ADRM1

Summary

ADRM1 (ADRM1 26S proteasome ubiquitin receptor, HGNC:15759) is a protein-coding gene on chromosome 20q13.33, encoding Proteasomal ubiquitin receptor ADRM1 (Q16186). Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. It is a selective cancer dependency (DepMap: 35.8% of cell lines).

This gene encodes a member of the adhesion regulating molecule 1 protein family. The encoded protein is a component of the proteasome where it acts as a ubiquitin receptor and recruits the deubiquitinating enzyme, ubiquitin carboxyl-terminal hydrolase L5. Increased levels of the encoded protein are associated with increased cell adhesion, which is likely an indirect effect of this intracellular protein. Dysregulation of this gene has been implicated in carcinogenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11047 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 84 total — 1 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 35.8% of screened cell lines
• MANE Select transcript: NM_007002

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15759
Approved symbol	ADRM1
Name	ADRM1 26S proteasome ubiquitin receptor
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	GP110, Rpn13, ARM1, PSMD16
Ensembl gene	ENSG00000130706
Ensembl biotype	protein_coding
OMIM	610650
Entrez	11047

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 37 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000253003, ENST00000462554, ENST00000465805, ENST00000491935, ENST00000620230, ENST00000906311, ENST00000906312, ENST00000906313, ENST00000906314, ENST00000906315, ENST00000906316, ENST00000906317, ENST00000906318, ENST00000906319, ENST00000906320, ENST00000906321, ENST00000906322, ENST00000906323, ENST00000906324, ENST00000906326, ENST00000906327, ENST00000906328, ENST00000906329, ENST00000906330, ENST00000913435, ENST00000913436, ENST00000913437, ENST00000913438, ENST00000913439, ENST00000913440, ENST00000913441, ENST00000913442, ENST00000913443, ENST00000913444, ENST00000913445, ENST00000946004, ENST00000946005, ENST00000946006

RefSeq mRNA: 4 — MANE Select: NM_007002 NM_001281437, NM_001281438, NM_007002, NM_175573

CCDS: CCDS13496, CCDS74747

Canonical transcript exons

ENST00000253003 — 10 exons

Exon	Start	End
ENSE00003605128	62306197	62306320
ENSE00003789475	62306648	62306734
ENSE00003846646	62302997	62303049
ENSE00003888697	62307596	62307828
ENSE00003889186	62304461	62304577
ENSE00003890387	62308368	62308470
ENSE00003891605	62308021	62308178
ENSE00003893481	62307371	62307452
ENSE00003894119	62303568	62303781
ENSE00003895466	62308655	62308862

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.6747 / max 489.2355, expressed in 1824 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185717	73.4509	1824
185713	0.8831	419
185714	0.2174	86
185718	0.0371	9
185716	0.0362	9
185719	0.0313	8
185720	0.0100	4
185715	0.0086	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.65	gold quality
right testis	UBERON:0004534	98.22	gold quality
left testis	UBERON:0004533	98.20	gold quality
muscle of leg	UBERON:0001383	97.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.72	gold quality
apex of heart	UBERON:0002098	97.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.16	gold quality
right adrenal gland	UBERON:0001233	97.10	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.09	gold quality
lower esophagus	UBERON:0013473	97.08	gold quality
skin of leg	UBERON:0001511	97.06	gold quality
right adrenal gland cortex	UBERON:0035827	97.05	gold quality
left adrenal gland	UBERON:0001234	97.01	gold quality
cerebellar hemisphere	UBERON:0002245	96.99	gold quality
mucosa of stomach	UBERON:0001199	96.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.93	gold quality
cerebellar cortex	UBERON:0002129	96.92	gold quality
mucosa of transverse colon	UBERON:0004991	96.89	gold quality
left adrenal gland cortex	UBERON:0035825	96.83	gold quality
lower esophagus mucosa	UBERON:0035834	96.82	gold quality
granulocyte	CL:0000094	96.77	gold quality
skin of abdomen	UBERON:0001416	96.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.74	gold quality
left coronary artery	UBERON:0001626	96.64	gold quality
popliteal artery	UBERON:0002250	96.64	gold quality
tibial artery	UBERON:0007610	96.64	gold quality
right atrium auricular region	UBERON:0006631	96.60	gold quality
left uterine tube	UBERON:0001303	96.50	gold quality
right coronary artery	UBERON:0001625	96.47	gold quality
right lobe of liver	UBERON:0001114	96.39	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	802.28
E-GEOD-134144	yes	27.84
E-ENAD-17	no	177.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting ADRM1, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-194-3P	97.36	65.96	1027

