PSMD14

Summary

PSMD14 (proteasome 26S subunit, non-ATPase 14, HGNC:16889) is a protein-coding gene on chromosome 2q24.2, encoding Ubiquitin C-terminal hydrolase PSMD14 (O00487). 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 99.8% of cancer cell lines).

This gene encodes a component of the 26S proteasome. The 26S proteasome is a large multiprotein complex that catalyzes the degradation of ubiquitinated intracellular proteins. The encoded protein is a component of the 19S regulatory cap complex of the 26S proteasome and mediates substrate deubiquitination. A pseudogene of this gene is also located on the long arm of chromosome 2.

Source: NCBI Gene 10213 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 25 total — 2 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_005805

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16889
Approved symbol	PSMD14
Name	proteasome 26S subunit, non-ATPase 14
Location	2q24.2
Locus type	gene with protein product
Status	Approved
Aliases	POH1, pad1, Rpn11
Ensembl gene	ENSG00000115233
Ensembl biotype	protein_coding
OMIM	607173
Entrez	10213

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 23 protein_coding, 3 retained_intron

ENST00000409682, ENST00000437630, ENST00000477232, ENST00000478123, ENST00000492908, ENST00000899668, ENST00000899669, ENST00000899670, ENST00000899671, ENST00000899672, ENST00000915190, ENST00000915191, ENST00000915192, ENST00000915193, ENST00000915194, ENST00000915195, ENST00000915196, ENST00000915197, ENST00000915198, ENST00000961540, ENST00000961541, ENST00000961542, ENST00000961543, ENST00000961544, ENST00000961545, ENST00000961546

RefSeq mRNA: 1 — MANE Select: NM_005805 NM_005805

CCDS: CCDS46437

Canonical transcript exons

ENST00000409682 — 12 exons

Exon	Start	End
ENSE00001130164	161367478	161367549
ENSE00001130723	161385464	161385571
ENSE00001130727	161371172	161371322
ENSE00001130731	161370107	161370177
ENSE00001130738	161367784	161367903
ENSE00001579538	161316437	161316569
ENSE00001583846	161318822	161318873
ENSE00001750108	161411302	161411717
ENSE00001920587	161308425	161308604
ENSE00003464676	161391104	161391178
ENSE00003487962	161408837	161408899
ENSE00003488545	161395078	161395203

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.7999 / max 1329.5877, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23313	59.9376	1821
23314	1.8623	1024

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.11	gold quality
endothelial cell	CL:0000115	98.03	gold quality
deltoid	UBERON:0001476	97.69	gold quality
gluteal muscle	UBERON:0002000	97.66	gold quality
tibialis anterior	UBERON:0001385	97.59	gold quality
triceps brachii	UBERON:0001509	97.56	gold quality
biceps brachii	UBERON:0001507	97.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.43	gold quality
tongue squamous epithelium	UBERON:0006919	97.39	gold quality
adrenal tissue	UBERON:0018303	97.36	gold quality
cortical plate	UBERON:0005343	97.03	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.03	gold quality
gingival epithelium	UBERON:0001949	96.96	gold quality
islet of Langerhans	UBERON:0000006	96.89	gold quality
ganglionic eminence	UBERON:0004023	96.89	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.88	gold quality
gingiva	UBERON:0001828	96.84	gold quality
heart right ventricle	UBERON:0002080	96.82	gold quality
hair follicle	UBERON:0002073	96.81	gold quality
gastrocnemius	UBERON:0001388	96.69	gold quality
cranial nerve II	UBERON:0000941	96.60	gold quality
vastus lateralis	UBERON:0001379	96.59	gold quality
epithelium of nasopharynx	UBERON:0001951	96.50	gold quality
squamous epithelium	UBERON:0006914	96.50	gold quality
cervix squamous epithelium	UBERON:0006922	96.45	gold quality
quadriceps femoris	UBERON:0001377	96.41	gold quality
muscle organ	UBERON:0001630	96.36	gold quality
muscle of leg	UBERON:0001383	96.35	gold quality
upper leg skin	UBERON:0004262	96.30	gold quality
entorhinal cortex	UBERON:0002728	96.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	18.70
E-ANND-3	yes	10.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting PSMD14, 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-1277-5P	100.00	73.95	5056
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-4725-5P	98.67	65.42	628

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 31)

• Ectopic expression of POH1 in HEK293 cells decreased the level of c-Jun ubiquitination, leading to significant accumulation of the protein and a corresponding increase in AP1-mediated gene expression (PMID:16569633)
• An intact zinc metalloproteinase motif of Poh1 is essential for cell viability and 26S proteasome function. (PMID:17237285)
• Specificity for K63-linked polyubiquitin is a common property of the JAMM/MPN+ family of deubiquitinating enzymes. (PMID:19214193)
• Disorder of POH1 expression is involved in the onset of idiopathic nephrotic syndrome (INS), and confers multidrug resistance in children with INS (PMID:19419512)
• Down-regulation of PSMD14 results in decreased cell proliferation, cell cycle arrest and senescence. A comparative study with PSMB5, revealed that PSMB5 and PSMD14 have different effects on cell cycle, senescence and associated molecular events. (PMID:19732767)
• The data demonstrated that proteasomal POH1 is a key de-ubiquitinating enzyme that regulates ubiquitin conjugates generated in response to damage and that several aspects of the DNA double-strand break response are regulated by the proteasome. (PMID:22909820)
• Deubiquitylase POH1 stabilizes E2F1 protein through binding to and deubiquitylating E2F1 in liver cancer. (PMID:26510456)
• overexpression of RPN11 in breast cancer tissues was associated with an advanced clinical stage. Patients with tumors with high expression of RPN11 had worse prognosis. (PMID:28535005)
• Findings suggest proteasome 26S subunit non-ATPase 14 (PSMD14) as a deubiquitinating enzyme to regulate Snail transcription factor (SNAIL) at the post-translational level and provide a promising therapeutic strategy against tumor metastasis of esophageal cancer. (PMID:29331416)
• POH1 knockdown induced cell apoptosis through increased expression of p53 and Bim. (PMID:29573636)
• POH1 expression positively correlates with activities of TGF-beta signaling in tumors and with malignant disease progression. Functionally, POH1 intensifies TGF-beta signaling delivery and, as a consequence, promotes HCC cell metastatic properties both in vitro and in vivo. (PMID:30745168)
• POH1 was overexpressed in prostate cancer and was correlated with pathological grades in human prostate cancers. (PMID:31212367)
• PSMD14 was significantly upregulated in hepatocellular carcinoma (HCC) tissues. Overexpression of PSMD14 correlated with vascular invasion, tumor number, tumor recurrence, and poor tumor-free and overall survival of patients with HCC. Mechanistically, study identified PSMD14 as a novel post-translational regulator of GRB2.PSMD14 inhibits degradation of GRB2 via deubiquitinating this oncoprotein in HCC cells. (PMID:31634528)
• These findings suggest that the PSMD14-ALK2 axis plays an essential role in initiation of the BMP6 signaling pathway and contributes to tumorigenesis and chemoresistance of colorectal cancers. (PMID:31685442)
• The Proteasomal Deubiquitinating Enzyme PSMD14 Regulates Macroautophagy by Controlling Golgi-to-ER Retrograde Transport. (PMID:32210007)
• Cryo-EM Reveals Unanchored M1-Ubiquitin Chain Binding at hRpn11 of the 26S Proteasome. (PMID:32783951)
• Targeting PSMD14 inhibits melanoma growth through SMAD3 stabilization. (PMID:33154524)
• Blockade of deubiquitinating enzyme PSMD14 overcomes chemoresistance in head and neck squamous cell carcinoma by antagonizing E2F1/Akt/SOX2-mediated stemness. (PMID:33456565)
• The PSMD14 inhibitor Thiolutin as a novel therapeutic approach for esophageal squamous cell carcinoma through facilitating SNAIL degradation. (PMID:33897885)
• Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2. (PMID:34382324)
• Identification of PSMD14 as a potential novel prognosis biomarker and therapeutic target for osteosarcoma. (PMID:34383385)
• PSMD14 Targeting Triggers Paraptosis in Breast Cancer Cells by Inducing Proteasome Inhibition and Ca(2+) Imbalance. (PMID:35269789)
• Deubiquitinating enzyme PSMD14 facilitates gastric carcinogenesis through stabilizing PTBP1. (PMID:35405117)
• The prognostic role of PSMD14 in head and neck squamous cell carcinoma. (PMID:35750900)
• Novel insights into the non-canonical roles of PSMD14/POH1/Rpn11 in proteostasis and in the modulation of cancer progression. (PMID:36241058)
• Deubiquitylase PSMD14 inhibits autophagy to promote ovarian cancer progression via stabilization of LRPPRC. (PMID:36328147)
• Depletion of PSMD14 suppresses bladder cancer proliferation by regulating GPX4. (PMID:36632137)
• POH1 facilitates pancreatic carcinogenesis through MYC-driven acinar-to-ductal metaplasia and is a potential therapeutic target. (PMID:37844756)
• Regulation of Drp1 and enhancement of mitochondrial fission by the deubiquitinating enzyme PSMD14 facilitates the proliferation of bladder cancer cells. (PMID:37975230)
• PSMD14 stabilizes estrogen signaling and facilitates breast cancer progression via deubiquitinating ERalpha. (PMID:38017133)
• POH1 induces Smad3 deubiquitination and promotes lung cancer metastasis. (PMID:38061486)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd14	ENSDARG00000063100
mus_musculus	Psmd14	ENSMUSG00000026914
rattus_norvegicus	Psmd14	ENSRNOG00000061129
drosophila_melanogaster	Rpn11	FBGN0028694
caenorhabditis_elegans		WBGENE00004467

