PSMC2

Summary

PSMC2 (proteasome 26S subunit, ATPase 2, HGNC:9548) is a protein-coding gene on chromosome 7q22.1, encoding 26S proteasome regulatory subunit 7 (P35998). 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 99.5% 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 ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. This subunit has been shown to interact with several of the basal transcription factors so, in addition to participation in proteasome functions, this subunit may participate in the regulation of transcription. This subunit may also compete with PSMC3 for binding to the HIV tat protein to regulate the interaction between the viral protein and the transcription complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 5701 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total — 1 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_002803

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9548
Approved symbol	PSMC2
Name	proteasome 26S subunit, ATPase 2
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MSS1, S7, Nbla10058, RPT1
Ensembl gene	ENSG00000161057
Ensembl biotype	protein_coding
OMIM	154365
Entrez	5701

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay

ENST00000292644, ENST00000425206, ENST00000435765, ENST00000457587, ENST00000460021, ENST00000676908, ENST00000677281, ENST00000677769, ENST00000677943, ENST00000678488, ENST00000678493, ENST00000678587, ENST00000679046, ENST00000679205, ENST00000679250, ENST00000679341, ENST00000864378, ENST00000915465

RefSeq mRNA: 2 — MANE Select: NM_002803 NM_001204453, NM_002803

CCDS: CCDS5731

Canonical transcript exons

ENST00000292644 — 12 exons

Exon	Start	End
ENSE00002250553	103347643	103347781
ENSE00003578476	103355694	103355793
ENSE00003620849	103354868	103354949
ENSE00003889056	103362686	103362758
ENSE00003889309	103367413	103367615
ENSE00003890230	103363344	103363439
ENSE00003890548	103366076	103366163
ENSE00003891044	103367713	103367809
ENSE00003891061	103353921	103353958
ENSE00003892422	103364143	103364307
ENSE00003893359	103367897	103369395
ENSE00003895330	103361957	103362088

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 98.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 93.4468 / max 2038.7012, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80283	91.5520	1825
80284	1.8948	1202

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.86	gold quality
biceps brachii	UBERON:0001507	98.78	gold quality
esophagus squamous epithelium	UBERON:0006920	98.78	gold quality
epithelium of nasopharynx	UBERON:0001951	98.70	gold quality
nasopharynx	UBERON:0001728	98.69	gold quality
sperm	CL:0000019	98.60	gold quality
gingival epithelium	UBERON:0001949	98.58	gold quality
gingiva	UBERON:0001828	98.45	gold quality
palpebral conjunctiva	UBERON:0001812	98.39	gold quality
visceral pleura	UBERON:0002401	98.39	gold quality
skin of hip	UBERON:0001554	98.36	gold quality
parietal pleura	UBERON:0002400	98.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.31	gold quality
tibia	UBERON:0000979	98.29	gold quality
male germ cell	CL:0000015	98.27	gold quality
pleura	UBERON:0000977	98.27	gold quality
trabecular bone tissue	UBERON:0002483	98.16	gold quality
oral cavity	UBERON:0000167	98.15	gold quality
epithelium of esophagus	UBERON:0001976	98.13	gold quality
diaphragm	UBERON:0001103	98.08	gold quality
eye	UBERON:0000970	98.07	gold quality
heart right ventricle	UBERON:0002080	98.07	gold quality
amniotic fluid	UBERON:0000173	98.06	gold quality
germinal epithelium of ovary	UBERON:0001304	98.06	gold quality
penis	UBERON:0000989	97.96	gold quality
upper leg skin	UBERON:0004262	97.93	gold quality
triceps brachii	UBERON:0001509	97.75	gold quality
mammalian vulva	UBERON:0000997	97.71	gold quality
squamous epithelium	UBERON:0006914	97.68	gold quality
corpus epididymis	UBERON:0004359	97.64	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): ZNF160

miRNA regulators (miRDB)

111 targeting PSMC2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• structural determinants for the binding of ubiquitin-like domains to 26s proteasome (PMID:12970176)
• the finding of this study provided the new insight into the mechanism how PSMC2 contribute to osteosarcoma malignancy and further suggested PSMC2 might serve as an attractive potential therapeutic target drug target for osteosarcoma treatment. (PMID:27888613)
• Overexpression of PSMC2 promotes the tumorigenesis and development of human breast cancer via regulating plasminogen activator urokinase (PLAU). (PMID:34244472)
• PSMC2/CCND1 axis promotes development of ovarian cancer through regulating cell growth, apoptosis and migration. (PMID:34294689)
• Knockdown of PSMC2 contributes to suppression of cholangiocarcinoma development by regulating CDK1. (PMID:34499615)
• PSMC2 knockdown inhibits the progression of oral squamous cell carcinoma by promoting apoptosis via PI3K/Akt pathway. (PMID:34979867)
• PSMC2 is overexpressed in glioma and promotes proliferation and anti-apoptosis of glioma cells. (PMID:35287689)
• PSMC2 knockdown exerts an anti-tumor role in nasopharyngeal carcinoma through regulating AKT signaling pathway. (PMID:38123344)
• PSMC2 promotes glioma progression by regulating immune microenvironment and PI3K/AKT/mTOR pathway. (PMID:38569452)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmc2	ENSDARG00000020101
mus_musculus	Psmc2	ENSMUSG00000028932
rattus_norvegicus	Psmc2	ENSRNOG00000012026
drosophila_melanogaster	Rpt1	FBGN0028687
caenorhabditis_elegans		WBGENE00004501

Paralogs (5): PSMC4 (ENSG00000013275), PSMC5 (ENSG00000087191), PSMC6 (ENSG00000100519), PSMC1 (ENSG00000100764), PSMC3 (ENSG00000165916)

Protein

Protein identifiers

26S proteasome regulatory subunit 7 — P35998 (reviewed: P35998)

Alternative names: 26S proteasome AAA-ATPase subunit RPT1, Proteasome 26S subunit ATPase 2

All UniProt accessions (5): P35998, A0A140VK70, A0A7I2YQ68, C9JLS9, C9JX88

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. PSMC2 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.

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 including PSMC2 and few additional components. Interacts with NDC80/HEC; this interaction is detected only during M phase. Interacts and SQSTM1. Interacts with PAAF1. Directly interacts with TRIM5. (Microbial infection) Interacts with HIV-1 Tat.

Subcellular location. Cytoplasm.

Post-translational modifications. Monoubiquitinated by RNF181. Phosphorylated. Dephosphorylated by UBLCP1 which impairs PSMC2 ATPase activity and disrupts 26S proteasome assembly.

Induction. Expression is not cell cycle-dependent and occurs throughout the cell cycle.

Similarity. Belongs to the AAA ATPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35998-1	1	yes
P35998-2	2

RefSeq proteins (2): NP_001191382, NP_002794* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR003960	ATPase_AAA_CS	Conserved_site
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041569	AAA_lid_3	Domain
IPR048723	OB_PRS7	Domain
IPR050221	26S_Proteasome_ATPase	Family

Pfam: PF00004, PF17862, PF21236

UniProt features (43 total): helix 21, strand 10, turn 3, modified residue 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, binding site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

131 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9K53	ELECTRON MICROSCOPY	2.5
8USD	ELECTRON MICROSCOPY	2.7
8USB	ELECTRON MICROSCOPY	2.73
9MBP	ELECTRON MICROSCOPY	2.75
9PDL	ELECTRON MICROSCOPY	2.76
9NKG	ELECTRON MICROSCOPY	2.8
9E8I	ELECTRON MICROSCOPY	2.87
9E8H	ELECTRON MICROSCOPY	2.9
9NKF	ELECTRON MICROSCOPY	2.9
9BV3	ELECTRON MICROSCOPY	2.9
9K4J	ELECTRON MICROSCOPY	2.9
9U3L	ELECTRON MICROSCOPY	2.91
9NKI	ELECTRON MICROSCOPY	2.94
9PDI	ELECTRON MICROSCOPY	2.98
6MSB	ELECTRON MICROSCOPY	3
7W37	ELECTRON MICROSCOPY	3
8CVT	ELECTRON MICROSCOPY	3
9E8G	ELECTRON MICROSCOPY	3.01
9PDN	ELECTRON MICROSCOPY	3.04
9MBQ	ELECTRON MICROSCOPY	3.08
7W38	ELECTRON MICROSCOPY	3.1
8USC	ELECTRON MICROSCOPY	3.1
9E8O	ELECTRON MICROSCOPY	3.1
9BV1	ELECTRON MICROSCOPY	3.1
9K4R	ELECTRON MICROSCOPY	3.1
9E8Q	ELECTRON MICROSCOPY	3.16
9U7R	ELECTRON MICROSCOPY	3.17
6MSD	ELECTRON MICROSCOPY	3.2
6MSK	ELECTRON MICROSCOPY	3.2
7W39	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35998-F1	80.73	0.21

