PSMD1

Summary

PSMD1 (proteasome 26S subunit, non-ATPase 1, HGNC:9554) is a protein-coding gene on chromosome 2q37.1, encoding 26S proteasome non-ATPase regulatory subunit 1 (Q99460). 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 99.6% 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 the largest non-ATPase subunit of the 19S regulator lid, which is responsible for substrate recognition and binding. There is evidence that this proteasome and its subunits interact with viral proteins, including those of coronaviruses. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 5707 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 88 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_002807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9554
Approved symbol	PSMD1
Name	proteasome 26S subunit, non-ATPase 1
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	S1, P112, Rpn2
Ensembl gene	ENSG00000173692
Ensembl biotype	protein_coding
OMIM	617842
Entrez	5707

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 21 protein_coding, 14 retained_intron, 10 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000308696, ENST00000373635, ENST00000409643, ENST00000431051, ENST00000440838, ENST00000444007, ENST00000447633, ENST00000467792, ENST00000477120, ENST00000481003, ENST00000488354, ENST00000491229, ENST00000619128, ENST00000676506, ENST00000676739, ENST00000676740, ENST00000676818, ENST00000677000, ENST00000677158, ENST00000677180, ENST00000677195, ENST00000677229, ENST00000677230, ENST00000677233, ENST00000677259, ENST00000677724, ENST00000678112, ENST00000678140, ENST00000678141, ENST00000678241, ENST00000678261, ENST00000678460, ENST00000678632, ENST00000678679, ENST00000678837, ENST00000679034, ENST00000679095, ENST00000932105, ENST00000932106, ENST00000932107, ENST00000932108, ENST00000932109, ENST00000971492, ENST00000971493, ENST00000971494, ENST00000971495

RefSeq mRNA: 2 — MANE Select: NM_002807 NM_001191037, NM_002807

CCDS: CCDS2482, CCDS54436

Canonical transcript exons

ENST00000308696 — 25 exons

Exon	Start	End
ENSE00001182912	231062506	231062675
ENSE00001236618	231165871	231166017
ENSE00001236626	231165200	231165286
ENSE00001236794	231062248	231062321
ENSE00001236802	231061267	231061310
ENSE00001236811	231170566	231170721
ENSE00001674957	231056867	231057041
ENSE00001917136	231172535	231172827
ENSE00003475982	231153564	231153666
ENSE00003492980	231072189	231072415
ENSE00003501142	231161340	231161509
ENSE00003504499	231077034	231077162
ENSE00003509175	231083567	231083763
ENSE00003509716	231070025	231070168
ENSE00003519341	231080141	231080314
ENSE00003527206	231066906	231067111
ENSE00003531652	231075511	231075571
ENSE00003555155	231085019	231085114
ENSE00003589948	231138736	231138850
ENSE00003620832	231163635	231163727
ENSE00003621552	231082883	231082994
ENSE00003629392	231087117	231087181
ENSE00003646137	231078659	231078747
ENSE00003682482	231079536	231079614
ENSE00003688576	231146240	231146356

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 98.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.9552 / max 864.2320, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25861	82.1462	1826
25864	0.8090	448