Paralogs (3): COPS5 (ENSG00000121022), EIF3H (ENSG00000147677), BRCC3 (ENSG00000185515)

Protein

Protein identifiers

Ubiquitin C-terminal hydrolase PSMD14 — O00487 (reviewed: O00487)

Alternative names: 26S proteasome non-ATPase regulatory subunit 14, 26S proteasome regulatory subunit RPN11, 26S proteasome-associated PAD1 homolog 1

All UniProt accessions (3): O00487, A0A140VKF2, C9JW37

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. The PSMD14 subunit is a metalloprotease that specifically cleaves ‘Lys-63’-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving ‘Lys-63’-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading. Regulates macroautophagy by ensuring Golgi-to-ER retrograde transport through its deubiquitinating activity on K63-linked ubiquitin chains. This activity prevents the retention of essential autophagy proteins at the Golgi, enabling their trafficking to autophagosome formation sites and supporting Golgi-ER membrane recycling critical for effective autophagy.

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 including PSMD4, a base containing 6 ATPases and few additional components. Within the complex, PSMD4 interacts with subunit PSMD7 through their respective MPN domain. Interacts with TXNL1.

Tissue specificity. Widely expressed. Highest levels in heart and skeletal muscle.

Domain organisation. The JAMM motif is required for the deubiquitination and degradation of ubiquitinated substrates.

Similarity. Belongs to the peptidase M67A family. PSMD14 subfamily.

RefSeq proteins (1): NP_005796* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000555	JAMM/MPN+_dom	Domain
IPR037518	MPN	Domain
IPR050242	JAMM_MPN+_peptidase_M67A	Family
IPR056263	RPN11_C	Domain

Pfam: PF01398, PF23594

UniProt features (37 total): helix 11, strand 8, turn 8, binding site 3, modified residue 3, chain 1, domain 1, short sequence motif 1, mutagenesis site 1

Structure

Experimental structures (PDB)

123 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9K53	ELECTRON MICROSCOPY	2.5
8USB	ELECTRON MICROSCOPY	2.73
9MBP	ELECTRON MICROSCOPY	2.75
9PDL	ELECTRON MICROSCOPY	2.76
9NKG	ELECTRON MICROSCOPY	2.8
9E8I	ELECTRON MICROSCOPY	2.87
9E8H	ELECTRON MICROSCOPY	2.9
9NKF	ELECTRON MICROSCOPY	2.9
9BV3	ELECTRON MICROSCOPY	2.9
9K4J	ELECTRON MICROSCOPY	2.9
9U3L	ELECTRON MICROSCOPY	2.91
9NKI	ELECTRON MICROSCOPY	2.94
9PDI	ELECTRON MICROSCOPY	2.98
6MSB	ELECTRON MICROSCOPY	3
7W37	ELECTRON MICROSCOPY	3
8CVT	ELECTRON MICROSCOPY	3
9E8G	ELECTRON MICROSCOPY	3.01
9PDN	ELECTRON MICROSCOPY	3.04
9MBQ	ELECTRON MICROSCOPY	3.08
7W38	ELECTRON MICROSCOPY	3.1
8USC	ELECTRON MICROSCOPY	3.1
9E8O	ELECTRON MICROSCOPY	3.1
9BV1	ELECTRON MICROSCOPY	3.1
9K4R	ELECTRON MICROSCOPY	3.1
9E8Q	ELECTRON MICROSCOPY	3.16
9U7R	ELECTRON MICROSCOPY	3.17
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-O00487-F1	82.12	0.37

Functional residue map

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

Ligand- & substrate-binding residues (3): 113; 115; 126

Post-translational modifications (3): 150, 224, 266

Mutagenesis-validated functional residues (1):

Position	Phenotype
113–115	abolishes ubiquitin thioesterase activity, leading to prevent maintenance of jmjd2a/kdm4a on chromatin.

Function

Pathways and Gene Ontology

Reactome pathways

69 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: 457 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOMF_METALLOPEPTIDASE_ACTIVITY, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME

GO Biological Process (11): double-strand break repair via homologous recombination (GO:0000724), double-strand break repair via nonhomologous end joining (GO:0006303), ubiquitin-dependent protein catabolic process (GO:0006511), protein deubiquitination (GO:0016579), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), response to ethanol (GO:0045471), regulation of proteasomal protein catabolic process (GO:0061136), protein K63-linked deubiquitination (GO:0070536), DNA repair (GO:0006281), proteolysis (GO:0006508), DNA damage response (GO:0006974)

GO Molecular Function (9): metallopeptidase activity (GO:0008237), metal ion binding (GO:0046872), endopeptidase activator activity (GO:0061133), K63-linked deubiquitinase activity (GO:0061578), proteasome binding (GO:0070628), metal-dependent deubiquitinase activity (GO:0140492), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (10): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle, lid subcomplex (GO:0008541), proteasome accessory complex (GO:0022624), cytosolic proteasome complex (GO:0031597), secretory granule lumen (GO:0034774), 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	3
double-strand break repair	2
proteasomal protein catabolic process	2
deubiquitinase activity	2
protein-containing complex	2
proteasome complex	2
recombinational repair	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
ubiquitin-dependent protein catabolic process	1
response to alcohol	1
regulation of protein catabolic process	1
protein deubiquitination	1
DNA metabolic process	1
DNA damage response	1
protein metabolic process	1
cellular response to stress	1
peptidase activity	1
cation binding	1
endopeptidase activity	1
peptidase activator activity	1
endopeptidase regulator activity	1
protein-containing complex binding	1
metallopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
proteasome regulatory particle	1
intracellular anatomical structure	1
cytosol	1
secretory granule	1
cytoplasmic vesicle lumen	1

Protein interactions and networks

STRING

5301 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD14	PSMD7	P51665	999
PSMD14	PSMD8	P48556	997
PSMD14	PSMD12	O00232	997
PSMD14	PSMD3	O43242	996
PSMD14	PSMD13	Q9UNM6	996
PSMD14	PSMD11	O00231	995
PSMD14	PSMD6	Q15008	991
PSMD14	PSMD4	P55036	989
PSMD14	ADRM1	Q16186	989
PSMD14	SEM1	Q6ZVN7	980
PSMD14	USP14	P54578	969
PSMD14	UCHL5	Q9Y5K5	945
PSMD14	PSMD1	Q99460	928
PSMD14	PSMC1	P49014	920
PSMD14	TXNL1	O43396	876

IntAct

213 interactions, top by confidence:

A	B	Type	Score
PSMD14	PSMD7	psi-mi:“MI:0915”(physical association)	0.900
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD4	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD11	PSMD12	psi-mi:“MI:0915”(physical association)	0.730
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD12	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
DPY30	PSMD14	psi-mi:“MI:0915”(physical association)	0.720
PSMD14	DPY30	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (1148): PSMD14 (Affinity Capture-MS), PSMD14 (Two-hybrid), PSMD14 (Two-hybrid), DPY30 (Two-hybrid), FAM9B (Two-hybrid), UBA1 (Affinity Capture-MS), UBE3A (Affinity Capture-MS), UBE3C (Affinity Capture-MS), HERC2 (Affinity Capture-MS), HUWE1 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), PSMB5 (Affinity Capture-MS), UBA1 (Affinity Capture-Western), UBE3A (Affinity Capture-Western)

ESM2 similar proteins: A7SA47, A8QCY3, A8WVY9, A9V3P1, B0WDA9, B3MP94, B3N4F1, B4HBD2, B4I1C2, B4JAS7, B4KGS4, B4LTW0, B4N116, B4P3T9, B5DJJ2, B5E1N0, B5FY35, B5RI54, O00487, O01974, O15372, O35593, O74440, O76577, O94454, P41878, P41883, P43588, P91001, Q170C2, Q18967, Q56JZ5, Q5ZLE6, Q6C1I3, Q6FKS1, Q6P381, Q6P9U8, Q750E9, Q7PVR3, Q86IJ1

Diamond homologs: A0A8M3B525, A5PJP6, A6ZXB7, B0KWU8, B2RYM5, B3LH96, B5X8M4, O00487, O35593, O35864, O76577, O94454, P0CQ24, P0CQ25, P41878, P41883, P43588, P46736, P46737, P91001, Q12468, Q4IJM4, Q4P804, Q4VA72, Q4WZP2, Q54PF3, Q59PG6, Q5BBF1, Q5R9L6, Q66GV6, Q6BMQ3, Q6C703, Q6CRJ8, Q6FKS1, Q6FT36, Q6GLM9, Q6P635, Q6PC30, Q750E9, Q75E19

