PSMD2

Summary

PSMD2 (proteasome 26S subunit ubiquitin receptor, non-ATPase 2, HGNC:9559) is a protein-coding gene on chromosome 3q27.1, encoding 26S proteasome non-ATPase regulatory subunit 2 (Q13200). Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. It is a common-essential gene (DepMap: required in 98.4% of cancer cell lines).

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the non-ATPase subunits of the 19S regulator lid. In addition to participation in proteasome function, this subunit may also participate in the TNF signalling pathway since it interacts with the tumor necrosis factor type 1 receptor. A pseudogene has been identified on chromosome 1. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 5708 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 203 total — 1 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_002808

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9559
Approved symbol	PSMD2
Name	proteasome 26S subunit ubiquitin receptor, non-ATPase 2
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Aliases	S2, P97, TRAP2, MGC14274, Rpn1
Ensembl gene	ENSG00000175166
Ensembl biotype	protein_coding
OMIM	606223
Entrez	5708

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 18 protein_coding, 10 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000310118, ENST00000417952, ENST00000432855, ENST00000433010, ENST00000435761, ENST00000439383, ENST00000445558, ENST00000459910, ENST00000460628, ENST00000463602, ENST00000466987, ENST00000473991, ENST00000476461, ENST00000485937, ENST00000487475, ENST00000488085, ENST00000491149, ENST00000491494, ENST00000492191, ENST00000496925, ENST00000894414, ENST00000894415, ENST00000894416, ENST00000894417, ENST00000926941, ENST00000926942, ENST00000926943, ENST00000926944, ENST00000926945, ENST00000926946, ENST00000926947, ENST00000926948, ENST00000941412

RefSeq mRNA: 3 — MANE Select: NM_002808 NM_001278708, NM_001278709, NM_002808

CCDS: CCDS3258, CCDS63853, CCDS63854

Canonical transcript exons

ENST00000310118 — 21 exons

Exon	Start	End
ENSE00001179852	184308449	184308567
ENSE00001179894	184304304	184304391
ENSE00001179901	184303947	184304074
ENSE00001179906	184303643	184303749
ENSE00001285279	184308708	184309050
ENSE00001826396	184299241	184299401
ENSE00002524628	184301847	184302071
ENSE00003462519	184303002	184303062
ENSE00003480078	184300280	184300444
ENSE00003520792	184302370	184302528
ENSE00003521574	184306054	184306155
ENSE00003521748	184305768	184305930
ENSE00003530895	184306350	184306495
ENSE00003542514	184307890	184308016
ENSE00003555789	184307357	184307525
ENSE00003566961	184303320	184303466
ENSE00003566976	184307614	184307708
ENSE00003596815	184301537	184301658
ENSE00003615646	184306751	184306834
ENSE00003662724	184299851	184299907
ENSE00003679207	184302679	184302823

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.5235 / max 864.2320, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40159	76.3447	1826
40162	0.1788	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.21	gold quality
oocyte	CL:0000023	99.18	gold quality
endothelial cell	CL:0000115	99.09	gold quality
stromal cell of endometrium	CL:0002255	98.90	gold quality
right testis	UBERON:0004534	98.89	gold quality
gastrocnemius	UBERON:0001388	98.83	gold quality
left testis	UBERON:0004533	98.82	gold quality
muscle of leg	UBERON:0001383	98.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.54	gold quality
gluteal muscle	UBERON:0002000	98.47	gold quality
islet of Langerhans	UBERON:0000006	98.40	gold quality
right adrenal gland	UBERON:0001233	98.38	gold quality
testis	UBERON:0000473	98.34	gold quality
right adrenal gland cortex	UBERON:0035827	98.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.29	gold quality
skin of leg	UBERON:0001511	98.28	gold quality
left adrenal gland	UBERON:0001234	98.27	gold quality
skin of abdomen	UBERON:0001416	98.25	gold quality
right frontal lobe	UBERON:0002810	98.24	gold quality
left adrenal gland cortex	UBERON:0035825	98.21	gold quality
muscle organ	UBERON:0001630	98.18	gold quality
skeletal muscle organ	UBERON:0014892	98.18	gold quality
ganglionic eminence	UBERON:0004023	98.17	gold quality
cerebellar hemisphere	UBERON:0002245	98.12	gold quality
adenohypophysis	UBERON:0002196	98.11	gold quality
cortical plate	UBERON:0005343	98.10	gold quality
cerebellar cortex	UBERON:0002129	98.09	gold quality
ventricular zone	UBERON:0003053	98.08	gold quality
metanephros cortex	UBERON:0010533	98.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting PSMD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-1285-5P	98.01	68.71	779
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-4797-3P	97.48	67.14	989

