PSMD4

Summary

PSMD4 (proteasome 26S subunit ubiquitin receptor, non-ATPase 4, HGNC:9561) is a protein-coding gene on chromosome 1q21.3, encoding 26S proteasome non-ATPase regulatory subunit 4 (P55036). Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the non-ATPase subunits of the 19S regulator lid. Pseudogenes have been identified on chromosomes 10 and 21.

Source: NCBI Gene 5710 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 49 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_002810

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9561
Approved symbol	PSMD4
Name	proteasome 26S subunit ubiquitin receptor, non-ATPase 4
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	S5A, AF-1, AF, Rpn10
Ensembl gene	ENSG00000159352
Ensembl biotype	protein_coding
OMIM	601648
Entrez	5710

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 41 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000368881, ENST00000368884, ENST00000427779, ENST00000437736, ENST00000445776, ENST00000453615, ENST00000461434, ENST00000462970, ENST00000469786, ENST00000470396, ENST00000476855, ENST00000491857, ENST00000902813, ENST00000902814, ENST00000902815, ENST00000902816, ENST00000902817, ENST00000902818, ENST00000902819, ENST00000902820, ENST00000902821, ENST00000902822, ENST00000902823, ENST00000902824, ENST00000902825, ENST00000902826, ENST00000902827, ENST00000927813, ENST00000927814, ENST00000927815, ENST00000927816, ENST00000927817, ENST00000927818, ENST00000927819, ENST00000927820, ENST00000927821, ENST00000927822, ENST00000927823, ENST00000927824, ENST00000927825, ENST00000927826, ENST00000927827, ENST00000927828, ENST00000927829, ENST00000950631, ENST00000950632, ENST00000950633, ENST00000950634

RefSeq mRNA: 2 — MANE Select: NM_002810 NM_001330692, NM_002810

CCDS: CCDS81375, CCDS991

Canonical transcript exons

ENST00000368884 — 10 exons

Exon	Start	End
ENSE00001448199	151267173	151267479
ENSE00001633563	151266004	151266112
ENSE00001810732	151254734	151254808
ENSE00003498568	151263914	151264028
ENSE00003536253	151264832	151264918
ENSE00003587378	151266308	151266439
ENSE00003607968	151262161	151262301
ENSE00003668859	151265166	151265234
ENSE00003671650	151266520	151266587
ENSE00003786930	151265394	151265609

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.7868 / max 531.8351, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5218	45.4843	1819
5219	0.3025	68

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.01	gold quality
left testis	UBERON:0004533	98.95	gold quality
right testis	UBERON:0004534	98.94	gold quality
gastrocnemius	UBERON:0001388	98.91	gold quality
muscle of leg	UBERON:0001383	98.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.71	gold quality
right frontal lobe	UBERON:0002810	98.70	gold quality
lower esophagus	UBERON:0013473	98.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.45	gold quality
amygdala	UBERON:0001876	98.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.39	gold quality
monocyte	CL:0000576	98.38	gold quality
mononuclear cell	CL:0000842	98.36	gold quality
muscle organ	UBERON:0001630	98.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.35	gold quality
granulocyte	CL:0000094	98.34	gold quality
leukocyte	CL:0000738	98.34	gold quality
nucleus accumbens	UBERON:0001882	98.33	gold quality
cingulate cortex	UBERON:0003027	98.32	gold quality
colonic epithelium	UBERON:0000397	98.29	gold quality
anterior cingulate cortex	UBERON:0009835	98.28	gold quality
caudate nucleus	UBERON:0001873	98.26	gold quality
mucosa of transverse colon	UBERON:0004991	98.26	gold quality
prefrontal cortex	UBERON:0000451	98.25	gold quality
right adrenal gland cortex	UBERON:0035827	98.23	gold quality
cerebellar hemisphere	UBERON:0002245	98.20	gold quality
right adrenal gland	UBERON:0001233	98.19	gold quality
popliteal artery	UBERON:0002250	98.19	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ESR1, ESR2, HNF4A, ID1, LEF1, MYB, MYOD1, NCOA1, NCOA2, NFE2L2, TADA2A, TBP, TCF3

miRNA regulators (miRDB)

8 targeting PSMD4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-6501-5P	97.41	68.24	712

