| Structural highlights
Function
[PSA1_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Mediates the lipopolysaccharide-induced signal transduction in the macrophage proteasome (By similarity). Might be involved in the anti-inflammatory response of macrophages during the interaction with C.albicans heat-inactivated cells (By similarity). [PSB4_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Mediates the lipopolysaccharide-induced signal macrophage proteasome (By similarity). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.[1] [PSA4_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSA3_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2.[2] [3] [PSB2_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit has a trypsin-like activity. [PSA2_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation. [PRS6B_HUMAN] The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex.[4] [PSB5_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This unit is responsible of the chymotrypsin-like activity of the proteasome and is one of the principal target of the proteasome inhibitor bortezomib. May catalyze basal processing of intracellular antigens. Plays a role in the protection against oxidative damage through the Nrf2-ARE pathway (By similarity). [PRS8_HUMAN] The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. [PRS7_HUMAN] The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. In case of HIV-1 infection, positive modulator of Tat-mediated transactivation.[5] [PSB7_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This unit is responsible of the trypsin-like activity. [PSB1_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSA7_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Plays an important role in the regulation of cell proliferation or cell cycle control, transcriptional regulation, immune and stress response, cell differentiation, and apoptosis. Interacts with some important proteins involved in transcription factor regulation, cell cycle transition, viral replication and even tumor initiation and progression. Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions. Plays a role in hepatitis C virus internal ribosome entry site-mediated translation. Mediates nuclear translocation of the androgen receptor (AR) and thereby enhances androgen-mediated transactivation. Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response.[6] [7] [8] [9] [10] [PSA6_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PRS10_HUMAN] The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. [PRS6A_HUMAN] The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex (By similarity). In case of HIV-1 infection, suppresses Tat-mediated transactivation. [PSB3_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSB6_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This unit is responsible of the peptidyl glutamyl-like activity. May catalyze basal processing of intracellular antigens. [PRS4_HUMAN] The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. [PSA5_HUMAN] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.
Publication Abstract from PubMed
Protein degradation in eukaryotic cells is performed by the Ubiquitin-Proteasome System (UPS). The 26S proteasome holocomplex consists of a core particle (CP) that proteolytically degrades polyubiquitylated proteins, and a regulatory particle (RP) containing the AAA-ATPase module. This module controls access to the proteolytic chamber inside the CP and is surrounded by non-ATPase subunits (Rpns) that recognize substrates and deubiquitylate them before unfolding and degradation. The architecture of the 26S holocomplex is highly conserved between yeast and humans. The structure of the human 26S holocomplex described here reveals previously unidentified features of the AAA-ATPase heterohexamer. One subunit, Rpt6, has ADP bound, whereas the other five have ATP in their binding pockets. Rpt6 is structurally distinct from the other five Rpt subunits, most notably in its pore loop region. For Rpns, the map reveals two main, previously undetected, features: the C terminus of Rpn3 protrudes into the mouth of the ATPase ring; and Rpn1 and Rpn2, the largest proteasome subunits, are linked by an extended connection. The structural features of the 26S proteasome observed in this study are likely to be important for coordinating the proteasomal subunits during substrate processing.
Structure of the human 26S proteasome at a resolution of 3.9 A.,Schweitzer A, Aufderheide A, Rudack T, Beck F, Pfeifer G, Plitzko JM, Sakata E, Schulten K, Forster F, Baumeister W Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7816-21. doi:, 10.1073/pnas.1608050113. Epub 2016 Jun 24. PMID:27342858[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin Y, Martin J, Gruendler C, Farley J, Meng X, Li BY, Lechleider R, Huff C, Kim RH, Grasser WA, Paralkar V, Wang T. A novel link between the proteasome pathway and the signal transduction pathway of the bone morphogenetic proteins (BMPs). BMC Cell Biol. 2002 Jun 21;3:15. PMID:12097147
- ↑ Touitou R, Richardson J, Bose S, Nakanishi M, Rivett J, Allday MJ. A degradation signal located in the C-terminus of p21WAF1/CIP1 is a binding site for the C8 alpha-subunit of the 20S proteasome. EMBO J. 2001 May 15;20(10):2367-75. PMID:11350925 doi:http://dx.doi.org/10.1093/emboj/20.10.2367
- ↑ Sasaki M, Sukegawa J, Miyosawa K, Yanagisawa T, Ohkubo S, Nakahata N. Low expression of cell-surface thromboxane A2 receptor beta-isoform through the negative regulation of its membrane traffic by proteasomes. Prostaglandins Other Lipid Mediat. 2007 Jun;83(4):237-49. Epub 2006 Dec 27. PMID:17499743 doi:http://dx.doi.org/10.1016/j.prostaglandins.2006.12.001
- ↑ Dubiel W, Ferrell K, Rechsteiner M. Tat-binding protein 7 is a subunit of the 26S protease. Biol Chem Hoppe Seyler. 1994 Apr;375(4):237-40. PMID:8060531
- ↑ Chen Y, Sharp ZD, Lee WH. HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins. J Biol Chem. 1997 Sep 19;272(38):24081-7. PMID:9295362
- ↑ Cho S, Choi YJ, Kim JM, Jeong ST, Kim JH, Kim SH, Ryu SE. Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7. FEBS Lett. 2001 Jun 1;498(1):62-6. PMID:11389899
- ↑ Kruger M, Beger C, Welch PJ, Barber JR, Manns MP, Wong-Staal F. Involvement of proteasome alpha-subunit PSMA7 in hepatitis C virus internal ribosome entry site-mediated translation. Mol Cell Biol. 2001 Dec;21(24):8357-64. PMID:11713272 doi:http://dx.doi.org/10.1128/MCB.21.24.8357-8364.2001
- ↑ Lin HK, Altuwaijri S, Lin WJ, Kan PY, Collins LL, Chang C. Proteasome activity is required for androgen receptor transcriptional activity via regulation of androgen receptor nuclear translocation and interaction with coregulators in prostate cancer cells. J Biol Chem. 2002 Sep 27;277(39):36570-6. Epub 2002 Jul 15. PMID:12119296 doi:http://dx.doi.org/10.1074/jbc.M204751200
- ↑ Du H, Huang X, Wang S, Wu Y, Xu W, Li M. PSMA7, a potential biomarker of diseases. Protein Pept Lett. 2009;16(5):486-9. PMID:19442227
- ↑ Jia Y, Song T, Wei C, Ni C, Zheng Z, Xu Q, Ma H, Li L, Zhang Y, He X, Xu Y, Shi W, Zhong H. Negative regulation of MAVS-mediated innate immune response by PSMA7. J Immunol. 2009 Oct 1;183(7):4241-8. doi: 10.4049/jimmunol.0901646. Epub 2009 Sep, 4. PMID:19734229 doi:http://dx.doi.org/10.4049/jimmunol.0901646
- ↑ Schweitzer A, Aufderheide A, Rudack T, Beck F, Pfeifer G, Plitzko JM, Sakata E, Schulten K, Forster F, Baumeister W. Structure of the human 26S proteasome at a resolution of 3.9 A. Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7816-21. doi:, 10.1073/pnas.1608050113. Epub 2016 Jun 24. PMID:27342858 doi:http://dx.doi.org/10.1073/pnas.1608050113
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