Functional residue map

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

Ligand- & substrate-binding residues (1): 216–223

Post-translational modifications (2): 116, 422

Function

Pathways and Gene Ontology

Reactome pathways

68 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-180534	Vpu mediated degradation of CD4
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-202424	Downstream TCR signaling
R-HSA-211733	Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-349425	Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-350562	Regulation of ornithine decarboxylase (ODC)
R-HSA-382556	ABC-family protein mediated transport
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-4608870	Asymmetric localization of PCP proteins
R-HSA-4641257	Degradation of AXIN
R-HSA-4641258	Degradation of DVL
R-HSA-5358346	Hedgehog ligand biogenesis
R-HSA-5362768	Hh mutants are degraded by ERAD
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5610780	Degradation of GLI1 by the proteasome
R-HSA-5610783	Degradation of GLI2 by the proteasome

MSigDB gene sets: 426 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, MODULE_52, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MBD4, MORF_RAB5A, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE

GO Biological Process (4): osteoblast differentiation (GO:0001649), ubiquitin-dependent protein catabolic process (GO:0006511), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of proteasomal protein catabolic process (GO:1901800)

GO Molecular Function (5): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), proteasome-activating activity (GO:0036402), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (13): proteasome complex (GO:0000502), P-body (GO:0000932), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome regulatory particle, base subcomplex (GO:0008540), membrane (GO:0016020), proteasome accessory complex (GO:0022624), secretory granule lumen (GO:0034774), cytoplasmic ribonucleoprotein granule (GO:0036464), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
APC/C-mediated degradation of cell cycle proteins	2
Host Interactions of HIV factors	2
Downstream signaling events of B Cell Receptor (BCR)	1
Cellular response to hypoxia	1
Regulation of APC/C activators between G1/S and early anaphase	1
APC/C:Cdc20 mediated degradation of mitotic proteins	1
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1
Cyclin E associated events during G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Signaling by WNT	1
TCR signaling	1
Regulation of Apoptosis	1
Mitotic Anaphase	1
Fc epsilon receptor (FCERI) signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
proteasomal protein catabolic process	3
ATP-dependent activity	2
intracellular anatomical structure	2
cytoplasm	2
protein-containing complex	2
ossification	1
cell differentiation	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
polypeptide conformation or assembly isomerase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
proteasome regulatory particle	1
proteasome complex	1
secretory granule	1
cytoplasmic vesicle lumen	1
ribonucleoprotein granule	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

3856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMC2	PSMD1	Q99460	924
PSMC2	PSMB4	P28070	896
PSMC2	PSMD2	Q13200	878
PSMC2	PSMB1	P20618	838
PSMC2	PSMD7	P51665	818
PSMC2	PSMD3	O43242	818
PSMC2	PSMD14	O00487	815
PSMC2	PSMB3	P31147	814
PSMC2	PSMD12	O00232	813
PSMC2	PSMA1	P25786	784
PSMC2	PSMD8	P48556	783
PSMC2	PSMD11	O00231	779
PSMC2	PSMC5	P47210	775
PSMC2	PSMB7	Q99436	771
PSMC2	PSMA5	P28066	769

IntAct

313 interactions, top by confidence:

A	B	Type	Score
PSMD5	PSMC2	psi-mi:“MI:0915”(physical association)	0.960
PSMC2	PSMD5	psi-mi:“MI:0915”(physical association)	0.960
PSMD5	PSMC2	psi-mi:“MI:0914”(association)	0.960
PSMD5	PSMC2	psi-mi:“MI:0407”(direct interaction)	0.960
PSMC6	PSMC3	psi-mi:“MI:0915”(physical association)	0.950
PSMC6	PSMC3	psi-mi:“MI:0914”(association)	0.950
PSMC1	PSMC2	psi-mi:“MI:0407”(direct interaction)	0.890
PSMC5	PSMC2	psi-mi:“MI:0914”(association)	0.860
PSMC5	PSMD10	psi-mi:“MI:0914”(association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMC2	PSMD2	psi-mi:“MI:0915”(physical association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMC5	PSMC3	psi-mi:“MI:0914”(association)	0.760
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD3	psi-mi:“MI:0914”(association)	0.730

BioGRID (817): PSMC2 (Affinity Capture-MS), PSMD5 (Two-hybrid), PSMC2 (Affinity Capture-RNA), PSMC2 (Affinity Capture-RNA), UBC (Reconstituted Complex), PSMC2 (Affinity Capture-MS), PSMC2 (Reconstituted Complex), PSMC2 (Co-fractionation), PSMC2 (Affinity Capture-MS), PSMC2 (Affinity Capture-MS), PSMC2 (Affinity Capture-MS), PSMC2 (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC3 (Affinity Capture-MS)

ESM2 similar proteins: A0JMA9, A8QFF6, A9RA82, B2RYN7, B3EX35, B4USW8, B5X3X5, B7NZ88, O04019, O14126, O16368, O17071, O23894, O42931, O61577, O75449, O76371, P34808, P35998, P36612, P46465, P46466, P46470, P46471, P46472, P48601, P54776, P62191, P62192, P62193, Q0IIR9, Q1HGK7, Q4R407, Q4R4R0, Q55BV5, Q5E9F9, Q5RII9, Q5U3S1, Q5XIK7, Q63347

Diamond homologs: A3CV35, A4G0S4, A6UQT3, A6VHR1, A7I8B8, A9A916, B6YXR2, B8GGN4, C3MRF1, C3MY47, C3MZI6, C3N7K8, C3NFW6, C4KIR6, C5A6P8, D4GUJ7, O04019, O16368, O17071, O18413, O23894, O26824, O28303, O57940, O64982, O74445, P0DKJ9, P0DKK0, P34123, P34124, P35998, P40327, P41836, P43686, P46465, P46466, P46470, P46471, P46472, P46502

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PSMC2	“form complex”	“26S Proteasome”	binding
UBE3A	“down-regulates quantity by destabilization”	PSMC2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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	72.3×	1e-44
Regulation of ornithine decarboxylase (ODC)	27	70.6×	2e-44
Vpu mediated degradation of CD4	27	69.0×	3e-44
Autodegradation of the E3 ubiquitin ligase COP1	27	69.0×	3e-44
Ubiquitin-dependent degradation of Cyclin D	27	69.0×	3e-44
Cross-presentation of soluble exogenous antigens (endosomes)	28	68.3×	3e-45
Vif-mediated degradation of APOBEC3G	27	65.9×	2e-43
Antigen processing: Ub, ATP-independent proteasomal degradation	12	65.9×	2e-19

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	34	15.2×	5e-28

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	18
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1459935	NC_000007.13:g.(?102937907)(103629803_?)del	Pathogenic

SpliceAI

1652 predictions. Top by Δscore:

Variant	Effect	Δscore
7:103337728:GTAC:G	donor_loss	1.0000
7:103337729:TACT:T	donor_loss	1.0000
7:103337730:A:AC	donor_gain	1.0000
7:103337730:ACTT:A	donor_loss	1.0000
7:103337731:C:CC	donor_gain	1.0000
7:103337731:CTT:C	donor_loss	1.0000
7:103337732:TTA:T	donor_loss	1.0000
7:103337733:TACGA:T	donor_loss	1.0000
7:103337734:A:AC	donor_gain	1.0000
7:103337734:ACGA:A	donor_loss	1.0000
7:103337734:ACGAG:A	donor_gain	1.0000
7:103337735:C:CT	donor_gain	1.0000
7:103337735:CG:C	donor_gain	1.0000
7:103337735:CGA:C	donor_gain	1.0000
7:103337735:CGAG:C	donor_gain	1.0000
7:103337735:CGAGC:C	donor_gain	1.0000
7:103337807:TGGTT:T	acceptor_gain	1.0000
7:103337808:GGTT:G	acceptor_gain	1.0000
7:103337809:GTT:G	acceptor_gain	1.0000
7:103337810:TT:T	acceptor_gain	1.0000
7:103337810:TTCTG:T	acceptor_loss	1.0000
7:103337811:TC:T	acceptor_loss	1.0000
7:103337812:C:CC	acceptor_gain	1.0000
7:103337812:C:T	acceptor_loss	1.0000
7:103337813:T:C	acceptor_loss	1.0000
7:103341760:ATAC:A	donor_loss	1.0000
7:103341761:TACCT:T	donor_loss	1.0000
7:103341762:A:AT	donor_loss	1.0000
7:103341766:T:A	donor_gain	1.0000
7:103344554:CTTA:C	donor_loss	1.0000

AlphaMissense

2869 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:103355735:T:A	W78R	1.000
7:103355735:T:C	W78R	1.000
7:103355737:G:C	W78C	1.000
7:103355737:G:T	W78C	1.000
7:103355790:C:A	A96D	1.000
7:103361958:T:C	C98R	1.000
7:103361959:G:A	C98Y	1.000
7:103361960:T:G	C98W	1.000
7:103362022:C:A	A119D	1.000
7:103362027:T:C	F121L	1.000
7:103362029:T:A	F121L	1.000
7:103362029:T:G	F121L	1.000
7:103362085:T:A	V140E	1.000
7:103362087:G:C	G141R	1.000
7:103362088:G:A	G141D	1.000
7:103362709:T:A	I149N	1.000
7:103362721:T:C	L153S	1.000
7:103362721:T:G	L153W	1.000
7:103363408:T:C	L187P	1.000
7:103363420:T:A	V191D	1.000
7:103364182:G:C	G211R	1.000
7:103364183:G:A	G211D	1.000
7:103364189:T:C	L213P	1.000
7:103364197:G:C	G216R	1.000
7:103364198:G:A	G216D	1.000
7:103364198:G:T	G216V	1.000
7:103364206:G:C	G219R	1.000
7:103364206:G:T	G219C	1.000
7:103364207:G:A	G219D	1.000
7:103364212:G:C	G221R	1.000

dbSNP variants (sampled 300 via entrez): RS1000008716 (7:103350284 A>G), RS1000452377 (7:103357786 G>C,T), RS1000834450 (7:103361354 T>A), RS1000861919 (7:103349613 C>T), RS1000881444 (7:103359744 G>A), RS1001095756 (7:103357889 T>A,C), RS1001414153 (7:103345599 T>A), RS1001527948 (7:103353263 T>C), RS1001700565 (7:103360255 T>C,G), RS1001710658 (7:103360514 C>T), RS1001915655 (7:103351680 T>C), RS1001976855 (7:103353518 G>A,T), RS1002015339 (7:103346819 TGTGTGTGTGTG>T), RS1002037646 (7:103359080 C>T), RS1002044121 (7:103359252 C>G,T)

Disease associations

OMIM: gene MIM:154365 | disease phenotypes: MIM:257320, MIM:616436

GenCC curated gene-disease

Mondo (2): Norman-Roberts syndrome (MONDO:0009760), familial temporal lobe epilepsy 7 (MONDO:0014639)

Orphanet (2): Epilepsy with auditory features (Orphanet:101046), Lissencephaly syndrome, Norman-Roberts type (Orphanet:89844)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831203 (SINGLE PROTEIN)

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 66 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 137 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

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	3
sodium arsenite	affects binding, increases reaction, increases expression	2
arsenic disulfide	affects expression, increases expression	2
Arsenic Trioxide	decreases expression, affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Hydrogen Peroxide	affects expression, increases expression	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
beta-Naphthoflavone	increases expression	2
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
bisphenol A	increases expression, decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, increases reaction	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
sulindac sulfide	decreases expression	1
arsenic trichloride	decreases expression, increases abundance	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
chromium hexavalent ion	increases expression	1
chloropicrin	increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
bromovanin	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 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.