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• S5a component of the 19S complex interacts with different ubiquitin-like (ubl) modules (PMID:11827521)
• HHr23a binds to this protein, which changes its own conformation. (PMID:14557549)
• structure of the ubiquitin-interacting motif of the proteasome subunit S5a bound to the ubiquitin-like domain of HR23B (PMID:14585839)
• Results report the structure of S5a (196-306) alone and complexed with two monoubiquitin molecules, and present a model for how S5a and other ubiquitin-binding proteins recognize polyubiquitin. (PMID:15826667)
• These results are consistent with the conclusion that the anti-tumor activity of angiocidin arises from its ability to ligate collagen and alpha2beta1 on endothelial cells and tumor cells. (PMID:16762342)
• Overexpression of the S5a subunit of proteasome activator PA700 did not recover proteasome function in Huntington disease cells. S5a. (PMID:17327906)
• UIM2 domain of S5a binds preferentially to hHR23a over polyubiquitin, and a model is provided for the ternary complex that represents one of the mechanisms used by the proteasome to capture ubiquitylated substrates. (PMID:17408689)
• results suggest that S5a is regulated during apoptosis at the transcriptional level and S5a upregulation by antiapoptotic signals can contribute to cell survival. (PMID:17459097)
• S5a-UIMs can be used as upstream inhibitors of the proteasome pathway. (PMID:17949686)
• In autoimmune disorders like MS, angiocidin activates T cells, macrophages, microglia & astrocytes to produce inflammatory cytokines and to stimulate antigen presentation. (PMID:18207252)
• angiocidin activates monocytes to secrete cytokines and differentiates them to a macrophage-like phenotype through at least two pathways mediated by MAPK and NF-kappaB, as well as PI3K (PMID:18632645)
• The presence of S5a in the reaction containing a substrate (luciferase), ubiquitination enzymes (an E2, UbcH5, and the U-box E3 ligase CHIP) and 26S proteasome significantly increased the rate of luciferase degradation. (PMID:19387488)
• Angiocidin’s ability to elicit tumor cell death may be mediated in part by it’s pro-inflammatory effects on immune cells in the tumor microenvironment. (PMID:19519434)
• The binding of S5a to K48-linked diubiquitin is defined at an atomic level resolution. (PMID:19683493)
• parkin Ubld uses differential surfaces to recruit UIM regions from the S5a proteasomal subunit compared with Eps15 involved in cell signaling. (PMID:19875440)
• results suggest that there is different substrate specificity between S5a and hRpn13 at the level of delivery and S5a may be the major docking site for ERAD substrates. (PMID:20417181)
• Both higher PSMD4 expression levels and higher 1q21 copy numbers affected clinical outcome adversely. (PMID:21628408)
• identified the VWA domain of hRpn10 as a receptor for ubiquitin-like proteins within the 26S proteasome and elucidated how FAT10 mediates efficient proteolysis by the proteasome (PMID:22434192)
• These studies suggest that diminished 26S activity in failing human hearts may be related ti impaired docking of the 19S to the 20S as a result of decreased Rpt subunit ATPase activity and alpha7 subunit phosphorylation. (PMID:23515276)
• Authors demonstrate that human cytomegalovirus UL76 induces a novel nuclear aggresome, likely by subverting S5a of the ubiquitin-proteasome system. (PMID:23966401)
• One consequence of the interaction between E6/E6AP and S5a is enhanced ubiquitination of this proteasome subunit. (PMID:24074603)
