PSMB5

Summary

PSMB5 (proteasome 20S subunit beta 5, HGNC:9542) is a protein-coding gene on chromosome 14q11.2, encoding Proteasome subunit beta type-5 (P28074). 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 95.0% 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 in the proteasome. This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic subunit 3i (proteasome beta 8 subunit). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5693 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 36 total
• GTEx eGene: eQTL in 45 tissues, sQTL in 32 (q < 0.05)
• ChEMBL bioactivity: 15 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 95.0% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.26 (highly constrained)
• MANE Select transcript: NM_002797
• Interaction hub: 2,626 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9542
Approved symbol	PSMB5
Name	proteasome 20S subunit beta 5
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MB1
Ensembl gene	ENSG00000100804
Ensembl biotype	protein_coding
OMIM	600306
Entrez	5693

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 29 protein_coding, 11 nonsense_mediated_decay

MANE Select: ENST00000361611

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1, TSL 3: 1, TSL 5: 1

ENST00000361611, ENST00000334454, ENST00000425762, ENST00000460922, ENST00000493471, ENST00000555895, ENST00000896864, ENST00000896865, ENST00000896866, ENST00000926152, ENST00000926153, ENST00000926154, ENST00001022780, ENST00001022781, ENST00001022783, ENST00001084170, ENST00001084171, ENST00001084172, ENST00001084173, ENST00001084174, ENST00001084175, ENST00001084176, ENST00001084177, ENST00001084178, ENST00001084181, ENST00001084182, ENST00001084187, ENST00001096105, ENST00001096106, ENST00001096107, ENST00001096108, ENST00001096109, ENST00001096110, ENST00001096111, ENST00001106097, ENST00001106098, ENST00001106099, ENST00001113171, ENST00001130789, ENST00001136025

RefSeq mRNA: 3 — MANE Select: NM_002797 NM_001130725, NM_001144932, NM_002797

CCDS: CCDS45083, CCDS45084, CCDS9584

Canonical transcript exons

ENST00000361611 — 3 exons

Exon	Start	End
ENSE00000889197	23025856	23026375
ENSE00001149729	23034684	23034900
ENSE00003535354	23033368	23033674

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 169.8429 / max 793.4199, expressed in 1824 samples.

Highest expression (Bgee): gastrocnemius, islet of Langerhans, muscle of leg, stromal cell of endometrium, hindlimb stylopod muscle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PSMB5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 32 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 77 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	6.6e-54	-0.98	14:23025068:A:G
Skin Not Sun Exposed Suprapubic	sqtl	1.7e-37	-0.73	14:23025068:A:G
Nerve Tibial	sqtl	1.3e-34	-0.75	14:23025068:A:G
Esophagus Muscularis	sqtl	1.4e-28	-0.67	14:23025068:A:G
Heart Atrial Appendage	sqtl	3.9e-27	-0.72	14:23025068:A:G
Brain Cortex	sqtl	6.2e-24	-0.88	14:23025068:A:G
Brain Hypothalamus	sqtl	1.0e-21	-0.87	14:23028146:A:AAAAC
Brain Nucleus accumbens basal ganglia	sqtl	1.1e-21	-0.77	14:23022075:C:G
Colon Sigmoid	sqtl	3.3e-21	-0.66	14:23025068:A:G
Brain Caudate basal ganglia	sqtl	1.1e-19	-0.87	14:23025068:A:G
Brain Frontal Cortex BA9	sqtl	1.3e-19	-0.83	14:23028146:A:AAAAC
Brain Anterior cingulate cortex BA24	sqtl	4.7e-19	-0.90	14:23022075:C:G
Muscle Skeletal	eqtl	1.2e-18	-0.23	14:23034812:G:A
Esophagus Gastroesophageal Junction	sqtl	1.4e-17	-0.68	14:23028146:A:AAAAC
Thyroid	eqtl	1.6e-17	-0.24	14:23034812:G:A
Brain Hippocampus	sqtl	2.0e-17	-0.78	14:23028146:A:AAAAC
Whole Blood	eqtl	4.2e-17	-0.25	14:23034812:G:A
Adipose Subcutaneous	eqtl	7.7e-17	-0.31	14:23034812:G:A
Adipose Visceral Omentum	sqtl	1.9e-16	-0.51	14:23025068:A:G
Brain Putamen basal ganglia	sqtl	1.6e-15	-0.88	14:23025068:A:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
142293	167.3078	1824
142294	1.8065	1116
142295	0.7286	496

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.84	gold quality
islet of Langerhans	UBERON:0000006	98.67	gold quality
muscle of leg	UBERON:0001383	98.64	gold quality
stromal cell of endometrium	CL:0002255	98.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.35	gold quality
cortical plate	UBERON:0005343	98.30	gold quality
muscle organ	UBERON:0001630	98.27	gold quality
right adrenal gland	UBERON:0001233	98.26	gold quality
ganglionic eminence	UBERON:0004023	98.18	gold quality
right adrenal gland cortex	UBERON:0035827	98.13	gold quality
left adrenal gland	UBERON:0001234	98.01	gold quality
deltoid	UBERON:0001476	97.92	gold quality
embryo	UBERON:0000922	97.88	gold quality
left adrenal gland cortex	UBERON:0035825	97.86	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.83	gold quality
adrenal tissue	UBERON:0018303	97.79	gold quality
smooth muscle tissue	UBERON:0001135	97.78	gold quality
prefrontal cortex	UBERON:0000451	97.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.73	gold quality
apex of heart	UBERON:0002098	97.72	gold quality
ventricular zone	UBERON:0003053	97.69	gold quality
tibialis anterior	UBERON:0001385	97.64	gold quality
right atrium auricular region	UBERON:0006631	97.64	gold quality
heart left ventricle	UBERON:0002084	97.58	gold quality
adrenal cortex	UBERON:0001235	97.53	gold quality
cardiac ventricle	UBERON:0002082	97.48	gold quality
adrenal gland	UBERON:0002369	97.47	gold quality
skeletal muscle tissue	UBERON:0001134	97.46	gold quality
lower esophagus	UBERON:0013473	97.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.42	gold quality
right frontal lobe	UBERON:0002810	97.41	gold quality
adenohypophysis	UBERON:0002196	97.39	gold quality
spinal cord	UBERON:0002240	97.39	gold quality
left coronary artery	UBERON:0001626	97.38	gold quality
esophagus mucosa	UBERON:0002469	97.34	gold quality
heart	UBERON:0000948	97.31	gold quality
esophagus	UBERON:0001043	97.30	gold quality
cardiac atrium	UBERON:0002081	97.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.28	gold quality
mucosa of transverse colon	UBERON:0004991	97.26	gold quality
pituitary gland	UBERON:0000007	97.24	gold quality
gluteal muscle	UBERON:0002000	97.24	gold quality
rectum	UBERON:0001052	97.23	gold quality
body of stomach	UBERON:0001161	97.23	gold quality
quadriceps femoris	UBERON:0001377	97.23	gold quality
cingulate cortex	UBERON:0003027	97.22	gold quality
triceps brachii	UBERON:0001509	97.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.21	gold quality
anterior cingulate cortex	UBERON:0009835	97.19	gold quality
amygdala	UBERON:0001876	97.18	gold quality
nucleus accumbens	UBERON:0001882	97.17	gold quality
caudate nucleus	UBERON:0001873	97.16	gold quality
muscle tissue	UBERON:0002385	97.15	gold quality
putamen	UBERON:0001874	97.12	gold quality
descending thoracic aorta	UBERON:0002345	97.12	gold quality
vastus lateralis	UBERON:0001379	97.11	gold quality
endometrium epithelium	UBERON:0004811	97.09	gold quality
biceps brachii	UBERON:0001507	97.07	gold quality
thoracic aorta	UBERON:0001515	97.07	gold quality
ascending aorta	UBERON:0001496	97.06	gold quality
coronary artery	UBERON:0001621	97.06	gold quality
pons	UBERON:0000988	97.04	gold quality
pancreas	UBERON:0001264	97.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.02	gold quality
lower esophagus mucosa	UBERON:0035834	97.00	gold quality
aorta	UBERON:0000947	96.98	gold quality
hypothalamus	UBERON:0001898	96.98	gold quality
popliteal artery	UBERON:0002250	96.97	gold quality
tibial artery	UBERON:0007610	96.97	gold quality
metanephros cortex	UBERON:0010533	96.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.94	gold quality
right coronary artery	UBERON:0001625	96.93	gold quality
body of pancreas	UBERON:0001150	96.91	gold quality
peritoneum	UBERON:0002358	96.89	gold quality
omental fat pad	UBERON:0010414	96.89	gold quality
diaphragm	UBERON:0001103	96.87	gold quality
ectocervix	UBERON:0012249	96.85	gold quality
substantia nigra	UBERON:0002038	96.79	gold quality
gall bladder	UBERON:0002110	96.76	gold quality
right lobe of thyroid gland	UBERON:0001119	96.72	gold quality
frontal cortex	UBERON:0001870	96.72	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.71	gold quality
skin of leg	UBERON:0001511	96.70	gold quality
skin of abdomen	UBERON:0001416	96.69	gold quality
neocortex	UBERON:0001950	96.69	gold quality
minor salivary gland	UBERON:0001830	96.67	gold quality
body of uterus	UBERON:0009853	96.65	gold quality
body of tongue	UBERON:0011876	96.64	gold quality
cartilage tissue	UBERON:0002418	96.62	gold quality
midbrain	UBERON:0001891	96.59	gold quality
left uterine tube	UBERON:0001303	96.54	gold quality
right uterine tube	UBERON:0001302	96.53	gold quality
forebrain	UBERON:0001890	96.52	gold quality
mucosa of stomach	UBERON:0001199	96.49	gold quality
left lobe of thyroid gland	UBERON:0001120	96.48	gold quality
mouth mucosa	UBERON:0003729	96.48	gold quality
transverse colon	UBERON:0001157	96.47	gold quality
telencephalon	UBERON:0001893	96.46	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	9.80
E-MTAB-10042	yes	8.41
E-CURD-53	no	254.26
E-GEOD-125970	no	3.24
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	299.5	not detected
Tongue	tissue	255.7
Frontal cortex	tissue	215.3
Caudate putamen	tissue	196.0
Pons	tissue	152.3
Spinal cord	tissue	141.1
Thalamus	tissue	137.5
Medulla oblongata	tissue	136.5
Parathyroid gland	tissue	134.7	medium
Superior colliculi	tissue	131.1
Midbrain	tissue	125.0
Epididymis	tissue	122.1	low
Substantia nigra	tissue	120.3
Heart muscle	tissue	115.9	not detected
Hippocampal formation	tissue	112.9
Cerebral cortex	tissue	112.2	medium
Somatosensory cortex	tissue	112.2
Locus coeruleus	tissue	112.0
Liver	tissue	111.3	not detected
Hypothalamus	tissue	102.2
Choroid plexus	tissue	102.0
Putamen	tissue	101.1
Occipital cortex	tissue	97.1
Smooth muscle	tissue	96.6	low
Septum	tissue	96.6
Motor cortex	tissue	95.8
Corpus callosum	tissue	95.3
Pituitary gland	tissue	93.9
Ventral forebrain	tissue	93.9
Periaqueductal gray	tissue	92.2
Kidney	tissue	91.8	medium
Retrosplenial and cingulate cortex	tissue	90.8
Ovary	tissue	88.7	not detected
Prefrontal cortex	tissue	88.4
Fallopian tube	tissue	87.7	medium
Retrosplenial cortex	tissue	86.9
Basal ganglia	tissue	86.6	medium
Urinary bladder	tissue	86.0	medium
Placenta	tissue	84.6	not detected
Entorhinal cortex	tissue	84.6
Rectum	tissue	83.3	not detected
Temporal cortex	tissue	83.2
Vagina	tissue	80.5	not detected
Adipose tissue	tissue	78.7	not detected
Cerebellum	tissue	78.6	high
Adrenal gland	tissue	78.5	medium
Nucleus accumbens	tissue	77.5
Hippocampus	tissue	77.2	low
Pancreas	tissue	76.3	medium
Breast	tissue	75.8	low
Colon	tissue	75.7	low
Esophagus	tissue	75.6	not detected
Seminal vesicle	tissue	74.1	not detected
Thymus	tissue	74.0
Prostate	tissue	72.0	not detected
Amygdala	tissue	71.3
Insular cortex	tissue	71.3
Salivary gland	tissue	69.2	low
Thyroid gland	tissue	67.7	medium
Cervix	tissue	67.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Ventral spinal cord (141.1), Dorsal hippocampus (112.9), Dorsal spinal cord (112.5), Lateral funiculus (white matter) (111.3), Dorsal funiculus (white matter) (110.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, GABPA, NFE2L2, SP1, STAT3

miRNA regulators (miRDB)

Targeting PSMB5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

20 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-455-5P	98.74	67.31	795
HSA-MIR-4669	97.94	62.71	224
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-27B-5P	97.34	66.55	549
HSA-MIR-6802-3P	97.29	65.42	613
HSA-MIR-6869-5P	97.17	67.06	634
HSA-MIR-921	97.09	66.45	562
HSA-MIR-3174	94.63	63.64	577

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.255, missense Z 1.84 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000361611 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:23,026,092–23,033,386	113 / 130.2	0.87	no
14:23,033,387–23,034,719	75 / 143.2	0.52	no
14:23,034,720–23,034,881	81 / 70.4	1.15	no
DepMap (CRISPR cell-line fitness): dependent in 95.0% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): MFE-280 (-3.866), RERF-GC-1B (-3.787), NCI-H1915 (-3.747), AsPC-1 (-3.695), Hs 578T (-3.604), DK-MG (-3.408), RERF-LC-Sq1 (-3.348), NCI-H520 (-3.296), CAL-120 (-3.235), Panc 10.05 (-3.189), OV-90 (-3.126), NCI-H1693 (-3.085), SNU-398 (-3.054), Calu-6 (-3.048), HCC1419 (-2.972).

Literature-anchored findings (GeneRIF, showing 26)

• interaction of TAP1 and TAP2 and P-glycoprotein with proteasome subunits beta-5 and beta-5i suggest direct targeting of antigenic peptides to the ER via a TAP-proteasome association and a possible role for P-glycoprotein (PMID:15488952)
• Proteasome activity can be genetically “upregulated” in lens cells by overexpression of beta5 catalytic subunit. Resulting increase in proteasome activity leads to decrease in oxidized proteins and enhanced cell survival following oxidative stress. (PMID:17262013)
• G322A mutation of the PSMB5 gene is a novel mechanism for bortezomib resistance. (PMID:18502982)
• nonsynonymous coding single nucleotide polymorphismsin the proteasome beta 5 subunit gene did not show significant effects on proteasome activity, but SNPs did influence transcription (PMID:18519783)
• Overexpression of PSMB5 is an important mechanism for bortezomib resistance in Jurkat cell lines. (PMID:18562081)
• a novel mechanism of bortezomib resistance associated with the selective overexpression of a mutant PSMB5 protein (PMID:18565852)
• Nuclear MB1 expression was an independent predictor of worse survival in ovarian cancer. (PMID:19243813)
• Mutations of the PSMB5 gene resulting in substitutions of Ala49 and Ala50 of PSMB5 protein can confer varying bortezomib resistance (PMID:19426847)
• Expression of mutated PSMB5 was associated with the prevention of the accumulation of unfolded proteins (PMID:20555361)
• CDK5 regulation of proteasome subunit PSMB5 was identified as a probable route to antineoplastic drug sensitization. (PMID:21289309)
• No mutations or differences in PSMB5 mRNA expression were seen before bortezomib treatment in 3 multiple myeloma patients, but after treatment, 1 patient showed PSMB5 upregulation associated with bortezomib resistance. (PMID:21920470)
• PSMB5 overexpression is associated with Bortezomib resistance in myeloma. (PMID:21978467)
• Letter/Case Reports: proteasome subunit beta5t is expressed in cervical ectopic thymoma. (PMID:22523338)
• The expression of proteasome beta5 decreases markedly in human atherosclerotic plaques. (PMID:22781773)
• Data indicate that treatment-emergent resistance to single-agent bortezomib was independent of variants in the proteasome genes PSMB1, PSMB5, PSMB6, PSMB8, PSMB9, and PSMB10. (PMID:23018640)
• critical role of PSMB5 in 20S proteasome-mediated protection against replicative senescence, pointing to a possible strategy for maintaining the integrity of culture-expanded bone marrow stromal cells by manipulating the expression of PSMB5 (PMID:24393841)
• Data indicate that proteasomal subunit X PSMB5 is a target of signal transducer and activator of transcription 3 (STAT3). (PMID:24627483)
• Results identified PSMB5 Q62P mutation to underlie bortezomib resistance in Down-syndrome-associated acute myeloid leukemia cells. (PMID:28143565)
• We also discovered and replicated three genome-wide significant variants in previously unreported loci for RDW (SLC12A2 rs17764730, PSMB5 rs941718), and hematocrit (PROX1 rs3754140) and an upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant (PMID:28453575)
• Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for Triple-negative breast cancer (PMID:28623645)
• PSMB5 knockdown could increase the expression of pro-apoptosis gene Bax and cleaved caspase-3 (PMID:29365400)
• PSMB5 mutations are associated with multiple myeloma. (PMID:30026573)
• Transcriptional downregulation of miR-127-3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5. (PMID:31562641)
• Identification of PSMB5 as a genetic modifier of fragile X-associated tremor/ataxia syndrome. (PMID:35617426)
• PSMB5 overexpression is correlated with tumor proliferation and poor prognosis in hepatocellular carcinoma. (PMID:36062301)
• MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5. (PMID:38252234)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb5	ENSDARG00000075445
mus_musculus	Psmb5	ENSMUSG00000022193
rattus_norvegicus	Psmb5	ENSRNOG00000013386
drosophila_melanogaster	Prosbeta1	FBGN0010590
caenorhabditis_elegans		WBGENE00003947

Paralogs (18): PSMB1 (ENSG00000008018), PSMA4 (ENSG00000041357), PSMA3 (ENSG00000100567), PSMA6 (ENSG00000100902), PSMA7 (ENSG00000101182), PSMA2 (ENSG00000106588), PSMB2 (ENSG00000126067), PSMA1 (ENSG00000129084), PSMB7 (ENSG00000136930), PSMB6 (ENSG00000142507), PSMA5 (ENSG00000143106), PSMA8 (ENSG00000154611), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

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
Mycobacterium sp. KMS	A1UHS7	100.0%	Diamond
Mycobacterium sp. JLS	A3Q193	100.0%	Diamond
Mycobacterium sp. MCS	Q1B797	100.0%	Diamond
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
Bos taurus	Q32KL2	96.2%	Diamond
Sus scrofa	Q29576	93.3%	Diamond
Arabidopsis thaliana	O23717	93.0%	Diamond
Frankia alni ACN14a	Q0RLT7	92.3%	Diamond
Frankia casuarinae	Q2J9Q3	92.3%	Diamond
Canis lupus familiaris	Q5W416	86.5%	Diamond
Parafrankia sp. EAN1pec	A8LH54	85.8%	Diamond
Mycolicibacterium vanbaalenii PYR-1	A1TAP4	84.6%	Diamond
Mycolicibacterium gilvum PYR-GCK	A4TB64	84.6%	Diamond
Spinacia oleracea	O24361	83.3%	Diamond
Renibacterium salmoninarum ATCC 33209	A9WSI1	76.2%	Diamond
Gallus gallus	P34065	70.4%	Diamond
Schizosaccharomyces pombe 972h-	P30655	67.9%	Diamond
Saccharomyces cerevisiae S288C	P30656	67.9%	Diamond
Thermomonospora curvata DSM 43183	D1A2S9	67.2%	Diamond
Dictyostelium discoideum	Q54BC8	66.3%	Diamond
Acidimicrobium ferrooxidans DSM 10331	C7LYP7	63.5%	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
MIR4707	ncRNA	100616424
HAUS4	protein-coding	54930
C14orf93	protein-coding	60686
AJUBA	protein-coding	84962
AJUBA-DT	ncRNA	107984660
PSMB11	protein-coding	122706
CDH24	protein-coding	64403
ACIN1	protein-coding	22985

Protein

Protein identifiers

Proteasome subunit beta type-5 — P28074 (reviewed: P28074)

Alternative names: Macropain epsilon chain, Multicatalytic endopeptidase complex epsilon chain, Proteasome chain 6, Proteasome epsilon chain, Proteasome subunit MB1, Proteasome subunit X, Proteasome subunit beta-5

All UniProt accessions (5): A0A140VJS7, P28074, G3V3K3, G8JLC2, H0YJM8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity.

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. Directly interacts with POMP. Interacts with ABCB1 and TAP1. (Microbial infection) Interacts with HIV-1 TAT protein.

Subcellular location. Cytoplasm. Nucleus.

Induction. Down-regulated by IFNG/IFN-gamma (at protein level). Induced in breast cancer tissue. Up-regulated by sulforaphane in breast cancer cells.

Similarity. Belongs to the peptidase T1B family.

Isoforms (3)

UniProt ID	Names	Canonical?
P28074-1	1	yes
P28074-2	2
P28074-3	3

RefSeq proteins (3): NP_001124197, NP_001138404, NP_002788* (*=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 (43 total): strand 17, helix 8, sequence conflict 5, turn 3, mutagenesis site 3, splice variant 2, propeptide 1, chain 1, active site 1, binding site 1, sequence variant 1

Structure

Experimental structures (PDB)

showing 30 of 156 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
5LF0	Human 20S proteasome complex with Epoxomicin at 2.4 Angstrom	X-RAY DIFFRACTION	2.41
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
5L5Y	Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in …	X-RAY DIFFRACTION	2.7
5L5Z	Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in …	X-RAY DIFFRACTION	2.7
5L60	Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in …	X-RAY DIFFRACTION	2.7
5L63	Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in …	X-RAY DIFFRACTION	2.7
5L64	Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in …	X-RAY DIFFRACTION	2.7
8CVR	Human 20S proteasome with MG-132	ELECTRON MICROSCOPY	2.7
6KWY	human PA200-20S complex	ELECTRON MICROSCOPY	2.72
9MBP	Substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral …	ELECTRON MICROSCOPY	2.75
5L5W	Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133)	X-RAY DIFFRACTION	2.8
5L61	Yeast 20S proteasome with human beta5c (1-138) and human beta6 (99-132) in complex with …	X-RAY DIFFRACTION	2.8
5L62	Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in …	X-RAY DIFFRACTION	2.8
7NAN	Human 20S proteasome core particle	ELECTRON MICROSCOPY	2.8
8TM6	Human premature 20S proteasome assembly intermediate	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28074-F1	83.34	0.76

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, 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; centrosome; mid piece; principal piece

Antibody reliability (HPA): IH approved · IF supported

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
60	nucleophile

Ligand- & substrate-binding residues (1)

Position	Role
108	bortezomib

Mutagenesis-validated functional residues (3)

Position	Phenotype
108	displays resistance to the bortezomib, a proteasome inhibitor of the chymotrypsin-like activity. displays high resistance to the …
108	displays high resistance to the bortezomib, a proteasome inhibitor of the chymotrypsin-like activity.
109	displays high resistance to the bortezomib, a proteasome inhibitor of the chymotrypsin-like activity; when associated with t-108.

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: 412 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, REACTOME_DNA_REPLICATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, REACTOME_SIGNALING_BY_NOTCH, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, PAL_PRMT5_TARGETS_UP, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION

GO Biological Process (15): DNA repair (GO:0006281), proteolysis (GO:0006508), 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), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), proteasome assembly (GO:0043248), meiotic cell cycle (GO:0051321), regulation of proteasomal protein catabolic process (GO:0061136), cellular response to type I interferon (GO:0071357), regulation of G1/S transition of mitotic cell cycle (GO:2000045)

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 (10): 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), 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

49 GO namespaces:

Category	Terms
proteasomal protein catabolic process	3
cellular anatomical structure	3
intracellular protein-containing complex	2
intracellular anatomical structure	2
cytoplasm	2
DNA metabolic process	1
DNA damage response	1
protein metabolic process	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
ubiquitin-dependent protein catabolic process	1
protein-containing complex assembly	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
regulation of protein catabolic process	1
response to type I interferon	1
cellular response to cytokine stimulus	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
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
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) — 12 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 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
proteolysis	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
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
proteasome complex	CC	direct assay
proteasome core complex	CC	direct assay
peptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,626 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB5	PSMB2	P31145	932
PSMB5	PSMB4	P28070	913
PSMB5	PSME1	Q06323	850
PSMB5	PSME2	Q9UL46	840
PSMB5	CTRL	P40313	823
PSMB5	PSMB7	Q99436	786
PSMB5	PSMB6	P28072	786
PSMB5	PSMA1	P25786	725
PSMB5	PSMA5	P28066	683
PSMB5	PSMC2	P35998	660
PSMB5	PSMA3	P25788	658
PSMB5	PSMB1	P20618	656
PSMB5	PSMD1	Q99460	656
PSMB5	PSMA6	P34062	633
PSMB5	PSMD11	O00231	629

IntAct

Human interaction partners of PSMB5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 32 partners by confidence:

Partner	Interaction type	MIscore	Records
PSMB7	physical association	0.890	2
PSMB1	physical association	0.800	3
POMP	physical association	0.760	3
PSMB3	physical association	0.750	2
PSMB2	physical association	0.740	1
LSM1	physical association	0.670	4
PSMB4	physical association	0.660	1
BAG4	physical association	0.560	5
CCDC150	physical association	0.560	3
CLP1	physical association	0.560	3
DUSP29	physical association	0.560	3
IKBKG	physical association	0.560	3
NTAQ1	physical association	0.560	3
TCHP	physical association	0.560	3
PLEKHN1	physical association	0.400	1
SLC25A31	physical association	0.400	1
E6	physical association	0.370	10
BCRF1	physical association	0.370	1
PSMA3	physical association	0.370	1
ARHGEF9	association	0.350	1
ERG	association	0.350	1
PSMA7	association	0.350	1
PSMD1	association	0.350	1
TRAF6	physical association	0.000	2
EPB41	physical association	0.000	1
FTSJ1	physical association	0.000	1
NFKB2	physical association	0.000	1
PINX1	physical association	0.000	1
PSMD6	physical association	0.000	1
RIPK2	physical association	0.000	1

BioGRID (538 interactions; top human partners by supporting records): PSMB1 (Co-fractionation; 18 records), PSMB3 (Co-fractionation; 17 records), PSMA2 (Co-fractionation; 13 records), PSMB7 (Affinity Capture-MS; 11 records), POMP (Affinity Capture-MS; 10 records), PSMB4 (Affinity Capture-MS; 10 records), PSMA1 (Affinity Capture-MS; 9 records), PSMB2 (Co-fractionation; 9 records), PSMD14 (Affinity Capture-MS; 9 records), PSMA4 (Co-fractionation; 8 records), PSMA3 (Co-fractionation; 7 records), PSMA5 (Co-fractionation; 7 records), PSMA7 (Co-fractionation; 7 records), PSMB6 (Co-fractionation; 7 records), PSMC4 (Co-fractionation; 7 records)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
ixazomib	down-regulates	PSMB5	“chemical inhibition”
“ixazomib citrate”	down-regulates	PSMB5	“chemical inhibition”
carfilzomib	“down-regulates activity”	PSMB5	“chemical inhibition”
bortezomib	“down-regulates activity”	PSMB5	“chemical inhibition”
PSMB5	“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 32 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	7	190.3×	7e-15
Regulation of activated PAK-2p34 by proteasome mediated degradation	9	119.4×	2e-16
Regulation of ornithine decarboxylase (ODC)	9	116.5×	3e-16
Vpu mediated degradation of CD4	9	113.8×	3e-16
Autodegradation of the E3 ubiquitin ligase COP1	9	113.8×	3e-16
Ubiquitin-dependent degradation of Cyclin D	9	113.8×	3e-16
NIK–>noncanonical NF-kB signaling	10	108.8×	1e-17
Cross-presentation of soluble exogenous antigens (endosomes)	9	108.8×	4e-16

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	10	18.0×	2e-08

Disease & clinical

Genetic variants

Variant evidence for PSMB5: 36 ClinVar records (0 pathogenic / likely pathogenic); 19 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 341):

Position(s)	Effect	Δscore	Sites
14:23033362	donor_gain	1.0000
14:23033481	donor_gain	1.0000
14:23034658	donor_gain	1.0000
14:23026376–23026377	acceptor_loss	0.9900	6
14:23033363	donor_loss	0.9900
14:23033366–23033367	donor_loss	0.9900	6
14:23033420	donor_gain	0.9900
14:23033675–23033676	acceptor_loss	0.9900	5
14:23033686	acceptor_gain	0.9900
14:23033363	donor_loss	0.9800

AlphaMissense

954 missense substitutions predicted likely pathogenic (of 1,680 scored), across 191 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
M159	9	0.911	0.999
M104	9	0.866	0.993
M145	9	0.806	0.975
D110	8	0.998	0.999
D226	8	0.998	0.999
D76	8	0.997	0.999
D164	8	0.994	0.999
D174	8	0.992	0.998
D199	8	0.978	0.994
F65	8	0.969	0.999
F185	8	0.966	0.998
H237	8	0.945	0.995
F67	8	0.937	0.998
H58	8	0.933	0.991
W114	7	0.997	1.000
F113	7	0.995	0.999
R78	7	0.994	0.999
K92	7	0.994	0.999
W243	7	0.993	0.999
C111	7	0.991	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

7 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	2.93e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	7.07e-06
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	2.6e-05
Colon Adenocarcinoma (TCGA)	favorable	9.63e-05
Ovary Serous Cystadenocarcinoma (TCGA)	favorable	0.000102
Lung Adenocarcinoma (validation)	unfavorable	0.000212
Bladder Urothelial Carcinoma (TCGA)	unfavorable	0.000444

Disease associations

OMIM: gene MIM:600306 | disease phenotypes:

GWAS associations

19 associations:

Study	Trait	p-value
GCST90002404_136	Red cell distribution width	3e-243
GCST004621_89	Red cell distribution width	2e-96
GCST006804_45	Red cell distribution width	2e-85
GCST90002406_572	Reticulocyte fraction of red cells	2e-84
GCST90002386_354	High light scatter reticulocyte percentage of red cells	1e-76
GCST90002405_350	Reticulocyte count	2e-72
GCST90002385_444	High light scatter reticulocyte count	2e-70
GCST90002390_175	Mean corpuscular hemoglobin	2e-45
GCST004619_165	Reticulocyte fraction of red cells	4e-39
GCST90002392_595	Mean corpuscular volume	2e-38
GCST004622_36	Reticulocyte count	4e-34
GCST004612_169	High light scatter reticulocyte percentage of red cells	3e-26
GCST004611_45	High light scatter reticulocyte count	1e-23
GCST90002387_362	Immature fraction of reticulocytes	2e-22
GCST004630_247	Mean corpuscular hemoglobin	1e-15
GCST004602_23	Mean corpuscular volume	3e-15
GCST90002404_137	Red cell distribution width	1e-14
GCST90002391_139	Mean corpuscular hemoglobin concentration	3e-12
GCST90002397_128	Mean spheric corpuscular volume	3e-11

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831201 (PROTEIN COMPLEX GROUP), CHEMBL3885625 (PROTEIN FAMILY), CHEMBL4662 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 753,508 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

15 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL325041	BORTEZOMIB	4	13,415
CHEMBL451887	CARFILZOMIB	4	13,156
CHEMBL3545432	IXAZOMIB CITRATE	4	2,589
CHEMBL159	VINBLASTINE	4	416,858
CHEMBL140	CURCUMIN	3	95,185
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	23,201
CHEMBL2141296	IXAZOMIB	3	6,376
CHEMBL371405	MARIZOMIB	3	7,520
CHEMBL50	QUERCETIN	3	75,572
CHEMBL270515	DELANZOMIB	2	1,958
CHEMBL44	GENISTEIN	2	44,589
CHEMBL151	LUTEOLIN	2	23,845
CHEMBL2103884	OPROZOMIB	2	2,853
CHEMBL4297468	ZETOMIPZOMIB	2	145
CHEMBL150	KAEMPFEROL	1	26,246

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 (9 total), top 9:

Ligand	Action	Affinity	Parameter
ixazomib	Inhibition	9.03	pKi
NIC-0102	Inhibition	8.43	pIC50
MG-132	Inhibition	8.43	pKi
compound 3b [PMID: 24946214]	Inhibition	8.29	pKi
carfilzomib	Inhibition	8.24	pIC50
oprozomib	Inhibition	8.0	pIC50
bortezomib	Inhibition	7.7	pIC50
zetomipzomib	Inhibition	6.16	pIC50
WLL-vs	Inhibition	6.0	pIC50

Binding affinities (BindingDB)

1339 measured of 2068 human assays (2119 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3629678	KI	0.14 nM
CHEMBL4061262	IC50	0.6 nM
CHEMBL392916	IC50	0.6 nM
Cinnabaramide G	IC50	0.6 nM
CHEMBL4104744	IC50	0.7 nM
CHEMBL3793848	IC50	0.76 nM
CHEMBL4747480	IC50	0.8 nM
CHEMBL4794118	IC50	0.9 nM
CHEMBL4102324	IC50	0.92 nM
CHEMBL3786398	IC50	1 nM
CHEMBL4078056	IC50	1 nM
CHEMBL4064404	IC50	1 nM
CINNABARAMIDE A	IC50	1 nM
CHEMBL3794168	IC50	1.1 nM
CHEMBL4072652	IC50	1.1 nM
CHEMBL3218837	IC50	1.1 nM
CHEMBL3793581	IC50	1.15 nM
CHEMBL3793238	IC50	1.16 nM
CHEMBL3794310	IC50	1.16 nM
CHEMBL499361	IC50	1.2 nM
CHEMBL4078693	IC50	1.2 nM
CHEMBL3794136	IC50	1.26 nM
CHEMBL3794207	IC50	1.3 nM
MARIZOMIB	IC50	1.3 nM
CHEMBL3890793	IC50	1.4 nM
CHEMBL4749316	IC50	1.4 nM
CHEMBL3793242	IC50	1.46 nM
CHEMBL4094582	IC50	1.5 nM
CHEMBL4460323	IC50	1.5 nM
CHEMBL499504	IC50	1.6 nM
CHEMBL606394	IC50	1.9 nM
CHEMBL3792511	IC50	1.9 nM
Alpha-ketocarbonyl derivative	IC50	2 nM
CHEMBL4249022	IC50	2 nM
CHEMBL4451741	IC50	2.1 nM
CHEMBL3792573	IC50	2.3 nM
CHEMBL4246480	IC50	2.3 nM
(R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-6-carboxamido)propanamido)butylboronic acid	IC50	2.4 nM
CHEMBL3918862	IC50	2.4 nM
CHEMBL4099839	IC50	2.4 nM
CHEMBL4517600	IC50	2.4 nM
CHEMBL3793093	IC50	2.46 nM
CHEMBL4587036	IC50	2.5 nM
CHEMBL4082676	IC50	2.6 nM
CHEMBL3793863	IC50	2.7 nM
CHEMBL4748075	IC50	2.7 nM
CHEMBL4102973	IC50	2.9 nM
CHEMBL3890040	IC50	3 nM
CHEMBL3792854	IC50	3.2 nM
CHEMBL4238198	IC50	3.2 nM

ChEMBL bioactivities

1663 potent at pChembl≥5 of 1872 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	CHEMBL3347481
9.89	Ki	0.13	nM	CHEMBL4749207
9.85	Ki	0.14	nM	CHEMBL3629678
9.66	IC50	0.22	nM	CHEMBL3347627
9.52	IC50	0.3	nM	CHEMBL4070336
9.47	IC50	0.34	nM	CHEMBL3347641
9.42	IC50	0.38	nM	CHEMBL3347480
9.41	IC50	0.39	nM	CHEMBL3347642
9.40	IC50	0.4	nM	CHEMBL3347625
9.38	IC50	0.42	nM	CHEMBL3347640
9.30	Ki	0.5	nM	CHEMBL207598
9.30	IC50	0.5	nM	BORTEZOMIB
9.29	Ki	0.51	nM	CHEMBL205757
9.26	Ki	0.55	nM	BORTEZOMIB
9.26	IC50	0.55	nM	CHEMBL3347626
9.22	Ki	0.6	nM	BORTEZOMIB
9.22	IC50	0.6	nM	CHEMBL4061262
9.22	IC50	0.6	nM	CINNABARAMIDE G
9.22	Ki	0.6	nM	CHEMBL5624541
9.19	Ki	0.65	nM	CHEMBL206413
9.15	IC50	0.7	nM	CHEMBL4104744
9.15	IC50	0.7079	nM	CHEMBL5206237
9.14	Ki	0.72	nM	CHEMBL377532
9.14	Ki	0.72	nM	CHEMBL383674
9.12	IC50	0.76	nM	CHEMBL3793848
9.10	IC50	0.8	nM	CHEMBL4747480
9.05	IC50	0.9	nM	CHEMBL4102324
9.05	IC50	0.9	nM	CHEMBL4794118
9.04	IC50	0.92	nM	CHEMBL4102324
9.03	Ki	0.93	nM	IXAZOMIB CITRATE
9.00	IC50	1	nM	CHEMBL4064404
9.00	IC50	1	nM	CHEMBL4078056
9.00	IC50	1	nM	CINNABARAMIDE A
9.00	IC50	1	nM	CHEMBL5208208
9.00	Ki	1.01	nM	CHEMBL5569360
9.00	IC50	1	nM	CHEMBL578478
8.99	IC50	1.02	nM	CHEMBL3786398
8.96	IC50	1.1	nM	CHEMBL204992
8.96	IC50	1.1	nM	CHEMBL4072652
8.96	IC50	1.1	nM	CHEMBL3218837
8.95	IC50	1.12	nM	CHEMBL3794168
8.95	IC50	1.122	nM	CHEMBL5183504
8.94	IC50	1.16	nM	CHEMBL3793238
8.94	IC50	1.15	nM	CHEMBL3793581
8.94	IC50	1.16	nM	CHEMBL3794310
8.92	IC50	1.2	nM	CHEMBL3218837
8.92	IC50	1.2	nM	CHEMBL499361
8.92	IC50	1.2	nM	CHEMBL4078693
8.92	IC50	1.2	nM	MG-132
8.92	IC50	1.202	nM	CHEMBL5196305

PubChem BioAssay actives

1501 with measured affinity, of 3560 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
[(1R)-1-[[(2S)-2-(3,4-dihydro-1H-isoquinoline-2-carbonylamino)-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1459637: Inhibition of chymotrypsin-like activity of 20S proteasome in human HL60 cells using Suc-LLVYaminoluciferin as substrate after 2 hrs by fluorescence analysis	ic50	<0.0001	uM
[(1R)-1-[[(2S)-2-[[2-(4-hydroxyphenyl)acetyl]amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1687111: Binding affinity to human 20S constitutive proteasome beta 5 subunit assessed as equilibrium constant using fluorogenic peptide Ac-WLA-AMC as substrate in presence of PA28alpha by fluorescence based microplate reader assay	ki	0.0001	uM
N-[(2S)-1-[[(3E,5S,8S,9E)-2,7-dioxo-5-propan-2-yl-1,6-diazacyclododeca-3,9-dien-8-yl]amino]-1-oxo-3-phenylpropan-2-yl]decanamide	1252350: Inhibition of proteasome beta-5 (unknown origin)	ki	0.0001	uM
[(1R)-3-methyl-1-[[(2S)-3-phenyl-2-[(3-phenylphenyl)methylcarbamoylamino]propanoyl]amino]butyl]boronic acid	1459637: Inhibition of chymotrypsin-like activity of 20S proteasome in human HL60 cells using Suc-LLVYaminoluciferin as substrate after 2 hrs by fluorescence analysis	ic50	0.0003	uM
(2S)-N-[(2S)-1-[[(2S)-1-[5-[4-(dimethylamino)phenyl]-1,3,4-oxadiazol-2-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-methoxy-1-oxopropan-2-yl]-N’-(2,2-dimethylpropyl)-2-[(4-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0005	uM
(2S)-N-[(2S)-1-[[(2S)-1-[5-[4-(dimethylamino)phenyl]-1,3,4-oxadiazol-2-yl]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]-N’-(2,2-dimethylpropyl)-2-[(4-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0005	uM
Bortezomib	1382147: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-MCA as substrate measured for 1 hr by fluorescence assay	ic50	0.0005	uM
(2S)-N’-(2,2-dimethylpropyl)-N-[(2S)-1-[[(2S)-4-methyl-1-oxo-1-(5-phenyl-1,3,4-oxadiazol-2-yl)pentan-2-yl]amino]-1-oxopropan-2-yl]-2-[(3-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	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-pyrazin-2-ylpiperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0006	uM
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
(2S)-N’-(2,2-dimethylpropyl)-N-[(2S)-1-[[(2S)-4-methyl-1-oxo-1-(5-phenyl-1,3,4-oxadiazol-2-yl)pentan-2-yl]amino]-1-oxopropan-2-yl]-2-[(4-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0007	uM
(2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide	1604186: Inhibition of 20S proteasome beta 5c (unknown origin) after 1 hr by fluorescence based assay	ic50	0.0007	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-pyridin-3-ylpiperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0007	uM
[(1R)-1-[[(2S)-2-[(2,5-dichlorobenzoyl)amino]-3-methylbutanoyl]amino]-3-methylbutyl]boronic acid	1864383: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis	ic50	0.0007	uM
(2S)-N’-(2,2-dimethylpropyl)-N-[(2S)-3-methoxy-1-[[(2S)-4-methyl-1-oxo-1-(5-phenyl-1,3,4-oxadiazol-2-yl)pentan-2-yl]amino]-1-oxopropan-2-yl]-2-[(4-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0007	uM
N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxo-3-phenylpropan-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0008	uM
1-N-[(2S)-5-(tert-butylamino)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-1,5-dioxopentan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1683221: 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 by fluorescence assay	ic50	0.0008	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	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0009	uM
1-N-[(2S)-5-(tert-butylamino)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-1,5-dioxopentan-2-yl]-4-N-pyrazin-2-ylpiperidine-1,4-dicarboxamide	1683221: 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 by fluorescence assay	ic50	0.0009	uM
2-[4-(carboxymethyl)-2-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-5-oxo-1,3,2-dioxaborolan-4-yl]acetic acid	2131635: Binding affinity to 20s proteasome beta5 site (unknown origin) mediated chymotrypsin-like activity assessed as inhibition constant	ki	0.0009	uM
[(1S)-1-[[3-(3-fluorophenyl)-3-[[(1S)-1,2,3,4-tetrahydronaphthalene-1-carbonyl]amino]propanoyl]amino]-3-methylbutyl]boronic acid	1291318: Inhibition of chymotrypsin like activity of human erythrocyte-derived 20S proteasome preincubated for 10 mins using Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	0.0010	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-pyridin-2-ylpiperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0010	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-ylmethyl)piperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0010	uM
[(1R)-1-[[(2S)-2-[(2,5-dichlorobenzoyl)amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutyl]boronic acid	1864383: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis	ic50	0.0010	uM
N-[(2S)-1-[[(3E,5S,8S)-5-benzyl-2,7-dioxo-1,6-diazacyclododec-3-en-8-yl]amino]-1-oxo-3-phenylpropan-2-yl]decanamide	2108291: Inhibition of 20S proteasome beta-5 in human erythrocytes using Suc-LLVY-AMC as substrate by AK-740 assay	ki	0.0010	uM
(2S)-2-[[(2S)-2-[[(2S)-2-azido-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]-3-phenylpropanamide	459970: Inhibition of 26S proteasome beta 5 using LLVY as substrate	ic50	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
tert-butyl (4S)-5-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoate	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0010	uM
tert-butyl (4S)-4-(benzenesulfonamido)-5-[[(2S)-3-hydroxy-1-[[(E,3S)-5-methyl-1-methylsulfonylhex-1-en-3-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoate	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ic50	0.0011	uM
N-[(2S)-4-methyl-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxopentan-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0011	uM
(1S)-N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxo-3-phenylpropan-2-yl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0011	uM
(2S)-N-[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]-N’-(2,2-dimethylpropyl)-2-[[4-(pyrazine-2-carbonylamino)piperidine-1-carbonyl]amino]butanediamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0011	uM
[(1R)-1-[[(2S)-2-[(2,3-difluorobenzoyl)amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1864383: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis	ic50	0.0011	uM
(2S)-N-[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-3-pyridin-4-ylpropan-2-yl]-N’-(2,2-dimethylpropyl)-2-[[2-(1H-indol-3-yl)-2-oxoacetyl]amino]butanediamide	1436355: Inhibition of 20s constitutive proteasome chymotrypsin-like activity in human erythrocyte using Ac-WLA-AMC as substrate in presence of proteasomal activator 28alpha by fluorimetric method	ic50	0.0011	uM
N-[(2S)-1-[[(1R)-2-(4-methylphenyl)-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethyl]amino]-1-oxo-3-phenylpropan-2-yl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0012	uM
N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0012	uM
(2S)-N-[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]-N’-(2,2-dimethylpropyl)-2-[[4-[(4-fluorobenzoyl)amino]piperidine-1-carbonyl]amino]butanediamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0012	uM
[(1R)-1-[[(2S)-2-[(2,3-dichlorobenzoyl)amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1864383: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis	ic50	0.0012	uM
[(1R)-3-methyl-1-[[(2S)-3-phenyl-2-[[(1S)-1,2,3,4-tetrahydronaphthalene-1-carbonyl]amino]propanoyl]amino]butyl]boronic acid	1291318: Inhibition of chymotrypsin like activity of human erythrocyte-derived 20S proteasome preincubated for 10 mins using Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	0.0012	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	1515537: Inhibition of chymotrypsin like activity of 26S proteasome beta 5 subunit (unknown origin) by fluorescence assay	ic50	0.0012	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
N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-3-naphthalen-1-yl-1-oxopropan-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0013	uM
(1S)-N-[(2S)-1-[[(1R)-2-(4-fluorophenyl)-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethyl]amino]-1-oxo-3-phenylpropan-2-yl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0013	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-1-oxo-4-phenylbutan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1325161: Inhibition of chymotrypsin-like activity of human 20S proteasome preincubated for 15 mins followed by addition of Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence analysis	ic50	0.0014	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-5-(2,2-dimethylpropylamino)-1,5-dioxopentan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1683221: 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 by fluorescence assay	ic50	0.0014	uM
benzyl N-[(2S,3S)-1-[[(2S)-4-(2,2-dimethylpropylamino)-1-[[(2S)-1-[[(E,3S)-5-methyl-1-methylsulfonylhex-1-en-3-yl]amino]-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ic50	0.0015	uM
N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxo-3-phenylpropan-2-yl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0015	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-(4-fluorophenyl)piperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0015	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases reaction, decreases reaction, affects response to substance (+3 more)	5
Resveratrol	affects reaction, decreases secretion, decreases expression, affects cotreatment, increases expression	3
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, increases reaction, affects cotreatment, decreases reaction, increases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
bisphenol A	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tanshinone	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
sibutramine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CV 6504	decreases reaction, increases expression	1
chloropicrin	affects expression	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
stattic	decreases reaction, increases expression, decreases expression	1
WP1066	decreases reaction, increases expression, decreases expression	1
EGFR tyrosine kinase inhibitor 324674	decreases reaction, increases expression	1
bisphenol AF	increases expression	1
Bortezomib	affects binding, decreases response to substance, affects response to substance	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cannabidiol	decreases expression, affects cotreatment	1
Clozapine	affects cotreatment, increases expression	1

ChEMBL screening assays

486 unique, capped per target: 466 binding, 15 admet, 5 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 PSMB5 across ~30M SureChEMBL compounds — explore on Sugi Predict.