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.05	gold quality
secondary oocyte	CL:0000655	98.01	gold quality
gastrocnemius	UBERON:0001388	97.52	gold quality
deltoid	UBERON:0001476	97.49	gold quality
tibialis anterior	UBERON:0001385	97.45	gold quality
gluteal muscle	UBERON:0002000	97.36	gold quality
muscle of leg	UBERON:0001383	97.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.24	gold quality
stromal cell of endometrium	CL:0002255	97.23	gold quality
adrenal tissue	UBERON:0018303	97.18	gold quality
muscle organ	UBERON:0001630	97.12	gold quality
medial globus pallidus	UBERON:0002477	97.12	gold quality
skeletal muscle organ	UBERON:0014892	97.12	gold quality
mucosa of transverse colon	UBERON:0004991	97.07	gold quality
tongue squamous epithelium	UBERON:0006919	96.96	gold quality
substantia nigra pars compacta	UBERON:0001965	96.93	gold quality
pons	UBERON:0000988	96.91	gold quality
adenohypophysis	UBERON:0002196	96.84	gold quality
left ventricle myocardium	UBERON:0006566	96.76	gold quality
globus pallidus	UBERON:0001875	96.74	gold quality
quadriceps femoris	UBERON:0001377	96.71	gold quality
skeletal muscle tissue	UBERON:0001134	96.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.60	gold quality
pituitary gland	UBERON:0000007	96.58	gold quality
middle temporal gyrus	UBERON:0002771	96.56	gold quality
vastus lateralis	UBERON:0001379	96.55	gold quality
biceps brachii	UBERON:0001507	96.51	gold quality
right frontal lobe	UBERON:0002810	96.48	gold quality
muscle tissue	UBERON:0002385	96.46	gold quality
apex of heart	UBERON:0002098	96.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.19
E-MTAB-7606	no	1342.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting PSMD1, 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-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-432-5P	98.00	68.13	989
HSA-MIR-7161-3P	96.79	68.79	798
HSA-MIR-4683	95.29	65.98	631
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-4304	90.01	61.07	99

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• neurotoxic products of inflammation, such as PGJ2, may play a role in neurodegenerative disorders by impairing 26 S proteasome activity and inducing a chain of events that culminates in neuronal cell death (PMID:16737963)
• analysis of how subunit radial displacements open the gate into the proteolytic core in the human 26S proteasome (PMID:18534977)
• p38 MAPK negatively regulates the proteasome activity by phosphorylating Thr-273 of Rpn2 (PMID:21044959)
• The 26S proteasome plays a key role in promoting apoptosis induced by high doses of UV irradiation. (PMID:22031102)
• Increased 26S proteasome non-ATPase regulatory subunit 1 in the aqueous humor of patients with age-related macular degeneration compared to control subjects. (PMID:24286321)
• Together, our findings suggest that the interaction of Psmd1 with Adrm1 is controlled by SUMOylation in a manner that may alter proteasome composition and function. (PMID:24910440)
• RPN13 binds ubiquitin with an affinity similar to that of other proteasome-associated ubiquitin receptors and that RPN2, ubiquitin, and the deubiquitylase UCH37 bind to RPN13 with independent energetics. (PMID:28442575)
• we firstly demonstrate that BCRC-3 is down-regulated in BC tissues and cell lines for the first time. BCRC-3 is capable of functioning as ceRNA for miR-182-5p to regulate the expression of p27. (PMID:30285878)
• The authors demonstrate that PSMD1 and PSMD2 promote the proliferation of HepG2 cells via facilitating cellular lipid droplet accumulation. (PMID:31703613)
• Identification of Hub Genes in Gastric Cancer with High Heterogeneity Based on Weighted Gene Co-Expression Network. (PMID:32558489)
• Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B. (PMID:33712704)
• 26S Proteasome Non-ATPase Regulatory Subunits 1 (PSMD1) and 3 (PSMD3) as Putative Targets for Cancer Prognosis and Therapy. (PMID:34572038)
• Proteasome 26S subunit, non-ATPase 1 (PSMD1) facilitated the progression of lung adenocarcinoma by the de-ubiquitination and stability of PTEN-induced kinase 1 (PINK1). (PMID:35192838)
• PSMD1 as a prognostic marker and potential target in oropharyngeal cancer. (PMID:38104103)
• Depletion of proteasome subunit PSMD1 induces cancer cell death via protein ubiquitination and DNA damage, irrespective of p53 status. (PMID:38580756)
• Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma. (PMID:38725862)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd1	ENSDARG00000003189
mus_musculus	Psmd1	ENSMUSG00000026229
rattus_norvegicus	Psmd1	ENSRNOG00000017730
drosophila_melanogaster	Rpn2	FBGN0028692
caenorhabditis_elegans		WBGENE00004459