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 35.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• ARM-1 is a cytosolic protein associated with the plasma membrane. However, no cell surface expression of the protein was observed. These results suggest an indirect role of ARM-1 in adhesion rather than a direct role as an adhesion molecule itself.[ARM-1] (PMID:15819879)
• Adrm1 has a specialised role in proteasome function. Identified Adrm1 as a novel component of the regulatory ATPase complex of the 26 S proteasome (PMID:16815440)
• Neither Uch37 alone nor the Uch37-Adrm1 or Uch37-Adrm1-S1 complexes can hydrolyse di-ubiquitin efficiently; rather, incorporation into the 19S complex is required to enable processing of polyubiquitin chains. (PMID:16906146)
• These results indicate that hRpn13 (Adrm1) is essential for the activity of UCH37. (PMID:16990800)
• In human 26S proteasomes, hRpn13 appears to be important for the binding of UCH37 to the 19S complex and for efficient proteolysis. (PMID:17139257)
• identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome (PMID:18497817)
• ADRM1 overexpression was the most highly correlated with amplification and is associated with ovarian cancer. (PMID:18615678)
• Adrm1 is potentially oncogenic and may play an important role in colon tumorigenesis (PMID:19148532)
• these data suggest that Adrm1, a new Atp6v0d2-interacting protein, plays an important role in osteoclast differentiation, and in particular the fusion of preosteoclasts. (PMID:19818731)
• Silencing of Adrm1 by RNA interference can significantly suppress proliferation of colorectal cancer cells through inducing apoptosis and arresting the cell cycle. (PMID:20137344)
• results suggest that there is different substrate specificity between S5a and hRpn13 at the level of delivery and S5a may be the major docking site for ERAD substrates. (PMID:20417181)
• Rpn13 binding to the proteasome scaffolding protein hRpn2/S1 abrogates its interdomain interactions, thus activating hRpn13 for ubiquitin binding. (PMID:20471946)
• show that Rpn13 is involved in inducible nitric oxide synthase degradation and is required for iNOS interaction with the deubiquitination protein UCH37. (PMID:20634424)
• Phosphorylated TP63 induces transcription of RPN13, leading to NOS2 protein degradation (PMID:20959455)
• In tumor cells non-phosphorylated DeltaNp63alpha failed to form protein complexes with Rpn13, allowing the latter to bind and target LKB1 into a proteasome-dependent degradation pathway, modulating cisplatin-induced autophagy. (PMID:21191146)
• this study provides a possible mechanism of action in ovarian cancer for amplification and overexpression of ADRM1 (PMID:21432940)
• hRpn13 modulates the influence of osteoblasts on osteoclasts by controlling the stability of regulatory proteins in osteoblasts. (PMID:22057889)
• mRNA and protein levels of ADRM1 were increased in hepatocellular carcinoma tissues and was parallel to the metastatic potential (PMID:22576803)
• Inherent asymmetry in the 26S proteasome is defined by the ubiquitin receptor RPN13. (PMID:24429290)
• Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of ubiquitin conjugates. (PMID:24811749)
• Together, our findings suggest that the interaction of Psmd1 with Adrm1 is controlled by SUMOylation in a manner that may alter proteasome composition and function. (PMID:24910440)
• ADRM1 is a candidate target gene in the chromosome 20q13.33 amplicon that may possibly be linked to development of gastric cancer (PMID:24968865)