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• U87 glioblastoma cells transduced to express the epidermal growth factor receptor vIII (EGFRvIII) mutant do not respond toirrradiation with 26s proteasome inhibition. (PMID:18337449)
• Data show that data provide a novel mechanism whereby CaMKII may regulate the proteasome in neurons to facilitate remodeling of synaptic connections through protein degradation. (PMID:19638347)
• These data suggest that p97 recruits proteasomes to polytopic ER proteins, such as Insig-1, even before they are extracted from membranes. (PMID:19815544)
• the 26S proteasome may provide a general predictive biomarker for radiotherapy outcome. (PMID:19881955)
• Results suggest that PSMD2 may be a good molecular target candidate. (PMID:21465578)
• the high-resolution solution structure of the UBL domain of human UBLCP1 and its interaction with Rpn1 (PMID:23667555)
• Study found that PSMD2 was markedly upregulated in breast cancer. High PSMD2 expression was significantly correlated with poor prognosis. PSMD2 knockdown inhibited cell proliferation and arrested cell cycle at G0/G1 phase in vitro, as well as suppressed tumor growth in vivo. Mechanically, PSMD2 physically interacted with p21 and p27 and mediated their ubiquitin-proteasome degradation with the cooperation of USP14. (PMID:29777785)
• By recruiting the 26S proteasome and the ubiquitin-selective ATPase p97 to arsenite-induced stress granules, ZFAND1 ensures their timely clearance and prevents their aberration. (PMID:29804830)
• Asporin (ASPN) interacts with proteasome 26S subunit non-ATPase 2 (PSMD2) and promotes the proliferation of gastric cancer (GC) cells. (PMID:31136974)
• The authors demonstrate that PSMD1 and PSMD2 promote the proliferation of HepG2 cells via facilitating cellular lipid droplet accumulation. (PMID:31703613)
• TRAF2 Knockdown in Nasopharyngeal Carcinoma Induced Cell Cycle Arrest and Enhanced the Sensitivity to Radiotherapy. (PMID:32566659)
• Diverse Ras-related GTPase DIRAS2, downregulated by PSMD2 in a proteasome-mediated way, inhibits colorectal cancer proliferation by blocking NF-kappaB signaling. (PMID:35173535)
• Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy. (PMID:35983756)
• DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation. (PMID:37875476)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000099653
		ENSDARG00000103190
mus_musculus	Psmd2	ENSMUSG00000006998
rattus_norvegicus	Psmd2	ENSRNOG00000001719
drosophila_melanogaster	Rpn1	FBGN0028695
caenorhabditis_elegans		WBGENE00004458

Paralogs (1): PSMD1 (ENSG00000173692)

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 2 — Q13200 (reviewed: Q13200)

Alternative names: 26S proteasome regulatory subunit RPN1, 26S proteasome regulatory subunit S2, 26S proteasome subunit p97, Protein 55.11, Tumor necrosis factor type 1 receptor-associated protein 2

All UniProt accessions (5): C9JPC0, Q13200, F8WBS8, H7C1H2, H7C2Q3

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1.

Subunit / interactions. Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD2. Interacts with RPGRIP1L. Interacts with CRY1 in a KDM8-dependent manner. Interacts (via C-terminus) with phosphatase UBLCP1 (via ubiquitin-like domain); the interaction recruits UBLCP1 to the 19S regulatory particle where it dephosphorylates 19S subunit PSMC2/RPT1 which impairs PSMC2 ATPase activity and disrupts 26S proteasome assembly.

Tissue specificity. Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung and placenta.

