PSMA3

Summary

PSMA3 (proteasome 20S subunit alpha 3, HGNC:9532) is a protein-coding gene on chromosome 14q23.1, encoding Proteasome subunit alpha type-3 (P25788). Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 a member of the peptidase T1A family, that is a 20S core alpha subunit. Two alternative transcripts encoding different isoforms have been identified.

Source: NCBI Gene 5684 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 252 total — 1 pathogenic
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_002788

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9532
Approved symbol	PSMA3
Name	proteasome 20S subunit alpha 3
Location	14q23.1
Locus type	gene with protein product
Status	Approved
Aliases	HC8
Ensembl gene	ENSG00000100567
Ensembl biotype	protein_coding
OMIM	176843
Entrez	5684

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 9 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000216455, ENST00000412908, ENST00000553665, ENST00000553677, ENST00000554207, ENST00000554456, ENST00000554812, ENST00000555743, ENST00000555931, ENST00000556321, ENST00000557087, ENST00000557290, ENST00000557508, ENST00000876655, ENST00000876656, ENST00000925587, ENST00000925588, ENST00000964944

RefSeq mRNA: 2 — MANE Select: NM_002788 NM_002788, NM_152132

CCDS: CCDS45113, CCDS9731

Canonical transcript exons

ENST00000216455 — 11 exons

Exon	Start	End
ENSE00001911174	58244843	58244941
ENSE00003465022	58260948	58261020
ENSE00003470996	58252119	58252242
ENSE00003497225	58270418	58270485
ENSE00003563120	58257745	58257846
ENSE00003574077	58263705	58263770
ENSE00003580836	58267474	58267520
ENSE00003644546	58270934	58270998
ENSE00003682410	58247750	58247832
ENSE00003688321	58257925	58257998
ENSE00003844789	58271851	58272004

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.0481 / max 1839.2630, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139816	79.0295	1822
139815	2.0186	1189

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.49	gold quality
rectum	UBERON:0001052	98.29	gold quality
metanephros cortex	UBERON:0010533	98.17	gold quality
right adrenal gland	UBERON:0001233	98.16	gold quality
right adrenal gland cortex	UBERON:0035827	98.13	gold quality
calcaneal tendon	UBERON:0003701	98.12	gold quality
smooth muscle tissue	UBERON:0001135	98.10	gold quality
body of pancreas	UBERON:0001150	98.09	gold quality
left adrenal gland	UBERON:0001234	98.04	gold quality
right lobe of thyroid gland	UBERON:0001119	98.03	gold quality
islet of Langerhans	UBERON:0000006	97.99	gold quality
left lobe of thyroid gland	UBERON:0001120	97.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.98	gold quality
upper lobe of left lung	UBERON:0008952	97.96	gold quality
vermiform appendix	UBERON:0001154	97.94	gold quality
left uterine tube	UBERON:0001303	97.93	gold quality
right uterine tube	UBERON:0001302	97.91	gold quality
upper lobe of lung	UBERON:0008948	97.91	gold quality
left adrenal gland cortex	UBERON:0035825	97.91	gold quality
right lung	UBERON:0002167	97.90	gold quality
monocyte	CL:0000576	97.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.82	gold quality
gastrocnemius	UBERON:0001388	97.81	gold quality
adenohypophysis	UBERON:0002196	97.80	gold quality
body of uterus	UBERON:0009853	97.80	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.79	gold quality
mucosa of stomach	UBERON:0001199	97.78	gold quality
endocervix	UBERON:0000458	97.74	gold quality
descending thoracic aorta	UBERON:0002345	97.74	gold quality
right lobe of liver	UBERON:0001114	97.73	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

miRNA regulators (miRDB)

14 targeting PSMA3, 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-4282	99.99	75.36	6408
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-664B-5P	96.74	67.50	509
HSA-MIR-4515	95.70	65.73	716
HSA-MIR-5009-5P	94.82	63.89	775
HSA-MIR-1269A	92.75	64.61	542
HSA-MIR-1269B	92.75	64.73	538

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 15)

• Aurora-B might undergo degradation by binding to HC8 in a proteasome-dependent manner during mitosis (PMID:14674694)
• EBNA3C binds to human the C8/alpha7 subunit of the 20S proteasome; degraded by purified 20S proteasomes in vitro but, found to be very stable and apparently turned over at a very low rate in B cells infected latently with EBV (PMID:15831937)
• The authors propose that the full-length HCV F protein as well as the F protein initiating from codon 26 is degraded by an ubiquitin-independent pathway that is mediated by the proteasome subunit alpha3. (PMID:18971267)
• Serum 20S proteasome concentration and percentage of lymphocytic apoptosis predicted survival and patient prognosis in critically ill patients. (PMID:21108816)
• Plasminogen activator inhibitor type 1 interacts with alpha3 subunit of proteasome and modulates its activity. (PMID:21135093)
• A combination of two-dimensional gel electrophoresis (2D-GE) and tandem mass-spectrometry revealed a large number of PSMA3-bound proteins that are involved in various aspects of mRNA metabolism, including splicing. (PMID:22079093)
• Evidence of a sex-specific association of PSMA3 genetic variants with subtypes of juvenile idiopathic arthritis. (PMID:24875235)
• Protein interaction between Ambn and Psma3 can facilitate redistribution of ameloblastin domains within forming enamel. (PMID:26070558)
• Our results provide evidence on new T1DM-susceptible loci in the PSMA3, PSMA6 and PSMC6 proteasome genes and give a new insight into the T1DM pathogenesis (PMID:26661414)
• In thyroid hemiagenesis, genomic examinations revealed the presence of four recurrent defects (three deletions and one duplication) affecting highly conservative proteasome genes PSMA1, PSMA3, and PSMD3. (PMID:28390009)
• High PSMA3 expression is associated with cholangiocarcinoma. (PMID:28560424)
• Study identified that PSMA3 and PSMA3-AS1 in mesenchymal stem cells (MSCs) could be packaged into exosomes and transferred to myeloma cells, thus promoting proteasome inhibitor resistance through a novel exosomal PSMA3-AS1/PSMA3 signaling pathway. PSMA3-AS1 could form an RNA duplex with pre-PSMA3, which transcriptionally promoted PSMA3 expression by increasing its stability. (PMID:30610101)
• Structural Fluctuations of the Human Proteasome alpha7 Homo-Tetradecamer Double Ring Imply the Proteasomal alpha-Ring Assembly Mechanism. (PMID:33926037)
• LncRNA PSMA3-AS1 promotes cell proliferation, migration, and invasion in ovarian cancer by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis. (PMID:34520102)
• Immuno-oncological role of 20S proteasome alpha-subunit 3 in aggravating the progression of esophageal squamous cell carcinoma. (PMID:34755333)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psma3	ENSDARG00000086618
mus_musculus	Psma3	ENSMUSG00000060073
rattus_norvegicus	Psma3	ENSRNOG00000007851
drosophila_melanogaster	Prosalpha7	FBGN0023175
caenorhabditis_elegans		WBGENE00003928

Paralogs (18): PSMB1 (ENSG00000008018), PSMA4 (ENSG00000041357), PSMB5 (ENSG00000100804), PSMA6 (ENSG00000100902), PSMA7 (ENSG00000101182), PSMA2 (ENSG00000106588), PSMB2 (ENSG00000126067), PSMA1 (ENSG00000129084), PSMB7 (ENSG00000136930), PSMB6 (ENSG00000142507), PSMA5 (ENSG00000143106), PSMA8 (ENSG00000154611), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Protein

Protein identifiers

Proteasome subunit alpha type-3 — P25788 (reviewed: P25788)

Alternative names: Macropain subunit C8, Multicatalytic endopeptidase complex subunit C8, Proteasome component C8, Proteasome subunit alpha-7

All UniProt accessions (6): P25788, A0A140VK43, G3V3W4, G3V4X5, G3V5N4, H0YJ03

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2.

Subunit / interactions. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with AURKB. Interacts with CDKN1A. Interacts with MDM2 and RB1. Interacts with the C-terminus of TBXA2R isoform 2. Interacts with DNAJB2. (Microbial infection) Interacts with HIV-1 Tat protein. (Microbial infection) Interacts with hepatitis C virus (HCV) F protein. (Microbial infection) Interacts with Epstein-Barr virus EBNA3 proteins.

