26S proteasome regulatory subunit 4

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. PSMC1 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

ABC Transporter ATPases & DnaJ 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 · 17

• GO:0005829 cytosol
• GO:0016020 membrane
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• 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:0036402 proteasome-activating activity
• GO:0003723 RNA binding
• GO:0071357 cellular response to type I interferon
• 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

• neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss MONDO:0859296

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 4 1.00
• 26S proteasome regulatory subunit 4 1.00
• 26S proteasome regulatory subunit 4 1.00
• 26S proteasome regulatory subunit 4 0.98
• 26S proteasome regulatory subunit 4 homolog 0.95
• 26S proteasome regulatory subunit 4 homolog 0.94
• Probable 26S proteasome regulatory subunit 4 0.94
• 26S proteasome regulatory subunit 4 homolog 0.93
• 26S proteasome regulatory subunit 4 homolog A 0.90
• 26S proteasome regulatory subunit 4 homolog B 0.88
• 26S proteasome regulatory subunit 7 0.88
• 26S proteasome regulatory subunit 4 homolog 0.88

Co-cited proteins · studied together in the literature

• Ataxin-7 1 shared papers
• 26S proteasome regulatory subunit 10B 4 shared papers
• Proteasomal ATPase-associated factor 1 1 shared papers
• 2-oxoglutarate dehydrogenase complex component E1 1 shared papers
• Biorientation of chromosomes in cell division protein 1-like 1 1 shared papers
• 26S proteasome regulatory subunit 6A 4 shared papers
• Gamma-aminobutyric acid receptor subunit alpha-5 1 shared papers
• 26S proteasome regulatory subunit 6B 4 shared papers
• Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase 1 shared papers
• 26S proteasome regulatory subunit 7 4 shared papers
• 26S proteasome regulatory subunit 8 4 shared papers
• Sodium/hydrogen exchanger 6 1 shared papers

Literature · 22 cited papers

• PSMC1 variant causes a novel neurological syndrome. Clin. Genet. · 2022
• 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
• Multifunctional reagents for quantitative proteome-wide analysis of protein modification in human cells and dynamic profiling of protein lipidation during vertebrate development. Angew. Chem. Int. Ed. · 2015
• Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nat. Commun. · 2014
• 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
• Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
• Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry. Proteomics · 2007
• … and 10 more in the literature graph