Similarity. Belongs to the proteasome subunit S2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13200-1	1	yes
Q13200-2	2
Q13200-3	3

RefSeq proteins (3): NP_001265637, NP_001265638, NP_002799* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002015	Proteasome/cyclosome_rpt	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR016643	26S_Psome_Rpn1	Family
IPR040892	RPN1_N	Domain
IPR041433	RPN1_C	Domain

Pfam: PF01851, PF17781, PF18051

UniProt features (122 total): helix 53, turn 17, sequence conflict 13, strand 11, modified residue 9, repeat 7, region of interest 3, compositionally biased region 3, sequence variant 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

123 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7UJD	ELECTRON MICROSCOPY	2.5
9K53	ELECTRON MICROSCOPY	2.5
8USD	ELECTRON MICROSCOPY	2.7
8USB	ELECTRON MICROSCOPY	2.73
9MBP	ELECTRON MICROSCOPY	2.75
9NKG	ELECTRON MICROSCOPY	2.8
9MBO	ELECTRON MICROSCOPY	2.83
9E8I	ELECTRON MICROSCOPY	2.87
9BV3	ELECTRON MICROSCOPY	2.9
9E8H	ELECTRON MICROSCOPY	2.9
9K4J	ELECTRON MICROSCOPY	2.9
9NKF	ELECTRON MICROSCOPY	2.9
9U3L	ELECTRON MICROSCOPY	2.91
9NKI	ELECTRON MICROSCOPY	2.94
6MSB	ELECTRON MICROSCOPY	3
7W37	ELECTRON MICROSCOPY	3
8CVT	ELECTRON MICROSCOPY	3
9E8G	ELECTRON MICROSCOPY	3.01
9MBQ	ELECTRON MICROSCOPY	3.08
7UIH	ELECTRON MICROSCOPY	3.1
7W38	ELECTRON MICROSCOPY	3.1
8USC	ELECTRON MICROSCOPY	3.1
9BV1	ELECTRON MICROSCOPY	3.1
9E8O	ELECTRON MICROSCOPY	3.1
9K4R	ELECTRON MICROSCOPY	3.1
9E8Q	ELECTRON MICROSCOPY	3.16
6MSD	ELECTRON MICROSCOPY	3.2
6MSK	ELECTRON MICROSCOPY	3.2
7W39	ELECTRON MICROSCOPY	3.2
7W3G	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13200-F1	64.98	0.00

Antibody-complex structures (SAbDab): 2 — 7UIH, 7UJD

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 (9): 1, 16, 24, 29, 147, 194, 361, 363, 551

Function

Pathways and Gene Ontology

Reactome pathways

68 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-180534	Vpu mediated degradation of CD4
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-202424	Downstream TCR signaling
R-HSA-211733	Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-349425	Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-350562	Regulation of ornithine decarboxylase (ODC)
R-HSA-382556	ABC-family protein mediated transport
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-4608870	Asymmetric localization of PCP proteins
R-HSA-4641257	Degradation of AXIN
R-HSA-4641258	Degradation of DVL
R-HSA-5358346	Hedgehog ligand biogenesis
R-HSA-5362768	Hh mutants are degraded by ERAD
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5610780	Degradation of GLI1 by the proteasome
R-HSA-5610783	Degradation of GLI2 by the proteasome

MSigDB gene sets: 501 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, AP1_01, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, 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, KEGG_PROTEASOME, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE

GO Biological Process (2): regulation of protein catabolic process (GO:0042176), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (2): enzyme regulator activity (GO:0030234), protein binding (GO:0005515)

GO Cellular Component (13): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle (GO:0005838), proteasome regulatory particle, base subcomplex (GO:0008540), membrane (GO:0016020), proteasome accessory complex (GO:0022624), proteasome storage granule (GO:0034515), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
APC/C-mediated degradation of cell cycle proteins	2
Host Interactions of HIV factors	2
Downstream signaling events of B Cell Receptor (BCR)	1
Cellular response to hypoxia	1
Regulation of APC/C activators between G1/S and early anaphase	1
APC/C:Cdc20 mediated degradation of mitotic proteins	1
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1
Cyclin E associated events during G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Signaling by WNT	1
TCR signaling	1
Regulation of Apoptosis	1
Mitotic Anaphase	1
Fc epsilon receptor (FCERI) signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein-containing complex	3
cytoplasm	2
regulation of catabolic process	1
protein catabolic process	1
regulation of protein metabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
catalytic activity	1
molecular function regulator activity	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
proteasome accessory complex	1
proteasome regulatory particle	1
proteasome complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD2	PSMC1	P49014	964
PSMD2	PSMD1	Q99460	949
PSMD2	PSMD3	O43242	940
PSMD2	RPGRIP1L	Q68CZ1	916
PSMD2	PSMD7	P51665	906
PSMD2	PSMD4	P55036	892
PSMD2	PSMC2	P35998	878
PSMD2	PSMC6	P49719	871
PSMD2	USP14	P54578	868
PSMD2	PSMC3	P17980	867
PSMD2	PSMC5	P47210	854
PSMD2	ADRM1	Q16186	854
PSMD2	PSMC4	P43686	852
PSMD2	PSMA5	P28066	843
PSMD2	PSMB1	P20618	828

