PSMB11

Summary

PSMB11 (proteasome subunit beta 11, HGNC:31963) is a protein-coding gene on chromosome 14q11.2, encoding Proteasome subunit beta type-11 (A5LHX3). The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH.

Proteasomes generate peptides that are presented by major histocompatibility complex (MHC) I molecules to other cells of the immune system. Proteolysis is conducted by 20S proteasomes, complexes of 28 subunits arranged as a cylinder in 4 heteroheptameric rings: alpha-1 to -7, beta-1 to -7, beta-1 to -7, and alpha-1 to -7. The catalytic subunits are beta-1 (PSMB6; MIM 600307), beta-2 (PSMB7; MIM 604030), and beta-5 (PSMB5; MIM 600306). Three additional subunits, beta-1i (PSMB9; MIM 177045), beta-2i (PSMB10; MIM 176847), and beta-5i (PSMB8; MIM 177046), are induced by gamma-interferon (IFNG; MIM 147570) and are preferentially incorporated into proteasomes to make immunoproteasomes. PSMB11, or beta-5t, is a catalytic subunit expressed exclusively in cortical thymic epithelial cells (Murata et al., 2007 [PubMed 17540904]).

Source: NCBI Gene 122706 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 69 total
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 5 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 1.97 (unconstrained)
• MANE Select transcript: NM_001099780
• Notable: 69 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31963
Approved symbol	PSMB11
Name	proteasome subunit beta 11
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	beta5t
Ensembl gene	ENSG00000222028
Ensembl biotype	protein_coding
OMIM	611137
Entrez	122706

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000408907

ENST00000408907

RefSeq mRNA: 1 — MANE Select: NM_001099780 NM_001099780

CCDS: CCDS41923

Canonical transcript exons

ENST00000408907 — 1 exons

Exon	Start	End
ENSE00001734086	23042212	23044060

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 41.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0315 / max 29.8245, expressed in 4 samples.

Highest expression (Bgee): colonic epithelium, ventricular zone, cortical plate, skeletal muscle tissue, lymph node.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PSMB11 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	5.0e-13	+0.36	14:23013195:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
138873	0.0315	4