Subcellular location. Cytoplasm. Nucleus.

Induction. Down-regulated by antioxidants BO-653 and probucol. Up-regulated by bacterial lipopolysaccharides (LPS) and TNF.

Similarity. Belongs to the peptidase T1A family.

Isoforms (2)

UniProt ID	Names	Canonical?
P25788-1	1	yes
P25788-2	2

RefSeq proteins (2): NP_002779, NP_687033 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000426	Proteasome_asu_N	Domain
IPR001353	Proteasome_sua/b	Family
IPR023332	Proteasome_alpha-type	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR050115	Proteasome_alpha	Family

Pfam: PF00227, PF10584

UniProt features (38 total): strand 15, helix 8, modified residue 6, turn 4, initiator methionine 1, chain 1, sequence conflict 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

173 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5LE5	X-RAY DIFFRACTION	1.8
5LEY	X-RAY DIFFRACTION	1.9
5LF4	X-RAY DIFFRACTION	1.99
5LF1	X-RAY DIFFRACTION	2
5LF7	X-RAY DIFFRACTION	2
8UD9	ELECTRON MICROSCOPY	2.04
5LF6	X-RAY DIFFRACTION	2.07
5LF3	X-RAY DIFFRACTION	2.1
8BZL	X-RAY DIFFRACTION	2.14
5LEZ	X-RAY DIFFRACTION	2.19
5LEX	X-RAY DIFFRACTION	2.2
7AWE	X-RAY DIFFRACTION	2.29
5LF0	X-RAY DIFFRACTION	2.41
7B12	X-RAY DIFFRACTION	2.43
9K53	ELECTRON MICROSCOPY	2.5
9HMN	ELECTRON MICROSCOPY	2.55
4R3O	X-RAY DIFFRACTION	2.6
6RGQ	ELECTRON MICROSCOPY	2.6
9YUZ	ELECTRON MICROSCOPY	2.6
8QYL	ELECTRON MICROSCOPY	2.67
8CVR	ELECTRON MICROSCOPY	2.7
6KWY	ELECTRON MICROSCOPY	2.72
8QYJ	ELECTRON MICROSCOPY	2.73
8QYM	ELECTRON MICROSCOPY	2.73
8USB	ELECTRON MICROSCOPY	2.73
9MBP	ELECTRON MICROSCOPY	2.75
9PDL	ELECTRON MICROSCOPY	2.76
6E5B	X-RAY DIFFRACTION	2.77
7NAN	ELECTRON MICROSCOPY	2.8
8TM6	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25788-F1	94.60	0.87

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 (6): 2, 57, 206, 230, 243, 250

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: 513 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MBD4, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_RAB5A, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, BASSO_B_LYMPHOCYTE_NETWORK

GO Biological Process (3): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), ubiquitin-dependent protein catabolic process (GO:0006511), obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (2): ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (8): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome core complex (GO:0005839), proteasome core complex, alpha-subunit complex (GO:0019773), extracellular exosome (GO:0070062)

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
intracellular protein-containing complex	3
cellular anatomical structure	3
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
ubiquitin-like protein ligase binding	1
binding	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
proteasome complex	1
catalytic complex	1
proteasome core complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

3664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMA3	PSMB1	P20618	978
PSMA3	PSMB4	P28070	941
PSMA3	PSMB3	P31147	897
PSMA3	POMP	Q9Y244	882
PSMA3	PSMB9	P28065	870
PSMA3	PSMA1	P25786	860
PSMA3	PSMC6	P49719	851
PSMA3	PSMC3	P17980	813
PSMA3	PSMD2	Q13200	813
PSMA3	PSMB2	P31145	812
PSMA3	PSMB6	P28072	811
PSMA3	PSMD9	O00233	781
PSMA3	PSMB5	P28074	781
PSMA3	PSMB7	Q99436	780
PSMA3	PSMA4	P25789	777

