USP28

Summary

USP28 (ubiquitin specific peptidase 28, HGNC:12625) is a protein-coding gene on chromosome 11q23.2, encoding Ubiquitin carboxyl-terminal hydrolase 28 (Q96RU2). Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability.

The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers.

Source: NCBI Gene 57646 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 145 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001346252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12625
Approved symbol	USP28
Name	ubiquitin specific peptidase 28
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1515
Ensembl gene	ENSG00000048028
Ensembl biotype	protein_coding
OMIM	610748
Entrez	57646

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 42 protein_coding, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000003302, ENST00000535607, ENST00000537490, ENST00000537642, ENST00000537706, ENST00000538224, ENST00000538475, ENST00000540438, ENST00000540925, ENST00000542033, ENST00000544272, ENST00000544750, ENST00000544967, ENST00000545540, ENST00000545608, ENST00000696972, ENST00000696973, ENST00000881761, ENST00000881762, ENST00000881763, ENST00000881764, ENST00000881765, ENST00000881766, ENST00000881767, ENST00000881768, ENST00000881769, ENST00000881770, ENST00000881771, ENST00000881772, ENST00000926116, ENST00000926117, ENST00000926118, ENST00000926119, ENST00000926120, ENST00000926121, ENST00000926122, ENST00000926123, ENST00000926124, ENST00000926125, ENST00000926126, ENST00000926127, ENST00000947932, ENST00000947933, ENST00000947934, ENST00000947935, ENST00000947936, ENST00000947937, ENST00000947938, ENST00000947939

RefSeq mRNA: 50 — MANE Select: NM_001346252 NM_001301029, NM_001346252, NM_001346253, NM_001346254, NM_001346255, NM_001346257, NM_001346258, NM_001346259, NM_001346260, NM_001346261, NM_001346262, NM_001346263, NM_001346264, NM_001346265, NM_001346267, NM_001346268, NM_001346269, NM_001346270, NM_001346271, NM_001346272, NM_001346273, NM_001400784, NM_001400785, NM_001400786, NM_001400787, NM_001400788, NM_001400789, NM_001400790, NM_001400791, NM_001400792, NM_001400793, NM_001400794, NM_001400795, NM_001400796, NM_001400797, NM_001400799, NM_001400800, NM_001400801, NM_001400802, NM_001400803, NM_001400804, NM_001400805, NM_001400806, NM_001400807, NM_001400809, NM_001400810, NM_001400811, NM_001400812, NM_001400813, NM_020886

CCDS: CCDS31680, CCDS73394, CCDS86248, CCDS91596

Canonical transcript exons

ENST00000696973 — 26 exons

Exon	Start	End
ENSE00000747349	113817658	113817837
ENSE00000930601	113831920	113831993
ENSE00001106032	113806489	113806584
ENSE00001126239	113812276	113812504
ENSE00001126249	113813885	113813955
ENSE00001126259	113815174	113815382
ENSE00003465095	113854258	113854335
ENSE00003469441	113841663	113841768
ENSE00003494106	113808298	113808437
ENSE00003502496	113834249	113834335
ENSE00003506144	113801483	113801678
ENSE00003507655	113827233	113827360
ENSE00003509132	113823605	113823700
ENSE00003531958	113840598	113840757
ENSE00003576391	113829197	113829345
ENSE00003581147	113803158	113803281
ENSE00003587826	113804868	113805046
ENSE00003618520	113809063	113809254
ENSE00003619097	113852501	113852633
ENSE00003637213	113804673	113804751
ENSE00003644996	113833420	113833557
ENSE00003669958	113830867	113830943
ENSE00003676615	113803798	113803877
ENSE00003969098	113807951	113808136
ENSE00003969105	113797875	113799415
ENSE00003969345	113875445	113875572

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 95.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3807 / max 159.9754, expressed in 1738 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122356	7.0188	1645
122357	3.3619	1474

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	95.30	gold quality
right atrium auricular region	UBERON:0006631	95.21	gold quality
heart left ventricle	UBERON:0002084	95.20	gold quality
cardiac atrium	UBERON:0002081	95.16	gold quality
cardiac ventricle	UBERON:0002082	95.16	gold quality
muscle of leg	UBERON:0001383	95.06	gold quality
heart right ventricle	UBERON:0002080	94.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.97	gold quality
muscle organ	UBERON:0001630	94.73	gold quality
skeletal muscle organ	UBERON:0014892	94.73	gold quality
apex of heart	UBERON:0002098	94.59	gold quality
left ventricle myocardium	UBERON:0006566	94.40	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.03	silver quality
heart	UBERON:0000948	93.92	gold quality
myocardium	UBERON:0002349	93.83	gold quality
vastus lateralis	UBERON:0001379	93.63	gold quality
skeletal muscle tissue	UBERON:0001134	93.57	gold quality
quadriceps femoris	UBERON:0001377	93.50	gold quality
cerebellar hemisphere	UBERON:0002245	93.28	gold quality
cerebellar cortex	UBERON:0002129	93.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.93	gold quality
muscle tissue	UBERON:0002385	92.90	gold quality
oviduct epithelium	UBERON:0004804	92.83	gold quality
ventricular zone	UBERON:0003053	92.76	gold quality
tibialis anterior	UBERON:0001385	92.33	gold quality
cerebellum	UBERON:0002037	92.25	gold quality
deltoid	UBERON:0001476	91.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.75	gold quality
buccal mucosa cell	CL:0002336	91.32	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	255.75
E-ANND-3	yes	6.62
E-MTAB-10018	no	191.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN

miRNA regulators (miRDB)

113 targeting USP28, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836

Literature-anchored findings (GeneRIF, showing 40)

• molecular cloning of USP28 & characterization of alternatively spliced products and tissue-specific isoforms (PMID:11597335)
• Using a human cell line that faithfully recapitulated the Chk2-p53-PUMA pathway, we show that USP28 is required to stabilize Chk2 and 53BP1 in response to DNA damage. (PMID:16901786)
• High expression levels of USP28 are found in colon and breast carcinomas, and stabilization of MYC by USP28 is essential for tumour-cell proliferation. (PMID:17558397)
• Usp28 dissociates from Fbw7alpha in response to UV irradiation, providing a mechanism how Fbw7-mediated degradation of Myc is enhanced upon DNA damage. (PMID:17873522)
• A new pathway that could be targeted at the level of GSK-3, Fbw7, or USP28 to influence HIF-1alpha-dependent processes like angiogenesis and metastasis. (PMID:22144179)
• USP28 gene expression is down regulated by oxidative stress through the mediation of reactive oxygen species (PMID:23832602)
• Study reveals a critical mechanism underlying the epigenetic regulation by USP28. (PMID:24075993)
• Usp28 expression was indentified as a independent predictors of survival (P = 0.001) and potentially valuable in prognostic evaluation of bladder cancer (PMID:24347490)
• USP28 is not a critical factor in double-strand break metabolism and is unlikely to be an attractive target for therapeutic intervention aimed at chemotherapy sensitization. (PMID:24687851)
• identified Usp28 as a c-MYC target gene highly expressed in colorectal cancers, which indicates that USP28 and c-MYC form a positive feedback loop that maintains high c-MYC protein levels in tumors (PMID:24960159)
• USP28 has a chain preference activity for Lys(11), Lys(48), and Lys(63) diubiquitin linkages (PMID:25359778)
• Dual regulation of Fbw7 activity by Usp28 is a safeguard mechanism for maintaining physiological levels of proto-oncogenic Fbw7 substrates, which is equivalently disrupted by loss or overexpression of Usp28. (PMID:25437563)
• Data indicte that deubiquitinating enzyme USP28 was targeted by microRNA miR-4295. (PMID:25656529)
• These results showed that USP28 is overexpressed in human glioblastomas and it contributes to glioma tumorigenicity. (PMID:26209720)
• findings provide a first insight into understanding how the enzymatic activity of Usp28 is regulated by its non-catalytic UBR and endogenous ligands. (PMID:26268556)
• The authors identified 53BP1 and USP28 as essential components acting upstream of p53, evoking p21-dependent cell cycle arrest in response not only to centrosome loss, but also to other distinct defects causing prolonged mitosis. (PMID:27371829)
• USP28-53BP1-p53-p21 signaling pathway is also required to arrest cell growth after a prolonged prometaphase. (PMID:27432896)
• analysis of centrinone resistance identified a 53BP1-USP28 module as critical for communicating mitotic challenges to the p53 circuit and TRIM37 as an enforcer of the singularity of centrosome assembly. (PMID:27432897)
• 53BP1-USP28 cooperation is essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DNA double-strand repair regulation. (PMID:27546791)
• USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP) (PMID:29089421)
• Lack of USP28 promotes a more malignant state of breast cancer cells, indicated by an epithelial-to-mesenchymal (EMT) transition, elevated proliferation, migration, and angiogenesis as well as a decreased adhesion. (PMID:29545478)
• USP28 enhances MAPK activity through the stabilization of RAF family members and is a key factor in BRAF inhibitor resistance. (PMID:29880484)
• Knockdown of USP28 enhanced the radiosensitivity of esophageal cancer cells by destabilizing c-Myc and enhancing the accumulation of HIF-1alpha. Therefore, USP28 may serve as a novel therapeutic target to overcome esophageal cancer radioresistance. (PMID:30206969)
• consequential impacts of USP28-mediated stabilization of LIN28A protein on enhancing cancer cell viability, migration and ultimately augmenting LIN28A-mediated tumor progression. Overall, these data suggest that a synergistic, combinatorial approach of targeting LIN28A with USP28 would contribute to effective cancer therapeutics. (PMID:30543854)
• The effect of USP28 on cell proliferation was mediated by regulating the expression of p53, p21 and p16(INK4a). (PMID:30910399)
• We confirm oligomeric states of USP25 and USP28 in cells and show that modulating oligomerization affects substrate stabilization in accordance with in vitro activity data (PMID:30926242)
• Our work led to the identification of significant differences between USP25 and USP28 and provided the molecular basis for the development of new and highly specific anti-cancer drugs (PMID:30926243)
• The MTH1 inhibitor TH588 is a microtubule-modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway. (PMID:31604991)
• Deubiquitinase USP28 inhibits ubiquitin ligase KLHL2-mediated uridine-cytidine kinase 1 degradation and confers sensitivity to 5’-azacytidine-resistant human leukemia cells. (PMID:31938050)
• A non-canonical role of caspase-8 exploited by cancer cells to override the p53-dependent G2/M cell-cycle checkpoint through cleavage of USP28. (PMID:31982308)
• MicroRNA-216b suppresses the cell growth of hepatocellular carcinoma by inhibiting Ubiquitin-specific peptidase 28 expression. (PMID:32053284)
• Maintaining protein stability of Np63 via USP28 is required by squamous cancer cells. (PMID:32128997)
• USP28 and USP25 are downregulated by Vismodegib in vitro and in colorectal cancer cell lines. (PMID:32578360)
• Exosomal miR-500a-5p derived from cancer-associated fibroblasts promotes breast cancer cell proliferation and metastasis through targeting USP28. (PMID:33664871)
• USP28 promotes aerobic glycolysis of colorectal cancer by increasing stability of FOXC1. (PMID:34106567)
• USP28 facilitates pancreatic cancer progression through activation of Wnt/beta-catenin pathway via stabilising FOXM1. (PMID:34584067)
• The deubiquitinase USP28 stabilizes the expression of RecQ family helicases and maintains the viability of triple negative breast cancer cells. (PMID:34822842)
• Loss of USP28 and SPINT2 expression promotes cancer cell survival after whole genome doubling. (PMID:34962618)
• USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K. (PMID:35364627)
• Inhibition of deubiquitinase USP28 attenuates cyst growth in autosomal dominant polycystic kidney disease. (PMID:36442624)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp28	ENSDARG00000008880
mus_musculus	Usp28	ENSMUSG00000032267
rattus_norvegicus	Usp28	ENSRNOG00000007325

Paralogs (71): USP2 (ENSG00000036672), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242), USP32 (ENSG00000170832)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 28 — Q96RU2 (reviewed: Q96RU2)

Alternative names: Deubiquitinating enzyme 28, Ubiquitin thioesterase 28, Ubiquitin-specific-processing protease 28

All UniProt accessions (14): A0A8V8TKW5, A0A8V8TLZ9, B4E3L3, Q96RU2, F5GZ74, F5H2G4, F5H6Q3, G3V1N5, H0YFA0, H0YFD7, H0YFT9, H0YFX3, H0YG96, H0YH19

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells.

Subunit / interactions. Interacts with ZNF304. Interacts with PRKD1. Interacts with TP53BP1. Interacts with isoform 1 of FBXW7; following DNA damage, dissociates from FBXW7 leading to degradation of MYC.

Subcellular location. Nucleus. Nucleoplasm.

Post-translational modifications. Degraded upon nickel ion level or hypoxia exposure. Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR. Phosphorylated by PRKD1.

Induction. Down-regulated upon hypoxia. Up-regulated by the transcription factor c-Jun/JUN in a KRAS-dependent manner in colorectal cancer (CRC) cells.

Similarity. Belongs to the peptidase C19 family. USP28 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96RU2-1	1	yes
Q96RU2-2	2
Q96RU2-3	3

RefSeq proteins (50): NP_001287958, NP_001333181, NP_001333182, NP_001333183, NP_001333184, NP_001333186, NP_001333187, NP_001333188, NP_001333189, NP_001333190, NP_001333191, NP_001333192, NP_001333193, NP_001333194, NP_001333196, NP_001333197, NP_001333198, NP_001333199, NP_001333200, NP_001333201, NP_001333202, NP_001387713, NP_001387714, NP_001387715, NP_001387716, NP_001387717, NP_001387718, NP_001387719, NP_001387720, NP_001387721, NP_001387722, NP_001387723, NP_001387724, NP_001387725, NP_001387726, NP_001387728, NP_001387729, NP_001387730, NP_001387731, NP_001387732, NP_001387733, NP_001387734, NP_001387735, NP_001387736, NP_001387738, NP_001387739, NP_001387740, NP_001387741, NP_001387742, NP_065937 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family
IPR054108	USP25/28_UIM	Conserved_site
IPR054109	UBA_8	Domain

Pfam: PF00443, PF21909, PF22566

UniProt features (74 total): helix 27, strand 18, modified residue 5, turn 5, splice variant 3, region of interest 3, compositionally biased region 3, domain 2, active site 2, cross-link 2, mutagenesis site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
6HEI	X-RAY DIFFRACTION	1.64
7TUO	X-RAY DIFFRACTION	1.96
6HEH	X-RAY DIFFRACTION	2.26
8P19	X-RAY DIFFRACTION	2.45
8P14	X-RAY DIFFRACTION	2.57
9SUU	X-RAY DIFFRACTION	2.75
8P1P	X-RAY DIFFRACTION	2.76
6HEJ	X-RAY DIFFRACTION	2.79
8P1Q	X-RAY DIFFRACTION	2.79
8HJE	X-RAY DIFFRACTION	2.85
6HEK	X-RAY DIFFRACTION	3.03
6H4I	X-RAY DIFFRACTION	3.22
6H4H	X-RAY DIFFRACTION	3.5
2LVA	SOLUTION NMR
2MUU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RU2-F1	74.20	0.33

Functional residue map

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

Catalytic / active sites (2): 600 (proton acceptor); 171 (nucleophile)

Post-translational modifications (7): 67, 375, 550, 714, 1048, 99, 759

Mutagenesis-validated functional residues (2):

Position	Phenotype
171	abolishes deubiquitinase activity.
899	prevents znf304 ubiquitination reduction.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 184 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, HORIUCHI_WTAP_TARGETS_DN, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CTATGCA_MIR153, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, WANG_LMO4_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY

GO Biological Process (12): DNA damage checkpoint signaling (GO:0000077), DNA repair (GO:0006281), DNA damage response (GO:0006974), cell population proliferation (GO:0008283), response to ionizing radiation (GO:0010212), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), cellular response to UV (GO:0034644), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), protein deubiquitination involved in ubiquitin-dependent protein catabolic process (GO:0071947), proteolysis (GO:0006508), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (6): cysteine-type deubiquitinase activity (GO:0004843), deubiquitinase activity (GO:0101005), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear body (GO:0016604), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ubiquitin-dependent protein catabolic process	2
cellular anatomical structure	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
cellular process	1
response to radiation	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
response to UV	1
cellular response to light stimulus	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
protein deubiquitination	1
protein metabolic process	1
proteasomal protein catabolic process	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
ubiquitin-like protein peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
cellular_component	1

Protein interactions and networks

STRING

1868 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP28	TP53BP1	Q12888	993
USP28	FBXW7	Q969H0	952
USP28	CHEK2	O96017	850
USP28	USP8	P40818	752
USP28	USP2	O75604	739
USP28	ZUP1	Q96AP4	693
USP28	USP14	P54578	660
USP28	USP36	Q9P275	650
USP28	USP13	Q92995	631
USP28	USP37	Q86T82	630
USP28	USP1	O94782	628
USP28	USP22	Q9UPT9	628
USP28	OTUB1	Q96FW1	626
USP28	USP5	P45974	613
USP28	PLK1	P53350	613

IntAct

45 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
BRCA1	BRCA1	psi-mi:“MI:0914”(association)	0.650
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
SENP2	PGK2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
USP28	PCNA	psi-mi:“MI:0915”(physical association)	0.370
CFTR	USP28	psi-mi:“MI:0915”(physical association)	0.370
FOXK1	PHKG2	psi-mi:“MI:0914”(association)	0.350
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
USP28	AQR	psi-mi:“MI:0914”(association)	0.350
USP25	ANXA1	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ANOS1	ZNF724	psi-mi:“MI:0914”(association)	0.350
SPPL2B	GPR89A	psi-mi:“MI:0914”(association)	0.350
KLHL2	DCTN6	psi-mi:“MI:0914”(association)	0.350
RPL35A	SMCHD1	psi-mi:“MI:0914”(association)	0.350
H2AP	GNPAT	psi-mi:“MI:0914”(association)	0.350
MRPS7	CALU	psi-mi:“MI:0914”(association)	0.350
USP28	OFD1	psi-mi:“MI:0914”(association)	0.350
ST6GAL1	HLA-B	psi-mi:“MI:0914”(association)	0.350
MSGN1	TCF4	psi-mi:“MI:0914”(association)	0.350
PAFAH2	CTU2	psi-mi:“MI:0914”(association)	0.350
MRPS7	RPSA2	psi-mi:“MI:0914”(association)	0.350
COMTD1	TARS3	psi-mi:“MI:0914”(association)	0.350
COMTD1	TNPO2	psi-mi:“MI:0914”(association)	0.350

BioGRID (192): PLA2G2A (Biochemical Activity), USP28 (Biochemical Activity), UBC (Biochemical Activity), KDM1A (Affinity Capture-Western), USP28 (Affinity Capture-Western), USP28 (Reconstituted Complex), KDM1A (Biochemical Activity), USP28 (Biochemical Activity), USP28 (Affinity Capture-MS), MYC (Affinity Capture-Western), USP28 (Affinity Capture-Western), USP28 (Affinity Capture-MS), USP28 (Affinity Capture-MS), USP28 (Affinity Capture-MS), UBC (Co-crystal Structure)

ESM2 similar proteins: A0A0R4IB93, A1A5P5, A1Z7K9, A2XDG4, A3AF13, A3KMI0, A6QR55, B2GUZ1, D3ZJ96, F6V6I0, F6Z5C0, F8VPZ3, O22207, P29375, P35123, P51784, Q09879, Q13107, Q14149, Q2HJE4, Q30DN6, Q3UXZ9, Q3V0C5, Q5D006, Q5I043, Q5RCD3, Q5ZID5, Q5ZM45, Q62240, Q6NZP1, Q76LT8, Q80U87, Q80Y84, Q86UV5, Q8BWR4, Q8NFA0, Q8R5C8, Q8R5H1, Q93Y01, Q96RU2

Diamond homologs: A0A0R4IB93, A0JM59, A1CIL1, A1CW53, A2XDG4, A3AF13, A5PN09, A6QNM7, A7Z056, B1WBD7, B2GUZ1, B8NSV5, D3ZJ96, F6Z5C0, O22207, O60079, O94966, Q0CT11, Q0E2F9, Q0VA64, Q13107, Q2HJE4, Q2UUG8, Q3UJD6, Q3V0C5, Q4VSI4, Q5I043, Q5R5Z6, Q5RCD3, Q5ZM45, Q60MK8, Q6A4J8, Q6J1Y9, Q6PAW2, Q6U7I1, Q6ZQ93, Q70CQ2, Q76LT8, Q7JKC3, Q84WU2

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
USP28	up-regulates	MYC	deubiquitination
ATM	“up-regulates activity”	USP28	phosphorylation
USP28	“up-regulates quantity by stabilization”	CDH1	deubiquitination
ATR	“up-regulates activity”	USP28	phosphorylation
ATM	“down-regulates activity”	USP28	phosphorylation
USP28	“up-regulates quantity by stabilization”	UCK1	deubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	117
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4857 predictions. Top by Δscore:

Variant	Effect	Δscore
11:113799412:TTTT:T	acceptor_gain	1.0000
11:113799413:TTT:T	acceptor_gain	1.0000
11:113799413:TTTC:T	acceptor_loss	1.0000
11:113799414:TT:T	acceptor_gain	1.0000
11:113799415:TCTG:T	acceptor_loss	1.0000
11:113799416:C:CC	acceptor_gain	1.0000
11:113799416:C:CG	acceptor_loss	1.0000
11:113799417:T:G	acceptor_loss	1.0000
11:113801479:ATAC:A	donor_loss	1.0000
11:113801481:A:AG	donor_loss	1.0000
11:113801482:C:A	donor_loss	1.0000
11:113801676:CTC:C	acceptor_gain	1.0000
11:113801677:TC:T	acceptor_gain	1.0000
11:113801678:CC:C	acceptor_gain	1.0000
11:113801679:C:CC	acceptor_gain	1.0000
11:113801679:C:T	acceptor_loss	1.0000
11:113803796:A:AC	donor_gain	1.0000
11:113803797:C:CC	donor_gain	1.0000
11:113803875:CTT:C	acceptor_gain	1.0000
11:113804669:TTACC:T	donor_loss	1.0000
11:113804670:TACCT:T	donor_loss	1.0000
11:113804671:A:AC	donor_gain	1.0000
11:113804671:A:C	donor_loss	1.0000
11:113804672:C:CC	donor_gain	1.0000
11:113804672:CCTT:C	donor_gain	1.0000
11:113804747:TTGAT:T	acceptor_gain	1.0000
11:113804748:TGAT:T	acceptor_gain	1.0000
11:113804749:GAT:G	acceptor_gain	1.0000
11:113804750:AT:A	acceptor_gain	1.0000
11:113804751:TCTG:T	acceptor_loss	1.0000

AlphaMissense

7513 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:113801513:A:G	W1010R	1.000
11:113801513:A:T	W1010R	1.000
11:113806496:A:G	L798P	1.000
11:113812452:C:T	G599E	1.000
11:113812482:A:T	V589D	1.000
11:113827310:A:C	F370L	1.000
11:113827310:A:T	F370L	1.000
11:113827312:A:G	F370L	1.000
11:113827314:C:G	R369T	1.000
11:113799376:A:G	L1033P	0.999
11:113799385:A:G	L1030P	0.999
11:113801511:C:A	W1010C	0.999
11:113801511:C:G	W1010C	0.999
11:113803162:A:G	L953P	0.999
11:113803174:C:G	R949P	0.999
11:113803822:C:T	G905D	0.999
11:113803823:C:G	G905R	0.999
11:113803874:A:G	W888R	0.999
11:113803874:A:T	W888R	0.999
11:113804728:G:T	A868D	0.999
11:113804883:A:G	L855P	0.999
11:113804898:A:G	F850S	0.999
11:113804907:A:G	L847P	0.999
11:113804910:A:G	L846P	0.999
11:113804916:C:G	R844P	0.999
11:113806500:C:A	G797W	0.999
11:113812309:A:C	Y647D	0.999
11:113812314:A:G	L645P	0.999
11:113812325:A:C	S641R	0.999
11:113812325:A:T	S641R	0.999

dbSNP variants (sampled 300 via entrez): RS1000009709 (11:113871101 C>G), RS1000023270 (11:113840844 T>C), RS1000044947 (11:113822790 A>G), RS1000070362 (11:113797991 G>T), RS1000095910 (11:113847141 C>T), RS1000116408 (11:113836645 T>C), RS1000128181 (11:113804526 C>T), RS1000154252 (11:113873651 C>T), RS1000248635 (11:113853332 A>C,T), RS1000313414 (11:113810687 T>G), RS1000336095 (11:113798407 T>C), RS1000343000 (11:113843199 T>C), RS1000350940 (11:113859354 T>C), RS1000356239 (11:113798091 T>G), RS1000442957 (11:113867053 G>A)

Disease associations

OMIM: gene MIM:610748 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

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

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007328_51	Alcohol consumption (drinks per week)	3.000000e-08
GCST010204_33	Low density lipoprotein cholesterol levels	2.000000e-08
GCST010320_89	PR interval	2.000000e-09
GCST010321_69	PR interval	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004462	PR interval

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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 (1): CHEMBL2157853 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,714 (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
CHEMBL473417	VISMODEGIB	4	6,714

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — C19: Ubiquitin-specific protease

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
CAS-010	Inhibition	8.66	pIC50
USP28 inhibitor 9p	Inhibition	7.4	pIC50
CT1113	Inhibition	7.0	pIC50

ChEMBL bioactivities

360 potent at pChembl≥5 of 366 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	IC50	40	nM	CHEMBL5401467
7.00	IC50	100	nM	CHEMBL5431014
6.96	IC50	110	nM	CHEMBL5398929
6.82	IC50	150	nM	CHEMBL5402874
6.70	IC50	200	nM	CHEMBL4162425
6.70	IC50	200	nM	CHEMBL4443504
6.70	IC50	200	nM	CHEMBL4584152
6.70	IC50	200	nM	CHEMBL4451295
6.70	IC50	200	nM	CHEMBL4166283
6.70	IC50	200	nM	CHEMBL4160957
6.70	IC50	200	nM	CHEMBL4462420
6.70	IC50	200	nM	CHEMBL4587318
6.70	IC50	200	nM	CHEMBL4459980
6.70	IC50	200	nM	CHEMBL4585832
6.70	IC50	200	nM	CHEMBL4564585
6.70	IC50	200	nM	CHEMBL4555140
6.70	IC50	200	nM	CHEMBL4520325
6.70	IC50	200	nM	CHEMBL4531717
6.70	IC50	200	nM	CHEMBL4555153
6.70	IC50	200	nM	CHEMBL4539234
6.70	IC50	200	nM	CHEMBL4553263
6.70	IC50	200	nM	CHEMBL4569824
6.70	IC50	200	nM	CHEMBL4554623
6.70	IC50	200	nM	CHEMBL4561492
6.70	IC50	200	nM	CHEMBL4550664
6.70	IC50	200	nM	CHEMBL4531444
6.70	IC50	200	nM	CHEMBL4521950
6.70	IC50	200	nM	CHEMBL4526620
6.70	IC50	200	nM	CHEMBL4565142
6.70	IC50	200	nM	CHEMBL4579716
6.70	IC50	200	nM	CHEMBL4576536
6.70	IC50	200	nM	CHEMBL4571060
6.70	IC50	200	nM	CHEMBL4522604
6.70	IC50	200	nM	CHEMBL4575903
6.70	IC50	200	nM	CHEMBL4559692
6.70	IC50	200	nM	CHEMBL4541160
6.70	IC50	200	nM	CHEMBL4579633
6.70	IC50	200	nM	CHEMBL4546319
6.70	IC50	200	nM	CHEMBL4535613
6.70	IC50	200	nM	CHEMBL4586422
6.70	IC50	200	nM	CHEMBL4565690
6.70	IC50	200	nM	CHEMBL4561805
6.70	IC50	200	nM	CHEMBL4547579
6.70	IC50	200	nM	CHEMBL4564730
6.70	IC50	200	nM	CHEMBL4563419
6.70	IC50	200	nM	CHEMBL4539562
6.70	IC50	200	nM	CHEMBL4526977
6.70	IC50	200	nM	CHEMBL4585155
6.70	IC50	200	nM	CHEMBL4569303
6.70	IC50	200	nM	CHEMBL4537585

PubChem BioAssay actives

27 with measured affinity, of 101 total; 18 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
2-chloro-N-[4-chloro-3-(2,3-dihydro-1H-isoindol-5-yl)phenyl]-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	0.0400	uM
2-chloro-N-[4-chloro-3-(1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl]-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	0.1000	uM
3-amino-N-[(2S)-6-(3,8-diazabicyclo[3.2.1]octan-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	0.1100	uM
N-[3-[3-(aminomethyl)phenyl]-4-chlorophenyl]-2-chloro-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	0.1500	uM
N-[3-[4-(1-aminocyclopropyl)phenyl]-4-chlorophenyl]-2-chloro-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	0.3000	uM
N-[3-[4-(aminomethyl)phenyl]-4-chlorophenyl]-2-chloro-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	0.3600	uM
2-[[5-bromo-2-[[4-fluoro-3-(trifluoromethyl)phenyl]methoxy]phenyl]methylamino]ethanol	1558728: Inhibition of USP28 (unknown origin)	ic50	0.6000	uM
2-[[5-bromo-2-[[3-(trifluoromethoxy)phenyl]methoxy]phenyl]methylamino]ethanol	1930831: Inhibition of USP28 (unknown origin) using Ub-Rho100 as substrate by calorimetric analysis	ic50	1.1000	uM
N’-[3-[(4-chlorophenyl)methyl]-5-propylsulfanyltriazolo[4,5-d]pyrimidin-7-yl]ethane-1,2-diamine	1995227: Inhibition of USP28 (unknown origin)	ic50	1.1000	uM
N-[3-[4-(aminomethyl)phenyl]-5-chlorophenyl]-2-chloro-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	1.1300	uM
2-[[5-bromo-2-[(2,4,5-trifluorophenyl)methoxy]phenyl]methylamino]ethanol	1930831: Inhibition of USP28 (unknown origin) using Ub-Rho100 as substrate by calorimetric analysis	ic50	2.0000	uM
N-[3-[5-(aminomethyl)-2-pyridinyl]-4-chlorophenyl]-2-chloro-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	2.1300	uM
2-chloro-N-[4-chloro-3-[4-(dimethylamino)phenyl]phenyl]-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	2.8200	uM
2-chloro-N-[4-chloro-3-(4-methoxyphenyl)phenyl]-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	2.9400	uM
2-chloro-N-[4-chloro-3-(4-piperazin-1-ylphenyl)phenyl]-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	4.2400	uM
Vismodegib	2080132: Inhibition of wild type UP28 (unknown origin) (1 to 651 residues) expressed in Escherichia coli BL21 (DE3) cells using Ub-AMC as substrate by fluorescence based analysis	ic50	4.4100	uM
N-[3-(4-aminophenyl)-4-chlorophenyl]-2-chloro-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	5.6800	uM
N-[3-(2-aminophenyl)-4-chlorophenyl]-2-chloro-4-methylsulfonylbenzamide	1974200: Inhibition of USP28 (149 to 703 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate by fluorescence based analysis	ic50	8.5800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	7
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases mutagenesis	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression	1
nickel sulfate	decreases expression, decreases reaction, affects cotreatment, affects reaction, increases degradation	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	increases expression, affects cotreatment	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Caffeine	affects phosphorylation	1
Dieldrin	decreases response to substance	1

ChEMBL screening assays

32 unique, capped per target: 32 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2163015	Binding	Inhibition of USP28 by Ub-CHOP reporter assay	Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7 and USP47. — ACS Med Chem Lett

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3KW	N/Tert-1 USP28	Telomerase immortalized cell line	Male
CVCL_D8Y1	Ubigene HCT 116 USP28 KO	Cancer cell line	Male
CVCL_DX67	HAP1 USP25 (-) USP28 (-) 1	Cancer cell line	Male
CVCL_DX68	HAP1 USP25 (-) USP28 (-) 2	Cancer cell line	Male
CVCL_TW81	HAP1 USP28 (-) 1	Cancer cell line	Male
CVCL_TW82	HAP1 USP28 (-) 2	Cancer cell line	Male
CVCL_XU91	HAP1 USP28 (-) 3	Cancer cell line	Male
CVCL_XU92	HAP1 USP28 (-) 4	Cancer cell line	Male
CVCL_XU93	HAP1 USP28 (-) 5	Cancer cell line	Male

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
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NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
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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
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NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
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NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
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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
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