Top tissues by expression

showing 100 of 124 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	41.29	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
skeletal muscle tissue	UBERON:0001134	36.32	gold quality
lymph node	UBERON:0000029	36.22	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
sural nerve	UBERON:0015488	35.85	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	33.22	gold quality
bone marrow	UBERON:0002371	32.90	gold quality
right uterine tube	UBERON:0001302	32.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
blood	UBERON:0000178	31.60	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.29	gold quality
muscle of leg	UBERON:0001383	29.03	gold quality
urinary bladder	UBERON:0001255	28.68	gold quality
gastrocnemius	UBERON:0001388	28.37	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.94	gold quality
leukocyte	CL:0000738	27.91	gold quality
primary visual cortex	UBERON:0002436	27.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	27.42	gold quality
left testis	UBERON:0004533	27.38	silver quality
left adrenal gland cortex	UBERON:0035825	27.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.35	gold quality
islet of Langerhans	UBERON:0000006	27.30	gold quality
right adrenal gland cortex	UBERON:0035827	27.17	gold quality
tonsil	UBERON:0002372	27.05	gold quality
calcaneal tendon	UBERON:0003701	26.50	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
left adrenal gland	UBERON:0001234	26.09	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
adrenal gland	UBERON:0002369	25.90	gold quality
nucleus accumbens	UBERON:0001882	25.88	gold quality
placenta	UBERON:0001987	25.81	gold quality
hypothalamus	UBERON:0001898	25.37	gold quality
putamen	UBERON:0001874	25.29	gold quality
substantia nigra	UBERON:0002038	25.27	gold quality
right adrenal gland	UBERON:0001233	25.18	gold quality
Ammon’s horn	UBERON:0001954	24.97	gold quality
pancreas	UBERON:0001264	24.91	gold quality
kidney	UBERON:0002113	24.72	gold quality
temporal lobe	UBERON:0001871	24.56	gold quality
caudate nucleus	UBERON:0001873	24.49	gold quality
amygdala	UBERON:0001876	24.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	24.40	gold quality
right lobe of liver	UBERON:0001114	24.37	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
uterine cervix	UBERON:0000002	23.65	gold quality
cortex of kidney	UBERON:0001225	23.63	gold quality
heart left ventricle	UBERON:0002084	23.61	gold quality
endometrium	UBERON:0001295	23.52	gold quality
adult mammalian kidney	UBERON:0000082	23.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	23.19	gold quality
myometrium	UBERON:0001296	22.98	gold quality
tibial nerve	UBERON:0001323	22.98	gold quality
stomach	UBERON:0000945	22.62	gold quality
body of pancreas	UBERON:0001150	22.42	gold quality
zone of skin	UBERON:0000014	22.23	gold quality
skin of abdomen	UBERON:0001416	22.21	gold quality
ectocervix	UBERON:0012249	22.18	gold quality
smooth muscle tissue	UBERON:0001135	22.15	gold quality
lower esophagus mucosa	UBERON:0035834	22.15	gold quality
skin of leg	UBERON:0001511	22.05	gold quality
esophagus	UBERON:0001043	21.91	gold quality
lung	UBERON:0002048	21.83	gold quality
tibial artery	UBERON:0007610	21.83	gold quality
popliteal artery	UBERON:0002250	21.82	gold quality
left coronary artery	UBERON:0001626	21.79	gold quality
esophagus mucosa	UBERON:0002469	21.74	gold quality
body of stomach	UBERON:0001161	21.67	gold quality
cerebellum	UBERON:0002037	21.59	gold quality
fallopian tube	UBERON:0003889	21.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	21.46	gold quality
lower esophagus	UBERON:0013473	21.45	gold quality
anterior cingulate cortex	UBERON:0009835	21.38	gold quality
right ovary	UBERON:0002118	21.32	gold quality
right atrium auricular region	UBERON:0006631	21.29	gold quality
right frontal lobe	UBERON:0002810	21.24	gold quality
cerebellar cortex	UBERON:0002129	21.23	gold quality
fundus of stomach	UBERON:0001160	21.15	gold quality
cerebellar hemisphere	UBERON:0002245	21.08	gold quality
prostate gland	UBERON:0002367	21.08	gold quality
adrenal tissue	UBERON:0018303	21.05	gold quality
colon	UBERON:0001155	21.04	gold quality
intestine	UBERON:0000160	21.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	20.94	gold quality
thoracic mammary gland	UBERON:0005200	20.74	gold quality
ovary	UBERON:0000992	20.69	gold quality
small intestine	UBERON:0002108	20.69	gold quality
thoracic aorta	UBERON:0001515	20.66	gold quality
granulocyte	CL:0000094	20.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	20.59	gold quality
ascending aorta	UBERON:0001496	20.58	gold quality
subcutaneous adipose tissue	UBERON:0002190	20.39	gold quality
vagina	UBERON:0000996	20.35	gold quality
spleen	UBERON:0002106	20.33	gold quality
adipose tissue	UBERON:0001013	20.31	gold quality
transverse colon	UBERON:0001157	20.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-79	yes	450.60
E-ANND-3	no	0.40

HPA expression

RNA tissue specificity: Tissue enriched

3 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	28.5	medium
Testis	tissue	0.1	not detected
Frontal cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 5; highest nTPM — Nucleus ambiguus (0.1), Nucleus gracilis (0.1), Parieto-temporal junction (white matter) (0.1), Periaquaductal grey, lateral (0.1), Precentral gyrus, ventral (0.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PSMB11 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 45 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-4725-5P	98.67	65.42	628

Functional genomics

gnomAD constraint: pLI 0.0106, LOEUF 1.97, missense Z 0.214 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000408907 — one region, missense o/e 1.01.

Literature-anchored findings (GeneRIF, showing 6)

• results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection (PMID:17540904)
• Human beta5t was expressed in approximately 80% of cortical thymic epithelial cells and some cortical dendritic cells (PMID:19289856)
• Proteasome beta5t is expressed in most type B and in some type AB thymomas and is a marker useful in differentiating type B3 thymomas from thymic carcinomas when used in combination with other diagnostic markers. (PMID:21836487)
• provide the first evidence that the mechanism underlying BTZ resistance in these tumor cells is impaired binding of BTZ to the mutant beta5 subunit of the proteasome (PMID:21941364)
• Histological diversity of type AB thymoma correlates with expression of a functional marker beta5t and abundance of TdT-positive lymphocytes. (PMID:24293611)
• We analysed thymic tissues from patients with trisomy 13 (n = 4), trisomy 18 (n = 14) and trisomy 21 (n = 13) for histological alterations, and for the expression of functionally important molecules such as beta5t, a thymoproteasome subunit, and cathepsins. (PMID:25556590)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb11b	ENSDARG00000068086
danio_rerio	psmb11a	ENSDARG00000108530
mus_musculus	Psmb11	ENSMUSG00000072423
rattus_norvegicus	Psmb11	ENSRNOG00000072044
drosophila_melanogaster	Prosbeta1	FBGN0010590
caenorhabditis_elegans		WBGENE00003947

Paralogs (18): PSMB1 (ENSG00000008018), PSMA4 (ENSG00000041357), PSMA3 (ENSG00000100567), 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), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1921152) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 29 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased CD8-positive, alpha-beta T cell number	3
abnormal heart morphology	1
enlarged heart	1
abnormal colon morphology	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal thymus morphology	1
enlarged thymus	1
abnormal testis morphology	1
small testis	1
abnormal skin morphology	1
abnormal digit morphology	1
abnormal T cell differentiation	1
abnormal ileum morphology	1
increased kidney weight	1
abnormal self tolerance	1
abnormal CD8-positive, alpha beta T cell morphology	1
increased T cell proliferation	1
increased NK T cell number	1
decreased memory T cell number	1
increased CD4-positive, alpha-beta T cell number	1
abnormal T cell receptor V(D)J recombination	1
increased effector memory CD8-positive, alpha-beta T cell number	1
decreased effector memory CD8-positive, alpha-beta T cell number	1
increased CD4-positive NK T cell number	1

+4 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R8S2	100.0%	Diamond
Mus musculus bactrianus	O35522	99.5%	Diamond
Mus spicilegus	O35524	99.5%	Diamond
Salmo salar	A7KE01	99.1%	Diamond
Mus terricolor	O35521	99.1%	Diamond
Mus platythrix	O35523	98.2%	Diamond
Oncorhynchus mykiss	Q9PT26	98.2%	Diamond
Sus scrofa	A1XQU1	97.8%	Diamond
Bos taurus	Q2TBP0	97.8%	Diamond
Arabidopsis thaliana	O23717	93.0%	Diamond
Canis lupus familiaris	Q5W416	86.5%	Diamond
Parafrankia sp. EAN1pec	A8LH54	85.8%	Diamond
Nicotiana tabacum	P93395	85.1%	Diamond
Oryzias latipes	Q8UW64	83.9%	Diamond
Spinacia oleracea	O24361	83.3%	Diamond
Gallus gallus	P34065	70.4%	Diamond
Schizosaccharomyces pombe 972h-	P30655	67.9%	Diamond
Saccharomyces cerevisiae S288C	P30656	67.9%	Diamond
Dictyostelium discoideum	Q54BC8	66.3%	Diamond
Acidimicrobium ferrooxidans DSM 10331	C7LYP7	63.5%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SR11	55.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CIROP	protein-coding	100128908
ACIN1	protein-coding	22985
C14orf119	protein-coding	55017
CDH24	protein-coding	64403
AJUBA-DT	ncRNA	107984660
PSMB5	protein-coding	5693
C14orf93	protein-coding	60686
AJUBA	protein-coding	84962
CEBPE	protein-coding	1053
MIR4707	ncRNA	100616424
HAUS4	protein-coding	54930

Protein

Protein identifiers

Proteasome subunit beta type-11 — A5LHX3 (reviewed: A5LHX3)

Alternative names: Proteasome subunit beta-5t

All UniProt accessions (1): A5LHX3

UniProt curated annotations — full annotation on UniProt →

Function. The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Incorporated instead of PSMB5 or PSMB8, this unit reduces the chymotrypsin-like activity of the proteasome. Plays a pivotal role in development of CD8-positive T cells.

Subunit / interactions. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Incorporated instead of PSMB5 and PSMB8.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the peptidase T1B family.

RefSeq proteins (1): NP_001093250* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000243	Pept_T1A_subB	Family
IPR001353	Proteasome_sua/b	Family
IPR016050	Proteasome_bsu_CS	Conserved_site
IPR023333	Proteasome_suB-type	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily

Pfam: PF00227

UniProt features (6 total): region of interest 2, propeptide 1, chain 1, active site 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5LHX3-F1	80.90	0.63

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Threonine-type peptidases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

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

Catalytic / active sites (1)

Position	Role
50	nucleophile

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-9907900	Proteasome assembly	electronic

MSigDB gene sets: 72 (showing top): KEGG_PROTEASOME, GOBP_THYMIC_T_CELL_SELECTION, GOBP_T_CELL_HOMEOSTASIS, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_T_CELL_SELECTION, GOBP_LEUKOCYTE_HOMEOSTASIS, GOBP_HOMEOSTATIC_PROCESS, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOBP_PROTEOLYSIS

GO Biological Process (6): proteolysis (GO:0006508), proteasomal protein catabolic process (GO:0010498), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), CD8-positive, alpha-beta T cell differentiation (GO:0043374), thymic T cell selection (GO:0045061), CD8-positive, alpha-beta T cell homeostasis (GO:0160165)

GO Molecular Function (5): endopeptidase activity (GO:0004175), threonine-type endopeptidase activity (GO:0004298), peptidase activity (GO:0008233), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), cytosol (GO:0005829), proteasome core complex, beta-subunit complex (GO:0019774), proteasome complex (GO:0000502), cytoplasm (GO:0005737), proteasome core complex (GO:0005839)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

26 GO namespaces:

Category	Terms
cellular anatomical structure	2
intracellular anatomical structure	2
intracellular protein-containing complex	2
protein metabolic process	1
protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
CD8-positive, alpha-beta T cell activation	1
alpha-beta T cell differentiation	1
T cell differentiation in thymus	1
T cell selection	1
T cell homeostasis	1
peptidase activity	1
endopeptidase activity	1
threonine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
proteasome core complex	1
protein-containing complex	1
endopeptidase complex	1
proteasome complex	1
catalytic complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
proteolysis	BP	direct assay
peptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 460 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB11	PRSS16	Q9NQE7	769
PSMB11	FOXN1	O15353	691
PSMB11	PSMA8	Q8TAA3	628
PSMB11	AIRE	O43918	597
PSMB11	LY75	O60449	584
PSMB11	PLET1	Q6UQ28	536
PSMB11	PSMB10	P40306	533
PSMB11	PSME4	Q14997	522
PSMB11	PSMB9	P28065	510
PSMB11	POMP	Q9Y244	501
PSMB11	CCL25	O15444	493
PSMB11	DLL4	Q9NR61	484
PSMB11	CTRL	P40313	482
PSMB11	PSMD4	P55036	453
PSMB11	PSMA7	O14818	452

IntAct

Human interaction partners of PSMB11 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
PROP1	physical association	0.560	5
ATG5	physical association	0.560	3
HGS	physical association	0.560	3
PITX1	physical association	0.560	3
TLX3	physical association	0.560	3

BioGRID (8 interactions; top human partners by supporting records): ATG5 (Two-hybrid), HGS (Two-hybrid), ILF3 (Affinity Capture-RNA), PITX1 (Two-hybrid), PROP1 (Two-hybrid), RNF8 (Proximity Label-MS), TLX3 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for PSMB11: 69 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	5
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 10 predictions of 101):

Position(s)	Effect	Δscore	Sites
14:23043113	donor_gain	0.9100
14:23043077	donor_gain	0.8500
14:23043052	donor_gain	0.7400
14:23043085	donor_gain	0.6100
14:23042914	donor_gain	0.5900
14:23043078	donor_gain	0.5700
14:23043130	donor_gain	0.5600
14:23043536	acceptor_gain	0.5300
14:23043124	donor_gain	0.5200
14:23043416	donor_gain	0.4900

AlphaMissense

431 missense substitutions predicted likely pathogenic (of 1,907 scored), across 131 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D66	8	0.921	0.964
D216	8	0.920	0.965
F55	8	0.877	0.984
D100	8	0.844	0.897
D189	8	0.714	0.843
F57	7	0.881	0.979
W104	7	0.852	0.970
F226	7	0.810	0.963
W233	7	0.789	0.931
W153	7	0.762	0.854
D224	7	0.674	0.742
K82	6	0.939	0.980
G178	6	0.882	0.952
G96	6	0.851	0.953
T50	6	0.846	0.962
F175	6	0.844	0.937
C101	6	0.830	0.948
G152	6	0.807	0.953
G220	6	0.807	0.927
T51	6	0.780	0.958

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:611137 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST90002404_138	Red cell distribution width	3e-23
GCST004621_90	Red cell distribution width	2e-20
GCST006804_102	Red cell distribution width	2e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831201 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,320 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL325041	BORTEZOMIB	4	13,415
CHEMBL451887	CARFILZOMIB	4	13,156
CHEMBL2141296	IXAZOMIB	3	6,376
CHEMBL371405	MARIZOMIB	3	7,520
CHEMBL2103884	OPROZOMIB	2	2,853

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

148 measured of 187 human assays (187 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Cinnabaramide G	IC50	0.6 nM
CHEMBL4102324	IC50	0.92 nM
CINNABARAMIDE A	IC50	1 nM
MARIZOMIB	IC50	1.3 nM
CHEMBL4460323	IC50	1.5 nM
Alpha-ketocarbonyl derivative	IC50	2 nM
(R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-6-carboxamido)propanamido)butylboronic acid	IC50	2.4 nM
CHEMBL4517600	IC50	2.4 nM
CHEMBL4587036	IC50	2.5 nM
CHEMBL4444107	IC50	3.4 nM
CHEMBL5197285	IC50	3.4 nM
CHEMBL4541038	IC50	3.6 nM
CHEMBL4547405	IC50	3.9 nM
CHEMBL5171225	IC50	4 nM
CHEMBL4581126	IC50	4.3 nM
CHEMBL4542373	IC50	4.6 nM
CHEMBL4558648	IC50	4.6 nM
CHEMBL4467618	IC50	4.8 nM
CHEMBL5186240	IC50	5.2 nM
Alpha-ketocarbonyl derivative	IC50	6 nM
Cinnabaramide F	IC50	6 nM
CHEMBL4447701	IC50	6.4 nM
CHEMBL4435814	IC50	6.4 nM
CHEMBL4436430	IC50	6.5 nM
CHEMBL432281	IC50	7 nM
CHEMBL5202627	IC50	7 nM
CHEMBL5208573	IC50	7.2 nM
CHEMBL4559271	IC50	7.7 nM
CHEMBL5172645	IC50	8.1 nM
CHEMBL5179570	IC50	8.4 nM
CHEMBL5209077	IC50	8.6 nM
CHEMBL5173459	IC50	8.9 nM
CHEMBL5188065	IC50	9.3 nM
CHEMBL5196378	IC50	9.3 nM
CHEMBL4572638	IC50	9.4 nM
CHEMBL5201055	IC50	9.4 nM
CHEMBL4441018	IC50	9.5 nM
Cinnabaramide C	IC50	12 nM
TP-103	IC50	14 nM
CHEMBL4578081	IC50	14 nM
MLN2238	IC50	15 nM
CHEMBL4443333	IC50	15 nM
CHEMBL4864661	IC50	16 nM
CHEMBL4875208	IC50	16 nM
CHEMBL4557130	IC50	17 nM
CHEMBL27225	IC50	18 nM
TP-108	IC50	18 nM
CHEMBL2114122	IC50	20 nM
TP-109	IC50	20 nM
CHEMBL5173758	IC50	20 nM

ChEMBL bioactivities

312 potent at pChembl≥5 of 336 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

312 with measured affinity, of 993 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
Bortezomib	2205591: Inhibition of 20S proteasome (unknown origin)	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
(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
4-methyl-N-[(2R)-1-[[(2R)-4-methyl-1-[(2S)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide	2236585: Activation of 26s proteosome (unknown origin)	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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation	2
dimethylselenide	decreases expression, increases expression, increases oxidation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Reactive Oxygen Species	decreases expression, increases expression, increases oxidation	1

ChEMBL screening assays

168 unique, capped per target: 159 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PSMB11 across ~30M SureChEMBL compounds — explore on Sugi Predict.