USP2

Summary

USP2 (ubiquitin specific peptidase 2, HGNC:12618) is a protein-coding gene on chromosome 11q23.3, encoding Ubiquitin carboxyl-terminal hydrolase 2 (O75604). Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1.

This gene encodes a member of the family of de-ubiquitinating enzymes, which belongs to the peptidase C19 superfamily. The encoded protein is a ubiquitin-specific protease which is required for TNF-alpha (tumor necrosis factor alpha) -induced NF-kB (nuclear factor kB) signaling. This protein deubiquitinates polyubiquitinated target proteins such as fatty acid synthase, murine double minute 2 (MDM2), MDM4/MDMX and cyclin D1. MDM2 and MDM4 are negative regulators of the p53 tumor suppressor and cyclin D1 is required for cell cycle G1/S transition. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 9099 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 89 total
• GTEx eGene: eQTL in 22 tissues, sQTL in 4 (q < 0.05)
• ChEMBL bioactivity: 124 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.62 (unconstrained)
• MANE Select transcript: NM_004205
• Notable: 89 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12618
Approved symbol	USP2
Name	ubiquitin specific peptidase 2
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	UBP41
Ensembl gene	ENSG00000036672
Ensembl biotype	protein_coding
OMIM	604725
Entrez	9099

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

MANE Select: ENST00000260187

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 2, TSL 4: 1, TSL 5: 1

ENST00000260187, ENST00000455332, ENST00000525189, ENST00000525735, ENST00000527843, ENST00000531070, ENST00000532613, ENST00000876643

RefSeq mRNA: 3 — MANE Select: NM_004205 NM_001243759, NM_004205, NM_171997

CCDS: CCDS58189, CCDS8422, CCDS8423

Canonical transcript exons

ENST00000260187 — 13 exons

Exon	Start	End
ENSE00000748555	119357981	119358061
ENSE00000796207	119357483	119357590
ENSE00000796208	119357187	119357307
ENSE00000930893	119357757	119357835
ENSE00001103488	119372707	119373521
ENSE00001206641	119381473	119381690
ENSE00001528116	119355215	119356922
ENSE00003482404	119358773	119358837
ENSE00003520403	119359537	119359660
ENSE00003604416	119360184	119360234
ENSE00003623976	119359231	119359342
ENSE00003631515	119359024	119359134
ENSE00003641240	119358149	119358252

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5069 / max 257.4886, expressed in 1151 samples.

Highest expression (Bgee): hindlimb stylopod muscle, gastrocnemius, testis, sperm, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

USP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	3.6e-30	+0.44	11:119368979:C:T
Cells Cultured fibroblasts	eqtl	4.9e-21	-0.57	11:119374639:G:A
Artery Tibial	eqtl	9.4e-16	-0.31	11:119379350:C:G
Colon Sigmoid	eqtl	3.2e-12	-0.33	11:119375998:C:T
Thyroid	eqtl	4.2e-12	-0.24	11:119375998:C:T
Breast Mammary Tissue	eqtl	1.8e-08	-0.27	11:119375998:C:T
Artery Aorta	eqtl	2.0e-08	-0.32	11:119373385:C:T
Esophagus Muscularis	eqtl	4.0e-07	-0.22	11:119398274:A:G
Pituitary	eqtl	5.7e-07	-0.31	11:119374639:G:A
Nerve Tibial	eqtl	8.6e-06	-0.17	11:119375998:C:T
Adipose Subcutaneous	eqtl	3.7e-05	-0.27	11:119375857:C:G
Adrenal Gland	eqtl	4.4e-04	-0.39	11:119374639:G:A
Esophagus Gastroesophageal Junction	eqtl	5.4e-04	+0.19	11:119475487:T:C
Esophagus Muscularis	sqtl	6.7e-03	+0.34	11:119456286:T:TTCTC
Brain Caudate basal ganglia	sqtl	8.0e-03	-2.06	11:119371808:CCCACCCA:C
Adipose Visceral Omentum	eqtl	1.3e-02	+0.23	11:119519622:G:T
Brain Putamen basal ganglia	eqtl	1.4e-02	-0.45	11:118494495:G:C
Adipose Subcutaneous	sqtl	1.4e-02	-1.16	11:118411189:C:T
Heart Atrial Appendage	sqtl	1.7e-02	-1.27	11:119442108:C:T
Stomach	eqtl	1.9e-02	-0.20	11:119379350:C:G

FANTOM5 promoters

showing 10 of 14 alternative TSS:

Promoter ID	TPM avg	Samples expressed
122713	5.2418	860
122719	0.8104	76
122721	0.3940	207
122720	0.3889	67
122722	0.3718	207
122724	0.3221	44
122718	0.2717	114
122723	0.1865	78
122717	0.1655	67
122714	0.1505	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	97.94	gold quality
gastrocnemius	UBERON:0001388	96.53	gold quality
left testis	UBERON:0004533	96.07	gold quality
sperm	CL:0000019	95.93	gold quality
apex of heart	UBERON:0002098	95.82	gold quality
right testis	UBERON:0004534	95.74	gold quality
secondary oocyte	CL:0000655	95.53	gold quality
muscle of leg	UBERON:0001383	95.34	gold quality
oocyte	CL:0000023	95.09	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.98	gold quality
heart left ventricle	UBERON:0002084	93.86	gold quality
cardiac ventricle	UBERON:0002082	93.62	gold quality
male germ cell	CL:0000015	93.55	gold quality
testis	UBERON:0000473	93.25	gold quality
right atrium auricular region	UBERON:0006631	93.22	gold quality
skeletal muscle organ	UBERON:0014892	92.22	gold quality
muscle organ	UBERON:0001630	92.21	gold quality
mucosa of transverse colon	UBERON:0004991	92.08	gold quality
metanephros cortex	UBERON:0010533	91.66	gold quality
cardiac atrium	UBERON:0002081	91.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.28	gold quality
heart	UBERON:0000948	89.85	gold quality
cerebellar hemisphere	UBERON:0002245	89.77	gold quality
cerebellar cortex	UBERON:0002129	89.71	gold quality
adenohypophysis	UBERON:0002196	89.17	gold quality
mucosa of stomach	UBERON:0001199	89.14	gold quality
cerebellum	UBERON:0002037	87.80	gold quality
right frontal lobe	UBERON:0002810	87.44	gold quality
caudate nucleus	UBERON:0001873	86.88	gold quality
adult mammalian kidney	UBERON:0000082	86.52	gold quality
skeletal muscle tissue	UBERON:0001134	86.47	gold quality
nucleus accumbens	UBERON:0001882	86.47	gold quality
biceps brachii	UBERON:0001507	86.38	gold quality
pituitary gland	UBERON:0000007	85.97	gold quality
putamen	UBERON:0001874	85.73	gold quality
vastus lateralis	UBERON:0001379	84.70	silver quality
right adrenal gland cortex	UBERON:0035827	84.24	gold quality
buccal mucosa cell	CL:0002336	83.95	silver quality
quadriceps femoris	UBERON:0001377	83.92	silver quality
popliteal artery	UBERON:0002250	83.92	gold quality
tibial artery	UBERON:0007610	83.90	gold quality
right uterine tube	UBERON:0001302	83.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.82	gold quality
muscle tissue	UBERON:0002385	83.67	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.50	gold quality
islet of Langerhans	UBERON:0000006	83.47	gold quality
heart right ventricle	UBERON:0002080	83.47	silver quality
left uterine tube	UBERON:0001303	83.25	gold quality
renal medulla	UBERON:0000362	83.17	gold quality
right adrenal gland	UBERON:0001233	83.05	gold quality
prefrontal cortex	UBERON:0000451	82.99	gold quality
left adrenal gland cortex	UBERON:0035825	82.77	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.58	gold quality
adrenal cortex	UBERON:0001235	82.54	gold quality
cingulate cortex	UBERON:0003027	82.41	gold quality
anterior cingulate cortex	UBERON:0009835	82.32	gold quality
left adrenal gland	UBERON:0001234	81.98	gold quality
frontal cortex	UBERON:0001870	81.82	gold quality
skin of leg	UBERON:0001511	81.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.79	gold quality
kidney	UBERON:0002113	81.75	gold quality
primary visual cortex	UBERON:0002436	81.72	gold quality
neocortex	UBERON:0001950	81.64	gold quality
brain	UBERON:0000955	81.60	gold quality
telencephalon	UBERON:0001893	81.57	gold quality
central nervous system	UBERON:0001017	81.51	gold quality
