PSMC4

Summary

PSMC4 (proteasome 26S subunit, ATPase 4, HGNC:9551) is a protein-coding gene on chromosome 19q13.11-q13.13, encoding 26S proteasome regulatory subunit 6B (P43686). 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 98.8% 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. This gene encodes a member of the triple-A family of ATPases that is a component of the 19S regulatory subunit and plays a role in 26S proteasome assembly. The encoded protein interacts with gankyrin, a liver oncoprotein, and may also play a role in Parkinson’s disease through interactions with synphilin-1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5704 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 37 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_006503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9551
Approved symbol	PSMC4
Name	proteasome 26S subunit, ATPase 4
Location	19q13.11-q13.13
Locus type	gene with protein product
Status	Approved
Aliases	TBP7, S6, MGC8570, MGC13687, MGC23214, TBP-7, RPT3
Ensembl gene	ENSG00000013275
Ensembl biotype	protein_coding
OMIM	602707
Entrez	5704

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 retained_intron

ENST00000157812, ENST00000455878, ENST00000593455, ENST00000596386, ENST00000601194, ENST00000601697, ENST00000875733, ENST00000875734, ENST00000934373

RefSeq mRNA: 2 — MANE Select: NM_006503 NM_006503, NM_153001

CCDS: CCDS12547, CCDS46076

Canonical transcript exons

ENST00000157812 — 11 exons

Exon	Start	End
ENSE00001140029	39980286	39980454
ENSE00003220968	39971165	39971238
ENSE00003485389	39974735	39974828
ENSE00003493897	39974294	39974440
ENSE00003550914	39972369	39972555
ENSE00003579173	39972146	39972244
ENSE00003628000	39979817	39979984
ENSE00003638294	39980070	39980146
ENSE00003654195	39980662	39980717
ENSE00003665744	39974524	39974633
ENSE00003890485	39981192	39981764

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 96.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 94.2222 / max 393.6424, expressed in 1828 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175810	94.1820	1828
175809	0.0309	5
175808	0.0094	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	96.33	gold quality
mucosa of transverse colon	UBERON:0004991	96.24	gold quality
stromal cell of endometrium	CL:0002255	96.14	gold quality
placenta	UBERON:0001987	96.08	gold quality
muscle of leg	UBERON:0001383	95.99	gold quality
vermiform appendix	UBERON:0001154	95.80	gold quality
prefrontal cortex	UBERON:0000451	95.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.37	gold quality
islet of Langerhans	UBERON:0000006	95.33	gold quality
granulocyte	CL:0000094	95.29	gold quality
smooth muscle tissue	UBERON:0001135	95.28	gold quality
right adrenal gland	UBERON:0001233	95.18	gold quality
primary visual cortex	UBERON:0002436	95.18	gold quality
heart left ventricle	UBERON:0002084	95.11	gold quality
duodenum	UBERON:0002114	95.11	gold quality
left adrenal gland	UBERON:0001234	95.10	gold quality
cortex of kidney	UBERON:0001225	95.06	gold quality
adult mammalian kidney	UBERON:0000082	95.03	gold quality
right lobe of thyroid gland	UBERON:0001119	95.01	gold quality
superior frontal gyrus	UBERON:0002661	95.01	gold quality
left adrenal gland cortex	UBERON:0035825	95.00	gold quality
left uterine tube	UBERON:0001303	94.99	gold quality
apex of heart	UBERON:0002098	94.97	gold quality
right adrenal gland cortex	UBERON:0035827	94.83	gold quality
esophagus mucosa	UBERON:0002469	94.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.78	gold quality
heart	UBERON:0000948	94.77	gold quality
left lobe of thyroid gland	UBERON:0001120	94.77	gold quality
lower esophagus	UBERON:0013473	94.77	gold quality
adenohypophysis	UBERON:0002196	94.75	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	3762.12
E-MTAB-7008	yes	2655.05
E-MTAB-10137	yes	1314.80
E-MTAB-7381	yes	344.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting PSMC4, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-6742-3P	97.95	64.50	1490

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• interacts with gankyrin through C-terminal 78 amino acids (PMID:11779854)
• a novel specific interaction of synphilin-1 with the regulatory proteasomal protein S6 ATPase (tbp7) in aggresome-like intracytoplasmic inclusions (PMID:17327361)
• An insertion/deletion variant in intron 5 of the S6 ATPase gene was more frequent in German Parkinson’s disease patients compared to controls (PMID:18446261)
• C terminus of Rpt3, an ATPase subunit of PA700 (19 S) regulatory complex, is essential for 26 S proteasome assembly but not for activation (PMID:20937828)
• The proposed TRAP1 network has an impact in vivo, as it is conserved in human colorectal cancers, is controlled by ER-localized TRAP1 interacting with TBP7 and provides a novel model of the ER-mitochondria crosstalk. (PMID:21979464)
• Saquinavir-NO inhibits activation of S6 protein in androgen-dependent prostate cancer cells. (PMID:22370480)
• Site-specific Rpt3 phosphorylation by DYRK2 controls cell proliferation and tumorigenesis in breast neoplasms. (PMID:26655835)
• This study demonstrated that particular distribution for HSC70 and PSMC4 in the cytoplasm and accumulation within Lewy body in the dopaminergic neurons of the substantia nigra in Parkinson patients. (PMID:29218503)
• Structural mechanism for nucleotide-driven remodeling of RPT3 and its homologs in the activated human 26S proteasome has been reported. (PMID:29636472)
• PSMC4 promotes prostate carcinoma progression by regulating the CBX3-EGFR-PI3K-AKT-mTOR pathway. (PMID:37436074)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmc4	ENSDARG00000027099
mus_musculus	Psmc4	ENSMUSG00000030603
rattus_norvegicus	Psmc4	ENSRNOG00000018994
drosophila_melanogaster	Rpt3	FBGN0028686
drosophila_melanogaster	Rpt3R	FBGN0037742
caenorhabditis_elegans		WBGENE00004503

Paralogs (5): PSMC5 (ENSG00000087191), PSMC6 (ENSG00000100519), PSMC1 (ENSG00000100764), PSMC2 (ENSG00000161057), PSMC3 (ENSG00000165916)

Protein

Protein identifiers

26S proteasome regulatory subunit 6B — P43686 (reviewed: P43686)

Alternative names: 26S proteasome AAA-ATPase subunit RPT3, MB67-interacting protein, MIP224, Proteasome 26S subunit ATPase 4, Tat-binding protein 7

All UniProt accessions (2): P43686, A8K2M0

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. PSMC4 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 PSMC4 and few additional components. Interacts with NR1I3. Interacts with PAAF1. Interacts with TRIM5. Interacts with ZFAND1.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the AAA ATPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P43686-1	1	yes
P43686-2	2

RefSeq proteins (2): NP_006494, NP_694546 (=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
IPR032501	Prot_ATP_ID_OB_2nd	Domain
IPR041569	AAA_lid_3	Domain
IPR050221	26S_Proteasome_ATPase	Family

Pfam: PF00004, PF16450, PF17862

UniProt features (44 total): helix 14, strand 11, modified residue 6, sequence conflict 5, turn 5, chain 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

131 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2DVW	X-RAY DIFFRACTION	2.3
9K53	ELECTRON MICROSCOPY	2.5
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-P43686-F1	80.33	0.23

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): 206–213

Post-translational modifications (6): 1, 21, 25, 28, 397, 401

Function

Pathways and Gene Ontology

Reactome pathways

67 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: 339 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, 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, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MATTIOLI_MGUS_VS_PCL, GOBP_RESPONSE_TO_TYPE_I_INTERFERON

GO Biological Process (4): blastocyst development (GO:0001824), proteolysis (GO:0006508), 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 (11): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle, base subcomplex (GO:0008540), membrane (GO:0016020), proteasome accessory complex (GO:0022624), ciliary basal body (GO:0036064), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), cytoplasm (GO:0005737)

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	6
proteasomal protein catabolic process	3
ATP-dependent activity	2
protein-containing complex	2
intracellular anatomical structure	2
sperm flagellum	2
in utero embryonic development	1
anatomical structure development	1
protein metabolic 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
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
proteasome regulatory particle	1
proteasome complex	1
microtubule organizing center	1
cilium	1

Protein interactions and networks

STRING

3504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMC4	PAAF1	Q9BRP4	976
PSMC4	ADRM1	Q16186	943
PSMC4	PSMD10	O75832	931
PSMC4	PSMD11	O00231	897
PSMC4	PSMD12	O00232	883
PSMC4	PSMD7	P51665	881
PSMC4	PSMD4	P55036	879
PSMC4	PSMD8	P48556	872
PSMC4	PSMD3	O43242	870
PSMC4	PSMD14	O00487	866
PSMC4	PSMD6	Q15008	861
PSMC4	PSMD1	Q99460	860
PSMC4	PSMD2	Q13200	852
PSMC4	PSMD13	Q9UNM6	852
PSMC4	PSMC3	P17980	830

IntAct

309 interactions, top by confidence:

A	B	Type	Score
PSMC4	PSMD10	psi-mi:“MI:0915”(physical association)	0.970
PSMD10	PSMC4	psi-mi:“MI:0915”(physical association)	0.970
PSMD10	PSMC4	psi-mi:“MI:0914”(association)	0.970
PSMD10	PSMC4	psi-mi:“MI:0407”(direct interaction)	0.970
PSMC6	PSMC3	psi-mi:“MI:0915”(physical association)	0.950
PSMC4	PSMC5	psi-mi:“MI:0915”(physical association)	0.940
PSMC4	PSMC5	psi-mi:“MI:0407”(direct interaction)	0.940
PSMC4	PSMC1	psi-mi:“MI:0915”(physical association)	0.860
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
PSMC4	PSMC6	psi-mi:“MI:0915”(physical association)	0.820
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMC5	PSMC3	psi-mi:“MI:0914”(association)	0.760

BioGRID (804): PSMC4 (Affinity Capture-MS), PSMD10 (Two-hybrid), PSMA2 (Reconstituted Complex), PSMC4 (Affinity Capture-RNA), PSMC4 (Affinity Capture-RNA), PSMC4 (Affinity Capture-MS), PSMC4 (Affinity Capture-MS), PSMC4 (Affinity Capture-MS), PSMC4 (Affinity Capture-MS), PSMC4 (Affinity Capture-MS), PSMC4 (Affinity Capture-MS), PSMC4 (Affinity Capture-MS), PSMC5 (Two-hybrid), PSMD10 (Two-hybrid), PSMC4 (Affinity Capture-MS)

ESM2 similar proteins: A3CV35, A4G0S4, A6UQT3, A6VHR1, A7I8B8, A9A916, B8GGN4, O17071, O18413, O26824, O74445, O74894, P34124, P41836, P42811, P43686, P46502, P46507, P53549, P54775, P54778, P54814, P62194, P62195, P62196, P62197, P62198, P62333, P62334, P62335, Q01939, Q0W257, Q25544, Q2FQ56, Q2KIW6, Q3T030, Q4R7L3, Q54PJ1, Q63570, Q6LWR0

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, O42586, O42587, O57940, O74445, O76371, O88685, P17980, P33297, P34123, P34124, P36612, P40327, P41836, P43686, P46465, P46466, P46470

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PSMC4	“form complex”	“26S Proteasome”	binding
DYRK2	“down-regulates quantity by destabilization”	PSMC4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 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	26	73.9×	8e-43
Regulation of ornithine decarboxylase (ODC)	26	72.1×	1e-42
Vpu mediated degradation of CD4	26	70.5×	1e-42
Autodegradation of the E3 ubiquitin ligase COP1	26	70.5×	1e-42
Ubiquitin-dependent degradation of Cyclin D	26	70.5×	1e-42
Antigen processing: Ub, ATP-independent proteasomal degradation	12	69.9×	8e-20
Cross-presentation of soluble exogenous antigens (endosomes)	26	67.3×	6e-42
Vif-mediated degradation of APOBEC3G	26	67.3×	6e-42

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of proteasomal protein catabolic process	5	45.9×	3e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	30	14.5×	8e-24

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1537 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39971209:GAGA:G	donor_gain	1.0000
19:39971212:A:G	donor_gain	1.0000
19:39971234:CTCAG:C	donor_loss	1.0000
19:39971237:AGGTA:A	donor_loss	1.0000
19:39971238:GGTA:G	donor_loss	1.0000
19:39971239:GTAC:G	donor_loss	1.0000
19:39971240:T:G	donor_loss	1.0000
19:39972360:T:TA	acceptor_gain	1.0000
19:39972367:A:AG	acceptor_gain	1.0000
19:39972368:G:GG	acceptor_gain	1.0000
19:39972368:GAA:G	acceptor_gain	1.0000
19:39972551:CACAG:C	donor_loss	1.0000
19:39972552:ACAG:A	donor_loss	1.0000
19:39972553:CAGGT:C	donor_loss	1.0000
19:39972555:GG:G	donor_loss	1.0000
19:39972556:G:GA	donor_loss	1.0000
19:39972557:T:A	donor_loss	1.0000
19:39972566:G:GT	donor_gain	1.0000
19:39974289:C:A	acceptor_gain	1.0000
19:39974292:A:AG	acceptor_gain	1.0000
19:39974292:AG:A	acceptor_gain	1.0000
19:39974293:G:A	acceptor_gain	1.0000
19:39974293:G:GA	acceptor_gain	1.0000
19:39974293:GGC:G	acceptor_gain	1.0000
19:39974293:GGCT:G	acceptor_gain	1.0000
19:39974293:GGCTC:G	acceptor_gain	1.0000
19:39974436:CTCAG:C	donor_loss	1.0000
19:39974437:TCAG:T	donor_loss	1.0000
19:39974438:CAG:C	donor_loss	1.0000
19:39974440:GGTAA:G	donor_loss	1.0000

AlphaMissense

2755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39972436:T:C	L68P	1.000
19:39972456:G:C	A75P	1.000
19:39972475:G:C	R81P	1.000
19:39972493:T:C	L87P	1.000
19:39972501:G:A	G90R	1.000
19:39972501:G:C	G90R	1.000
19:39972502:G:A	G90E	1.000
19:39972502:G:T	G90V	1.000
19:39972508:T:C	F92S	1.000
19:39972535:C:A	A101D	1.000
19:39972541:T:A	V103E	1.000
19:39974342:T:A	L124H	1.000
19:39974342:T:C	L124P	1.000
19:39974360:T:A	V130E	1.000
19:39974363:C:A	A131D	1.000
19:39974366:T:C	L132P	1.000
19:39974377:A:C	S136R	1.000
19:39974379:C:A	S136R	1.000
19:39974379:C:G	S136R	1.000
19:39974383:G:C	A138P	1.000
19:39974387:T:C	L139P	1.000
19:39974399:T:C	L143P	1.000
19:39974556:G:A	G168R	1.000
19:39974556:G:C	G168R	1.000
19:39974557:G:A	G168E	1.000
19:39974559:G:C	G169R	1.000
19:39974578:A:C	Q175P	1.000
19:39974587:G:C	R178P	1.000
19:39974592:G:C	A180P	1.000
19:39974593:C:A	A180D	1.000

dbSNP variants (sampled 300 via entrez): RS1000214609 (19:39974670 C>T), RS1000725695 (19:39981694 T>C), RS1000907688 (19:39981102 A>G), RS1000965218 (19:39973764 C>T), RS1001058734 (19:39974061 C>T), RS1001262819 (19:39972989 A>C), RS1001427562 (19:39969814 T>A,C), RS1001626104 (19:39975586 G>A,T), RS1001772799 (19:39969343 A>G), RS1002115418 (19:39982188 G>C), RS1002656405 (19:39977144 C>T), RS1002972242 (19:39977349 T>G), RS1003135623 (19:39970807 C>G), RS1003331307 (19:39971615 G>A,C), RS1003424676 (19:39971883 T>C)

Disease associations

OMIM: gene MIM:602707 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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), CHEMBL3831205 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 26,368 (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
CHEMBL2386889	SCH-900776	2	740

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

ChEMBL bioactivities

67 potent at pChembl≥5 of 69 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
8.30	Kd	5	nM	SCH-900776
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
6.29	Kd	507.6	nM	CHEMBL5653589
6.29	ED50	507.6	nM	CHEMBL5653589
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

PubChem BioAssay actives

63 with measured affinity, of 378 total; 35 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
6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3R)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine	1425141: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	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)-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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149118: Binding affinity to human PSMC4 incubated for 45 mins by Kinobead based pull down assay	kd	0.5077	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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149118: Binding affinity to human PSMC4 incubated for 45 mins by Kinobead based pull down assay	kd	6.1437	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment	3
Benzo(a)pyrene	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
cobaltous chloride	increases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
Doxorubicin	affects expression	2
Rotenone	decreases expression, increases expression	2
beta-Naphthoflavone	increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
epoxomicin	affects reaction, increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
elesclomol	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1

ChEMBL screening assays

29 unique, capped per target: 28 binding, 1 admet

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
CHEMBL4736579	ADMET	Inhibition of human 19s Rpt3 ATPase activity measured after 60 mins by biomol green reagent based assay	A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells. — Eur J Med Chem

Clinical trials (associated diseases)

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