26S proteasome regulatory subunit 6A

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. PSMC3 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

AAA+ ATPases & Chaperones

Experimental structures · PDB · 86

• 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
• 5VFP EM 4.20A
• 5VFQ EM 4.20A
• … and 74 more

A predicted model is available from AlphaFold.

Gene Ontology · 24

• GO:0005829 cytosol
• GO:0005576 extracellular region
• GO:1904813 ficolin-1-rich granule lumen
• GO:0016020 membrane
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0000932 P-body
• GO:0022624 proteasome accessory complex
• GO:0000502 proteasome complex
• GO:0008540 proteasome regulatory particle, base subcomplex
• GO:0034774 secretory granule lumen
• GO:0008021 synaptic vesicle
• GO:0005524 ATP binding
• GO:0016887 ATP hydrolysis activity
• GO:0042802 identical protein binding
• GO:0036402 proteasome-activating activity
• GO:0071357 cellular response to type I interferon
• GO:0043921 host-mediated perturbation of viral transcription
• GO:1901800 positive regulation of proteasomal protein catabolic process
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0010498 proteasomal protein catabolic process
• GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
• GO:0061136 regulation of proteasomal protein catabolic process
• GO:0006979 response to oxidative stress

Disease associations

• deafness, cataract, impaired intellectual development, and polyneuropathy MONDO:0859159

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 6A 1.00
• 26S proteasome regulatory subunit 6A 1.00
• 26S proteasome regulatory subunit 6A-A 0.99
• 26S proteasome regulatory subunit 6A-B 0.97
• 26S proteasome regulatory subunit 6A homolog B 0.94
• 26S proteasome regulatory subunit 6A homolog 0.92
• 26S proteasome regulatory subunit 6A homolog 0.92
• 26S proteasome regulatory subunit 6A homolog A 0.92
• 26S protease regulatory subunit 6A 0.92
• 26S proteasome regulatory subunit 6A homolog 0.91
• 26S proteasome regulatory subunit 6A 0.89
• 26S proteasome regulatory subunit 6A 0.88

Co-cited proteins · studied together in the literature

• 26S proteasome non-ATPase regulatory subunit 9 1 shared papers
• 26S proteasome regulatory subunit 6B 5 shared papers
• 26S proteasome regulatory subunit 10B 5 shared papers
• Protein Tat 1 shared papers
• Proteasomal ATPase-associated factor 1 1 shared papers
• Heat shock factor 2-binding protein 1 shared papers
• 26S proteasome regulatory subunit 4 4 shared papers
• Mediator of RNA polymerase II transcription subunit 7 1 shared papers
• 26S proteasome regulatory subunit 7 4 shared papers
• 26S proteasome regulatory subunit 8 4 shared papers
• Protein c-Fos 1 shared papers
• 26S proteasome non-ATPase regulatory subunit 6 3 shared papers

Literature · 19 cited papers

• Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress. EMBO Mol. Med. · 2020
• 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
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• 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
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation. Nucleic Acids Res. · 2007
• Mass spectrometric characterization of the affinity-purified human 26S proteasome complex. Biochemistry · 2007
• … and 7 more in the literature graph