• findings implicate Rpn13 in linking parkin to the 26 S proteasome and regulating the clearance of mitochondrial proteins during mitophagy (PMID:25666615)
• Data show that DEUBAD domain in RPN13 (ADRM1) activates ubiquitin thioesterase L5 (UCH-L5), and the related DEUBAD domain in INO80G (NFRKB) inhibits UCH-L5. (PMID:25702870)
• Data suggest that ADRM1 is involved in proliferation of acute leukemia cells; expression of ADRM1 is up-regulated in leukemia; knockdown of ADRM1 inhibits cell proliferation at G0/G1 phase of cell cycle but does not affect apoptosis/cell migration. (PMID:25896055)
• the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation. (PMID:26169395)
• regulation of NY-ESO-1 processing by the ubiquitin receptors Rpn10 and Rpn13 as a well as by the standard and immunoproteasome is governed by non-canonical ubiquitination on non-lysine sites. (PMID:26903513)
• this work implicates hRpn13 and Uch37 in cell cycle progression, providing a rationale for their function in cellular proliferation and for the apoptotic effect of the hRpn13-targeting molecule RA190. (PMID:26907685)
• The structures of proteasome substrate receptor complexes with the shuttle factors that deliver ubiquitinated proteins to proteasomes have been solved, namely human Rpn13 complexed with PLIC2 and Saccharomyces cerevisiae Rpn1 with Rad23. (PMID:27396824)
• evidence that the interaction can mediate the association of Rpn13 and SGTA in a cellular context. (PMID:27827410)
• RPN13 binds ubiquitin with an affinity similar to that of other proteasome-associated ubiquitin receptors and that RPN2, ubiquitin, and the deubiquitylase UCH37 bind to RPN13 with independent energetics. (PMID:28442575)
• Rpn13-Rpn2 complex structural analysis shows that RA190 targets hRpn13 and Uch37 through parallel mechanisms and at proteasomes, RA190-inactivated Uch37 cannot disassemble hRpn13-bound ubiquitin chains (PMID:28598414)
• We show that ADRM1 mRNA overexpression is an early event in high grade serous carcinoma of the ovary. This is associated with TP53 mutation and increased burden of misfolded proteins in carcinomas that likely renders the cancer cells particularly sensitive to RPN13 inhibitors. (PMID:28784174)
• findings indicate that up-regulated ADRM1 was involved in intrahepatic cholangiocarcinoma (ICC) progression and suggest the potential clinical application of ADRM1 inhibitors (e.g., RA190 and KDT-11) for ICC treatment. (PMID:29913454)
• Prognostic and Therapeutic Significance of Adhesion-regulating Molecule 1 in Estrogen Receptor-positive Breast Cancer. (PMID:31669266)
• An Extended Conformation for K48 Ubiquitin Chains Revealed by the hRpn2:Rpn13:K48-Diubiquitin Structure. (PMID:32160516)
• The CCDC43-ADRM1 axis regulated by YY1, promotes proliferation and metastasis of gastric cancer. (PMID:32278016)
• Proteomic analysis identifies mechanism(s) of overcoming bortezomib resistance via targeting ubiquitin receptor Rpn13. (PMID:32424294)
• ADRM1 as a therapeutic target in hepatocellular carcinoma. (PMID:32916039)
• Identification of novel anti-tumor therapeutic target via proteomic characterization of ubiquitin receptor ADRM1/Rpn13. (PMID:33441535)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	adrm1	ENSDARG00000058560
mus_musculus	Adrm1	ENSMUSG00000039041
mus_musculus	Adrm1b	ENSMUSG00000042165
rattus_norvegicus	Adrm1	ENSRNOG00000055984
drosophila_melanogaster	Rpn13R	FBGN0029745
drosophila_melanogaster	Rpn13	FBGN0033886
caenorhabditis_elegans		WBGENE00016981

Protein

Protein identifiers

Proteasomal ubiquitin receptor ADRM1 — Q16186 (reviewed: Q16186)

Alternative names: 110 kDa cell membrane glycoprotein, Adhesion-regulating molecule 1, Proteasome regulatory particle non-ATPase 13, Rpn13 homolog

All UniProt accessions (3): Q16186, A0A087WUX6, A0A087WX59

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. Within the complex, functions as a proteasomal ubiquitin receptor. Engages and activates 19S-associated deubiquitinases UCHL5 and PSMD14 during protein degradation. UCHL5 reversibly associate with the 19S regulatory particle whereas PSMD14 is an intrinsic subunit of the proteasome lid subcomplex.

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). Interacts with the proteasomal scaffolding protein PSMD1. Interacts with deubiquitinase UCHL5; this interaction activates the auto-inhibited UCHL5 by deoligomerizing it. Interacts with UBQLN2 and ubiquitin.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Ubiquitinated by UBE3C in response to proteotoxic stress.

Domain organisation. The Pru (pleckstrin-like receptor for ubiquitin) domain mediates interactions with PSMD1 and ubiquitin. Preferential binding to the proximal subunit of ‘Lys-48’-linked diubiquitin allows UCHL5 access to the distal subunit.

Similarity. Belongs to the ADRM1 family.

RefSeq proteins (4): NP_001268366, NP_001268367, NP_008933, NP_783163 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006773	Rpn13/ADRM1	Family
IPR032368	RPN13_DEUBAD	Domain
IPR038108	RPN13_DEUBAD_sf	Homologous_superfamily
IPR038633	Rpn13/ADRM1_Pru_sf	Homologous_superfamily
IPR044867	DEUBAD_dom	Domain
IPR044868	Rpn13/ADRM1_Pru	Domain

Pfam: PF04683, PF16550

UniProt features (51 total): strand 16, helix 14, modified residue 7, turn 4, region of interest 3, domain 2, initiator methionine 1, chain 1, cross-link 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
5V1Y	X-RAY DIFFRACTION	1.42
6OI4	X-RAY DIFFRACTION	1.76
5IRS	X-RAY DIFFRACTION	1.8
8VWO	X-RAY DIFFRACTION	1.85
4WLR	X-RAY DIFFRACTION	2
5V1Z	X-RAY DIFFRACTION	2
8FTQ	X-RAY DIFFRACTION	2.1
4UEL	X-RAY DIFFRACTION	2.3
9E7K	X-RAY DIFFRACTION	2.41
4UEM	X-RAY DIFFRACTION	2.82
4WLQ	X-RAY DIFFRACTION	2.85
2KQZ	SOLUTION NMR
2KR0	SOLUTION NMR
2L5V	SOLUTION NMR
2MKZ	SOLUTION NMR
2NBV	SOLUTION NMR
5YMY	SOLUTION NMR
6CO4	SOLUTION NMR
6UYI	SOLUTION NMR
6UYJ	SOLUTION NMR
7KXI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16186-F1	64.34	0.19

Antibody-complex structures (SAbDab): 1 — 9E7K

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 (8): 127, 140, 211, 217, 405, 34, 2, 15

Function

Pathways and Gene Ontology

Reactome pathways

162 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: 329 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_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, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR

GO Biological Process (3): transcription elongation by RNA polymerase II (GO:0006368), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), proteasome assembly (GO:0043248)

GO Molecular Function (5): protease binding (GO:0002020), endopeptidase activator activity (GO:0061133), proteasome binding (GO:0070628), molecular function inhibitor activity (GO:0140678), protein binding (GO:0005515)

GO Cellular Component (7): proteasome complex (GO:0000502), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), proteasome regulatory particle, lid subcomplex (GO:0008541), nucleus (GO:0005634), cytoplasm (GO:0005737)

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
DNA-templated transcription elongation	1
transcription by RNA polymerase II	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein-containing complex assembly	1
enzyme binding	1
endopeptidase activity	1
peptidase activator activity	1
endopeptidase regulator activity	1
protein-containing complex binding	1
molecular function regulator activity	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
proteasome regulatory particle	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRM1	UCHL5	Q9Y5K5	999
ADRM1	PSMD4	P55036	999
ADRM1	PSMD14	O00487	989
ADRM1	PSMD8	P48556	956
ADRM1	PSMC4	P43686	943
ADRM1	USP14	P54578	938
ADRM1	PSMD12	O00232	900
ADRM1	PSMD11	O00231	895
ADRM1	PSMD6	Q15008	891
ADRM1	PSMD3	O43242	881
ADRM1	PSMD7	P51665	873
ADRM1	UBQLN2	Q9UHD9	861
ADRM1	PSMD2	Q13200	854
ADRM1	PSMD13	Q9UNM6	852
ADRM1	PSMD1	Q99460	830

IntAct

192 interactions, top by confidence:

A	B	Type	Score
UCHL5	ADRM1	psi-mi:“MI:0915”(physical association)	0.970
ADRM1	UCHL5	psi-mi:“MI:0915”(physical association)	0.970
ADRM1	UCHL5	psi-mi:“MI:0407”(direct interaction)	0.970
UCHL5	ADRM1	psi-mi:“MI:0407”(direct interaction)	0.970
ADRM1	UCHL5	psi-mi:“MI:0403”(colocalization)	0.970
UCHL5	ADRM1	psi-mi:“MI:0403”(colocalization)	0.970
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
UCHL5	PSMD12	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
ADRM1	PSMD2	psi-mi:“MI:0915”(physical association)	0.760
PSMD2	ADRM1	psi-mi:“MI:0403”(colocalization)	0.760
PSMD1	ADRM1	psi-mi:“MI:0407”(direct interaction)	0.750
ADRM1	PSMD1	psi-mi:“MI:0407”(direct interaction)	0.750

BioGRID (558): ADRM1 (Affinity Capture-MS), UBC (Two-hybrid), UCHL5 (Two-hybrid), ADRM1 (Biochemical Activity), ADRM1 (Affinity Capture-Western), ADRM1 (Affinity Capture-MS), ADRM1 (Affinity Capture-MS), ADRM1 (Affinity Capture-MS), ADRM1 (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMC6 (Affinity Capture-MS), PSMC3 (Affinity Capture-MS)

ESM2 similar proteins: A1L5A6, A2VDN6, A4IGK4, O00401, O08816, O12940, O35226, O43395, O48726, O60784, O88746, P40855, P50503, P55036, Q15459, Q16186, Q2KIA6, Q3SZD1, Q4WTC0, Q58DA0, Q5R5F1, Q5R684, Q5R7U2, Q5XHH7, Q5ZLF0, Q60415, Q62698, Q68FJ8, Q6GN67, Q6NRL6, Q6NZ09, Q6P877, Q6PDL0, Q7ZXD6, Q84L30, Q84L31, Q84L33, Q8BUR9, Q8K4Z5, Q8R1Q8

Diamond homologs: A1L5A6, O48726, Q09289, Q16186, Q556N5, Q6GN67, Q6NZ09, Q6P877, Q7K2G1, Q7ZXD6, Q98SH3, Q9JKV1, Q9JMB5, Q9USM1, Q9Y7Y6, O13563

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ADRM1	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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	16	54.4×	2e-22
Vpu mediated degradation of CD4	16	51.8×	3e-22
Autodegradation of the E3 ubiquitin ligase COP1	16	51.8×	3e-22
Ubiquitin-dependent degradation of Cyclin D	16	51.8×	3e-22
Regulation of ornithine decarboxylase (ODC)	15	49.7×	4e-21
Vif-mediated degradation of APOBEC3G	16	49.5×	5e-22
AUF1 (hnRNP D0) binds and destabilizes mRNA	16	48.4×	5e-22
Degradation of AXIN	16	48.4×	5e-22

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of DNA repair	5	18.7×	1e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	21	11.4×	7e-14
ubiquitin-dependent protein catabolic process	9	7.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625661	GRCh37/hg19 20q13.2-13.33(chr20:54143747-62194881)	Pathogenic

SpliceAI

1524 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62303760:G:GT	donor_gain	1.0000
20:62303779:GAC:G	donor_gain	1.0000
20:62303780:ACGT:A	donor_loss	1.0000
20:62303781:CG:C	donor_loss	1.0000
20:62303782:G:GG	donor_gain	1.0000
20:62304450:T:TA	acceptor_gain	1.0000
20:62304455:TGCCA:T	acceptor_loss	1.0000
20:62304456:GCCAG:G	acceptor_loss	1.0000
20:62304457:CCAG:C	acceptor_loss	1.0000
20:62304458:CA:C	acceptor_loss	1.0000
20:62304459:A:AG	acceptor_gain	1.0000
20:62304459:AG:A	acceptor_gain	1.0000
20:62304459:AGGA:A	acceptor_loss	1.0000
20:62304460:G:GA	acceptor_loss	1.0000
20:62304460:G:GG	acceptor_gain	1.0000
20:62304460:GG:G	acceptor_gain	1.0000
20:62304574:GCAGG:G	donor_loss	1.0000
20:62304575:CAGG:C	donor_loss	1.0000
20:62304577:GGTAT:G	donor_loss	1.0000
20:62304578:G:A	donor_loss	1.0000
20:62304579:T:A	donor_loss	1.0000
20:62306192:TGCA:T	acceptor_loss	1.0000
20:62306195:AG:A	acceptor_gain	1.0000
20:62306196:GG:G	acceptor_gain	1.0000
20:62306237:TCAAC:T	donor_gain	1.0000
20:62306288:G:GT	donor_gain	1.0000
20:62306318:GCG:G	donor_gain	1.0000
20:62306319:CG:C	donor_loss	1.0000
20:62306320:GG:G	donor_loss	1.0000
20:62306322:T:G	donor_loss	1.0000

AlphaMissense

2647 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62303654:G:A	G29E	1.000
20:62303681:T:A	V38E	1.000
20:62303701:G:A	G45R	1.000
20:62303701:G:C	G45R	1.000
20:62303701:G:T	G45W	1.000
20:62303702:G:A	G45E	1.000
20:62303735:T:C	L56P	1.000
20:62303740:C:G	H58D	1.000
20:62303749:T:A	W61R	1.000
20:62303749:T:C	W61R	1.000
20:62304468:T:A	I74N	1.000
20:62304473:T:C	F76L	1.000
20:62304474:T:G	F76C	1.000
20:62304475:C:A	F76L	1.000
20:62304475:C:G	F76L	1.000
20:62304492:T:C	F82S	1.000
20:62304534:T:C	L96P	1.000
20:62304539:T:C	F98L	1.000
20:62304541:C:A	F98L	1.000
20:62304541:C:G	F98L	1.000
20:62307772:T:C	L267P	1.000
20:62308093:T:C	L310P	1.000
20:62308390:C:A	A346D	1.000
20:62308459:C:A	A369D	1.000
20:62303650:G:C	A28P	0.999
20:62303651:C:A	A28E	0.999
20:62303653:G:A	G29R	0.999
20:62303653:G:C	G29R	0.999
20:62303654:G:T	G29V	0.999
20:62303660:T:A	M31K	0.999

dbSNP variants (sampled 300 via entrez): RS1000405216 (20:62304266 C>G,T), RS1000471418 (20:62302400 C>G,T), RS1000561190 (20:62308847 T>C,G), RS1000627913 (20:62307956 T>C), RS1000736242 (20:62305240 A>G,T), RS1000746120 (20:62305053 G>A), RS1001114689 (20:62301634 CTATTAT>C,CTAT,CTATTATTAT), RS1001188217 (20:62301941 C>T), RS1001366858 (20:62305995 G>A), RS1002122838 (20:62308232 G>C), RS1002711399 (20:62304652 C>T), RS1002933558 (20:62302825 A>T), RS1003242293 (20:62308955 C>A,T), RS1004025830 (20:62305599 C>G,T), RS1004923612 (20:62305130 T>C)

Disease associations

OMIM: gene MIM:610650 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): prostate cancer (MONDO:0008315), breast ductal adenocarcinoma (MONDO:0005590), developmental and epileptic encephalopathy (MONDO:0100620)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001942_4	Prostate cancer	4.000000e-08

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3710002 (SINGLE PROTEIN), CHEMBL5291684 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195599 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195600 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195601 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195602 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195603 (PROTEIN-PROTEIN INTERACTION)

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

66 potent at pChembl≥5 of 68 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
7.87	Kd	13.47	nM	CHEMBL5653589
7.87	ED50	13.47	nM	CHEMBL5653589
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

PubChem BioAssay actives

62 with measured affinity, of 142 total; 34 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147810: Binding affinity to human ADRM1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0135	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
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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147810: Binding affinity to human ADRM1 incubated for 45 mins by Kinobead based pull down assay	kd	7.0887	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
Cyclosporine	increases expression	3
bisphenol A	affects expression, decreases expression	2
Cisplatin	increases activity, increases expression, increases reaction, affects binding, increases phosphorylation (+1 more)	2
Particulate Matter	affects expression, increases reaction, affects cotreatment, increases abundance, increases expression	2
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
JP8 aviation fuel	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

60 unique, capped per target: 60 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

Cellosaurus cell lines

4 cell lines: 3 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2R8	Abcam HEK293T ADRM1 KO	Transformed cell line	Female
CVCL_D9XB	Ubigene HeLa ADRM1 KO	Cancer cell line	Female
CVCL_E3BL	HEK293T ADRM1 K21R/K34R	Transformed cell line	Female
CVCL_E3BM	HEK293T ADRM1 K21R/K34R agDD-GFP	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer