PSME1

Summary

PSME1 (proteasome activator subunit 1, HGNC:9568) is a protein-coding gene on chromosome 14q12, encoding Proteasome activator complex subunit 1 (Q06323). Implicated in immunoproteasome assembly and required for efficient antigen processing.

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. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the alpha subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three alpha and three beta subunits combine to form a heterohexameric ring. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5720 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• Druggable target: yes
• MANE Select transcript: NM_006263

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9568
Approved symbol	PSME1
Name	proteasome activator subunit 1
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	IFI5111, PA28alpha
Ensembl gene	ENSG00000092010
Ensembl biotype	protein_coding
OMIM	600654
Entrez	5720

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000206451, ENST00000382708, ENST00000470718, ENST00000558112, ENST00000559123, ENST00000559741, ENST00000560420, ENST00000561059, ENST00000561142, ENST00000561435, ENST00000872363, ENST00000872364, ENST00000939856, ENST00000939857, ENST00000939858, ENST00000967336

RefSeq mRNA: 4 — MANE Select: NM_006263 NM_001281528, NM_001281529, NM_006263, NM_176783

CCDS: CCDS41930, CCDS61415, CCDS9612

Canonical transcript exons

ENST00000206451 — 11 exons

Exon	Start	End
ENSE00001921380	24136194	24136301
ENSE00003477939	24138736	24138962
ENSE00003479901	24138345	24138399
ENSE00003495831	24137520	24137565
ENSE00003515551	24138474	24138560
ENSE00003562631	24137143	24137205
ENSE00003582584	24138196	24138263
ENSE00003587474	24136985	24137017
ENSE00003598118	24138049	24138117
ENSE00003645735	24137700	24137797
ENSE00003675652	24137321	24137431

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 251.2839 / max 2203.3969, expressed in 1828 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138989	224.8679	1828
138988	24.7048	1817
138991	1.0160	545
138990	0.3755	166
138992	0.3197	129

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.53	gold quality
leukocyte	CL:0000738	99.33	gold quality
monocyte	CL:0000576	99.32	gold quality
lymph node	UBERON:0000029	99.26	gold quality
spleen	UBERON:0002106	99.17	gold quality
metanephros cortex	UBERON:0010533	99.11	gold quality
right adrenal gland	UBERON:0001233	99.10	gold quality
duodenum	UBERON:0002114	99.09	gold quality
right adrenal gland cortex	UBERON:0035827	99.07	gold quality
vermiform appendix	UBERON:0001154	99.06	gold quality
rectum	UBERON:0001052	99.05	gold quality
left adrenal gland	UBERON:0001234	99.05	gold quality
left adrenal gland cortex	UBERON:0035825	99.02	gold quality
mucosa of transverse colon	UBERON:0004991	98.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.97	gold quality
blood	UBERON:0000178	98.95	gold quality
right uterine tube	UBERON:0001302	98.95	gold quality
adrenal gland	UBERON:0002369	98.93	gold quality
small intestine	UBERON:0002108	98.91	gold quality
smooth muscle tissue	UBERON:0001135	98.87	gold quality
fallopian tube	UBERON:0003889	98.87	gold quality
cortex of kidney	UBERON:0001225	98.81	gold quality
transverse colon	UBERON:0001157	98.74	gold quality
gall bladder	UBERON:0002110	98.74	gold quality
right lung	UBERON:0002167	98.74	gold quality
upper lobe of left lung	UBERON:0008952	98.74	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.74	gold quality
intestine	UBERON:0000160	98.70	gold quality
left lobe of thyroid gland	UBERON:0001120	98.69	gold quality
colon	UBERON:0001155	98.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	10.12
E-MTAB-9801	yes	5.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZHX2

miRNA regulators (miRDB)

16 targeting PSME1, 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-6740-5P	100.00	65.64	932
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-1271-3P	97.56	64.85	865
HSA-MIR-550A-3-5P	97.56	65.35	823
HSA-MIR-550A-5P	97.56	65.35	823
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-550B-2-5P	96.56	64.61	646

Literature-anchored findings (GeneRIF, showing 14)