• The degradation of TP53 and MDM2 by the proteasome can be selectively dependent on S5a in human cells. (PMID:24121268)
• To examine angiocidin expression in SMMC-7221 and HepG2 cells and the role of angiocidin in liver cancer cell growth. Angiocidin is highly expressed in liver cancer cells, and it may play a key role in tumor growth of liver cancers. (PMID:24250289)
• binds to death receptor-6, and induces monocyte cell line differentiation via NF-kB pathway (PMID:24829148)
• The VWA domain regulation of ubiquitin and Ubl binding to S5a is restricted to the 26S proteasome. (PMID:25318673)
• Not only AF1, but an entire proteasome complex, seems to be present in blood. (PMID:25897558)
• regulation of NY-ESO-1 processing by the ubiquitin receptors Rpn10 and Rpn13 as a well as by the standard and immunoproteasome is governed by non-canonical ubiquitination on non-lysine sites. (PMID:26903513)
• We therefore suggest that PSMD4 or b-catenin might be potential targets for suppressing tumor aggressiveness, and consequently, improving outcomes in patients whose tumors express cNrf2. (PMID:27033953)
• The platelet 26S proteasome exhibits different basal activities of its catalytic subunits and chymotrypsin-like activity is most prominently enhanced by calcium dependent signaling. Collagen stimulation enhances 26S proteasome chymotrypsin-like activity in platelets. (PMID:27768934)
• Binding (especially high-affinity binding) of non-ubiquitinated proteins to the Rpn10 proteasome subunit can both regulate the functioning of this proteasomal ubiquitin receptor (by competing with ubiquitinated substrates) and promote activation of other pathways for proteolytic degradation of proteins destined to the proteasome. (PMID:28988533)
• Preterm delivery is associated with low levels of anti-secretory factor in placenta. Inflammation, a potential trigger of preterm birth, is more pronounced in the preterm placenta and inversely related to the placental level of anti-secretory factor. (PMID:29265188)
• Two Angelman syndrome point mutations of UBE3A that affect the AZUL domain show an impaired ability to bind PSMD4. (PMID:30257870)
• UBQLN2 UBL is fine-tuned for the hRpn10 UIM-1 site. (PMID:30664872)
• Rpn10 directly promoted PTEN degradation. (PMID:30673593)
• Findings indicated PSMD4 as a subunit of 26S proteasome exerts as an oncogene during tumor development of hepatocellular carcinoma. (PMID:30930224)
• Data shows upregulation of PSMD4 promoted the progression of esophageal cancer mainly by reducing ERS-induced cell apoptosis. (PMID:31162820)
• E6AP/UBE3A is distinguished from other E3 ligases by having a 12 nM binding site at the proteasome contributed by substrate receptor hRpn10/PSMD4/S5a. (PMID:32157086)
• The role of endogenous Antisecretory Factor (AF) in the treatment of Meniere’s Disease: A two-year follow-up study. Preliminary results. (PMID:32829060)
• Upregulation of Rpn10 promotes tumor progression via activation of the NF-kappaB pathway in clear cell renal cell carcinoma. (PMID:34133712)
• PSMD4 drives progression of hepatocellular carcinoma via Akt/COX2 pathway and p53 inhibition. (PMID:37336868)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd4b	ENSDARG00000023279
danio_rerio	psmd4a	ENSDARG00000101295
mus_musculus	Psmd4	ENSMUSG00000005625
rattus_norvegicus	Psmd4	ENSRNOG00000021042
drosophila_melanogaster	Rpn10	FBGN0015283
caenorhabditis_elegans	rpn-10	WBGENE00004466

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 4 — P55036 (reviewed: P55036)

Alternative names: 26S proteasome regulatory subunit RPN10, 26S proteasome regulatory subunit S5A, Antisecretory factor 1, Multiubiquitin chain-binding protein

All UniProt accessions (6): P55036, A6PVX3, H0Y3Y9, H0Y561, H7C2J9, Q5VWC4

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD4. Interacts with NUB1. Interacts with SQSTM1. Interacts with UBQLN4. Interacts with UBE3A. Interacts with UBQLN1 (via ubiquitin-like domain). Interacts with DDI2.

Domain organisation. The 2 UIM motifs are involved in the binding to a multi-ubiquitin chain in a cooperative way.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the proteasome subunit S5A family.

Isoforms (2)

UniProt ID	Names	Canonical?
P55036-1	Rpn10A	yes
P55036-2	Rpn10E

RefSeq proteins (2): NP_001317621, NP_002801* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR003903	UIM_dom	Conserved_site
IPR027040	PSMD4	Family
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR049590	PSMD4_RAZUL-like	Domain

Pfam: PF02809, PF13519

UniProt features (55 total): strand 17, helix 14, modified residue 6, region of interest 6, domain 3, turn 3, compositionally biased region 2, splice variant 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

127 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9K53	ELECTRON MICROSCOPY	2.5
8USB	ELECTRON MICROSCOPY	2.73
9MBP	ELECTRON MICROSCOPY	2.75
9NKG	ELECTRON MICROSCOPY	2.8
9E8I	ELECTRON MICROSCOPY	2.87
9BV3	ELECTRON MICROSCOPY	2.9
9E8H	ELECTRON MICROSCOPY	2.9
9K4J	ELECTRON MICROSCOPY	2.9
9NKF	ELECTRON MICROSCOPY	2.9
9U3L	ELECTRON MICROSCOPY	2.91
9NKI	ELECTRON MICROSCOPY	2.94
6MSB	ELECTRON MICROSCOPY	3
7W37	ELECTRON MICROSCOPY	3
8CVT	ELECTRON MICROSCOPY	3
9E8G	ELECTRON MICROSCOPY	3.01
9MBQ	ELECTRON MICROSCOPY	3.08
7W38	ELECTRON MICROSCOPY	3.1
8USC	ELECTRON MICROSCOPY	3.1
9BV1	ELECTRON MICROSCOPY	3.1
9E8O	ELECTRON MICROSCOPY	3.1
9K4R	ELECTRON MICROSCOPY	3.1
9E8Q	ELECTRON MICROSCOPY	3.16
6MSD	ELECTRON MICROSCOPY	3.2
6MSK	ELECTRON MICROSCOPY	3.2
7W39	ELECTRON MICROSCOPY	3.2
7W3G	ELECTRON MICROSCOPY	3.2
7W3H	ELECTRON MICROSCOPY	3.2
9K4M	ELECTRON MICROSCOPY	3.2
9K4Y	ELECTRON MICROSCOPY	3.2
9K50	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55036-F1	72.72	0.10

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 250, 253, 256, 266, 358, 361, 122

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9907900	Proteasome assembly

MSigDB gene sets: 181 (showing top): GOBP_RESPONSE_TO_PEPTIDE, KEGG_PROTEASOME, MATTIOLI_MGUS_VS_PCL, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AP1_Q4_01, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BACH2_01, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, TGANTCA_AP1_C, NRF2_Q4, ATF4_Q2, CAIRO_HEPATOBLASTOMA_UP

GO Biological Process (1): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (5): RNA binding (GO:0003723), polyubiquitin modification-dependent protein binding (GO:0031593), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (6): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle, base subcomplex (GO:0008540), proteasome accessory complex (GO:0022624)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
protein-containing complex	2
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
nucleic acid binding	1
modification-dependent protein binding	1
protein binding	1
molecular_function	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
proteasome regulatory particle	1
proteasome complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD4	ADRM1	Q16186	999
PSMD4	PSMD14	O00487	989
PSMD4	UCHL5	Q9Y5K5	987
PSMD4	PSMD5	Q16401	976
PSMD4	PSMD3	O43242	962
PSMD4	RAD23B	P54727	955
PSMD4	PSMD13	Q9UNM6	955
PSMD4	PSMD11	O00231	949
PSMD4	PSMD8	P48556	948
PSMD4	RAD23A	P54725	941
PSMD4	GABARAPL2	P60520	940
PSMD4	F5GZY7	F5GZY7	940
PSMD4	PSMC1	P49014	937
PSMD4	UBQLN1	Q9UMX0	934
PSMD4	PSMD12	O00232	920

IntAct

319 interactions, top by confidence:

A	B	Type	Score
RAD23A	PSMD4	psi-mi:“MI:0407”(direct interaction)	0.950
PSMD4	RAD23A	psi-mi:“MI:2364”(proximity)	0.950
PSMD4	RAD23A	psi-mi:“MI:0915”(physical association)	0.950
RAD23A	PSMD4	psi-mi:“MI:0915”(physical association)	0.950
RAD23B	PSMD4	psi-mi:“MI:0407”(direct interaction)	0.860
RAD23B	PSMD4	psi-mi:“MI:0915”(physical association)	0.860
PSMD4	RAD23B	psi-mi:“MI:0915”(physical association)	0.860
PSMD4	RAD23B	psi-mi:“MI:0407”(direct interaction)	0.860
PSMD4	UBC	psi-mi:“MI:0407”(direct interaction)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD4	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD4	UBE3A	psi-mi:“MI:0915”(physical association)	0.730

BioGRID (920): UBC (Reconstituted Complex), PSMD4 (Biochemical Activity), PSMD4 (Reconstituted Complex), PSMD4 (Two-hybrid), PSMD4 (Biochemical Activity), PSMD4 (Affinity Capture-Western), RAD23B (Co-crystal Structure), UBC (Reconstituted Complex), UBC (Reconstituted Complex), VCP (Affinity Capture-Western), UBXN1 (Affinity Capture-Western), UBC (Reconstituted Complex), UBC (Reconstituted Complex), PSMD4 (Affinity Capture-Western), UBC (Reconstituted Complex)

ESM2 similar proteins: A1CDT9, A1DCU5, A3KMV2, O00233, O17453, O35226, O61742, O74803, P0CS14, P0CS15, P40087, P54725, P54726, P54727, P54728, P55034, P55035, P55036, Q0CJ13, Q0U3Y6, Q10169, Q10256, Q1DNB9, Q1EBV4, Q29RK4, Q2H085, Q2USD7, Q3SZ19, Q40742, Q4I5I4, Q4KMA2, Q4WGS4, Q54JB0, Q54LV1, Q58DA0, Q5AY89, Q6BK42, Q6CFI3, Q6CNS3, Q6FQE9

Diamond homologs: A2A3N6, D3ZSI8, O13853, O14986, O17453, O35226, O48709, O60331, O61742, O70161, O82143, O88370, O88377, O94444, P38886, P38994, P55034, P55035, P55036, P70181, P70182, P78356, Q0P5F7, Q553E0, Q55GN6, Q56YP2, Q58DA0, Q5CZZ9, Q5F356, Q5I6B8, Q5PQ01, Q5R488, Q5ZJ58, Q6EX42, Q6GL14, Q6IQE1, Q80XI4, Q8I239, Q8L796, Q8L850

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
PSMD4	“form complex”	“26S Proteasome”	binding
TRIM63	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination
UBE3A	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination
SIAH2	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination
PRKN	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination
APC-c	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination
SCF-betaTRCP	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination
STUB1	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination
NEDD4	“down-regulates quantity by destabilization”	PSMD4	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of activated PAK-2p34 by proteasome mediated degradation	27	79.2×	1e-45
Vpu mediated degradation of CD4	27	75.5×	4e-45
Autodegradation of the E3 ubiquitin ligase COP1	27	75.5×	4e-45
Ubiquitin-dependent degradation of Cyclin D	27	75.5×	4e-45
Vif-mediated degradation of APOBEC3G	27	72.1×	2e-44
Regulation of ornithine decarboxylase (ODC)	25	71.5×	2e-41
AUF1 (hnRNP D0) binds and destabilizes mRNA	27	70.6×	3e-44
Degradation of AXIN	27	70.6×	3e-44

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of proteasomal protein catabolic process	5	44.2×	2e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	36	16.8×	1e-31
ubiquitin-dependent protein catabolic process	12	8.0×	2e-05

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

49 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1703 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151262146:A:G	acceptor_gain	1.0000
1:151262151:A:AG	acceptor_gain	1.0000
1:151262152:A:G	acceptor_gain	1.0000
1:151262296:GGC:G	donor_gain	1.0000
1:151262298:C:CG	donor_gain	1.0000
1:151262298:C:G	donor_gain	1.0000
1:151262302:G:GG	donor_gain	1.0000
1:151263908:T:G	acceptor_gain	1.0000
1:151263912:A:AG	acceptor_gain	1.0000
1:151263913:G:GA	acceptor_gain	1.0000
1:151263913:GT:G	acceptor_gain	1.0000
1:151264029:G:GG	donor_gain	1.0000
1:151264827:A:AG	acceptor_gain	1.0000
1:151264829:A:AG	acceptor_gain	1.0000
1:151264829:AAGCT:A	acceptor_gain	1.0000
1:151264830:A:AG	acceptor_gain	1.0000
1:151264830:AGCT:A	acceptor_gain	1.0000
1:151264831:G:GG	acceptor_gain	1.0000
1:151264831:GCT:G	acceptor_gain	1.0000
1:151264831:GCTG:G	acceptor_gain	1.0000
1:151264833:T:A	acceptor_gain	1.0000
1:151264915:GGAT:G	donor_gain	1.0000
1:151264916:GAT:G	donor_gain	1.0000
1:151264916:GATG:G	donor_gain	1.0000
1:151264919:G:GG	donor_gain	1.0000
1:151265160:TCCCA:T	acceptor_loss	1.0000
1:151265161:CCCAG:C	acceptor_loss	1.0000
1:151265163:CAG:C	acceptor_loss	1.0000
1:151265164:A:AG	acceptor_gain	1.0000
1:151265164:AGCT:A	acceptor_gain	1.0000

AlphaMissense

2497 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151254795:A:C	S5R	1.000
1:151254797:C:A	S5R	1.000
1:151254797:C:G	S5R	1.000
1:151262165:G:C	D11H	1.000
1:151262172:G:T	S13I	1.000
1:151262188:T:A	N18K	1.000
1:151262188:T:G	N18K	1.000
1:151262192:G:C	D20H	1.000
1:151262208:G:C	R25T	1.000
1:151262208:G:T	R25M	1.000
1:151262209:G:C	R25S	1.000
1:151262209:G:T	R25S	1.000
1:151262216:G:C	A28P	1.000
1:151262228:G:C	A32P	1.000
1:151262229:C:A	A32D	1.000
1:151262232:T:A	V33D	1.000
1:151262241:T:A	V36D	1.000
1:151262275:C:A	N47K	1.000
1:151262275:C:G	N47K	1.000
1:151262282:G:C	G50R	1.000
1:151262283:G:A	G50D	1.000
1:151262286:T:C	L51P	1.000
1:151263970:T:C	L75P	1.000
1:151264011:G:C	G89R	1.000
1:151264012:G:A	G89D	1.000
1:151264018:G:C	R91P	1.000
1:151264023:G:C	A93P	1.000
1:151264024:C:A	A93D	1.000
1:151264833:T:A	L95Q	1.000
1:151264833:T:C	L95P	1.000

dbSNP variants (sampled 300 via entrez): RS1000046817 (1:151267598 A>G), RS1000240095 (1:151256992 G>A), RS1000755458 (1:151262438 G>C), RS1000848881 (1:151258829 G>A), RS1000892292 (1:151256972 CTCCCACCCTCAGGTGA>C), RS1001068695 (1:151265382 T>C), RS1001416844 (1:151257933 T>C), RS1001430695 (1:151259407 T>C), RS1001884761 (1:151253816 T>C), RS1002022612 (1:151264060 T>A,C), RS1002200720 (1:151259671 A>G), RS1002313617 (1:151253539 T>C), RS1002855022 (1:151257356 T>A), RS1003098166 (1:151257686 T>C), RS1003297451 (1:151254018 C>A,T)

Disease associations

OMIM: gene MIM:601648 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005951_38	Body mass index	4.000000e-09
GCST90020028_624	Hip circumference adjusted for BMI	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364701 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,628 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL451887	CARFILZOMIB	4	12,508

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

62 potent at pChembl≥5 of 63 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.62	IC50	2.4	nM	BORTEZOMIB
8.59	IC50	2.56	nM	BORTEZOMIB
8.57	IC50	2.7	nM	CHEMBL3237863
8.47	IC50	3.4	nM	CHEMBL6143686
8.41	IC50	3.9	nM	CHEMBL3237862
8.39	IC50	4.1	nM	CHEMBL3237864
8.39	IC50	4.1	nM	CHEMBL3237867
8.32	IC50	4.8	nM	CHEMBL3237873
8.29	IC50	5.1	nM	CHEMBL3237865
8.24	IC50	5.7	nM	CHEMBL3237866
8.24	IC50	5.7	nM	CHEMBL3237860
8.23	IC50	5.9	nM	CHEMBL3237868
8.15	IC50	7	nM	BORTEZOMIB
8.15	IC50	7.1	nM	CHEMBL3237870
8.15	IC50	7.14	nM	BORTEZOMIB
8.12	IC50	7.5	nM	CHEMBL3237871
8.11	IC50	7.7	nM	CHEMBL3237874
8.11	IC50	7.8	nM	CHEMBL3237869
8.07	IC50	8.6	nM	CARFILZOMIB
7.54	IC50	29	nM	CHEMBL3237861
7.34	IC50	46	nM	CHEMBL3237867
7.27	IC50	54	nM	CHEMBL3237872
7.12	IC50	75	nM	CHEMBL3237865
7.12	IC50	76	nM	CHEMBL3237866
6.96	IC50	110	nM	CHEMBL3262766
6.92	IC50	120	nM	CHEMBL3237864
6.92	IC50	120	nM	BORTEZOMIB
6.89	IC50	130	nM	CHEMBL3237869
6.85	IC50	140	nM	CHEMBL3237862
6.82	IC50	150	nM	CHEMBL3237863
6.77	IC50	170	nM	CHEMBL3237873
6.77	IC50	170	nM	CHEMBL3262765
6.72	IC50	190	nM	CHEMBL3262758
6.68	IC50	210	nM	CHEMBL3237870
6.66	IC50	220	nM	CHEMBL3262756
6.60	IC50	250	nM	CHEMBL3237868
6.47	IC50	340	nM	CHEMBL3262752
6.47	IC50	340	nM	CHEMBL3262755
6.44	IC50	360	nM	CHEMBL3262757
6.42	IC50	380	nM	CHEMBL3262754
6.36	IC50	440	nM	CHEMBL3262753
6.30	IC50	500	nM	CHEMBL3237872
6.20	IC50	630	nM	CHEMBL3262762
6.02	IC50	950	nM	CHEMBL3262761
6.00	IC50	1000	nM	CHEMBL3237871
5.96	IC50	1100	nM	CHEMBL3237862
5.85	IC50	1400	nM	BELACTOSIN A
5.84	IC50	1440	nM	BELACTOSIN A
5.70	IC50	2000	nM	BORTEZOMIB
5.66	IC50	2170	nM	CHEMBL3237873

PubChem BioAssay actives

60 with measured affinity, of 133 total; 32 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Bortezomib	1985684: Inhibition of 26S proteasome (unknown origin)	ic50	0.0024	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0027	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0039	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-(4-phenylmethoxybutyl)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0048	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0051	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
benzyl N-[(2S)-1-[[(2R)-1-[(1R,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]-4-phenylbutan-2-yl]amino]-1-oxopropan-2-yl]carbamate	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
(2S)-2-[(2,5-dichlorobenzoyl)amino]-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0059	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-(pyrazine-2-carbonylamino)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0071	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-[(6-phenylpyridine-2-carbonyl)amino]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0075	uM
[(1R)-1-[[(2S)-2-acetamido-4-oxo-4-[[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]amino]butanoyl]amino]-3-methylbutyl]boronic acid	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0077	uM
(2S)-2-benzamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0078	uM
Carfilzomib	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.0086	uM
(2R,3S)-3-[(2S)-butan-2-yl]-4-oxo-N-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]oxetane-2-carboxamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0290	uM
(2S)-2-acetamido-N’-methyl-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0540	uM
N-[(1R)-3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]naphthalene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1100	uM
N-[(1R)-3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]-4-(trifluoromethyl)benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1700	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]naphthalene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1900	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]-4-(trifluoromethyl)benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.2200	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]pyridine-3-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3400	uM
4-methoxy-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3400	uM
4-cyano-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3600	uM
4-fluoro-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3800	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.4400	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]oxane-4-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.6300	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]thiophene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.9500	uM
(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-[(1S,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]propanoic acid	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	1.4000	uM
(2S)-2-acetamido-N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1152964: Inhibition of chymotrypsin-like of human 20S proteasome using chromophoric Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	2.3000	uM
N-[3-(2-oxo-1,3,4-oxathiazol-5-yl)phenyl]acetamide	1137840: Inhibition of chymotrypsin-like activity of 26S proteasome in intact human Karpas 1106p cells assessed as substrate hydrolysis using Suc-LLVY-(D)-aminoluciferin as substrate after 3 hrs by cell-based Proteasome-Glo assay	ec50	4.2000	uM
(2S)-2-acetamido-N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]-N’-(4-phenylmethoxybutyl)butanediamide	1152964: Inhibition of chymotrypsin-like of human 20S proteasome using chromophoric Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	5.7000	uM

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, affects expression, increases abundance	2
Arsenic	increases abundance, decreases ubiquitination, decreases expression	2
FR900359	increases phosphorylation	1
ginger extract	affects expression, increases abundance, affects cotreatment	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
tetrabromobisphenol A	decreases expression	1
quinoline	decreases expression	1
arsenic trichloride	decreases expression, increases abundance	1
4-hydroxy-equilenin	decreases expression	1
lactacystin	affects binding, increases reaction	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Dactinomycin	increases secretion, affects cotreatment	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3222879	Binding	Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate preincubated for 30 mins followed by substrate addition measured after 90 mins by fluorescence assay	Oxathiazole-2-one derivative of bortezomib: Synthesis, stability and proteasome inhibition activity — Medchemcomm

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.