forebrain	UBERON:0001890	81.38	gold quality
body of tongue	UBERON:0011876	81.29	gold quality
amygdala	UBERON:0001876	81.26	gold quality
cerebellar vermis	UBERON:0004720	80.87	silver quality
transverse colon	UBERON:0001157	80.49	gold quality
superior surface of tongue	UBERON:0007371	80.42	gold quality
cerebral cortex	UBERON:0000956	80.26	gold quality
triceps brachii	UBERON:0001509	80.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.96	gold quality
deltoid	UBERON:0001476	79.91	silver quality
adrenal gland	UBERON:0002369	79.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.82	gold quality
tibial nerve	UBERON:0001323	79.72	gold quality
skin of abdomen	UBERON:0001416	79.71	gold quality
occipital lobe	UBERON:0002021	79.56	gold quality
pancreas	UBERON:0001264	79.43	gold quality
tongue	UBERON:0001723	79.41	gold quality
body of pancreas	UBERON:0001150	79.28	gold quality
small intestine	UBERON:0002108	79.15	gold quality
left ventricle myocardium	UBERON:0006566	79.01	silver quality
Ammon’s horn	UBERON:0001954	78.90	gold quality
spinal cord	UBERON:0002240	78.90	gold quality
ectocervix	UBERON:0012249	78.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	78.66	gold quality
zone of skin	UBERON:0000014	78.64	gold quality
cortex of kidney	UBERON:0001225	78.62	gold quality
lower esophagus	UBERON:0013473	78.61	gold quality
temporal lobe	UBERON:0001871	78.57	gold quality
rectum	UBERON:0001052	78.44	gold quality
lower esophagus mucosa	UBERON:0035834	78.19	gold quality
right lobe of liver	UBERON:0001114	78.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-2983	no	1018.03
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	157.6	medium
Choroid plexus	tissue	82.8
Retina	tissue	70.7
Testis	tissue	60.8	medium
Tongue	tissue	58.6
Nucleus accumbens	tissue	51.4
Cerebellum	tissue	50.0	medium
Kidney	tissue	49.9	high
Superior colliculi	tissue	48.3
Heart muscle	tissue	46.7	low
Thalamus	tissue	43.8
Caudate putamen	tissue	42.4
Hippocampal formation	tissue	42.3
Frontal cortex	tissue	42.0
Midbrain	tissue	41.3
Cerebral cortex	tissue	40.8	medium
Somatosensory cortex	tissue	40.8
Occipital cortex	tissue	40.3
Postcentral gyrus	tissue	39.2
Spinal cord	tissue	36.7
Basal ganglia	tissue	36.5	medium
Entorhinal cortex	tissue	36.4
Medulla oblongata	tissue	36.0
Prefrontal cortex	tissue	35.6
Putamen	tissue	35.4
Hippocampus	tissue	35.3	medium
Temporal cortex	tissue	34.8
Motor cortex	tissue	34.7
Corpus callosum	tissue	34.6
Ventral forebrain	tissue	34.4
Substantia nigra	tissue	34.2
Pons	tissue	34.1
Retrosplenial and cingulate cortex	tissue	33.9
Retrosplenial cortex	tissue	32.2
Periaqueductal gray	tissue	32.0
Insular cortex	tissue	32.0
Olfactory bulb	tissue	31.4
Amygdala	tissue	28.3
Septum	tissue	26.1
Hypothalamus	tissue	25.5
Parathyroid gland	tissue	22.8	low
Locus coeruleus	tissue	19.6
Pituitary gland	tissue	18.1
Liver	tissue	17.7	medium
Pancreas	tissue	17.1	medium
Small intestine	tissue	16.4	medium
Duodenum	tissue	13.1	medium
Fallopian tube	tissue	10.9	medium
Colon	tissue	9.6	medium
Esophagus	tissue	9.2	low
Adrenal gland	tissue	7.1	medium
Smooth muscle	tissue	6.3	medium
Skin 1	tissue	5.7	low
Rectum	tissue	5.7	medium
Epididymis	tissue	5.4	medium
Vagina	tissue	4.3	not detected
Salivary gland	tissue	4.3	medium
Adipose tissue	tissue	4.2	not detected
Endometrium 1	tissue	3.4	medium
Prostate	tissue	3.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Caudate nucleus (60.7), Flocculonodular lobe (52.4), Hippocampus, CA3 (52.3), Nucleus basalis of Meynert (52.0), Angular gyrus (white matter) (50.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLOCK

miRNA regulators (miRDB)

Targeting USP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 61 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-548B-3P	99.38	67.26	1000

Functional genomics

gnomAD constraint: pLI 0.00284, LOEUF 0.623, missense Z 1.49 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000260187 — one region, missense o/e 0.87.

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of Ubp41 is sufficient to elicit all features of apoptosis in human cells. (PMID:12566314)
• the isopeptidase USP2a plays a critical role in prostate cancer cell survival (PMID:15050917)
• USP2a is a novel regulator of the p53 pathway that acts through its ability to selectively target Mdm2. (PMID:17290220)
• USP2 were over-expressed in ovarian serous cystadenocarcinoma tissues, suggesting that the activity of ubiquitin-proteasome system is obviously enhanced in ovarian cancer. (PMID:17553343)
• Data show that ectopic expression of wild-type USP2a but not a catalytic mutant prevents Mdm2-mediated degradation of MdmX. (PMID:19838211)
• Findings suggest that targeting USP2 is an effective approach to induce growth suppression in the cancer cells addicted to cyclin D1 expression. (PMID:19917254)
• USP2-69 was upregulated in mesangial cells during mesangial proliferative glomerulonephritides in vivo and in vitro, which may relate to the proliferation of mesangial cells. (PMID:20403044)
• Data indicate that CHIP and USP2 show antagonistic functions in the control of AIF-mediated cell death, and implicate the role of the enzymes as a switch for cells to live or die under stresses that cause truncated AIF release. (PMID:21293491)
• the data support the conclusion that Usp2-45 action on epithelial Na(+) channel is promoted by various interactions, including through binding to Nedd4-2 (PMID:21478478)
• our results implicate USP2 as a novel positive regulator of TNF-alpha-induced NF-kappaB signaling and show that its expression is altered in tumor cells. (PMID:21480224)
• Etiology of nodular fasciitis seems to involve USP6 transcriptional upregulation due to its fusion with a strong ectopic promoter (MYH9). (PMID:21826056)
• a novel mechanism for the role of USP2a in mediating the stability of Aurora-A. (PMID:21890637)
• De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. (PMID:22179575)
• USP2a loss attenuates proliferation and migration in T24 human bladder cancer cells. (PMID:22370483)
• we have demonstrated that USP2a plays a negative regulatory role in IL-1beta- and SeV-induced NF-kappaB activation. (PMID:22611252)
• TRAF2 inhibits USP2a effect on K48- but not on K63-linked ubiquitin chains. (PMID:22659130)
• USP2a potentially mediates circadian disruption by suppressing the CRY1 degradation during inflammation. (PMID:22669941)
• USP2a antagonizes EGFR endocytosis and thus amplifies signaling activity from the receptor. (PMID:22710717)
• USP2a plays an important role in TCR signaling by deSUMOylating TRAF6 and mediating TRAF6-MALT1 interaction (PMID:23264041)
• USP2 and its substrate, fatty acid synthase (FASN), are over-expressed in glioma tissue. (PMID:23416128)
• USP2a increases intracellular glutathione content, thus interfering with the oxidative cascade triggered by chemotherapeutic agents. (PMID:24071644)
• Loss of USP2a expression is associated with glioblastoma. (PMID:24445145)
• findings demonstrated that USP2b deubiquitinates K63-linked polyubiquitin chains from TBK1 to terminate TBK1 activation and negatively regulate IFN-beta signaling and antiviral immune response. (PMID:25070846)
• The present study showed that USP2 expression is associated with TNBC cell line’s invasiveness and poor survival of breast cancer patients and may serve as a prognostic biomarker and therapeutic target for TNBC (PMID:25687182)
• Data suggest up-regulation of ASAH1 (acid ceramidase) activity by androgen in androgen-sensitive prostate cancer cells (but not other cancer cells) is mainly due to prolonged stability of ASAH1 by androgen-stimulated induction of USP2 expression. (PMID:25888580)
• Modulation of USP-2 expression plays a crucial role in cell cycle regulation by leptin and adiponectin. (PMID:26033248)
• Our findings suggest that USP2a mRNA may be considered as a diagnostic marker candidate for bladder cancer, in particular, to stratify MIBC patients with a more invasive phenotype. (PMID:26250800)
• Identify USP2 as a novel regulator of lipoprotein clearance owing to its ability to control ubiquitylation-dependent degradation of the LDLR by IDOL. (PMID:26666640)
• Authors show here USP2 is expressed in quiescent and activated T-cells and its expression is 50% lower in CTCL cell lines (MyLa2000, SeAx and Hut-78) than in normal T-cells. (PMID:27351221)
• the deubiquitinase USP2a translocates into the nucleus and binds to pY701-STAT1, and inhibits K48-linked ubiquitination and degradation of pY701-STAT1 (PMID:27434509)
• Data show that ubiquitin variants (Ubvs) that bind to USP2 or USP21 contain a similar core functional epitope, or “hot spot,” consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences. (PMID:27436899)
• The results show a connection between miR-125b and USP2 gene the etiology of psoriasis. They proceeded to show that modulation of nuclear factor kappa B-mediated inflammation is the likely mechanism through which this miRNA gene pair function (PMID:27479112)
• ML364 also caused a decrease in homologous recombination-mediated DNA repair. These effects by a small molecule inhibitor support a key role for USP2 as a regulator of cell cycle, DNA repair, and tumor cell growth. (PMID:27681596)
• Data suggest that ubiquitin (Ub) and neural precursor cell expressed developmentally down-regulated 8 (NEDD8) residues 4, 12, 14, and 72 serve as the molecular determinants for specific recognition by ubiquitin specific protease 2 protein (USP2). (PMID:28536428)
• In general, we collect and summarize the factors involved in the alternative splicing of USP2 in this review to further understand the mechanism behind the USP2’s alternative splicing (PMID:29230097)
• These findings have characterized an essential role of USP2a as a potential target for treatment of metastatic cancers. (PMID:29490279)
• USP2-mediated Twist/Bmi1 pathway represents a cell-intrinsic mechanism crucial for CSC regulation besides EMT and provides pre-clinical evidence that targeting USP2 is indeed a promising approach for anti-CSC therapy. (PMID:30918246)
• The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer. (PMID:32327714)
• Ubiquitin-specific protease 2a promotes hepatocellular carcinoma progression via deubiquitination and stabilization of RAB1A. (PMID:33074477)
• Disulfiram and 6-Thioguanine synergistically inhibit the enzymatic activities of USP2 and USP21. (PMID:33582217)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp2a	ENSDARG00000020107
mus_musculus	Usp2	ENSMUSG00000032010
rattus_norvegicus	Usp2	ENSRNOG00000006663
caenorhabditis_elegans		WBGENE00019259

Paralogs (71): USP28 (ENSG00000048028), 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), USP19 (ENSG00000172046), USP18 (ENSG00000184979), USP7 (ENSG00000187555), USP17L2 (ENSG00000223443), USP17L15 (ENSG00000223569), USP17L3 (ENSG00000225327), USP17L7 (ENSG00000226430), USP17L5 (ENSG00000227140), USP17L12 (ENSG00000227551), USP17L30 (ENSG00000228856), USP17L26 (ENSG00000229579), USP17L25 (ENSG00000230430), USP17L1 (ENSG00000230549), USP17L28 (ENSG00000231051), USP17L10 (ENSG00000231396), USP17L29 (ENSG00000231637), USP17L24 (ENSG00000232264), USP17L13 (ENSG00000232399), USP17L11 (ENSG00000233136), USP17L27 (ENSG00000235780)

+11 more (showing top 60).