IntAct

467 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA3	psi-mi:“MI:0915”(physical association)	0.950
PSMA3	PSMA1	psi-mi:“MI:0915”(physical association)	0.950
PSMA3	PSMA6	psi-mi:“MI:0915”(physical association)	0.840
PSMA6	PSMA3	psi-mi:“MI:0915”(physical association)	0.840
PSMA3	DMC1	psi-mi:“MI:0915”(physical association)	0.780
DMC1	PSMA3	psi-mi:“MI:0915”(physical association)	0.780
PSMA3	GATA2	psi-mi:“MI:0915”(physical association)	0.740
PSMA3	ZNF366	psi-mi:“MI:0915”(physical association)	0.740
GATA2	PSMA3	psi-mi:“MI:0915”(physical association)	0.740
FBXO7	PSMA3	psi-mi:“MI:0915”(physical association)	0.720
PSMB4	PSMA3	psi-mi:“MI:0915”(physical association)	0.670
ZNF385C	PSMA3	psi-mi:“MI:0915”(physical association)	0.670
IQCE	PSMA3	psi-mi:“MI:0915”(physical association)	0.670
RBM42	PSMA3	psi-mi:“MI:0915”(physical association)	0.670
PSMA3	PSMB4	psi-mi:“MI:0915”(physical association)	0.670
PSMA3	ZNF385C	psi-mi:“MI:0915”(physical association)	0.670
PSMA3	RBM42	psi-mi:“MI:0915”(physical association)	0.670
LINC02913	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
VPS37C	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
PSMA3		psi-mi:“MI:0915”(physical association)	0.560
MIA2	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
PSMA3	RBFOX2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (804): PSMA3 (Affinity Capture-MS), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid), PSMA3 (Two-hybrid)

ESM2 similar proteins: A2YXU2, A2Z3I9, O13268, O14818, O16811, O17586, O23715, O24030, O24362, O24616, O48551, O70435, O81146, O94517, P18422, P21243, P22769, P25788, P30186, P34120, P40303, P48004, P52428, P60900, P60901, P90513, Q0J006, Q10329, Q24178, Q27563, Q2YDE4, Q3ZBG0, Q4R7D9, Q58DU5, Q5RDH8, Q6YT00, Q8TAA3, Q95005, Q9CWH6, Q9LSU0

Diamond homologs: A2Y9X7, A2YXU2, A2Z3I9, A3CW55, A4FZT6, A4YCU9, A5UJS2, A6URN9, A6VIP0, A7I9C7, A9A846, B6YSH9, B8GEZ3, C3MQ43, C3MVG1, C3N5R0, C3NEC6, C3NHC6, C4KHD9, C5A2C2, C6A459, F4JJE5, O13268, O14818, O24030, O24616, O24733, O26782, O29760, O59219, O70435, O81148, O81149, O82530, P0C8Y9, P0DKK3, P0DKK4, P18053, P18422, P21670

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PSMA3	“form complex”	“26S Proteasome”	binding
CSNK2A1	unknown	PSMA3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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
RUNX1 regulates transcription of genes involved in differentiation of HSCs	5	13.6×	2e-03
Separation of Sister Chromatids	5	8.7×	3e-03
Neddylation	5	6.8×	4e-03
Antigen processing: Ubiquitination & Proteasome degradation	5	5.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	101
Likely benign	126
Benign	11

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
548994	NM_002788.4(PSMA3):c.404+2T>C	Pathogenic

SpliceAI

1370 predictions. Top by Δscore:

Variant	Effect	Δscore
14:58247748:A:AG	acceptor_gain	1.0000
14:58247749:G:GG	acceptor_gain	1.0000
14:58252113:TTTCA:T	acceptor_loss	1.0000
14:58252114:TTCAG:T	acceptor_loss	1.0000
14:58252115:TCA:T	acceptor_loss	1.0000
14:58252116:CAG:C	acceptor_loss	1.0000
14:58252117:A:AG	acceptor_gain	1.0000
14:58252117:A:C	acceptor_loss	1.0000
14:58252118:G:GT	acceptor_gain	1.0000
14:58252118:GT:G	acceptor_gain	1.0000
14:58252118:GTAC:G	acceptor_gain	1.0000
14:58252118:GTACA:G	acceptor_gain	1.0000
14:58252238:GAATG:G	donor_gain	1.0000
14:58252241:TGGT:T	donor_loss	1.0000
14:58252242:GGTAA:G	donor_loss	1.0000
14:58252243:G:C	donor_loss	1.0000
14:58252243:G:GG	donor_gain	1.0000
14:58257742:CA:C	acceptor_loss	1.0000
14:58257743:A:AG	acceptor_gain	1.0000
14:58257743:AG:A	acceptor_gain	1.0000
14:58257743:AGGCA:A	acceptor_loss	1.0000
14:58257744:G:GG	acceptor_gain	1.0000
14:58257744:GG:G	acceptor_gain	1.0000
14:58257744:GGC:G	acceptor_gain	1.0000
14:58257842:TAAAA:T	donor_gain	1.0000
14:58257843:AAAA:A	donor_gain	1.0000
14:58257844:AAA:A	donor_gain	1.0000
14:58257845:AA:A	donor_gain	1.0000
14:58257846:AGT:A	donor_loss	1.0000
14:58257847:G:GG	donor_gain	1.0000

AlphaMissense

1685 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:58247750:T:C	Y8H	1.000
14:58247753:G:C	D9H	1.000
14:58247754:A:C	D9A	1.000
14:58247754:A:G	D9G	1.000
14:58247754:A:T	D9V	1.000
14:58247757:T:C	L10P	1.000
14:58247771:T:C	F15L	1.000
14:58247772:T:C	F15S	1.000
14:58247772:T:G	F15C	1.000
14:58247773:C:A	F15L	1.000
14:58247773:C:G	F15L	1.000
14:58247783:G:A	G19R	1.000
14:58247783:G:C	G19R	1.000
14:58247784:G:A	G19E	1.000
14:58247784:G:T	G19V	1.000
14:58247792:T:C	F22L	1.000
14:58247793:T:C	F22S	1.000
14:58247793:T:G	F22C	1.000
14:58247794:T:A	F22L	1.000
14:58247794:T:G	F22L	1.000
14:58247797:A:C	Q23H	1.000
14:58247797:A:T	Q23H	1.000
14:58247804:T:C	Y26H	1.000
14:58247805:A:G	Y26C	1.000
14:58247808:C:A	A27D	1.000
14:58252130:G:A	G39E	1.000
14:58252154:T:A	V47D	1.000
14:58252159:G:T	G49W	1.000
14:58252160:G:A	G49E	1.000
14:58257754:G:C	G80R	1.000

dbSNP variants (sampled 300 via entrez): RS1000181071 (14:58246978 T>C), RS1000215738 (14:58247312 A>T), RS1000286395 (14:58264051 C>A), RS1000401813 (14:58270327 T>A,C), RS1000610452 (14:58259099 CAA>C), RS1000686499 (14:58264079 C>A), RS1000717297 (14:58264370 C>A,G,T), RS1000883002 (14:58248290 C>T), RS1000946257 (14:58254212 T>C), RS1000960043 (14:58270094 C>A), RS1001294675 (14:58247374 T>G), RS1001327067 (14:58269851 CTTT>C,CTT,CTTTT), RS1001338178 (14:58254270 G>C), RS1001378758 (14:58254684 C>T), RS1001482937 (14:58259958 A>G)

Disease associations

OMIM: gene MIM:176843 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004602_203	Mean corpuscular volume	5.000000e-10
GCST004630_199	Mean corpuscular hemoglobin	3.000000e-11
GCST010703_93	Brain morphology (MOSTest)	6.000000e-54
GCST90002403_507	Red blood cell count	4.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004346	neuroimaging measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831201 (PROTEIN COMPLEX GROUP), CHEMBL6066934 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 41,720 (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
CHEMBL2141296	IXAZOMIB	3	6,022
CHEMBL371405	MARIZOMIB	3	7,332
CHEMBL2103884	OPROZOMIB	2	2,738

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

ChEMBL bioactivities

314 potent at pChembl≥5 of 340 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CINNABARAMIDE G
9.22	Ki	0.6	nM	CHEMBL5624541
9.22	Ki	0.6	nM	BORTEZOMIB
9.04	IC50	0.92	nM	CHEMBL4102324
9.00	IC50	1	nM	CINNABARAMIDE A
8.89	IC50	1.3	nM	MARIZOMIB
8.82	IC50	1.5	nM	CHEMBL4460323
8.70	IC50	2	nM	CHEMBL307387
8.66	IC50	2.2	nM	CHEMBL5419917
8.62	IC50	2.4	nM	CHEMBL4517600
8.62	IC50	2.4	nM	BORTEZOMIB
8.62	IC50	2.4	nM	CHEMBL5413513
8.60	IC50	2.5	nM	CHEMBL4587036
8.59	IC50	2.56	nM	BORTEZOMIB
8.57	IC50	2.7	nM	CHEMBL3237863
8.57	IC50	2.7	nM	CHEMBL5394365
8.52	IC50	3	nM	BORTEZOMIB
8.47	IC50	3.4	nM	CHEMBL4444107
8.47	IC50	3.4	nM	CHEMBL6143686
8.46	IC50	3.43	nM	CHEMBL5197285
8.44	IC50	3.6	nM	CHEMBL4541038
8.41	IC50	3.9	nM	CHEMBL3237862
8.41	IC50	3.9	nM	CHEMBL4547405
8.40	IC50	4	nM	CHEMBL5406440
8.39	IC50	4.1	nM	CHEMBL3237864
8.39	IC50	4.1	nM	CHEMBL3237867
8.39	IC50	4.03	nM	CHEMBL5171225
8.37	IC50	4.28	nM	CHEMBL4581126
8.34	IC50	4.6	nM	CHEMBL4542373
8.34	IC50	4.6	nM	CHEMBL4558648
8.32	IC50	4.8	nM	CHEMBL3237873
8.32	IC50	4.8	nM	CHEMBL4467618
8.30	IC50	5	nM	CHEMBL5398681
8.29	IC50	5.1	nM	CHEMBL3237865
8.29	IC50	5.15	nM	CHEMBL5186240
8.28	IC50	5.2	nM	CHEMBL5429323
8.28	IC50	5.2	nM	CHEMBL5431451
8.25	IC50	5.6	nM	CHEMBL5423645
8.24	IC50	5.7	nM	CHEMBL3237866
8.24	IC50	5.7	nM	CHEMBL3237860
8.23	IC50	5.9	nM	CHEMBL3237868
8.22	IC50	6	nM	CINNABARAMIDE F
8.22	IC50	6	nM	CHEMBL5412037
8.22	IC50	6	nM	CHEMBL74336
8.20	IC50	6.3	nM	CHEMBL5440712
8.19	IC50	6.4	nM	CHEMBL4447701
8.19	IC50	6.4	nM	CHEMBL4435814
8.19	IC50	6.5	nM	CHEMBL4436430
8.19	IC50	6.5	nM	IXAZOMIB
8.16	IC50	6.91	nM	BORTEZOMIB

PubChem BioAssay actives

281 with measured affinity, of 814 total; 50 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
methyl (2R)-2-acetamido-3-[(2R,3S,4R)-2-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-3-hydroxy-3-methyl-5-oxopyrrolidine-2-carbonyl]sulfanylpropanoate	277357: Inhibition of human 20S proteasome	ic50	0.0006	uM
[(1R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-(pyrazine-2-carbonyl)amino]-3-methylbutyl]boronic acid	2131634: Binding affinity to 20s proteosome (unknown origin) assessed as inhibition constant	ki	0.0006	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0009	uM
(1R,4R,5S)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	277357: Inhibition of human 20S proteasome	ic50	0.0010	uM
(1R,4R,5S)-4-(2-chloroethyl)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	1853759: Inhibition of 20S proteasome (unknown origin) by fluorescence based assay	ic50	0.0013	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0015	uM
N-[5-[[amino(nitramido)methylidene]amino]-1-[(4-methyl-1-oxopentan-2-yl)amino]-1-oxopentan-2-yl]-2-cyclopentyl-10-(1,3-dioxoisoindol-2-yl)decanamide	3028: Compound was evaluated for inhibitory activity against 20S proteasome from human liver and brain	ic50	0.0020	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-3-cyclopropylpropanoyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0022	uM
4-N-(4-benzoylphenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0024	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopentylacetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0024	uM
Bortezomib	1985684: Inhibition of 26S proteasome (unknown origin)	ic50	0.0024	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-N-[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[2-[[2-[[2-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]pentanediamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0025	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopropylacetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	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’-[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
4-N-(4-fluorophenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0034	uM
1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-methyl-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0034	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0036	uM
4-N-(1,3-benzothiazol-2-yl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	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’-[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
[(1R)-1-[[2-[(2,5-dibromobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0040	uM
1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0040	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-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-N-[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[2-[[2-[[2-[[(2S)-3-(4-hydroxyphenyl)-1-[[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]pentanediamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0043	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,3,4-thiadiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0046	uM
4-N-(4-chlorophenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0046	uM
4-N-(4-methoxyphenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	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’-(4-phenylmethoxybutyl)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0048	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-3-cyclopropylpropanoyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0050	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)-N’-(2,2-dimethylpropyl)-2-[[4-[methyl(pyridine-3-carbonyl)amino]piperidine-1-carbonyl]amino]-N-[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]butanediamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0052	uM
4-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0052	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]acetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0052	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopropylacetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0056	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
(2R)-2-acetamido-3-[(2R,3S,4R)-2-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-3-hydroxy-3-methyl-5-oxopyrrolidine-2-carbonyl]sulfanylpropanoic acid	277357: Inhibition of human 20S proteasome	ic50	0.0060	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopentylacetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0060	uM
N-[5-[[amino(nitramido)methylidene]amino]-1-[(4-methyl-1-oxopentan-2-yl)amino]-1-oxopentan-2-yl]-10-cyano-2-cyclopentyldecanamide	3028: Compound was evaluated for inhibitory activity against 20S proteasome from human liver and brain	ic50	0.0060	uM
4-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0063	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,2-oxazol-3-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0064	uM
(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]pentanamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0064	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-pyrazin-2-ylpiperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0065	uM
Ixazomib	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0065	uM
4-N-(4-chlorophenyl)-1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-methylpiperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0069	uM
(2S)-N-[(2S,3R,4R)-3-hydroxy-5-[[(2S)-1-[(2-hydroxy-4-methoxyphenyl)methylamino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxo-1-phenyl-4-[(3,4,5-trimethoxyphenyl)methylamino]pentan-2-yl]-3,3-dimethyl-2-[(2-naphthalen-1-ylacetyl)amino]butanamide	3027: Tested in vitro for inhibition of chymotrypsin like activity of purified human 20S proteasome	ic50	0.0070	uM
Carfilzomib	1770085: Inhibition of human 20S proteasome chymotrypsin-like activity in human RPMI-8226 cells using Suc-LLVY-AMC as fluorogenic substrate incubated for 3 hrs by fluorescence assay	ic50	0.0070	uM
(2S)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-naphthalen-1-ylacetyl)amino]propanoyl]amino]-N-[1-(4-hydroxyphenyl)-3-oxopropan-2-yl]-3-methylbutanamide	248827: Inhibitory concentration to inhibit chymotrypsin-like activity of 20S proteasome prepared from human leukemia HL-60 cells was determined	ic50	0.0070	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Arsenic	affects methylation, increases abundance, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
arsenite	affects binding, increases reaction	1
nickel subsulfide	increases expression	1
sodium arsenite	increases abundance, increases expression	1
bufalin	decreases expression	1
quinoline	decreases expression	1
phenethyl isothiocyanate	affects binding	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
pentabromodiphenyl ether	increases expression	1
dimethylarsinous acid	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1

ChEMBL screening assays

169 unique, capped per target: 160 binding, 6 admet, 3 functional

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
CHEMBL4736581	ADMET	Inhibition of human 20S proteasome stably expressed in HEK293 cells at 5 to 50 uM using succinyl-LLVY-AMC as substrate preincubated for 30 mins followed by substrate addition and measured at 3 mins interval for 30 mins by fluorescence assay	A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells. — Eur J Med Chem
CHEMBL834792	Functional	Inhibitory concentration to inhibit trypsin-like activity of 20S proteasome from human leukemia HL-60 cells was determined	Structure-based design of derivatives of tyropeptin A as the potent and selective inhibitors of mammalian 20S proteasome. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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