IntAct

486 interactions, top by confidence:

A	B	Type	Score
PSMC1	PSMD2	psi-mi:“MI:0915”(physical association)	0.960
PSMD2	PSMC1	psi-mi:“MI:0915”(physical association)	0.960
PSMD5	PSMC2	psi-mi:“MI:0914”(association)	0.960
PSMD2	PSMC1	psi-mi:“MI:0407”(direct interaction)	0.960
PSMC6	PSMC3	psi-mi:“MI:0915”(physical association)	0.950
PSMC6	PSMC3	psi-mi:“MI:0914”(association)	0.950
UBLCP1	PSMD2	psi-mi:“MI:0915”(physical association)	0.900
PSMD2	UBLCP1	psi-mi:“MI:0915”(physical association)	0.900
PSMC5	PSMC2	psi-mi:“MI:0914”(association)	0.860
PSMC5	PSMD10	psi-mi:“MI:0914”(association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMC2	PSMD2	psi-mi:“MI:0915”(physical association)	0.840
BAG1	PSMD2	psi-mi:“MI:0915”(physical association)	0.830
PSMD2	BAG1	psi-mi:“MI:0915”(physical association)	0.830
PSMC5	PSMC3	psi-mi:“MI:0914”(association)	0.760

BioGRID (871): PSMD2 (Affinity Capture-MS), PSMD2 (Two-hybrid), PSMD2 (Two-hybrid), UBLCP1 (Two-hybrid), PSMD2 (Affinity Capture-RNA), PSMD2 (Affinity Capture-RNA), PSMD2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS)

ESM2 similar proteins: A2VE21, B4MY75, D4ABY2, O00203, O43747, O81742, P22892, P45437, P53620, P56701, P87140, Q0WW26, Q13200, Q13367, Q22498, Q29AE5, Q29G21, Q32PG1, Q4AEF8, Q4FZT9, Q54HL0, Q54X82, Q5R5M2, Q5R9I6, Q66JI9, Q6DKD7, Q6XJG8, Q6Z382, Q7PVF6, Q7YRF1, Q84K16, Q8H852, Q8I0G5, Q8L5Y6, Q8L7A9, Q8VDM4, Q93VQ0, Q99128, Q9I8E6, Q9JME5

Diamond homologs: P38764, P56701, P87048, Q13200, Q4FZT9, Q54BC6, Q5R9I6, Q6FPV6, Q6XJG8, Q7S8R8, Q8VDM4, Q9SIV2

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
bortezomib	“down-regulates activity”	PSMD2	“chemical inhibition”
PSMD2	“form complex”	“26S Proteasome”	binding
UBE3A	“down-regulates quantity by destabilization”	PSMD2	ubiquitination
NEK6	“up-regulates activity”	PSMD2	phosphorylation
PIM1	“up-regulates activity”	PSMD2	phosphorylation
PIM2	“up-regulates activity”	PSMD2	phosphorylation
PIM3	“up-regulates activity”	PSMD2	phosphorylation
PKA	“up-regulates activity”	PSMD2	phosphorylation
MAP4K1	“up-regulates activity”	PSMD2	phosphorylation
MAP4K2	“up-regulates activity”	PSMD2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of activated PAK-2p34 by proteasome mediated degradation	17	47.4×	3e-23
Regulation of ornithine decarboxylase (ODC)	17	46.2×	4e-23
Cross-presentation of soluble exogenous antigens (endosomes)	18	45.7×	5e-24
Vif-mediated degradation of APOBEC3G	18	45.7×	5e-24
Vpu mediated degradation of CD4	17	45.1×	4e-23
Autodegradation of the E3 ubiquitin ligase COP1	17	45.1×	4e-23
Ubiquitin-dependent degradation of Cyclin D	17	45.1×	4e-23
Proteasome assembly	22	44.9×	6e-29