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSMD14	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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
Proteasome assembly	22	47.7×	9e-30
Regulation of activated PAK-2p34 by proteasome mediated degradation	16	47.4×	9e-22
Regulation of ornithine decarboxylase (ODC)	16	46.3×	1e-21
Cross-presentation of soluble exogenous antigens (endosomes)	17	45.9×	1e-22
Vpu mediated degradation of CD4	16	45.2×	1e-21
Autodegradation of the E3 ubiquitin ligase COP1	16	45.2×	1e-21
Ubiquitin-dependent degradation of Cyclin D	16	45.2×	1e-21
Hh mutants are degraded by ERAD	17	43.9×	2e-22

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	22	9.3×	2e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	9
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3062654	GRCh37/hg19 2q24.2(chr2:162167521-162365390)x1	Pathogenic
686247	GRCh37/hg19 2q24.2(chr2:162174796-162283469)x1	Pathogenic
523688	Single allele	Likely pathogenic
932938	GRCh37/hg19 2q24.2(chr2:161967492-162428730)	Likely pathogenic

SpliceAI

2355 predictions. Top by Δscore:

Variant	Effect	Δscore
2:161308604:GGT:G	donor_loss	1.0000
2:161308605:G:T	donor_loss	1.0000
2:161308606:T:G	donor_loss	1.0000
2:161316426:A:AG	acceptor_gain	1.0000
2:161316427:C:G	acceptor_gain	1.0000
2:161316433:TTAGG:T	acceptor_gain	1.0000
2:161316434:TAGG:T	acceptor_gain	1.0000
2:161316435:A:AG	acceptor_gain	1.0000
2:161316435:AG:A	acceptor_gain	1.0000
2:161316435:AGG:A	acceptor_loss	1.0000
2:161316435:AGGA:A	acceptor_gain	1.0000
2:161316436:G:GA	acceptor_gain	1.0000
2:161316436:GG:G	acceptor_gain	1.0000
2:161316436:GGA:G	acceptor_gain	1.0000
2:161316436:GGAG:G	acceptor_gain	1.0000
2:161316436:GGAGA:G	acceptor_gain	1.0000
2:161316568:AGG:A	donor_loss	1.0000
2:161316570:G:GC	donor_loss	1.0000
2:161316570:G:GG	donor_gain	1.0000
2:161316571:T:G	donor_loss	1.0000
2:161318812:T:A	acceptor_gain	1.0000
2:161318818:CTA:C	acceptor_loss	1.0000
2:161318820:A:AG	acceptor_gain	1.0000
2:161318821:G:GA	acceptor_gain	1.0000
2:161318821:GA:G	acceptor_gain	1.0000
2:161318821:GAA:G	acceptor_gain	1.0000
2:161318821:GAAA:G	acceptor_gain	1.0000
2:161318821:GAAAT:G	acceptor_gain	1.0000
2:161359829:A:T	donor_gain	1.0000
2:161367473:TCTA:T	acceptor_loss	1.0000

AlphaMissense

2056 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:161367527:T:A	I33N	1.000
2:161367542:T:C	L38P	1.000
2:161367549:A:C	K40N	1.000
2:161367549:A:T	K40N	1.000
2:161367785:T:A	M41K	1.000
2:161367785:T:C	M41T	1.000
2:161367785:T:G	M41R	1.000
2:161367795:T:A	H44Q	1.000
2:161367795:T:G	H44Q	1.000
2:161367796:G:C	G45R	1.000
2:161367797:G:A	G45D	1.000
2:161367805:G:A	G48R	1.000
2:161367805:G:C	G48R	1.000
2:161367806:G:A	G48E	1.000
2:161367812:C:A	P50Q	1.000
2:161367817:G:A	E52K	1.000
2:161367818:A:C	E52A	1.000
2:161367818:A:G	E52G	1.000
2:161367818:A:T	E52V	1.000
2:161367819:A:C	E52D	1.000
2:161367819:A:T	E52D	1.000
2:161367820:G:C	V53L	1.000
2:161367821:T:A	V53D	1.000
2:161367824:T:A	M54K	1.000
2:161367824:T:C	M54T	1.000
2:161367825:G:A	M54I	1.000
2:161367825:G:C	M54I	1.000
2:161367825:G:T	M54I	1.000
2:161367826:G:A	G55S	1.000
2:161367826:G:C	G55R	1.000

dbSNP variants (sampled 300 via entrez): RS1000013984 (2:161394983 G>A,T), RS1000045235 (2:161395381 C>A,T), RS1000060132 (2:161366295 T>A), RS1000100714 (2:161310679 T>C), RS1000113773 (2:161359091 T>G), RS1000169740 (2:161312083 A>G), RS1000189330 (2:161361142 A>T), RS1000209028 (2:161411490 T>C), RS1000249778 (2:161320706 GTTGT>G), RS1000252283 (2:161381027 A>C,G,T), RS1000261902 (2:161365013 G>T), RS1000277849 (2:161307542 T>C), RS1000294519 (2:161364704 A>G,T), RS1000297898 (2:161330326 A>C,G), RS1000348844 (2:161381441 G>T)

Disease associations

OMIM: gene MIM:607173 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002598_20	Educational attainment	2.000000e-07
GCST002774_3	Cognitive function	9.000000e-06
GCST003469_8	Response to cognitive-behavioural therapy in anxiety disorder	8.000000e-06
GCST007277_3	Tourette syndrome	2.000000e-07
GCST009391_569	Metabolite levels	6.000000e-07
GCST009391_570	Metabolite levels	6.000000e-07
GCST010698_7	Subcortical volume (min-P)	5.000000e-08
GCST010699_92	Brain morphology (min-P)	7.000000e-13
GCST010700_32	Cortical thickness (MOSTest)	1.000000e-08
GCST010701_4	Cortical surface area (MOSTest)	1.000000e-08
GCST010702_173	Subcortical volume (MOSTest)	5.000000e-16
GCST010703_19	Brain morphology (MOSTest)	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0004337	intelligence
EFO:0007820	cognitive behavioural therapy
EFO:0021604	hypoxanthine measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2007629 (SINGLE PROTEIN), CHEMBL2364701 (PROTEIN COMPLEX)

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)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9713	PSMD14		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M67: PSMD14 peptidase

Binding affinities (BindingDB)

402 measured of 410 human assays (436 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
MLS000565972	IC50	22.2 nM
SMR000147996	IC50	90 nM
4-chloranyl-N-(3,4-dihydro-2H-thiochromen-4-yl)-3-sulfamoyl-benzamide	IC50	121 nM
N-(pyridin-4-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	200 nM	US-10005735: Inhibitors of RPN11
N-[3-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]propyl]-8-sulfanylquinoline-3-carboxamide	IC50	200 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(2-thiophen-2-ylethyl)quinoline-3-carboxamide	IC50	300 nM	US-10005735: Inhibitors of RPN11
Capzimin	IC50	340 nM	US-10005735: Inhibitors of RPN11
N-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethyl]-8-sulfanylquinoline-3-carboxamide	IC50	400 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(1,3-thiazol-2-yl)quinoline-3-carboxamide	IC50	450 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(1,3-thiazol-2-ylmethyl)quinoline-3-carboxamide	IC50	500 nM	US-10005735: Inhibitors of RPN11
N-[2-(4,5-dimethyl-1,3-thiazol-2-yl)ethyl]-8-sulfanylquinoline-3-carboxamide	IC50	500 nM	US-10005735: Inhibitors of RPN11
N-(2-chlorophenyl)-2-[(2E)-2-[(2-morpholin-4-yl-4-phenyl-1,3-thiazol-5-yl)methylidene]hydrazinyl]-5-nitro-benzenesulfonamide	IC50	658 nM
8-sulfanyl-N-[[4-(trifluoromethyl)phenyl]methyl]quinoline-3-carboxamide	IC50	700 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(2-thiophen-2-ylethyl)quinoline-4-carboxamide	IC50	700 nM	US-10005735: Inhibitors of RPN11
ethyl 2-[2-[(8-sulfanylquinoline-3-carbonyl)amino]ethyl]-1,3-thiazole-4-carboxylate	IC50	700 nM	US-10005735: Inhibitors of RPN11
cid_1838043	IC50	798 nM
8-sulfanyl-N-(thiophen-2-ylmethyl)quinoline-3-carboxamide	IC50	800 nM	US-10005735: Inhibitors of RPN11
N-[(4-morpholin-4-ylphenyl)methyl]-8-sulfanylquinoline-3-carboxamide	IC50	800 nM	US-10005735: Inhibitors of RPN11
N-(furan-2-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	900 nM	US-10005735: Inhibitors of RPN11
N-(1,3-benzodioxol-5-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	900 nM	US-10005735: Inhibitors of RPN11
(2E)-2-[(2Z)-2-(3-bromo-5-methoxy-4-oxo-1-cyclohexa-2,5-dienylidene)ethylidene]-1H-quinazolin-4-one	IC50	914 nM
8-sulfanylquinoline-3-carboxamide	IC50	1000 nM	US-10005735: Inhibitors of RPN11
N-[2-(furan-2-yl)ethyl]-8-sulfanylquinoline-4-carboxamide	IC50	1000 nM	US-10005735: Inhibitors of RPN11
3-[[2-(3,4-dihydro-2H-quinolin-1-yl)-1-oxoethyl]amino]-5-methyl-1H-indole-2-carboxylic acid methyl ester	IC50	1030 nM
cid_56642849	IC50	1040 nM
N-benzyl-8-sulfanylquinoline-3-carboxamide	IC50	1100 nM	US-10005735: Inhibitors of RPN11
4-methyl-2-[2-[(8-sulfanylquinoline-3-carbonyl)amino]ethyl]-1,3-thiazole-5-carboxylic acid	IC50	1100 nM	US-10005735: Inhibitors of RPN11
N-[2-(furan-2-yl)ethyl]-8-sulfanylquinoline-3-carboxamide	IC50	1200 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(thiophen-2-ylmethyl)quinoline-4-carboxamide	IC50	1200 nM	US-10005735: Inhibitors of RPN11
3-Amino-6,7-dimethoxy-thieno[2,3-b]quinoline-2-carboxylic acid (3-cyano-4,5-dimethyl-thiophen-2-yl)-amide	IC50	1260 nM
cid_5328771	IC50	1300 nM
SMR000718768	IC50	1330 nM
4-[(5E)-5-[[5-(1,3-benzothiazol-2-yl)-2-furanyl]methylidene]-4-oxo-2-sulfanylidene-3-thiazolidinyl]butanoic acid	IC50	1380 nM
SMR000204142	IC50	1410 nM
(5E)-5-[(4-methoxyphenyl)methylidene]-1-(4-methylbenzoyl)-2-sulfanylideneimidazolidin-4-one	IC50	1530 nM
(2Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxy-coumaran-3-one	IC50	1530 nM
N-methyl-8-sulfanylquinoline-3-carboxamide	IC50	1600 nM	US-10005735: Inhibitors of RPN11
MLS000573812	IC50	1770 nM
cid_9658313	IC50	1820 nM
(6Z)-5-azanylidene-6-[[1-(3-chloranyl-4-methyl-phenyl)pyrrol-2-yl]methylidene]-3-methylsulfonyl-[1,2,4]thiadiazolo[4,5-a]pyrimidin-7-one	IC50	1860 nM
4-[[5-(4-bromophenyl)-2-furoyl]thiocarbamoylamino]benzoic acid	IC50	1880 nM
(5Z)-5-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-2-(4-methylphenyl)-4-thiazolone	IC50	2180 nM
N-(furan-2-ylmethyl)-8-sulfanylquinoline-4-carboxamide	IC50	2200 nM	US-10005735: Inhibitors of RPN11
2-chloranyl-4-[5-[(Z)-2-[(5-methyl-1H-1,2,4-triazol-3-yl)sulfanyl]-3-oxidanyl-3-oxidanylidene-prop-1-enyl]furan-2-yl]benzoic acid	IC50	2350 nM
SMR000555227	IC50	2360 nM
N-(1,3-oxazol-2-yl)-8-sulfanylquinoline-3-carboxamide	IC50	2600 nM	US-10005735: Inhibitors of RPN11
(6E)-5-azanylidene-6-[[5-(furan-2-ylmethylsulfanyl)furan-2-yl]methylidene]-2-propyl-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one	IC50	2650 nM
8-Mercaptoquinoline (8TQ)	IC50	2800 nM	US-10005735: Inhibitors of RPN11
methyl 2-[(8-sulfanylquinoline-3-carbonyl)amino]acetate	IC50	2800 nM	US-10005735: Inhibitors of RPN11
(3E)-3-(2-furanylmethylidene)-4-imino-8-methylsulfonyl-2-pyrimido[2,1-b][1,3]benzothiazolone	IC50	2840 nM

ChEMBL bioactivities

168 potent at pChembl≥5 of 502 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
7.05	IC50	90	nM	CHEMBL1610433
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
6.70	IC50	200	nM	CHEMBL4104719
6.68	IC50	210	nM	CHEMBL3237870
6.66	IC50	220	nM	CHEMBL3262756
6.60	IC50	250	nM	CHEMBL3237868
6.52	IC50	300	nM	CHEMBL4100384
6.47	IC50	340	nM	CHEMBL3262752
6.47	IC50	340	nM	CHEMBL3262755
6.44	IC50	360	nM	CHEMBL3262757
6.42	IC50	380	nM	CHEMBL3262754
6.41	IC50	390	nM	CHEMBL4073553
6.40	IC50	400	nM	CHEMBL4070821
6.36	IC50	440	nM	CHEMBL3262753
6.30	IC50	500	nM	CHEMBL3237872
6.30	IC50	500	nM	CHEMBL4093962
6.22	IC50	600	nM	CHEMBL4073553
6.20	IC50	630	nM	CHEMBL3262762

PubChem BioAssay actives

104 with measured affinity, of 216 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
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-(pyridin-4-ylmethyl)-8-[[3-(pyridin-4-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.2000	uM
N-[(4-methoxyphenyl)methyl]-8-[[3-[(4-methoxyphenyl)methylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.2000	uM
N-[(4-fluorophenyl)methyl]-8-[[3-[(4-fluorophenyl)methylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.2000	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-(2-thiophen-2-ylethyl)-8-[[3-(2-thiophen-2-ylethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.3000	uM
8-sulfanyl-N-[2-(1,3-thiazol-2-yl)ethyl]quinoline-3-carboxamide	1802700: In Vitro Rpn11 Activity Assay from Article 10.1038/nchembio.2326: “Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11.”	ic50	0.3400	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-[2-(1,3-thiazol-2-yl)ethyl]-8-[[3-[2-(1,3-thiazol-2-yl)ethylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.3900	uM
N-(1,3-thiazol-2-yl)-8-[[3-(1,3-thiazol-2-ylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.4000	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-(1,3-thiazol-2-ylmethyl)-8-[[3-(1,3-thiazol-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.5000	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-[[4-(trifluoromethyl)phenyl]methyl]-8-[[3-[[4-(trifluoromethyl)phenyl]methylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.8000	uM
N-(thiophen-2-ylmethyl)-8-[[3-(thiophen-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.8000	uM
8-[[3-[(4-morpholin-4-ylphenyl)methylcarbamoyl]quinolin-8-yl]disulfanyl]-N-[(4-piperidin-1-ylphenyl)methyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.8000	uM
N-(1,3-benzodioxol-5-ylmethyl)-8-[[3-(1,3-benzodioxol-5-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.9000	uM
N-(furan-2-ylmethyl)-8-[[3-(furan-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.9000	uM
6-methylquinoline-8-thiol	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.9000	uM
methyl 8-[(3-methoxycarbonylquinolin-8-yl)disulfanyl]quinoline-3-carboxylate	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	0.9000	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
N-(thiophen-2-ylmethyl)-8-[[4-(thiophen-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-4-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	1.0000	uM
8-[(3-carbamoylquinolin-8-yl)disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	1.0000	uM
N-(oxolan-2-ylmethyl)-8-[[3-(oxolan-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480587: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in beta5 inhibitor MG132 pretreated human HeLa cells expressing UbG76V-GFP assessed as reduction in UbG76V-GFP degradation rate by fluorescence microscopic method	ic50	1.0000	uM
methyl 8-[(4-methoxycarbonylquinolin-8-yl)disulfanyl]quinoline-4-carboxylate	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	1.0000	uM
8-[(3-carboxyquinolin-8-yl)disulfanyl]quinoline-3-carboxylic acid	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	1.1000	uM
N-benzyl-8-[[3-(benzylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	1.1000	uM
N-[2-(furan-2-yl)ethyl]-8-[[3-[2-(furan-2-yl)ethylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480589: Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in human erythrocytes using Ub4-pepOG protein substrate preincubated for 1 hr followed by substrate addition measured after 80 mins by fluorescence polarization assay	ic50	1.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, affects cotreatment, increases abundance	4
Arsenic	affects expression, decreases expression, increases abundance, affects cotreatment, increases expression	4
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
Cyclosporine	increases expression, increases methylation	3
Cadmium Chloride	increases abundance, increases palmitoylation, increases expression, decreases reaction	3
Cadmium	increases palmitoylation, increases expression, decreases reaction, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	decreases methylation	2
Particulate Matter	affects expression, increases reaction, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
beta-lapachone	increases expression	1
afimoxifene	decreases expression	1
cobaltous chloride	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	increases expression	1
cupric chloride	increases expression	1
beta-methylcholine	affects expression	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
chloropicrin	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
bisphenol B	increases expression	1

ChEMBL screening assays

32 unique, capped per target: 31 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1963965	Functional	PUBCHEM_BIOASSAY: Dose response confirmation of uHTS RPN11 inhibitor hits in a Fluorescence Polarization assay. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4049702	Binding	Inhibition of 26S proteasome regulatory subunit RPN11 deubiquitinating activity in beta5 inhibitor MG132 pretreated human HeLa cells expressing UbG76V-GFP assessed as reduction in UbG76V-GFP degradation rate by fluorescence microscopic meth	Discovery of an Inhibitor of the Proteasome Subunit Rpn11. — J Med Chem

Clinical trials (associated diseases)

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