PSMB2

Summary

PSMB2 (proteasome 20S subunit beta 2, HGNC:9539) is a protein-coding gene on chromosome 1p34.3, encoding Proteasome subunit beta type-2 (P49721). Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 5690 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total
• GTEx eGene: eQTL in 17 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 8 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.88 (unconstrained)
• MANE Select transcript: NM_002794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9539
Approved symbol	PSMB2
Name	proteasome 20S subunit beta 2
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	HC7-I
Ensembl gene	ENSG00000126067
Ensembl biotype	protein_coding
OMIM	602175
Entrez	5690

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000373237

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3

ENST00000373237, ENST00000621781, ENST00000630477, ENST00000911388, ENST00000999066, ENST00000999067, ENST00001046092, ENST00001046093, ENST00001081648, ENST00001099179, ENST00001099180, ENST00001099181, ENST00001099182, ENST00001145689

RefSeq mRNA: 3 — MANE Select: NM_002794 NM_001199779, NM_001199780, NM_002794

CCDS: CCDS394, CCDS72755

Canonical transcript exons

ENST00000373237 — 6 exons

Exon	Start	End
ENSE00000765308	35631274	35631344
ENSE00000861194	35636310	35636432
ENSE00001124812	35605233	35605282
ENSE00001124815	35609246	35609408
ENSE00001459837	35599541	35603374
ENSE00001930801	35641342	35641526

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 230.6521 / max 1002.0813, expressed in 1827 samples.

Highest expression (Bgee): ileal mucosa, tibialis anterior, adult organism, deltoid, embryo.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PSMB2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	7.0e-10	-0.37	1:35588650:T:C
Esophagus Muscularis	eqtl	3.3e-08	+0.59	1:35477441:A:G
Nerve Tibial	eqtl	6.6e-08	-0.35	1:35590926:A:G
Artery Tibial	eqtl	1.5e-07	-0.34	1:35603817:A:G
Skin Sun Exposed Lower leg	eqtl	2.8e-04	-0.22	1:35588650:T:C
Colon Transverse	eqtl	8.4e-04	-0.34	1:35588650:T:C
Whole Blood	eqtl	2.5e-03	-0.21	1:35588650:T:C
Adipose Subcutaneous	eqtl	4.6e-03	-0.33	1:36556123:A:G
Esophagus Gastroesophageal Junction	eqtl	6.4e-03	-0.42	1:35597110:A:AGAT
Stomach	eqtl	8.8e-03	-0.46	1:36557956:G:A
Colon Sigmoid	eqtl	1.1e-02	-0.34	1:36096252:C:T
Cells Cultured fibroblasts	eqtl	2.1e-02	-0.13	1:35588650:T:C
Lung	eqtl	2.3e-02	-0.20	1:35588650:T:C
Brain Hypothalamus	eqtl	2.5e-02	-0.33	1:35479285:T:C
Artery Aorta	eqtl	3.0e-02	-0.38	1:35589584:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.7e-02	-0.26	1:35597110:A:AGAT
Muscle Skeletal	eqtl	4.1e-02	-0.19	1:35588650:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
11687	227.9852	1827
11686	2.6669	1097

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.66	gold quality
tibialis anterior	UBERON:0001385	97.26	gold quality
adult organism	UBERON:0007023	97.10	gold quality
deltoid	UBERON:0001476	96.72	gold quality
embryo	UBERON:0000922	96.29	gold quality
ganglionic eminence	UBERON:0004023	96.28	gold quality
ventricular zone	UBERON:0003053	96.03	gold quality
biceps brachii	UBERON:0001507	96.01	gold quality
heart right ventricle	UBERON:0002080	95.95	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.75	gold quality
placenta	UBERON:0001987	95.69	gold quality
triceps brachii	UBERON:0001509	95.59	gold quality
gluteal muscle	UBERON:0002000	95.50	gold quality
gingiva	UBERON:0001828	95.39	gold quality
gingival epithelium	UBERON:0001949	95.38	gold quality
cartilage tissue	UBERON:0002418	95.34	gold quality
gastrocnemius	UBERON:0001388	95.30	gold quality
endometrium epithelium	UBERON:0004811	95.29	gold quality
mammalian vulva	UBERON:0000997	95.28	gold quality
skeletal muscle tissue	UBERON:0001134	95.21	gold quality
pericardium	UBERON:0002407	95.20	gold quality
upper leg skin	UBERON:0004262	95.20	gold quality
vastus lateralis	UBERON:0001379	95.19	gold quality
middle frontal gyrus	UBERON:0002702	95.17	gold quality
dorsal root ganglion	UBERON:0000044	95.15	gold quality
pharyngeal mucosa	UBERON:0000355	95.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.94	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.94	gold quality
muscle organ	UBERON:0001630	94.86	gold quality
oocyte	CL:0000023	94.85	gold quality
colonic mucosa	UBERON:0000317	94.85	gold quality
skin of hip	UBERON:0001554	94.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.81	gold quality
quadriceps femoris	UBERON:0001377	94.78	gold quality
muscle of leg	UBERON:0001383	94.78	gold quality
muscle tissue	UBERON:0002385	94.73	gold quality
liver	UBERON:0002107	94.72	gold quality
islet of Langerhans	UBERON:0000006	94.71	gold quality
left ventricle myocardium	UBERON:0006566	94.70	gold quality
smooth muscle tissue	UBERON:0001135	94.62	gold quality
nasal cavity epithelium	UBERON:0005384	94.58	gold quality
corpus epididymis	UBERON:0004359	94.52	gold quality
stromal cell of endometrium	CL:0002255	94.49	gold quality
body of tongue	UBERON:0011876	94.47	gold quality
trigeminal ganglion	UBERON:0001675	94.35	gold quality
pons	UBERON:0000988	94.30	gold quality
seminal vesicle	UBERON:0000998	94.20	gold quality
adrenal tissue	UBERON:0018303	94.18	gold quality
amniotic fluid	UBERON:0000173	94.17	gold quality
pigmented layer of retina	UBERON:0001782	94.15	gold quality
mucosa of transverse colon	UBERON:0004991	94.14	gold quality
bronchial epithelial cell	CL:0002328	94.13	gold quality
cortical plate	UBERON:0005343	94.11	gold quality
parotid gland	UBERON:0001831	94.04	gold quality
penis	UBERON:0000989	94.02	gold quality
nasal cavity mucosa	UBERON:0001826	93.98	gold quality
epithelium of bronchus	UBERON:0002031	93.97	gold quality
bronchus	UBERON:0002185	93.94	gold quality
oral cavity	UBERON:0000167	93.93	gold quality
frontal pole	UBERON:0002795	93.93	gold quality
cauda epididymis	UBERON:0004360	93.90	gold quality
pylorus	UBERON:0001166	93.88	gold quality
type B pancreatic cell	CL:0000169	93.83	gold quality
jejunum	UBERON:0002115	93.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.81	gold quality
rectum	UBERON:0001052	93.76	gold quality
right lobe of liver	UBERON:0001114	93.68	gold quality
right adrenal gland	UBERON:0001233	93.68	gold quality
prefrontal cortex	UBERON:0000451	93.67	gold quality
bone marrow	UBERON:0002371	93.61	gold quality
tongue	UBERON:0001723	93.57	gold quality
left adrenal gland	UBERON:0001234	93.56	gold quality
renal glomerulus	UBERON:0000074	93.55	gold quality
myocardium	UBERON:0002349	93.52	gold quality
cranial nerve II	UBERON:0000941	93.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.38	gold quality
saphenous vein	UBERON:0007318	93.36	gold quality
duodenum	UBERON:0002114	93.33	gold quality
vena cava	UBERON:0004087	93.32	gold quality
lymph node	UBERON:0000029	93.31	gold quality
urethra	UBERON:0000057	93.29	gold quality
left adrenal gland cortex	UBERON:0035825	93.28	gold quality
right adrenal gland cortex	UBERON:0035827	93.27	gold quality
adrenal gland	UBERON:0002369	93.26	gold quality
metanephros	UBERON:0000081	93.25	gold quality
adrenal cortex	UBERON:0001235	93.25	gold quality
jejunal mucosa	UBERON:0000399	93.24	gold quality
cortex of kidney	UBERON:0001225	93.22	gold quality
superior surface of tongue	UBERON:0007371	93.18	gold quality
metanephric glomerulus	UBERON:0004736	93.16	gold quality
nipple	UBERON:0002030	93.14	gold quality
thymus	UBERON:0002370	93.12	gold quality
trachea	UBERON:0003126	93.12	gold quality
caecum	UBERON:0001153	93.10	gold quality
trabecular bone tissue	UBERON:0002483	93.10	gold quality
caput epididymis	UBERON:0004358	93.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.07	gold quality
spinal cord	UBERON:0002240	93.05	gold quality
coronary artery	UBERON:0001621	92.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.24

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	149.5
Frontal cortex	tissue	146.7
Spinal cord	tissue	27.2
Corpus callosum	tissue	26.5
Hippocampal formation	tissue	25.8
Pons	tissue	25.6
Superior colliculi	tissue	25.6
Midbrain	tissue	25.2
Substantia nigra	tissue	25.2
Medulla oblongata	tissue	25.0
Olfactory bulb	tissue	25.0
Cerebellum	tissue	24.9	high
Thalamus	tissue	24.7
Putamen	tissue	24.0
Septum	tissue	23.9
Basal ganglia	tissue	23.8	medium
Hypothalamus	tissue	23.4
Ventral forebrain	tissue	23.3
Liver	tissue	23.1	high
Cerebral cortex	tissue	23.0	medium
Somatosensory cortex	tissue	23.0
Periaqueductal gray	tissue	22.7
Retrosplenial and cingulate cortex	tissue	22.5
Retrosplenial cortex	tissue	22.5
Temporal cortex	tissue	22.5
Occipital cortex	tissue	22.4
Entorhinal cortex	tissue	22.2
Prefrontal cortex	tissue	21.9
Amygdala	tissue	21.4
Motor cortex	tissue	20.8
Insular cortex	tissue	20.7
Bone marrow	tissue	20.4	medium
Thymus	tissue	19.1
Locus coeruleus	tissue	19.0
Skeletal muscle	tissue	18.0	high
Postcentral gyrus	tissue	16.2
Tonsil	tissue	15.6	high
Choroid plexus	tissue	15.3
Nucleus accumbens	tissue	14.9
Hippocampus	tissue	14.9	medium
Lymph node	tissue	14.7	high
Placenta	tissue	14.2	high
Tongue	tissue	13.8
Skin 1	tissue	13.2	medium
Appendix	tissue	13.0	high
Urinary bladder	tissue	12.9	high
Smooth muscle	tissue	12.5	not detected
Duodenum	tissue	12.1	high
Adipose tissue	tissue	11.9	not detected
Rectum	tissue	11.9	high
Small intestine	tissue	11.8	high
Colon	tissue	11.6	high
Spleen	tissue	11.4	medium
Retina	tissue	11.2
Fallopian tube	tissue	11.2	high
Lung	tissue	11.0	low
Esophagus	tissue	10.9	medium
Epididymis	tissue	10.8	high
Adrenal gland	tissue	10.7	medium
Vagina	tissue	10.6	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral spinal cord (27.2), White matter (26.5), Dorsal spinal cord (26.3), Dorsal hippocampus (25.8), Ventral hippocampus (24.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRD1

miRNA regulators (miRDB)

Targeting PSMB2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 151 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-12119	99.87	68.35	1653
HSA-LET-7A-2-3P	99.87	70.53	1921

Functional genomics

gnomAD constraint: pLI 0.0073, LOEUF 0.878, missense Z 1.42 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000373237 — one region, missense o/e 0.78. DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): MFE-280 (-2.955), SW 1990 (-2.826), Panc 08.13 (-2.792), SNU-620 (-2.722), AsPC-1 (-2.69), NCI-H226 (-2.677), NCI-H2171 (-2.673), KALS-1 (-2.608), DB (-2.606), SW1116 (-2.572), OE33 (-2.546), SK-MM-2 (-2.544), PA-TU-8988T (-2.524), VMRC-RCW (-2.515), LS1034 (-2.457).

Literature-anchored findings (GeneRIF, showing 3)

• This subunit propeptides influence cooperative proteasome assembly. (PMID:12456675)
• Results showed that the overexpression of beta2 subunit decreased homologous recombination in human cells without altering the cell proteasome activity and the Rad51p level. (PMID:21660142)
• NUDT21 inhibits HCC proliferation, metastasis and tumorigenesis, at least in part, by suppressing PSMB2 and CXXC5. (PMID:29780166)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb2	ENSDARG00000031511
mus_musculus	Psmb2	ENSMUSG00000028837
rattus_norvegicus	Psmb2	ENSRNOG00000011463
drosophila_melanogaster	Prosbeta4R1	FBGN0031442
drosophila_melanogaster	Prosbeta4R2	FBGN0031443
drosophila_melanogaster	Prosbeta4	FBGN0032596
caenorhabditis_elegans	pbs-4	WBGENE00003950

Paralogs (18): PSMB1 (ENSG00000008018), PSMA4 (ENSG00000041357), PSMA3 (ENSG00000100567), PSMB5 (ENSG00000100804), PSMA6 (ENSG00000100902), PSMA7 (ENSG00000101182), PSMA2 (ENSG00000106588), PSMA1 (ENSG00000129084), PSMB7 (ENSG00000136930), PSMB6 (ENSG00000142507), PSMA5 (ENSG00000143106), PSMA8 (ENSG00000154611), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

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
Cryptococcus deneoformans JEC21	P0CQ12	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CQ13	100.0%	Diamond
Bos taurus	Q5E9K0	98.5%	Diamond
Arabidopsis thaliana	O23714	93.9%	Diamond
Oryza sativa Japonica Group	Q9LST6	77.7%	Diamond
Meyerozyma guilliermondii ATCC 6260	A5DB52	68.6%	Diamond
Saccharomyces cerevisiae S288C	P22141	68.6%	Diamond
Neurospora crassa OR74A	Q9P6U7	60.5%	Diamond
Schizosaccharomyces pombe 972h-	Q09720	59.2%	Diamond
Dictyostelium discoideum	Q55DY7	46.6%	Diamond
Trypanosoma brucei brucei	Q9NHC6	41.3%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SRF1	32.1%	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
NCDN	protein-coding	23154
TFAP2E	protein-coding	339488
KIAA0319L	protein-coding	79932
TFAP2E-AS1	ncRNA	105378645
C1orf216	protein-coding	127703
CLSPN-AS1	ncRNA	139355217
CLSPN	protein-coding	63967
CLSPN-DT	ncRNA	139355247

Protein

Protein identifiers

Proteasome subunit beta type-2 — P49721 (reviewed: P49721)

Alternative names: Macropain subunit C7-I, Multicatalytic endopeptidase complex subunit C7-I, Proteasome component C7-I, Proteasome subunit beta-4

All UniProt accessions (4): A0A087WVV1, A0A140VJS6, B7Z478, P49721

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).

Subunit / interactions. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. (Microbial infection) Interacts with HIV-1 protein Tat.

Subcellular location. Cytoplasm. Nucleus.

Induction. Up-regulated in ovarian cancer cell lines.

Similarity. Belongs to the peptidase T1B family.

RefSeq proteins (3): NP_001186708, NP_001186709, NP_002785* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001353	Proteasome_sua/b	Family
IPR016050	Proteasome_bsu_CS	Conserved_site
IPR023333	Proteasome_suB-type	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR035206	Proteasome_beta2	Family

Pfam: PF00227

UniProt features (23 total): strand 14, helix 6, chain 1, modified residue 1, turn 1

Structure

Experimental structures (PDB)

showing 30 of 154 structures by resolution:

PDB	Title	Method	Resolution (Å)
5LE5	Native human 20S proteasome at 1.8 Angstrom	X-RAY DIFFRACTION	1.8
5LEY	Human 20S proteasome complex with Oprozomib at 1.9 Angstrom	X-RAY DIFFRACTION	1.9
5LF4	Human 20S proteasome complex with Delanzomib at 2.0 Angstrom	X-RAY DIFFRACTION	1.99
5LF1	Human 20S proteasome complex with Dihydroeponemycin at 2.0 Angstrom	X-RAY DIFFRACTION	2
5LF7	Human 20S proteasome complex with Ixazomib at 2.0 Angstrom	X-RAY DIFFRACTION	2
8UD9	Structure of human constitutive 20S proteasome complexed with the inhibitor TDI-8304	ELECTRON MICROSCOPY	2.04
5LF6	Human 20S proteasome complex with Z-LLY-ketoaldehyde at 2.1 Angstrom	X-RAY DIFFRACTION	2.07
5LF3	Human 20S proteasome complex with Bortezomib at 2.1 Angstrom	X-RAY DIFFRACTION	2.1
8BZL	Human 20S Proteasome in complex with peptide activator peptide BLM42	X-RAY DIFFRACTION	2.14
5LEZ	Human 20S proteasome complex with Oprozomib in Mg-Acetate at 2.2 Angstrom	X-RAY DIFFRACTION	2.19
5LEX	Native human 20S proteasome in Mg-Acetate at 2.2 Angstrom	X-RAY DIFFRACTION	2.2
7AWE	HUMAN IMMUNOPROTEASOME 20S PARTICLE IN COMPLEX WITH …	X-RAY DIFFRACTION	2.29
5LF0	Human 20S proteasome complex with Epoxomicin at 2.4 Angstrom	X-RAY DIFFRACTION	2.41
7B12	HUMAN IMMUNOPROTEASOME 20S PARTICLE IN COMPLEX WITH …	X-RAY DIFFRACTION	2.43
9K53	Structure of substrate-engaged human 26S proteasome RP-CP subcomplex in state ED2.1	ELECTRON MICROSCOPY	2.5
9HMN	CryoEM structure of human 20S proteasome in complex with proteasome inhibitor …	ELECTRON MICROSCOPY	2.55
4R3O	Human Constitutive 20S Proteasome	X-RAY DIFFRACTION	2.6
6RGQ	Human 20S Proteasome	ELECTRON MICROSCOPY	2.6
9YUZ	Structure of the human 20S proteasome in complex with a beta5-selective covalent …	ELECTRON MICROSCOPY	2.6
8CVR	Human 20S proteasome with MG-132	ELECTRON MICROSCOPY	2.7
6KWY	human PA200-20S complex	ELECTRON MICROSCOPY	2.72
8QYM	Human 20S proteasome assembly intermediate structure 3	ELECTRON MICROSCOPY	2.73
9MBP	Substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral …	ELECTRON MICROSCOPY	2.75
6E5B	Human Immunoproteasome 20S particle in complex with compound 1	X-RAY DIFFRACTION	2.77
7NAN	Human 20S proteasome core particle	ELECTRON MICROSCOPY	2.8
8TM6	Human premature 20S proteasome assembly intermediate	ELECTRON MICROSCOPY	2.8
9NKG	Structure of substrate engaged MIDN-bound human 26S proteasome, EB-MIDN (Composite map)	ELECTRON MICROSCOPY	2.8
8QYO	Human proteasome 20S core particle	ELECTRON MICROSCOPY	2.84
8QYN	Human 20S proteasome assembly intermediate structure 5	ELECTRON MICROSCOPY	2.88
4R67	Human constitutive 20S proteasome in complex with carfilzomib	X-RAY DIFFRACTION	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49721-F1	96.80	0.98

Human Protein Atlas

Protein class: Enzymes, Peptidases, Threonine-type peptidases, Predicted intracellular proteins, Plasma proteins, FDA approved drug targets, Small molecule drugs, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

Functional residue map

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

Post-translational modifications (1)

Type	Positions
N-acetylmethionine	1

Function

Pathways and Gene Ontology

Reactome pathways

58 curated (TAS) of 172; 13 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 172 pathways:

ID	Pathway	Evidence
R-HSA-5678895	Defective CFTR causes cystic fibrosis ⚕	curated
R-HSA-5362768	Hh mutants are degraded by ERAD ⚕	curated
R-HSA-180585	Vif-mediated degradation of APOBEC3G ⚕	curated
R-HSA-180534	Vpu mediated degradation of CD4 ⚕	curated
R-HSA-382556	ABC-family protein mediated transport	curated
R-HSA-9931269	AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	curated
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin	curated
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	curated
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA	curated
R-HSA-1169091	Activation of NF-kappaB in B cells	curated
R-HSA-9912633	Antigen processing: Ub, ATP-independent proteasomal degradation	curated
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation	curated
R-HSA-68867	Assembly of the pre-replicative complex	curated
R-HSA-4608870	Asymmetric localization of PCP proteins	curated
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C	curated
R-HSA-349425	Autodegradation of the E3 ubiquitin ligase COP1	curated
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6	curated
R-HSA-5607764	CLEC7A (Dectin-1) signaling	curated
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A	curated
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)	curated
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling	curated
R-HSA-4641257	Degradation of AXIN	curated
R-HSA-9766229	Degradation of CDH1	curated
R-HSA-4641258	Degradation of DVL	curated
R-HSA-5610780	Degradation of GLI1 by the proteasome	curated
R-HSA-195253	Degradation of beta-catenin by the destruction complex	curated
R-HSA-202424	Downstream TCR signaling	curated
R-HSA-8854050	FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	curated
R-HSA-2871837	FCERI mediated NF-kB activation	curated
R-HSA-69481	G2/M Checkpoints	curated
R-HSA-5610785	GLI3 is processed to GLI3R by the proteasome	curated
R-HSA-9762114	GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	curated
R-HSA-9929356	GSK3B-mediated proteasomal degradation of PD-L1(CD274)	curated
R-HSA-5632684	Hedgehog ‘on’ state	curated
R-HSA-5358346	Hedgehog ligand biogenesis	curated
R-HSA-9020702	Interleukin-1 signaling	curated
R-HSA-9755511	KEAP1-NFE2L2 pathway	curated
R-HSA-5687128	MAPK6/MAPK4 signaling	curated
R-HSA-5676590	NIK–>noncanonical NF-kB signaling	curated
R-HSA-8951664	Neddylation	curated
R-HSA-9974237	Negative Regulation of DNA Double Strand Break Response	curated
R-HSA-68949	Orc1 removal from chromatin	curated
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	curated
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs	curated
R-HSA-8948751	Regulation of PTEN stability and activity	curated
R-HSA-5658442	Regulation of RAS by GAPs	curated
R-HSA-8941858	Regulation of RUNX3 expression and activity	curated
R-HSA-350562	Regulation of ornithine decarboxylase (ODC)	curated
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21	curated
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1	curated
R-HSA-9929491	SPOP-mediated proteasomal degradation of PD-L1(CD274)	curated
R-HSA-2467813	Separation of Sister Chromatids	curated
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway	curated
R-HSA-8852276	The role of GTSE1 in G2/M progression after G2 checkpoint	curated
R-HSA-5689603	UCH proteinases	curated
R-HSA-5689880	Ub-specific processing proteases	curated
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	curated
R-HSA-75815	Ubiquitin-dependent degradation of Cyclin D	curated
R-HSA-5619084	ABC transporter disorders ⚕	—
R-HSA-1643685	Disease ⚕	—

MSigDB gene sets: 500 (showing top): MORF_MTA1, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_ESPL1, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, XU_GH1_AUTOCRINE_TARGETS_UP

GO Biological Process (24): immune system process (GO:0002376), DNA repair (GO:0006281), apoptotic process (GO:0006915), DNA damage response (GO:0006974), response to oxidative stress (GO:0006979), spermatogenesis (GO:0007283), proteasomal protein catabolic process (GO:0010498), proteasomal ubiquitin-independent protein catabolic process (GO:0010499), flagellated sperm motility (GO:0030317), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-2 production (GO:0032743), positive regulation of tumor necrosis factor production (GO:0032760), response to type II interferon (GO:0034341), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), CD8-positive, alpha-beta T cell differentiation (GO:0043374), thymic T cell selection (GO:0045061), T-helper 1 cell differentiation (GO:0045063), negative regulation of regulatory T cell differentiation (GO:0045590), meiotic cell cycle (GO:0051321), regulation of proteasomal protein catabolic process (GO:0061136), cellular response to type I interferon (GO:0071357), T-helper 17 cell differentiation (GO:0072539), CD8-positive, alpha-beta T cell homeostasis (GO:0160165), regulation of G1/S transition of mitotic cell cycle (GO:2000045)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (11): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome core complex (GO:0005839), synaptic vesicle (GO:0008021), membrane (GO:0016020), proteasome core complex, beta-subunit complex (GO:0019774), proteasome storage granule (GO:0034515), extracellular exosome (GO:0070062)

Reactome top-level categories

18 top-level categories:

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
Stabilization of p53	1
Metabolism of polyamines	1
Transport of small molecules	1

GO top-level categories

58 GO namespaces:

Category	Terms
cellular anatomical structure	4
proteasomal protein catabolic process	3
positive regulation of cytokine production	2
intracellular protein-containing complex	2
intracellular anatomical structure	2
cytoplasm	2
biological_process	1
DNA metabolic process	1
DNA damage response	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
response to stress	1
developmental process involved in reproduction	1
male gamete generation	1
protein catabolic process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
response to cytokine	1
innate immune response	1
ubiquitin-dependent 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
alpha-beta T cell activation involved in immune response	1
T cell differentiation involved in immune response	1
T-helper 1 type immune response	1
T-helper cell differentiation	1
regulatory T cell differentiation	1
negative regulation of T cell differentiation	1
regulation of regulatory T cell differentiation	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
regulation of protein catabolic process	1
binding	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
proteasome complex	1
catalytic complex	1
exocytic vesicle	1
presynapse	1
proteasome core complex	1
protein-containing complex	1
intracellular membraneless organelle	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 37 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
proteasomal protein catabolic process	BP	direct assay
proteasome-mediated ubiquitin-dependent protein catabolic process	BP	direct assay
regulation of proteasomal protein catabolic process	BP	direct assay
response to oxidative stress	BP	direct assay
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
membrane	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
proteasome complex	CC	direct assay
proteasome core complex	CC	direct assay

Protein interactions and networks

IntAct

Human interaction partners of PSMB2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

22 partners by confidence:

Partner	Interaction type	MIscore	Records
PSMA1	physical association	0.920	1
PSMB3	physical association	0.850	4
POMP	physical association	0.810	1
PSMB1	physical association	0.800	2
PSMA7	association	0.790	1
PSMB5	physical association	0.740	1
PSMD11	association	0.730	3
HTT	physical association	0.670	6
AXIN2	physical association	0.560	3
INCA1	physical association	0.560	3
KCTD9	physical association	0.560	3
KRT13	physical association	0.560	3
KRTAP19-1	physical association	0.560	3
KRTAP19-5	physical association	0.560	3
KRTAP19-6	physical association	0.560	3
KRTAP19-7	physical association	0.560	3
DDX49	physical association	0.370	1
E7	physical association	0.370	1
GPX2	physical association	0.370	1
HSPB1	physical association	0.370	1
PSMD1	association	0.350	1
TRAF6	physical association	0.000	1

BioGRID (520 interactions; top human partners by supporting records): PSMA1 (Affinity Capture-MS; 14 records), PSMA2 (Co-fractionation; 14 records), PSMA7 (Co-fractionation; 14 records), PSMB3 (Co-fractionation; 14 records), PSMB1 (Co-fractionation; 11 records), PSMA4 (Co-fractionation; 10 records), PSMB7 (Affinity Capture-MS; 10 records), PSMA5 (Co-fractionation; 9 records), PSMB4 (Affinity Capture-MS; 9 records), PSMB5 (Co-fractionation; 9 records), PSMB6 (Co-fractionation; 9 records), PSMA6 (Co-fractionation; 8 records), PSMA3 (Co-fractionation; 7 records), PSMD14 (Affinity Capture-MS; 7 records), POMP (Affinity Capture-MS; 6 records)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
bortezomib	“down-regulates activity”	PSMB2	“chemical inhibition”
carfilzomib	“down-regulates activity”	PSMB2	“chemical inhibition”
PSMB2	“form complex”	“26S Proteasome”	binding

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
★ PA700-20S-PA28 complex	36	PSMA5, PSMD4, PSMD6, PSMD9, PSME1, PSME2, PSMD11, PSMB1, PSMB4, PSMC1, PSMA3, PSMB5, PSMD10, PSMA7, PSMC5, PSMD14, PSMD7, PSMA6, PSMB6, PSMD12, PSMD3, PSMD1, PSMA4, PSMB7, PSMC3, PSMC4, PSMC6, PSMD8, PSMB3, PSMC2, PSMD13, PSMA1, PSMA2, PSMB2, PSMD2, PSMD5
★ 26S proteasome	22	PSMA2, PSMA7, PSMB3, PSMA5, PSMA6, PSMB4, PSMB7, PSMC1, PSMC2, PSMC5, PSMC6, PSMA3, PSMB2, PSMB5, PSMC3, PSMC4, PSMD13, PSMD4, PSMA1, PSMA4, PSMB1, PSMB6
★ PA28-20S proteasome	16	PSMA6, PSMB5, PSMA2, PSMA7, PSMB2, PSMB4, PSME1, PSMA3, PSMB1, PSMB3, PSMB6, PSME2, PSMA1, PSMA5, PSMB7, PSMA4
★ PA28gamma-20S proteasome	15	PSMB5, PSMA5, PSMB1, PSMB4, PSME3, PSMA1, PSMA4, PSMA7, PSMB2, PSMA2, PSMA3, PSMB6, PSMB7, PSMA6, PSMB3
★ 20S proteasome	14	PSMA5, PSMA6, PSMB1, PSMB6, PSMA2, PSMA7, PSMB2, PSMB3, PSMB4, PSMB5, PSMB7, PSMA1, PSMA3, PSMA4

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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	5	150.3×	2e-10
AUF1 (hnRNP D0) binds and destabilizes mRNA	8	104.5×	2e-13
Degradation of AXIN	8	104.5×	2e-13
Regulation of activated PAK-2p34 by proteasome mediated degradation	7	102.6×	4e-12
Regulation of ornithine decarboxylase (ODC)	7	100.2×	4e-12
Vpu mediated degradation of CD4	7	97.8×	4e-12
Autodegradation of the E3 ubiquitin ligase COP1	7	97.8×	4e-12
Ubiquitin-dependent degradation of Cyclin D	7	97.8×	4e-12

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	8	24.6×	7e-08

Disease & clinical

Genetic variants

Variant evidence for PSMB2: 36 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 368):

Position(s)	Effect	Δscore	Sites
1:35609244–35609245	donor_loss	1.0000	4
1:35609410	acceptor_loss	1.0000
1:35631272–35631273	donor_loss	1.0000	5
1:35631345–35631346	acceptor_loss	1.0000	6
1:35636433–35636434	acceptor_loss	1.0000	5
1:35641326	donor_gain	1.0000
1:35609409–35609410	acceptor_loss	0.9900	2
1:35609413	acceptor_gain	0.9900
1:35631348	acceptor_gain	0.9900
1:35636433	acceptor_loss	0.9900

AlphaMissense

685 missense substitutions predicted likely pathogenic (of 1,314 scored), across 167 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
D119	8	0.995	0.999
D52	8	0.983	0.994
D144	8	0.979	0.994
D18	8	0.970	0.991
F56	8	0.960	0.998
N63	8	0.917	0.989
H132	8	0.875	0.981
F83	7	0.990	0.998
F129	7	0.946	0.994
S141	7	0.921	0.997
F178	7	0.899	0.986
F36	7	0.880	0.970
F171	7	0.874	0.970
E166	7	0.871	0.974
E58	7	0.870	0.972
D108	7	0.855	0.933
E2	7	0.851	0.984
D184	7	0.849	0.974
M69	7	0.839	0.977
F137	7	0.793	0.941

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.02e-06
Colon Adenocarcinoma (TCGA)	favorable	6.59e-05
Lung Adenocarcinoma (TCGA)	unfavorable	0.000724

Disease associations

OMIM: gene MIM:602175 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST90014023_2	Type 1 diabetes	2e-8

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3492 (SINGLE PROTEIN), 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: 462,281 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

8 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL325041	BORTEZOMIB	4	13,415
CHEMBL451887	CARFILZOMIB	4	13,156
CHEMBL159	VINBLASTINE	4	416,858
CHEMBL2141296	IXAZOMIB	3	6,376
CHEMBL371405	MARIZOMIB	3	7,520
CHEMBL270515	DELANZOMIB	2	1,958
CHEMBL2103884	OPROZOMIB	2	2,853
CHEMBL4297468	ZETOMIPZOMIB	2	145

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — T1: Proteasome

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
MG-132	Inhibition	6.52	pKi
zetomipzomib	Inhibition	6.22	pIC50

Binding affinities (BindingDB)

370 measured of 521 human assays (524 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL392916	IC50	0.6 nM
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
(R)-1-((S)-2-((S)-2-(benzyloxycarbonyl)-4-methylpentanamido)-4-methylpentanamido)-3-methylbutylboronic acid	KI	6.1 nM
CHEMBL4447701	IC50	6.4 nM
CHEMBL4435814	IC50	6.4 nM
CHEMBL4436430	IC50	6.5 nM
CHEMBL432281	IC50	7 nM
CHEMBL5202627	IC50	7 nM
2,5-dichloro-N-[(2S)-1-[[(1R)-1-(1,3,6,2-dioxazaborocan-2-yl)-3-methylbutyl]amino]-3-methoxy-1-oxopropan-2-yl]benzamide	IC50	7.02 nM	US-11542283: Synthesis of peptide borate ester compound and use thereof
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
(R)-1-((2S,3R)-3-hydroxy-2-(6-phenylpicolinamido)butanamido)-3-methylbutylboronic acid	EC50	13.5 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

ChEMBL bioactivities

590 potent at pChembl≥5 of 658 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
9.00	Ki	1	nM	MG-132
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
8.63	Ki	2.36	nM	CHEMBL5571110
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	CHEMBL4451682
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	CHEMBL4440581
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

PubChem BioAssay actives

588 with measured affinity, of 2021 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
benzyl N-[(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]carbamate	1370838: Inhibition of 20s immunoproteasome beta2 trypsin-like activity in human spleen using Boc-Leu-Arg-Arg-AMC as substrate after 10 mins by fluorescence assay	ki	0.0010	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
N-[(2S)-1-[[(3E,5S,8S)-5-[[4-(aminomethyl)phenyl]methyl]-2,7-dioxo-1,6-diazacyclododec-3-en-8-yl]amino]-1-oxo-3-phenylpropan-2-yl]decanamide	2108292: Inhibition of 20S proteasome beta-2 in human erythrocytes using Boc-LRR-AMC as substrate by AK-740 assay	ki	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
(2S)-N-[(2S)-1-[[(E,2S)-1-[4-(aminomethyl)phenyl]-4-methylsulfonylbut-3-en-2-yl]amino]-1-oxopropan-2-yl]-2-[[(2S)-2-azido-3-phenylpropanoyl]amino]-4-methylpentanamide	1572418: Inhibition of 20S constitutive proteasome beta 2 trypsin-like activity in human Raji cell lysates after 1 hr by competitive ABPP assay	ic50	0.0050	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
(2S)-N-[(2S)-1-[[(E,2S)-1-[4-(aminomethyl)phenyl]-4-methylsulfonylbut-3-en-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]-2-[[(2S)-2-azido-3-phenylpropanoyl]amino]-4-methylpentanamide	1572418: Inhibition of 20S constitutive proteasome beta 2 trypsin-like activity in human Raji cell lysates after 1 hr by competitive ABPP assay	ic50	0.0060	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	affects methylation, decreases expression	2
Vorinostat	decreases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
Vehicle Emissions	affects expression, increases reaction, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
microcystin RR	decreases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
stattic	decreases expression	1
bisphenol S	increases expression	1
EGFR tyrosine kinase inhibitor 324674	decreases reaction, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1

ChEMBL screening assays

306 unique, capped per target: 288 binding, 15 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*
CHEMBL4040353	ADMET	Inhibition of human 20S proteasome beta2 using z-LRR-AMC as substrate at 150 nM after 60 to 120 mins by fluorescence assay relative to control	Development of a Potent Inhibitor of the Plasmodium Proteasome with Reduced Mammalian Toxicity. — *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 PSMB2 across ~30M SureChEMBL compounds — explore on Sugi Predict.