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of proteasomal protein catabolic process	6	48.8×	9e-07
proteasome-mediated ubiquitin-dependent protein catabolic process	23	9.8×	1e-13
ubiquitin-dependent protein catabolic process	11	6.7×	3e-04
response to xenobiotic stimulus	11	6.2×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	133
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
831903	NC_000003.12:g.(?128480999)(128912627_?)del	Pathogenic

SpliceAI

2327 predictions. Top by Δscore:

Variant	Effect	Δscore
3:184299905:GGG:G	donor_gain	1.0000
3:184299906:GG:G	donor_gain	1.0000
3:184299906:GGG:G	donor_gain	1.0000
3:184299907:GG:G	donor_gain	1.0000
3:184299908:G:C	donor_loss	1.0000
3:184299908:G:GG	donor_gain	1.0000
3:184300409:G:GT	donor_gain	1.0000
3:184300410:A:T	donor_gain	1.0000
3:184300436:GAGAA:G	donor_gain	1.0000
3:184300440:ATAAG:A	donor_loss	1.0000
3:184300441:TAAG:T	donor_loss	1.0000
3:184300442:AAGG:A	donor_loss	1.0000
3:184300443:AGG:A	donor_loss	1.0000
3:184300445:GTAAA:G	donor_loss	1.0000
3:184300446:T:A	donor_loss	1.0000
3:184301533:ATAG:A	acceptor_loss	1.0000
3:184301533:ATAGC:A	acceptor_gain	1.0000
3:184301534:T:G	acceptor_gain	1.0000
3:184301535:A:AG	acceptor_gain	1.0000
3:184301535:AGC:A	acceptor_gain	1.0000
3:184301535:AGCG:A	acceptor_loss	1.0000
3:184301536:G:GA	acceptor_gain	1.0000
3:184301536:GC:G	acceptor_gain	1.0000
3:184301536:GCG:G	acceptor_gain	1.0000
3:184301536:GCGT:G	acceptor_gain	1.0000
3:184301536:GCGTT:G	acceptor_gain	1.0000
3:184301832:T:TA	acceptor_gain	1.0000
3:184302070:AG:A	donor_loss	1.0000
3:184302071:GG:G	donor_loss	1.0000
3:184302073:T:A	donor_loss	1.0000

AlphaMissense

5932 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:184299860:G:C	D49H	1.000
3:184299870:T:C	L52P	1.000
3:184299882:T:C	L56P	1.000
3:184300311:T:C	L75P	1.000
3:184300332:T:A	I82N	1.000
3:184300332:T:C	I82T	1.000
3:184300332:T:G	I82S	1.000
3:184300335:G:C	R83P	1.000
3:184300340:T:C	S85P	1.000
3:184300349:T:C	S88P	1.000
3:184300350:C:A	S88Y	1.000
3:184300350:C:T	S88F	1.000
3:184300353:T:A	M89K	1.000
3:184300358:T:C	S91P	1.000
3:184300362:T:A	V92E	1.000
3:184300364:C:A	P93T	1.000
3:184300364:C:T	P93S	1.000
3:184300365:C:A	P93H	1.000
3:184300365:C:G	P93R	1.000
3:184300365:C:T	P93L	1.000
3:184300367:A:G	K94E	1.000
3:184300369:G:C	K94N	1.000
3:184300369:G:T	K94N	1.000
3:184300371:C:A	P95H	1.000
3:184300374:T:A	L96H	1.000
3:184300374:T:C	L96P	1.000
3:184300376:A:G	K97E	1.000
3:184300378:A:C	K97N	1.000
3:184300378:A:T	K97N	1.000
3:184300379:T:C	F98L	1.000

dbSNP variants (sampled 300 via entrez): RS1000343232 (3:184298055 T>C), RS1000665288 (3:184309522 A>G), RS1002384820 (3:184299226 C>A,G,T), RS1003199616 (3:184307986 G>C), RS1003407965 (3:184302216 G>A), RS1003424478 (3:184302898 C>G,T), RS1003551759 (3:184309058 C>G), RS1003793554 (3:184300686 G>A,C), RS1003863151 (3:184307181 G>A), RS1004112123 (3:184300655 T>C,G), RS1004850618 (3:184299573 G>A,T), RS1005176019 (3:184299802 C>T), RS1005375071 (3:184309125 A>G), RS1005408599 (3:184306166 T>C), RS1005839245 (3:184302663 C>T)

Disease associations

OMIM: gene MIM:606223 | disease phenotypes: MIM:614038, MIM:614172

GenCC curated gene-disease

Mondo (3): deafness-lymphedema-leukemia syndrome (MONDO:0013540), monocytopenia with susceptibility to infections (MONDO:0013607), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (3): GATA2 deficiency spectrum (Orphanet:228423), Deafness-lymphedema-leukemia syndrome (Orphanet:3226), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST001137_1	White blood cell count	4.000000e-13
GCST001137_5	White blood cell count	6.000000e-13
GCST001887_5	Monocyte count	2.000000e-16
GCST004606_103	Eosinophil count	4.000000e-18
GCST004609_116	Monocyte percentage of white cells	9.000000e-33
GCST004624_36	Sum eosinophil basophil counts	1.000000e-21
GCST004625_76	Monocyte count	4.000000e-39
GCST005975_10	Eosinophil count	3.000000e-56
GCST005976_15	White blood cell count (basophil)	2.000000e-123
GCST005977_31	Monocyte count	4.000000e-19
GCST006585_582	Blood protein levels	6.000000e-21
GCST007611_8	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	9.000000e-10
GCST008129_13	Body mass index	2.000000e-12
GCST008362_103	Birth weight	2.000000e-08
GCST008394_2	Mild to moderate chronic kidney disease	5.000000e-08
GCST009066_6	Mosaic loss of chromosome Y (Y chromosome dosage)	7.000000e-10
GCST009067_8	Mosaic loss of chromosome Y (Y chromosome dosage)	3.000000e-12
GCST012020_48	Serum metabolite levels	5.000000e-23
GCST90000025_679	Appendicular lean mass	8.000000e-43
GCST90000026_19	Appendicular lean mass	3.000000e-21
GCST90000027_8	Appendicular lean mass	9.000000e-25
GCST90002390_159	Mean corpuscular hemoglobin	7.000000e-13
GCST90002392_305	Mean corpuscular volume	2.000000e-10
GCST90002392_306	Mean corpuscular volume	5.000000e-11
GCST90002393_251	Monocyte count	1.000000e-61
GCST90002393_253	Monocyte count	2.000000e-17
GCST90002394_257	Monocyte percentage of white cells	5.000000e-18
GCST90002398_104	Neutrophil count	9.000000e-17
GCST90002401_128	Platelet distribution width	2.000000e-12
GCST90002407_408	White blood cell count	2.000000e-27

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0004842	eosinophil count
EFO:0007989	monocyte percentage of leukocytes
EFO:0004340	body mass index
EFO:0004344	birth weight
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004980	appendicular lean mass
EFO:0004527	mean corpuscular hemoglobin
EFO:0004833	neutrophil count
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831209 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,628 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL451887	CARFILZOMIB	4	12,508

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

ChEMBL bioactivities

64 potent at pChembl≥5 of 67 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.62	IC50	2.4	nM	BORTEZOMIB
8.59	IC50	2.56	nM	BORTEZOMIB
8.57	IC50	2.7	nM	CHEMBL3237863
8.47	IC50	3.4	nM	CHEMBL6143686
8.41	IC50	3.9	nM	CHEMBL3237862
8.39	IC50	4.1	nM	CHEMBL3237864
8.39	IC50	4.1	nM	CHEMBL3237867
8.32	IC50	4.8	nM	CHEMBL3237873
8.29	IC50	5.1	nM	CHEMBL3237865
8.24	IC50	5.7	nM	CHEMBL3237866
8.24	IC50	5.7	nM	CHEMBL3237860
8.23	IC50	5.9	nM	CHEMBL3237868
8.15	IC50	7	nM	BORTEZOMIB
8.15	IC50	7.1	nM	CHEMBL3237870
8.15	IC50	7.14	nM	BORTEZOMIB
8.12	IC50	7.5	nM	CHEMBL3237871
8.11	IC50	7.7	nM	CHEMBL3237874
8.11	IC50	7.8	nM	CHEMBL3237869
8.07	IC50	8.6	nM	CARFILZOMIB
7.54	IC50	29	nM	CHEMBL3237861
7.34	IC50	46	nM	CHEMBL3237867
7.27	IC50	54	nM	CHEMBL3237872
7.12	IC50	75	nM	CHEMBL3237865
7.12	IC50	76	nM	CHEMBL3237866
6.96	IC50	110	nM	CHEMBL3262766
6.92	IC50	120	nM	CHEMBL3237864
6.92	IC50	120	nM	BORTEZOMIB
6.89	IC50	130	nM	CHEMBL3237869
6.85	IC50	140	nM	CHEMBL3237862
6.82	IC50	150	nM	CHEMBL3237863
6.77	IC50	170	nM	CHEMBL3237873
6.77	IC50	170	nM	CHEMBL3262765
6.72	IC50	190	nM	CHEMBL3262758
6.68	IC50	210	nM	CHEMBL3237870
6.66	IC50	220	nM	CHEMBL3262756
6.60	IC50	250	nM	CHEMBL3237868
6.47	IC50	340	nM	CHEMBL3262752
6.47	IC50	340	nM	CHEMBL3262755
6.44	IC50	360	nM	CHEMBL3262757
6.42	IC50	380	nM	CHEMBL3262754
6.36	IC50	440	nM	CHEMBL3262753
6.30	IC50	500	nM	CHEMBL3237872
6.20	IC50	630	nM	CHEMBL3262762
6.02	IC50	950	nM	CHEMBL3262761
6.00	IC50	1000	nM	CHEMBL3237871
5.96	IC50	1100	nM	CHEMBL3237862
5.85	IC50	1400	nM	BELACTOSIN A
5.84	IC50	1440	nM	BELACTOSIN A
5.70	IC50	2000	nM	BORTEZOMIB
5.66	IC50	2170	nM	CHEMBL3237873

PubChem BioAssay actives

61 with measured affinity, of 137 total; 33 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Bortezomib	1985684: Inhibition of 26S proteasome (unknown origin)	ic50	0.0024	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0027	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0039	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-(4-phenylmethoxybutyl)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0048	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0051	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
benzyl N-[(2S)-1-[[(2R)-1-[(1R,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]-4-phenylbutan-2-yl]amino]-1-oxopropan-2-yl]carbamate	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
(2S)-2-[(2,5-dichlorobenzoyl)amino]-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0059	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-(pyrazine-2-carbonylamino)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0071	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-[(6-phenylpyridine-2-carbonyl)amino]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0075	uM
[(1R)-1-[[(2S)-2-acetamido-4-oxo-4-[[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]amino]butanoyl]amino]-3-methylbutyl]boronic acid	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0077	uM
(2S)-2-benzamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0078	uM
Carfilzomib	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.0086	uM
(2R,3S)-3-[(2S)-butan-2-yl]-4-oxo-N-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]oxetane-2-carboxamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0290	uM
(2S)-2-acetamido-N’-methyl-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0540	uM
N-[(1R)-3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]naphthalene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1100	uM
N-[(1R)-3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]-4-(trifluoromethyl)benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1700	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]naphthalene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1900	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]-4-(trifluoromethyl)benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.2200	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]pyridine-3-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3400	uM
4-methoxy-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3400	uM
4-cyano-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3600	uM
4-fluoro-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3800	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.4400	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]oxane-4-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.6300	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]thiophene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.9500	uM
(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-[(1S,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]propanoic acid	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	1.4000	uM
(2S)-2-acetamido-N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1152964: Inhibition of chymotrypsin-like of human 20S proteasome using chromophoric Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	2.3000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149126: Binding affinity to human PSMD2 incubated for 45 mins by Kinobead based pull down assay	kd	3.1417	uM
N-[3-(2-oxo-1,3,4-oxathiazol-5-yl)phenyl]acetamide	1137840: Inhibition of chymotrypsin-like activity of 26S proteasome in intact human Karpas 1106p cells assessed as substrate hydrolysis using Suc-LLVY-(D)-aminoluciferin as substrate after 3 hrs by cell-based Proteasome-Glo assay	ec50	4.2000	uM
(2S)-2-acetamido-N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]-N’-(4-phenylmethoxybutyl)butanediamide	1152964: Inhibition of chymotrypsin-like of human 20S proteasome using chromophoric Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	5.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
cobaltous chloride	increases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Lead	affects expression, decreases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Metribolone	affects binding, increases reaction, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment	1
beta-lapachone	increases expression	1
tanshinone	increases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	increases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression	1
arsenic trichloride	decreases expression, increases abundance	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
azoxystrobin	decreases expression	1
elesclomol	increases expression	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Acrolein	decreases expression, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome