26S proteasome regulatory subunit 8

Function

Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC5 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.

Classification

Family (Pfam)

PF00004 AAA, PF17862 AAA_lid_3, PF16450 Prot_ATP_ID_OB_C

InterPro

26S_Proteasome_ATPase, AAA+_ATPase, AAA_lid_3, ATPase_AAA_core, ATPase_AAA_CS, NA-bd_OB-fold, P-loop_NTPase, Prot_ATP_ID_OB_2nd

Functional cluster

Archaeal Ribosomal & Replication Proteins

Experimental structures · PDB · 87

• 2KRK NMR
• 3KW6 X-ray 2.10A
• 5GJQ EM 4.50A
• 5GJR EM 3.50A
• 5L4G EM 4.02A
• 5LN3 EM 6.80A
• 5M32 EM 3.80A
• 5T0C EM 3.80A
• 5T0G EM 4.40A
• 5T0H EM 6.80A
• 5T0I EM 8.00A
• 5T0J EM 8.00A
• … and 75 more

A predicted model is available from AlphaFold.

Gene Ontology · 34

• GO:0072562 blood microparticle
• GO:0005737 cytoplasm
• GO:0031410 cytoplasmic vesicle
• GO:0005829 cytosol
• GO:0031597 cytosolic proteasome complex
• GO:0070062 extracellular exosome
• GO:0016234 inclusion body
• GO:0016020 membrane
• GO:0031595 nuclear proteasome complex
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0022624 proteasome accessory complex
• GO:0000502 proteasome complex
• GO:0008540 proteasome regulatory particle, base subcomplex
• GO:0008021 synaptic vesicle
• GO:0005524 ATP binding
• GO:0016887 ATP hydrolysis activity
• GO:0140297 DNA-binding transcription factor binding
• GO:0140296 general transcription initiation factor binding
• GO:0036402 proteasome-activating activity
• GO:0017025 TBP-class protein binding
• GO:0031531 thyrotropin-releasing hormone receptor binding
• GO:0008134 transcription factor binding
• GO:0071357 cellular response to type I interferon
• GO:0043069 negative regulation of programmed cell death
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0090261 positive regulation of inclusion body assembly
• GO:1901800 positive regulation of proteasomal protein catabolic process
• GO:0010498 proteasomal protein catabolic process
• GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
• GO:0061136 regulation of proteasomal protein catabolic process
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0006979 response to oxidative stress

Drugs targeting this protein · 6

• OPROZOMIB inhibitor
• IXAZOMIB inhibitor
• BORTEZOMIB inhibitor
• IXAZOMIB CITRATE inhibitor
• CARFILZOMIB inhibitor
• BORTEZOMIB D-MANNITOL inhibitor

Related proteins · sequence + function similarity

• 26S proteasome regulatory subunit 8 1.00
• 26S proteasome regulatory subunit 8 1.00
• 26S proteasome regulatory subunit 8 1.00
• 26S proteasome regulatory subunit 8 0.98
• 26S proteasome regulatory subunit 8 0.98
• 26S proteasome regulatory subunit 8 homolog 0.96
• 26S proteasome regulatory subunit 8 homolog 0.96
• 26S proteasome regulatory subunit 8 homolog A 0.96
• 26S proteasome regulatory subunit 8 homolog B 0.95
• 26S proteasome regulatory subunit 8 homolog 0.94
• 26S proteasome regulatory subunit 8 homolog 0.92
• 26S proteasome regulatory subunit 8 0.92

Co-cited proteins · studied together in the literature

• 26S proteasome regulatory subunit 7 7 shared papers
• Structural maintenance of chromosomes protein 1A 2 shared papers
• 26S proteasome regulatory subunit 6B 5 shared papers
• 26S proteasome regulatory subunit 10B 4 shared papers
• Proteasomal ATPase-associated factor 1 1 shared papers
• 26S proteasome non-ATPase regulatory subunit 7 4 shared papers
• Kinetochore protein NDC80 homolog 2 shared papers
• 26S proteasome regulatory subunit 4 4 shared papers
• 26S proteasome regulatory subunit 6A 4 shared papers
• 26S proteasome non-ATPase regulatory subunit 6 3 shared papers
• 26S proteasome non-ATPase regulatory subunit 12 4 shared papers
• Pachytene checkpoint protein 2 homolog 1 shared papers

Literature · 24 cited papers

• An atomic structure of the human 26S proteasome. Nat. Struct. Mol. Biol. · 2016
• Structure of the human 26S proteasome at a resolution of 3.9 Aa. Proc. Natl. Acad. Sci. U.S.A. · 2016
• Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics. PLoS ONE · 2015
• Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects. Hum. Mol. Genet. · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA splicing. Genes Dev. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
• TRIM5alpha associates with proteasomal subunits in cells while in complex with HIV-1 virions. Retrovirology · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
• … and 12 more in the literature graph