26S proteasome non-ATPase 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. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. Displays a preferred selectivity for longer polyubiquitin chains.

Classification

Family (Pfam)

PF02809 UIM, PF13519 VWA_2

InterPro

PSMD4, PSMD4_RAZUL-like, UIM_dom, VWF_A, vWFA_dom_sf

Functional cluster

Protein Serine/Threonine Kinases

Experimental structures · PDB · 89

• 1P9C NMR
• 1P9D NMR
• 1UEL NMR
• 1YX4 NMR
• 1YX5 NMR
• 1YX6 NMR
• 2KDE NMR
• 2KDF NMR
• 5GJQ EM 4.50A
• 5GJR EM 3.50A
• 5L4K EM 4.50A
• 5LN3 EM 6.80A
• … and 77 more

A predicted model is available from AlphaFold.

Gene Ontology · 15

• GO:0005829 cytosol
• GO:0005634 nucleus
• GO:0022624 proteasome accessory complex
• GO:0000502 proteasome complex
• GO:0008540 proteasome regulatory particle, base subcomplex
• GO:0008021 synaptic vesicle
• GO:0042802 identical protein binding
• GO:0060090 molecular adaptor activity
• GO:0031593 polyubiquitin modification-dependent protein binding
• 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

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 non-ATPase regulatory subunit 4 1.00
• 26S proteasome non-ATPase regulatory subunit 4 0.99
• 26S proteasome non-ATPase regulatory subunit 4 0.93
• 26S proteasome non-ATPase regulatory subunit 4 0.88
• 26S proteasome non-ATPase regulatory subunit 4 0.85
• 26S proteasome non-ATPase regulatory subunit 4 homolog 0.81
• 26S proteasome non-ATPase regulatory subunit 4 homolog 0.76
• 26S proteasome non-ATPase regulatory subunit 4 0.72
• 26S proteasome regulatory subunit RPN10 0.69
• 26S proteasome regulatory subunit rpn10 0.66
• Ubiquitin receptor RAD23d 0.54
• Probable ubiquitin receptor RAD23a 0.52

Co-cited proteins · studied together in the literature

• 26S proteasome non-ATPase regulatory subunit 4 1 shared papers
• NEDD8 ultimate buster 1 1 shared papers
• Lysine-specific demethylase RAD23A 1 shared papers
• Ubiquilin-4 1 shared papers
• Lysine-specific demethylase RAD23B 1 shared papers
• 26S proteasome regulatory subunit 7 4 shared papers
• 26S proteasome non-ATPase regulatory subunit 3 4 shared papers
• Neuralized-like protein 4 1 shared papers
• Mitogen-activated protein kinase 6 1 shared papers
• Replication termination factor 2 1 shared papers
• 26S proteasome non-ATPase regulatory subunit 8 4 shared papers
• Protein DDI1 homolog 1 1 shared papers

Literature · 31 cited papers

• Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome Integrity. Mol. Cell · 2018
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• 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
• Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes. Mol. Cell. Biol. · 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
• Structure of the s5a:k48-linked diubiquitin complex and its interactions with rpn13. Mol. Cell · 2009
• … and 19 more in the literature graph