/jbc.271.6.3112 }}
*{{cite journal | author=DeMartino GN, Proske RJ, Moomaw CR, ''et al.'' |title=Identification, purification, and characterization of a PA700-dependent activator of the proteasome. |journal=J. Biol. Chem. |volume=271 |issue= 6 |pages= 3112-8 |year= 1996 |pmid= 8621709 |doi= }}
* {{cite journal | vauthors = Seeger M, Ferrell K, Frank R, Dubiel W | title = HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation | journal = The Journal of Biological Chemistry | volume = 272 | issue = 13 | pages = 8145–8 | date = Mar 1997 | pmid = 9079628 | doi = 10.1074/jbc.272.13.8145 }}
*{{cite journal  | author=Fujiwara T, Watanabe TK, Tanaka K, ''et al.'' |title=cDNA cloning of p42, a shared subunit of two proteasome regulatory proteins, reveals a novel member of the AAA protein family. |journal=FEBS Lett. |volume=387 |issue= 2-3 |pages= 184-8 |year= 1996 |pmid= 8674546 |doi=  }}
* {{cite journal | vauthors = Tipler CP, Hutchon SP, Hendil K, Tanaka K, Fishel S, Mayer RJ | title = Purification and characterization of 26S proteasomes from human and mouse spermatozoa | journal = Molecular Human Reproduction | volume = 3 | issue = 12 | pages = 1053–60 | date = Dec 1997 | pmid = 9464850 | doi = 10.1093/molehr/3.12.1053 }}
*{{cite journal | author=Seeger M, Ferrell K, Frank R, Dubiel W |title=HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation. |journal=J. Biol. Chem. |volume=272 |issue= 13 |pages= 8145-8 |year= 1997 |pmid= 9079628 |doi= }}
* {{cite journal | vauthors = Madani N, Kabat D | title = An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein | journal = Journal of Virology | volume = 72 | issue = 12 | pages = 10251–5 | date = Dec 1998 | pmid = 9811770 | pmc = 110608 | doi =  }}
*{{cite journal | author=Tipler CP, Hutchon SP, Hendil K, ''et al.'' |title=Purification and characterization of 26S proteasomes from human and mouse spermatozoa. |journal=Mol. Hum. Reprod. |volume=3 |issue= 12 |pages= 1053-60 |year= 1998 |pmid= 9464850 |doi= }}
* {{cite journal | vauthors = Simon JH, Gaddis NC, Fouchier RA, Malim MH | title = Evidence for a newly discovered cellular anti-HIV-1 phenotype | journal = Nature Medicine | volume = 4 | issue = 12 | pages = 1397–400 | date = Dec 1998 | pmid = 9846577 | doi = 10.1038/3987 }}
*{{cite journal  | author=Tanahashi N, Suzuki M, Fujiwara T, ''et al.'' |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 |year= 1998 |pmid= 9473509 |doi=  }}
* {{cite journal | vauthors = Russell SJ, Steger KA, Johnston SA | title = Subcellular localization, stoichiometry, and protein levels of 26 S proteasome subunits in yeast | journal = The Journal of Biological Chemistry | volume = 274 | issue = 31 | pages = 21943–52 | date = Jul 1999 | pmid = 10419517 | doi = 10.1074/jbc.274.31.21943 }}
*{{cite journal | author=Madani N, Kabat D |title=An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein. |journal=J. Virol. |volume=72 |issue= 12 |pages= 10251-5 |year= 1998 |pmid= 9811770 |doi=  }}
* {{cite journal | vauthors = Mulder LC, Muesing MA | title = Degradation of HIV-1 integrase by the N-end rule pathway | journal = The Journal of Biological Chemistry | volume = 275 | issue = 38 | pages = 29749–53 | date = Sep 2000 | pmid = 10893419 | doi = 10.1074/jbc.M004670200 }}
*{{cite journal | author=Simon JH, Gaddis NC, Fouchier RA, Malim MH |title=Evidence for a newly discovered cellular anti-HIV-1 phenotype. |journal=Nat. Med. |volume=4 |issue= 12 |pages= 1397-400 |year= 1998 |pmid= 9846577 |doi= 10.1038/3987 }}
* {{cite journal | vauthors = Russell SJ, Gonzalez F, Joshua-Tor L, Johnston SA | title = Selective chemical inactivation of AAA proteins reveals distinct functions of proteasomal ATPases | journal = Chemistry & Biology | volume = 8 | issue = 10 | pages = 941–50 | date = Oct 2001 | pmid = 11590019 | doi = 10.1016/S1074-5521(01)00060-6 }}
*{{cite journal | author=Russell SJ, Steger KA, Johnston SA |title=Subcellular localization, stoichiometry, and protein levels of 26 S proteasome subunits in yeast. |journal=J. Biol. Chem. |volume=274 |issue= 31 |pages= 21943-52 |year= 1999 |pmid= 10419517 |doi= }}
* {{cite journal | vauthors = Sheehy AM, Gaddis NC, Choi JD, Malim MH | title = Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein | journal = Nature | volume = 418 | issue = 6898 | pages = 646–50 | date = Aug 2002 | pmid = 12167863 | doi = 10.1038/nature00939 | bibcode = 2002Natur.418..646S }}
*{{cite journal | author=Mulder LC, Muesing MA |title=Degradation of HIV-1 integrase by the N-end rule pathway. |journal=J. Biol. Chem. |volume=275 |issue= 38 |pages= 29749-53 |year= 2000 |pmid= 10893419 |doi= 10.1074/jbc.M004670200 }}
* {{cite journal | vauthors = Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, Henke W, Sijts AJ, Kloetzel PM, Dubiel W | title = 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 = Journal of Molecular Biology | volume = 323 | issue = 4 | pages = 771–82 | date = Nov 2002 | pmid = 12419264 | doi = 10.1016/S0022-2836(02)00998-1 }}
*{{cite journal | author=Russell SJ, Gonzalez F, Joshua-Tor L, Johnston SA |title=Selective chemical inactivation of AAA proteins reveals distinct functions of proteasomal ATPases. |journal=Chem. Biol. |volume=8 |issue= 10 |pages= 941-50 |year= 2002 |pmid= 11590019 |doi= }}
* {{cite journal | vauthors = Reiser G, Bernstein HG | title = Neurons and plaques of Alzheimer's disease patients highly express the neuronal membrane docking protein p42IP4/centaurin alpha | journal = NeuroReport | volume = 13 | issue = 18 | pages = 2417–9 | date = Dec 2002 | pmid = 12499840 | doi = 10.1097/01.wnr.0000048005.96487.10 | doi-broken-date = 2017-01-15 }}
*{{cite journal | author=Sheehy AM, Gaddis NC, Choi JD, Malim MH |title=Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. |journal=Nature |volume=418 |issue= 6898 |pages= 646-50 |year= 2002 |pmid= 12167863 |doi= 10.1038/nature00939 }}
* {{cite journal | vauthors = Gaddis NC, Chertova E, Sheehy AM, Henderson LE, Malim MH | title = Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions | journal = Journal of Virology | volume = 77 | issue = 10 | pages = 5810–20 | date = May 2003 | pmid = 12719574 | pmc = 154025 | doi = 10.1128/JVI.77.10.5810-5820.2003 }}
*{{cite journal | author=Huang X, Seifert U, Salzmann U, ''et al.'' |title=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=J. Mol. Biol. |volume=323 |issue= 4 |pages= 771-82 |year= 2002 |pmid= 12419264 |doi= }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal | author=Reiser G, Bernstein HG |title=Neurons and plaques of Alzheimer's disease patients highly express the neuronal membrane docking protein p42IP4/centaurin alpha. |journal=Neuroreport |volume=13 |issue= 18 |pages= 2417-9 |year= 2003 |pmid= 12499840 |doi= 10.1097/01.wnr.0000048005.96487.10 }}
*{{cite journal | author=Gaddis NC, Chertova E, Sheehy AM, ''et al.'' |title=Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions. |journal=J. Virol. |volume=77 |issue= 10 |pages= 5810-20 |year= 2003 |pmid= 12719574 |doi= }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{Proteasome subunits}}
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Revision as of 18:51, 7 September 2017

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SpeciesHumanMouse
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26S protease regulatory subunit S10B, also known as 26S proteasome AAA-ATPase subunit Rpt4,is an enzyme that in humans is encoded by the PSMC6 gene.[1][2][3] This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex[4] Six 26S proteasome AAA-ATPase subunits (Rpt1, Rpt2, Rpt3, Rpt4 (this protein), 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.[4]

Gene

The gene PSMC6 encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. Pseudogenes have been identified on chromosomes 8 and 12.[3] The human gene PSMC6 has 15 exons and locates at chromosome band 14q22.1.

Protein

The human protein 26S protease regulatory subunit S10B is 44kDa in size and composed of 389 amino acids. The calculated theoretical pI of this protein is 7.09.[5]

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 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, 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]

Function

As 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]

References

  1. ↑ Fujiwara T, Watanabe TK, Tanaka K, Slaughter CA, DeMartino GN (Jun 1996). "cDNA cloning of p42, a shared subunit of two proteasome regulatory proteins, reveals a novel member of the AAA protein family". FEBS Letters. 387 (2–3): 184–8. doi:10.1016/0014-5793(96)00489-9. PMID 8674546.
  2. ↑ Tanahashi N, Suzuki M, Fujiwara T, Takahashi E, Shimbara N, Chung CH, Tanaka K (Feb 1998). "Chromosomal localization and immunological analysis of a family of human 26S proteasomal ATPases". Biochemical and Biophysical Research Communications. 243 (1): 229–32. doi:10.1006/bbrc.1997.7892. PMID 9473509.
  3. ↑ 3.0 3.1 "Entrez Gene: PSMC6 proteasome (prosome, macropain) 26S subunit, ATPase, 6".
  4. ↑ 4.0 4.1 4.2 Gu ZC, Enenkel C (Dec 2014). "Proteasome assembly". Cellular and Molecular Life Sciences. 71 (24): 4729–45. doi:10.1007/s00018-014-1699-8. PMID 25107634.
  5. ↑ "Uniprot: P62333 - PRS10_HUMAN".
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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): 31813–31822. doi:10.1074/jbc.M805935200. PMC 2581596. PMID 18796432.
  16. ↑ 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): 731–744. doi:10.1016/j.molcel.2007.06.033. PMC 2083707. PMID 17803938.
  17. ↑ Jacobson AD, MacFadden A, Wu Z, Peng J, Liu CW (Jun 2014). "Autoregulation of the 26S proteasome by in situ ubiquitination". Molecular Biology of the Cell. 25 (12): 1824–35. doi:10.1091/mbc.E13-10-0585. PMC 4055262. PMID 24743594.

Further reading

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