Paralogs (1): PSMD2 (ENSG00000175166)

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 1 — Q99460 (reviewed: Q99460)

Alternative names: 26S proteasome regulatory subunit RPN2, 26S proteasome regulatory subunit S1, 26S proteasome subunit p112

All UniProt accessions (17): Q99460, A0A087WW66, A0A7I2V262, A0A7I2V2K8, A0A7I2V479, A0A7I2V491, A0A7I2V4A5, A0A7I2V4X0, A0A7I2V523, A0A7I2V5C8, A0A7I2V641, A0A7I2YQI9, A0A7I2YQY1, A0A7P0MW50, C9J9M4, F8WCE3, H7BZR6

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.

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 PSMD1. Interacts with ADRM1. Interacts with ZFAND1.

Similarity. Belongs to the proteasome subunit S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99460-1	1	yes
Q99460-2	2

RefSeq proteins (2): NP_001177966, NP_002798* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002015	Proteasome/cyclosome_rpt	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR016642	26S_Psome_Rpn2	Family
IPR040623	RPN2_C	Domain
IPR048570	PSMD1_RPN2_N	Domain

Pfam: PF01851, PF13646, PF18004, PF21505

Enzyme classification (BRENDA):

• EC 5.6.1.5 — proteasome ATPase (BRENDA: 37 organisms, 65 substrates, 19 inhibitors, 13 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.03–0.55	9
CTP	0.307–0.493	2
K48-GREEN-TAIL POLYPEPTIDE	0.0003	1
K48-RED POLYPEPTIDE	0.0044	1

UniProt features (101 total): helix 47, strand 13, turn 11, repeat 10, modified residue 9, compositionally biased region 4, region of interest 3, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

125 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5V1Y	X-RAY DIFFRACTION	1.42
6OI4	X-RAY DIFFRACTION	1.76
5V1Z	X-RAY DIFFRACTION	2
9K53	ELECTRON MICROSCOPY	2.5
8USD	ELECTRON MICROSCOPY	2.7
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99460-F1	79.29	0.17

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 (9): 1, 273, 290, 310, 311, 315, 720, 830, 834

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: 611 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, HONMA_DOCETAXEL_RESISTANCE, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, WHITEHURST_PACLITAXEL_SENSITIVITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION

GO Biological Process (2): regulation of protein catabolic process (GO:0042176), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (3): enzyme regulator activity (GO:0030234), ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (11): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle (GO:0005838), proteasome regulatory particle, base subcomplex (GO:0008540), membrane (GO:0016020), proteasome accessory complex (GO:0022624), proteasome storage granule (GO:0034515), azurophil granule lumen (GO:0035578)

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	4
protein-containing complex	3
cytoplasm	2
regulation of catabolic process	1
protein catabolic process	1
regulation of protein metabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
catalytic activity	1
molecular function regulator activity	1
ubiquitin-like protein ligase binding	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
proteasome accessory complex	1
proteasome regulatory particle	1
proteasome complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1

Protein interactions and networks

STRING

2944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD1	PSMC1	P49014	957
PSMD1	PSMD2	Q13200	949
PSMD1	PSMD14	O00487	928
PSMD1	PSMD3	O43242	926
PSMD1	PSMC2	P35998	924
PSMD1	PSMD7	P51665	897
PSMD1	PSMC3	P17980	896
PSMD1	PSMD11	O00231	875
PSMD1	PSMD8	P48556	874
PSMD1	PSMC6	P49719	873
PSMD1	PSMD6	Q15008	862
PSMD1	PSMC4	P43686	860
PSMD1	PSMC5	P47210	846
PSMD1	PSMD4	P55036	838
PSMD1	ADRM1	Q16186	830

IntAct

234 interactions, top by confidence:

A	B	Type	Score
PSMC6	PSMC3	psi-mi:“MI:0915”(physical association)	0.950
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
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
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMB7	PSMA4	psi-mi:“MI:0914”(association)	0.790
PSMC5	PSMC3	psi-mi:“MI:0914”(association)	0.760
PSMD1	ADRM1	psi-mi:“MI:0407”(direct interaction)	0.750
ADRM1	PSMD1	psi-mi:“MI:0407”(direct interaction)	0.750
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD4	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMC5	PSMD3	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD11	PSMD12	psi-mi:“MI:0915”(physical association)	0.730
PSMC5	ADRM1	psi-mi:“MI:0914”(association)	0.730
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730

BioGRID (806): PSMD1 (Affinity Capture-MS), PSMD1 (Affinity Capture-RNA), PSMD1 (Affinity Capture-RNA), PSMD1 (Affinity Capture-MS), PSMD1 (Affinity Capture-Western), UBC (Reconstituted Complex), PSMD1 (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), PSMD1 (Reconstituted Complex), PSMD1 (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), PSMD1 (Affinity Capture-MS)

ESM2 similar proteins: A0JN27, A0PJN4, A1L167, C1C3R6, O88761, O94973, P17427, P18484, P22234, P38024, P48444, P51583, P97834, Q08211, Q0VCK5, Q13042, Q13098, Q28141, Q28F89, Q2YDL1, Q3MHJ2, Q3TXS7, Q4R9A8, Q4VC33, Q5F398, Q5F418, Q5R532, Q5R5S4, Q5R874, Q5RA77, Q5RB59, Q5RBN9, Q5RDU4, Q5RKJ1, Q6GR10, Q6NRB5, Q6NRT5, Q76EZ2, Q7L5Y9, Q7SXR3

Diamond homologs: O48844, O74762, O88761, P32565, Q18115, Q3TXS7, Q54JM5, Q5F418, Q5R5S4, Q6FIP2, Q75CF3, Q99460, Q9MAT0, Q9V3P6, Q8SSH5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
bortezomib	“down-regulates activity”	PSMD1	“chemical inhibition”
PSMD1	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 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	23	58.8×	7e-35
Vpu mediated degradation of CD4	23	56.0×	2e-34
Autodegradation of the E3 ubiquitin ligase COP1	23	56.0×	2e-34
Ubiquitin-dependent degradation of Cyclin D	23	56.0×	2e-34
Regulation of ornithine decarboxylase (ODC)	22	54.9×	4e-33
Cross-presentation of soluble exogenous antigens (endosomes)	23	53.5×	5e-34
Vif-mediated degradation of APOBEC3G	23	53.5×	5e-34
Hh mutants are degraded by ERAD	24	53.5×	6e-35

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	34	12.5×	8e-25
ubiquitin-dependent protein catabolic process	12	6.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3958 predictions. Top by Δscore:

Variant	Effect	Δscore
2:231057037:GGCCG:G	donor_gain	1.0000
2:231057038:GCCG:G	donor_gain	1.0000
2:231057038:GCCGG:G	donor_gain	1.0000
2:231057039:CCGGT:C	donor_loss	1.0000
2:231057042:G:GG	donor_gain	1.0000
2:231057043:T:A	donor_loss	1.0000
2:231061262:CATAG:C	acceptor_loss	1.0000
2:231061263:ATAGC:A	acceptor_loss	1.0000
2:231061264:TAGCT:T	acceptor_loss	1.0000
2:231061265:A:AG	acceptor_gain	1.0000
2:231061265:AG:A	acceptor_loss	1.0000
2:231061266:G:GA	acceptor_loss	1.0000
2:231061266:G:GG	acceptor_gain	1.0000
2:231062242:TTACA:T	acceptor_loss	1.0000
2:231062244:ACAGG:A	acceptor_loss	1.0000
2:231062245:CAGGA:C	acceptor_loss	1.0000
2:231062246:A:AG	acceptor_gain	1.0000
2:231062246:A:C	acceptor_loss	1.0000
2:231062247:G:GA	acceptor_loss	1.0000
2:231062247:G:GG	acceptor_gain	1.0000
2:231062318:AAAT:A	donor_gain	1.0000
2:231062318:AAATG:A	donor_loss	1.0000
2:231062319:AAT:A	donor_gain	1.0000
2:231062319:AATG:A	donor_loss	1.0000
2:231062320:AT:A	donor_gain	1.0000
2:231062320:ATGTA:A	donor_loss	1.0000
2:231062321:TGT:T	donor_loss	1.0000
2:231062322:G:GA	donor_loss	1.0000
2:231062322:G:GG	donor_gain	1.0000
2:231062323:T:TC	donor_loss	1.0000

AlphaMissense

6308 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:231062290:T:A	W35R	1.000
2:231062290:T:C	W35R	1.000
2:231062292:G:C	W35C	1.000
2:231062292:G:T	W35C	1.000
2:231062564:T:C	S65P	1.000
2:231062565:C:A	S65Y	1.000
2:231062565:C:T	S65F	1.000
2:231062613:C:A	A81D	1.000
2:231072241:T:C	L236P	1.000
2:231072281:T:G	C249W	1.000
2:231077107:T:C	L339P	1.000
2:231077112:T:C	F341L	1.000
2:231077114:C:A	F341L	1.000
2:231077114:C:G	F341L	1.000
2:231077149:T:C	L353P	1.000
2:231077162:G:C	K357N	1.000
2:231077162:G:T	K357N	1.000
2:231078683:C:G	H366D	1.000
2:231078689:G:C	A368P	1.000
2:231078690:C:A	A368E	1.000
2:231078696:T:A	V370D	1.000
2:231078701:G:C	A372P	1.000
2:231078706:C:A	N373K	1.000
2:231078706:C:G	N373K	1.000
2:231078734:G:C	D383H	1.000
2:231078734:G:T	D383Y	1.000
2:231078735:A:C	D383A	1.000
2:231078735:A:G	D383G	1.000
2:231078735:A:T	D383V	1.000
2:231078740:T:C	F385L	1.000

dbSNP variants (sampled 300 via entrez): RS1000012769 (2:231126126 G>A), RS1000020354 (2:231079713 A>G), RS1000023009 (2:231123042 G>T), RS1000036910 (2:231058018 G>A), RS1000044502 (2:231100087 G>A,T), RS1000167529 (2:231106639 T>C), RS1000167772 (2:231152643 T>C,G), RS1000199242 (2:231161675 C>T), RS1000199626 (2:231106952 A>C), RS1000202378 (2:231149555 C>A), RS1000243445 (2:231072805 A>G), RS1000263528 (2:231159511 C>T), RS1000265779 (2:231156727 C>A), RS1000324531 (2:231143063 C>T), RS1000324811 (2:231096579 C>A,T)

Disease associations

OMIM: gene MIM:617842 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010917_4	Proportion of activated microglia (midfrontal cortex)	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1934 (SINGLE PROTEIN), 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

66 potent at pChembl≥5 of 67 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
7.86	Kd	13.81	nM	CHEMBL3752910
7.86	ED50	13.81	nM	CHEMBL3752910
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

PubChem BioAssay actives

62 with measured affinity, of 137 total; 34 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149121: Binding affinity to human PSMD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0138	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149121: Binding affinity to human PSMD1 incubated for 45 mins by Kinobead based pull down assay	kd	4.3215	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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	4
sodium arsenite	increases expression, decreases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
arsenic disulfide	increases expression, affects expression	2
Arsenic Trioxide	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	increases abundance, affects methylation, decreases expression	2
Tunicamycin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment, decreases expression	1
beta-lapachone	decreases expression, increases expression	1
cobaltous chloride	increases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
elesclomol	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Caffeine	affects phosphorylation	1
Cycloheximide	affects reaction, increases degradation	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
CHEMBL5652163	Binding	Binding affinity to human PSMD1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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