• PA28 selectively up-regulates the presentation of viral MHC class I epitopes and that down regulation PA28 in tumor cells results in impaired presentation of a human TRP2 tumor antigen. (PMID:12200048)
• Impaired expression of proteasome subunits is involved in the loss of HLA class I expression in human colon cancer cells. (PMID:12519221)
• The relationship between anti-PA28alpha and Ki antibodies suggests the importance of an antigen-driven system in the induction of an autoimmune response to PA28 complex. (PMID:14760793)
• DJ-1 and PA28alpha may have roles in the onset of hepatocarcinogenesis (PMID:17671684)
• the 11S proteasome activator complex, Reg alpha fragment, may have a role in ovarian cancer (PMID:17939699)
• bortezomib-adapted HL-60 cells showed increased expression and proteasome association of the 11S proteasome activator (PMID:19225532)
• the first evidence of a novel ovarian cancer-specific marker (PMID:22532226)
• Reduction in ATP levels triggers immunoproteasome activation by the 11S (PA28) regulator during early antiviral response mediated by IFNbeta in mouse pancreatic beta-cells. (PMID:23383295)
• PA28 is a tumor marker and a potential target for therapeutic intervention in prostate cancer. (PMID:23918357)
• Constitutive expression of PA28 and ERAP1 in melanoma cells indicate that both interfere with MART-1(26-35) epitope generation even in the absence of IFN-gamma (PMID:26399368)
• Results show that PA28alpha was found to be overexpressed in oral squamous cell carcinoma cell lines and tumor tissues. High expression of PA28alpha was significantly associated with recurrence and poorer overall survival. (PMID:26892607)
• Such a modulation of proteasome activity is explained, at least in part, by the circadian expression of both Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the proteasome activator PA28ab (PMID:26944190)
• Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks. (PMID:33262340)
• Downregulation of PA28alpha induces proteasome remodeling and results in resistance to proteasome inhibitors in multiple myeloma. (PMID:33318477)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	psme1	ENSDARG00000002165
mus_musculus	Psme1	ENSMUSG00000022216
rattus_norvegicus	Psme1	ENSRNOG00000019041
rattus_norvegicus	Psme1-ps1	ENSRNOG00000061359
drosophila_melanogaster	REG	FBGN0029133
caenorhabditis_elegans		WBGENE00013435

Paralogs (2): PSME2 (ENSG00000100911), PSME3 (ENSG00000131467)

Protein

Protein identifiers

Proteasome activator complex subunit 1 — Q06323 (reviewed: Q06323)

Alternative names: 11S regulator complex subunit alpha, Activator of multicatalytic protease subunit 1, Interferon gamma up-regulated I-5111 protein, Proteasome activator 28 subunit alpha

All UniProt accessions (4): Q06323, A0A0K0K1L8, H0YKK6, H0YLU2

UniProt curated annotations — full annotation on UniProt →

Function. Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome.

Subunit / interactions. Heterodimer of PSME1 and PSME2, which forms a hexameric ring. PSME1 can form homoheptamers.

Induction. By IFNG/IFN-gamma.

Similarity. Belongs to the PA28 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q06323-1	1	yes
Q06323-2	2
Q06323-3	3

RefSeq proteins (4): NP_001268457, NP_001268458, NP_006254, NP_788955 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003185	Proteasome_activ_PA28_N	Domain
IPR003186	PA28_C	Domain
IPR009077	Proteasome_activ_PA28	Family
IPR036252	Proteasome_activ_sf	Homologous_superfamily
IPR036996	PA28_N_sf	Homologous_superfamily
IPR036997	PA28_C_sf	Homologous_superfamily

Pfam: PF02251, PF02252

UniProt features (17 total): helix 7, splice variant 3, sequence variant 2, chain 1, region of interest 1, turn 1, strand 1, compositionally biased region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1AVO	X-RAY DIFFRACTION	2.8
7NAO	ELECTRON MICROSCOPY	2.9
8CXB	ELECTRON MICROSCOPY	2.9
7NAP	ELECTRON MICROSCOPY	3.2
7DR6	ELECTRON MICROSCOPY	4.1
7DRW	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06323-F1	90.72	0.79

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-9907900	Proteasome assembly
R-HSA-9912633	Antigen processing: Ub, ATP-independent proteasomal degradation

MSigDB gene sets: 307 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, SHEPARD_BMYB_MORPHOLINO_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GCM_MSN, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES

GO Biological Process (3): antigen processing and presentation of exogenous antigen (GO:0019884), regulation of proteasomal protein catabolic process (GO:0061136), regulation of G1/S transition of mitotic cell cycle (GO:2000045)

GO Molecular Function (2): endopeptidase activator activity (GO:0061133), protein binding (GO:0005515)

GO Cellular Component (6): proteasome complex (GO:0000502), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome activator complex (GO:0008537), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
antigen processing and presentation	1
proteasomal protein catabolic process	1
regulation of protein catabolic process	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
endopeptidase activity	1
peptidase activator activity	1
endopeptidase regulator activity	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
proteasome accessory complex	1
protein-containing complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

1650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSME1	PSME2	Q9UL46	984
PSME1	PSMB10	P40306	935
PSME1	PSMB8	P28062	928
PSME1	PSMB9	P28065	884
PSME1	PSMB5	P28074	855
PSME1	IFNG	P01579	730
PSME1	PSME4	Q14997	716
PSME1	PSMA6	P34062	715
PSME1	PSMA1	P25786	698
PSME1	PSMB4	P28070	695
PSME1	PSMA4	P25789	628
PSME1	PSME3	P61289	618
PSME1	IRF9	Q00978	616
PSME1	PSMA7	O14818	607
PSME1	TAPBP	O15533	588

IntAct

169 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:2364”(proximity)	0.950
PSMA1	PSMA7	psi-mi:“MI:0915”(physical association)	0.950
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
FBXO7	SKP1	psi-mi:“MI:0914”(association)	0.900
PSME1	PSME2	psi-mi:“MI:0915”(physical association)	0.850
PSMA2	PSMA7	psi-mi:“MI:0914”(association)	0.850
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
PSMB7	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMB3	PSMA7	psi-mi:“MI:0914”(association)	0.770
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMB4	PSMA7	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB7	PSMD11	psi-mi:“MI:0914”(association)	0.640
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
PSMB1	PSMA7	psi-mi:“MI:0914”(association)	0.640
PSME1	PSMB1	psi-mi:“MI:0914”(association)	0.640
	PSME1	psi-mi:“MI:0915”(physical association)	0.560
PSME1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PSME1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (427): PSME1 (Affinity Capture-MS), PSME1 (Two-hybrid), PSME1 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME2 (Two-hybrid), GARS (Co-fractionation), PAK2 (Co-fractionation), PSME1 (Proximity Label-MS), PSME1 (Affinity Capture-MS)

ESM2 similar proteins: A0A223HDI2, A2BG43, B0BLT4, B0BNM9, B0YN54, O64587, O74432, P68265, P68266, P97371, P97372, Q06323, Q0VCQ0, Q19555, Q29RK9, Q4U5R3, Q54QV0, Q58D63, Q5E9G3, Q5F495, Q5HZ92, Q5R5Z0, Q5RDB1, Q5TA50, Q5XIS2, Q63797, Q63798, Q63ZQ3, Q64L94, Q66JG2, Q6DBQ8, Q6NLQ3, Q6NU44, Q6PEB6, Q7K0E3, Q7XVN7, Q863Z0, Q86TA1, Q8BS40, Q8L7U7

Diamond homologs: P58238, P61289, P61290, P61291, P97371, P97372, Q06323, Q4R4V3, Q4U5R3, Q5E9G3, Q5F3J5, Q5RFD3, Q63797, Q63798, Q64L94, Q863Z0, Q967U1, Q9UL46

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSME1	“up-regulates activity”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
Antigen processing: Ub, ATP-independent proteasomal degradation	16	88.7×	4e-29
Cross-presentation of soluble exogenous antigens (endosomes)	25	61.6×	3e-38
Proteasome assembly	31	61.4×	9e-48
Regulation of activated PAK-2p34 by proteasome mediated degradation	22	59.5×	2e-33
Vpu mediated degradation of CD4	23	59.3×	1e-34
Regulation of ornithine decarboxylase (ODC)	22	58.1×	3e-33
Autodegradation of the E3 ubiquitin ligase COP1	22	56.7×	4e-33
Ubiquitin-dependent degradation of Cyclin D	22	56.7×	4e-33

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	28	11.6×	3e-19
ubiquitin-dependent protein catabolic process	10	5.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1398 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24137314:A:AG	acceptor_gain	1.0000
14:24137316:ACCAG:A	acceptor_gain	1.0000
14:24137416:G:GT	donor_gain	1.0000
14:24137429:G:GT	donor_gain	1.0000
14:24137437:C:G	donor_gain	1.0000
14:24137441:G:GT	donor_gain	1.0000
14:24137441:G:T	donor_gain	1.0000
14:24137518:A:AG	acceptor_gain	1.0000
14:24137519:G:GG	acceptor_gain	1.0000
14:24137519:GAA:G	acceptor_gain	1.0000
14:24137565:GG:G	donor_loss	1.0000
14:24137696:CTAG:C	acceptor_loss	1.0000
14:24137698:A:AG	acceptor_gain	1.0000
14:24137699:G:GA	acceptor_gain	1.0000
14:24137699:GGT:G	acceptor_gain	1.0000
14:24137699:GGTC:G	acceptor_gain	1.0000
14:24137699:GGTCC:G	acceptor_gain	1.0000
14:24137774:G:GT	donor_gain	1.0000
14:24137793:ACCTG:A	donor_gain	1.0000
14:24137794:CCTG:C	donor_gain	1.0000
14:24137795:CTG:C	donor_gain	1.0000
14:24137796:TG:T	donor_gain	1.0000
14:24137797:GG:G	donor_gain	1.0000
14:24137798:G:GG	donor_gain	1.0000
14:24137799:T:A	donor_loss	1.0000
14:24138047:A:AG	acceptor_gain	1.0000
14:24138047:A:AT	acceptor_loss	1.0000
14:24138047:AG:A	acceptor_gain	1.0000
14:24138048:G:GT	acceptor_gain	1.0000
14:24138048:GG:G	acceptor_gain	1.0000

AlphaMissense

1655 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:24138099:T:A	N147K	1.000
14:24138099:T:G	N147K	1.000
14:24138100:T:C	F148L	1.000
14:24138102:T:A	F148L	1.000
14:24138102:T:G	F148L	1.000
14:24138104:G:A	G149E	1.000
14:24138113:T:A	V152D	1.000
14:24138088:G:C	D144H	0.999
14:24138091:G:C	G145R	0.999
14:24138091:G:T	G145C	0.999
14:24138092:G:A	G145D	0.999
14:24138092:G:C	G145A	0.999
14:24138092:G:T	G145V	0.999
14:24138101:T:G	F148C	0.999
14:24138103:G:A	G149R	0.999
14:24138103:G:C	G149R	0.999
14:24138117:G:C	Q153H	0.999
14:24138117:G:T	Q153H	0.999
14:24138358:C:A	R181S	0.999
14:24138359:G:C	R181P	0.999
14:24138362:G:A	G182D	0.999
14:24138367:G:C	A184P	0.999
14:24138490:T:C	L200P	0.999
14:24138504:G:C	D205H	0.999
14:24138550:G:C	R220P	0.999
14:24138765:C:A	N233K	0.999
14:24138765:C:G	N233K	0.999
14:24138058:T:A	W134R	0.998
14:24138058:T:C	W134R	0.998
14:24138068:T:C	L137P	0.998

dbSNP variants (sampled 300 via entrez): RS1001130970 (14:24134259 T>A), RS1001520840 (14:24136144 G>GCCCTC), RS1001890608 (14:24134267 A>T), RS1002144510 (14:24139041 A>G), RS1003582189 (14:24135089 C>G,T), RS1004580954 (14:24136495 C>A), RS1008252224 (14:24134992 A>G), RS1008301546 (14:24136482 G>A), RS1008482103 (14:24137783 G>T), RS1008672404 (14:24135143 C>G,T), RS1008849921 (14:24136421 C>T), RS1009478129 (14:24139383 G>T), RS1011221156 (14:24136577 A>C), RS1011404680 (14:24135907 G>A), RS1011747564 (14:24134281 T>A)

Disease associations

OMIM: gene MIM:600654 | 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 (1): CHEMBL4295804 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.59	Kd	2586	nM	CHEMBL5653589
5.59	ED50	2586	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 12 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149133: Binding affinity to human PSME1 incubated for 45 mins by Kinobead based pull down assay	kd	2.5857	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	decreases expression, affects binding, increases reaction	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Benzo(a)pyrene	increases expression, decreases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
microcystin RR	increases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Decitabine	affects expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Cisplatin	affects expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118639	Binding	Binding affinity to PSME1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3F6	Abcam HEK293T PSME1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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