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1858178) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired fertilization	1
hyperactivity	1
reduced male fertility	1
decreased litter size	1
abnormal seminiferous tubule morphology	1
decreased mean corpuscular volume	1
abnormal sperm motility	1
abnormal male germ cell morphology	1
abnormal circadian behavior period	1
delayed circadian behavior phase	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saccharomyces cerevisiae RM11-1a	B3LGK1	99.8%	Diamond
Saccharomyces cerevisiae S288C	P32571	99.8%	Diamond
Saccharomyces cerevisiae YJM789	A6ZY34	99.6%	Diamond
Pongo abelii	Q5R407	99.5%	Diamond
Xenopus laevis	Q6DCJ1	99.0%	Diamond
Macaca fascicularis	Q4R6X7	98.1%	Diamond
Bos taurus	P0C8Z3	97.7%	Diamond
Drosophila simulans	B4QIS3	96.5%	Diamond
Drosophila erecta	B3NC86	92.9%	Diamond
Xenopus tropicalis	F6Z5C0	85.6%	Diamond
Arabidopsis thaliana	Q84WC6	83.0%	Diamond
Canis lupus familiaris	Q01988	79.3%	Diamond
Gallus gallus	O57429	77.8%	Diamond
Drosophila mojavensis	B4KXJ5	74.2%	Diamond
Drosophila virilis	B4LG38	74.2%	Diamond
Drosophila melanogaster	Q8IQ27	68.8%	Diamond
Drosophila grimshawi	B4IXE0	68.5%	Diamond
Oryza sativa Japonica Group	Q2R4I5	66.0%	Diamond
Eremothecium gossypii ATCC 10895	Q754R5	51.9%	Diamond
Vanderwaltozyma polyspora DSM 70294	A7TGY3	51.4%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q9HFS7	50.0%	Diamond
Schizosaccharomyces pombe 972h-	O60079	48.1%	Diamond
Nakaseomyces glabratus CBS 138	Q6FQF0	48.0%	Diamond
Dictyostelium discoideum	O96612	45.5%	Diamond
Simkania negevensis Z	F8L8G5	35.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
USP2-AS1	ncRNA	100499227
C1QTNF5	protein-coding	114902
THY1	protein-coding	7070
MFRP	protein-coding	83552
RNF26	protein-coding	79102
MIR6756	ncRNA	102465453
MCAM	protein-coding	4162

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 2 — O75604 (reviewed: O75604)

Alternative names: 41 kDa ubiquitin-specific protease, Deubiquitinating enzyme 2, Ubiquitin thioesterase 2, Ubiquitin-specific-processing protease 2

All UniProt accessions (3): E9PJ34, E9PSH6, O75604

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities. Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity. Has no deubiquitinase activity against p53/TP53. Prevents MDM2-mediated degradation of MDM4. Plays a role in the G1/S cell-cycle progression in normal and cancer cells. Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues. Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability. Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and BMAL1. Plays a role in the regulation of myogenic differentiation of embryonic muscle cells. Circadian clock output effector that regulates Ca(2+) absorption in the small intestine. Probably functions by regulating protein levels of the membrane scaffold protein NHERF4 in a rhythmic manner, and is therefore likely to control Ca(2+) membrane permeability mediated by the Ca(2+) channel TRPV6 in the intestine.

Subunit / interactions. Homooligomer. Found in trimeric complex with MDM2 and MDM4 and USP2. Interacts with CCND1; the interaction is direct and promotes its stabilization by antagonizing ubiquitin-dependent degradation. Interacts (via N-terminus and C-terminus) with MDM2. Interacts with MDM4. Interacts with PER1. Interacts with KCNQ1; counteracts the NEDD4L-specific down-regulation of I(Ks) and restore plasma membrane localization of KCNQ1. Isoform 4: Interacts with NHERF4 and CLTC.

Subcellular location. Cytoplasm. Perinuclear region Nucleus. Membrane.

Tissue specificity. Expressed in mesangial cells of the kidney and in different types of glomerulonephritides (at protein level).

Activity regulation. Cleavage is inhibited by ubiquitin in a dosage-dependent manner. Cleavage is blocked by ubiquitin aldehyde.

Domain organisation. The different N-terminus extensions of isoform 1 and isoform 4 determine their respective subcellular localization and differential effect on myoblast fusion and accumulation of muscle-specific proteins. The different N-terminus extensions of isoform 1 and isoform 4 are not essential for their catalytic activity.

Induction. Down-regulated by cisplatin (at protein level).

Similarity. Belongs to the peptidase C19 family. USP2 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
O75604-1	1, USP2a, USP2-69	yes
O75604-2	2, USP2b
O75604-3	3
O75604-4	4

RefSeq proteins (3): NP_001230688, NP_004196, NP_741994 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050185	Ub_carboxyl-term_hydrolase	Family

Pfam: PF00443

UniProt features (63 total): strand 18, helix 15, sequence conflict 5, binding site 4, splice variant 4, region of interest 4, turn 3, sequence variant 2, mutagenesis site 2, compositionally biased region 2, active site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
5XVE	Crystal structure of human USP2 C276S mutant in complex with ubiquitin	X-RAY DIFFRACTION	1.24
3NHE	High Resolution Structure (1.26A) of USP2a in Complex with Ubiquitin	X-RAY DIFFRACTION	1.26
3V6C	Crystal Structure of USP2 in complex with mutated ubiquitin	X-RAY DIFFRACTION	1.7
5XU8	Crystal structure of human USP2 in complex with ubiquitin and 6-thioguanine	X-RAY DIFFRACTION	1.81
2HD5	USP2 in complex with ubiquitin	X-RAY DIFFRACTION	1.85
3V6E	Crystal Structure of USP2 and a mutant form of Ubiquitin	X-RAY DIFFRACTION	2.1
2IBI	Covalent Ubiquitin-USP2 Complex	X-RAY DIFFRACTION	2.2
6DGF	Ubiquitin Variant bound to USP2	X-RAY DIFFRACTION	2.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75604-F1	69.00	0.50

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Cysteine-type peptidases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

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

Catalytic / active sites (2)

Position	Role
276	nucleophile
557	proton acceptor

Ligand- & substrate-binding residues (4)

Position	Role
425	Zn(2+)
428	Zn(2+)
476	Zn(2+)
479	Zn(2+)

Mutagenesis-validated functional residues (2)

Position	Phenotype
276	loss of enzymatic activity. increases the steady-state level of ccnd1.
549	loss of enzymatic activity. increases the steady-state level of mdm2 and mdm4 that leads to attenuation of mdm2-mediated degradation of …

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 17; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-5357905	Regulation of TNFR1 signaling	curated
R-HSA-6804757	Regulation of TP53 Degradation	curated
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway	curated
R-HSA-5357786	TNFR1-induced proapoptotic signaling	curated
R-HSA-5689880	Ub-specific processing proteases	curated
R-HSA-73887	Death Receptor Signaling	—
R-HSA-5688426	Deubiquitination	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5633007	Regulation of TP53 Activity	—
R-HSA-6806003	Regulation of TP53 Expression and Degradation	—
R-HSA-162582	Signal Transduction	—
R-HSA-75893	TNF signaling	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

MSigDB gene sets: 295 (showing top): GOBP_CIRCADIAN_RHYTHM, E2F_Q4_01, GOBP_BEHAVIOR, MODULE_169, CCAWYNNGAAR_UNKNOWN, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_PHOTOPERIODISM, GCANCTGNY_MYOD_Q6, CMYB_01, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, AREB6_01, CREBP1_Q2

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), proteolysis (GO:0006508), muscle organ development (GO:0007517), protein deubiquitination (GO:0016579), circadian regulation of gene expression (GO:0032922), entrainment of circadian clock by photoperiod (GO:0043153), locomotor rhythm (GO:0045475), positive regulation of mitotic cell cycle (GO:0045931), circadian behavior (GO:0048512), protein stabilization (GO:0050821), regulation of signal transduction by p53 class mediator (GO:1901796), rhythmic process (GO:0048511)

GO Molecular Function (10): cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), cyclin binding (GO:0030332), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471), nucleus (GO:0005634)

Reactome top-level categories

12 top-level categories:

Category	Pathways
TNF signaling	3
Deubiquitination	1
Regulation of TP53 Expression and Degradation	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Post-translational protein modification	1
Metabolism of proteins	1
Regulation of TP53 Activity	1
Gene expression (Transcription)	1
Signal Transduction	1
Death Receptor Signaling	1

GO top-level categories

40 GO namespaces:

Category	Terms
cellular anatomical structure	5
circadian rhythm	2
cysteine-type peptidase activity	2
protein binding	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
protein metabolic process	1
animal organ development	1
muscle structure development	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of gene expression	1
photoperiodism	1
entrainment of circadian clock	1
locomotory behavior	1
circadian behavior	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1
positive regulation of cell cycle	1
rhythmic behavior	1
regulation of protein stability	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
biological_process	1
endopeptidase activity	1
deubiquitinase activity	1
ubiquitin-like protein ligase binding	1
cation binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of transcription by RNA polymerase II	BP	mutant phenotype
positive regulation of mitotic cell cycle	BP	mutant phenotype
protein deubiquitination	BP	direct assay
protein stabilization	BP	direct assay
cytosol	CC	direct assay
cyclin binding	MF	physical interaction
cysteine-type deubiquitinase activity	MF	direct assay
ubiquitin protein ligase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,342 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP2	USP14	P54578	786
USP2	ZUP1	Q96AP4	747
USP2	OTUB1	Q96FW1	719
USP2	UCHL3	P15374	674
USP2	OTULIN	Q96BN8	668
USP2	STAMBP	O95630	645
USP2	USP13	Q92995	633
USP2	OTUD3	Q5T2D3	632
USP2	UCHL5	Q9Y5K5	586
USP2	USP28	Q96RU2	563
USP2	CYLD	Q9NQC7	560
USP2	OTUD7B	Q6GQQ9	547
USP2	STAMBPL1	Q96FJ0	540
USP2	PER2	O15055	526
USP2	USP25	Q9UHP3	523

IntAct

Human interaction partners of USP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 112 partners by confidence:

Partner	Interaction type	MIscore	Records
TRAF2	physical association	0.780	7
GOLGA2	physical association	0.720	6
HOMER3	physical association	0.720	6
KRT40	physical association	0.720	6
LZTS2	physical association	0.720	6
NDEL1	physical association	0.720	6
TRIM27	physical association	0.720	6
VPS52	physical association	0.720	6
KRT15	physical association	0.700	5
LHX4	physical association	0.670	4
KIFC3	physical association	0.560	6
MTUS2	physical association	0.560	6
NEFL	physical association	0.560	6
TLE5	physical association	0.560	5
HOOK2	physical association	0.560	4
ABI2	physical association	0.560	3
ACTN1	physical association	0.560	3
ACTN2	physical association	0.560	3
ACTN3	physical association	0.560	3
ASPG	physical association	0.560	3
ATN1	physical association	0.560	3
BCAR1	physical association	0.560	3
BICD2	physical association	0.560	3
BIRC7	physical association	0.560	3
CADPS	physical association	0.560	3
CALCOCO2	physical association	0.560	3
CARD9	physical association	0.560	3
CCDC136	physical association	0.560	3
CCDC57	physical association	0.560	3
CCDC88B	physical association	0.560	3

BioGRID (382 interactions; top human partners by supporting records): UBC (Biochemical Activity; 24 records), TRAF2 (Two-hybrid; 8 records), CTNNB1 (Affinity Capture-Western; 6 records), E2F4 (Affinity Capture-MS; 6 records), FASN (Affinity Capture-Western; 6 records), AURKA (Affinity Capture-Western; 5 records), CCND1 (Affinity Capture-Western; 5 records), MDM2 (Affinity Capture-Western; 5 records), MDM4 (Affinity Capture-Western; 5 records), TRAF6 (Two-hybrid; 5 records), CD274 (Affinity Capture-Western; 4 records), RIPK1 (Affinity Capture-Western; 4 records), SMAD7 (Affinity Capture-Western; 4 records), VPRBP (Affinity Capture-MS; 4 records), ARID2 (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 2 of 3 signaling interactions:

A	Effect	B	Mechanism
TGFBR2	“up-regulates activity”	USP2	phosphorylation
USP2	“up-regulates activity”	TGFBR1	deubiquitination

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
TNF-alpha/NF-kappa B signaling complex (SEC16A, CHUK, IKBKB, NFKB2, REL, IKBKG, MAP3K14, RELA, FBXW7, USP2)	10	REL, SEC16A, IKBKB, MAP3K14, NFKB2, RELA, USP2, CHUK, FBXW7, IKBKG

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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 TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	5	56.0×	3e-06
Regulation of NF-kappa B signaling	5	46.6×	5e-06
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	5	44.2×	6e-06
TNFR1-induced NF-kappa-B signaling pathway	6	29.6×	5e-06
NOD1/2 Signaling Pathway	5	23.3×	5e-05
Regulation of TNFR1 signaling	7	23.1×	3e-06
Ovarian tumor domain proteases	5	20.5×	9e-05
DDX58/IFIH1-mediated induction of interferon-alpha/beta	5	18.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	7	23.1×	7e-06
intermediate filament organization	8	18.5×	7e-06
epithelial cell differentiation	7	11.8×	5e-04
regulation of apoptotic process	9	7.2×	8e-04

Disease & clinical

Genetic variants

Variant evidence for USP2: 89 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	6
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 895):

Position(s)	Effect	Δscore	Sites
11:119357979–119357980	donor_loss	1.0000	4
11:119358062–119358063	acceptor_loss	1.0000	6
11:119358147–119358148	donor_loss	1.0000	2
11:119358253–119358254	acceptor_loss	1.0000	5
11:119358756	donor_gain	1.0000
11:119358846–119358847	acceptor_gain	1.0000	2
11:119359022–119359023	donor_loss	1.0000	5
11:119359098	acceptor_gain	1.0000
11:119359142	acceptor_gain	1.0000
11:119359234	donor_gain	1.0000

AlphaMissense

1,239 missense substitutions predicted likely pathogenic (of 3,915 scored), across 282 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H549	8	0.999	1.000
D575	8	0.999	1.000
D357	8	0.998	0.999
H557	8	0.998	1.000
N271	8	0.997	1.000
N279	8	0.990	0.999
N274	8	0.987	1.000
F505	8	0.986	1.000
D440	8	0.985	0.995
F415	8	0.984	0.998
F350	8	0.983	1.000
H501	8	0.982	0.995
F361	8	0.978	0.998
F595	8	0.978	0.998
F438	8	0.974	0.998
F462	8	0.971	0.998
H370	8	0.968	0.994
F339	8	0.965	0.999
S421	8	0.964	0.999
F277	8	0.952	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.68e-08
Kidney Renal Clear Cell Carcinoma (validation)	favorable	2.13e-05

Disease associations

OMIM: gene MIM:604725 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

GWAS associations

6 associations:

Study	Trait	p-value
GCST010002_51	Refractive error	3e-34
GCST008972_210	Urate levels	3e-15
GCST008971_146	Urate levels	3e-13
GCST010637_33	Urate levels	6e-9
GCST007733_16	Serum uric acid levels	5e-8
GCST001791_23	Urate levels	2e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004761	uric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293227 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,109,423 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 124 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1201038	ACRISORCIN	4	1,965
CHEMBL184	ACYCLOVIR	4	98,123
CHEMBL1113	AMOXAPINE	4	20,303
CHEMBL296419	ASTEMIZOLE	4	21,684
CHEMBL158	AZTREONAM	4	35,015
CHEMBL388590	BENZBROMARONE	4	8,286
CHEMBL1201323	BETAZOLE	4	1,592
CHEMBL277535	BIFONAZOLE	4	12,615
CHEMBL223448	BROXYQUINOLINE	4	859
CHEMBL1072	BUMETANIDE	4	22,269
CHEMBL820	BUSULFAN	4	160,484
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,240
CHEMBL454446	CEFDITOREN PIVOXIL	4	3,202
CHEMBL497	CLIOQUINOL	4	13,056
CHEMBL104	CLOTRIMAZOLE	4	56,839
CHEMBL160	CYCLOSPORINE	4	169,776
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4	29,081
CHEMBL411	DIETHYLSTILBESTROL	4	373,838
CHEMBL898	DIFLUNISAL	4	55,163
CHEMBL1697	DILTIAZEM HYDROCHLORIDE	4	14,033
CHEMBL932	DIPYRIDAMOLE	4
CHEMBL421701	DITHIAZANINE IODIDE	4
CHEMBL219916	DOMPERIDONE	4
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4
CHEMBL1201049	ECONAZOLE NITRATE	4
CHEMBL672	FENOFIBRATE	4
CHEMBL726	FLUPHENAZINE	4
CHEMBL1448187	FLUPHENAZINE HYDROCHLORIDE	4
CHEMBL46516	FLUSPIRILENE	4
CHEMBL940	GABAPENTIN	4
CHEMBL64894	GENTIAN VIOLET	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL1200467	HYDROXYZINE PAMOATE	4
CHEMBL1117	IDARUBICIN	4
CHEMBL53292	ISOXICAM	4
CHEMBL157101	KETOCONAZOLE	4
CHEMBL1009	LEVODOPA	4
CHEMBL1201119	LIOTHYRONINE SODIUM	4
CHEMBL841	LOPERAMIDE	4
CHEMBL998	LORATADINE	4
CHEMBL313972	MASOPROCOL	4
CHEMBL685	MEBENDAZOLE	4
CHEMBL261772	MECLOCYCLINE SULFOSALICYLATE	4
CHEMBL1562610	MECLOFENAMATE SODIUM	4
CHEMBL590	MENADIONE	4
CHEMBL459	METHYLDOPA	4
CHEMBL1201356	METHYLERGONOVINE	4
CHEMBL1200938	METHYSERGIDE MALEATE	4
CHEMBL1559	MICONAZOLE NITRATE	4
CHEMBL58	MITOXANTRONE	4
CHEMBL1417019	MITOXANTRONE HYDROCHLORIDE	4
CHEMBL1410	NONOXYNOL 9	4
CHEMBL715	OLANZAPINE	4
CHEMBL1200836	OXICONAZOLE NITRATE	4
CHEMBL1517	OXYTETRACYCLINE	4
CHEMBL428647	PACLITAXEL	4
CHEMBL673	PARGYLINE	4
CHEMBL628	PENTOXIFYLLINE	4
CHEMBL567	PERPHENAZINE	4
CHEMBL1423	PIMOZIDE	4

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — C19: Ubiquitin-specific protease

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
ML364	Inhibition	5.28	pKd

Binding affinities (BindingDB)

40 measured of 75 human assays (81 total across all organisms); most potent 40 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
ML323	IC50	76 nM
CHEMBL5556193	IC50	250 nM
LCAK	EC50	270 nM
LCAME	EC50	590 nM
CHEMBL5561761	IC50	800 nM
CHEMBL5523555	IC50	890 nM
CHEMBL3392741	IC50	1100 nM
CHEMBL5523445	IC50	1300 nM
CHEMBL5560776	IC50	1400 nM
CHEMBL5562321	IC50	1500 nM
CHEMBL5542690	IC50	1600 nM
MLS000028461	IC50	2800 nM
CHEMBL5562765	IC50	3200 nM
CHEMBL4216958	IC50	3300 nM
CHEMBL5532378	IC50	3300 nM
CHEMBL5560773	IC50	3400 nM
CHEMBL5557100	IC50	3800 nM
Acetyl Isogambogic Acid	IC50	4070 nM
CHEMBL5557814	IC50	4400 nM
CHEMBL5562196	IC50	4600 nM
CHEMBL5559526	IC50	5500 nM
CHEMBL5566850	IC50	5500 nM
CHEMBL5565871	IC50	5900 nM
CDDO-Me, 2	IC50	6000 nM
CHEMBL5559268	IC50	6400 nM
CHEMBL4458718	IC50	9700 nM
5beta-cholanic acid-3alpha-ol	IC50	10000 nM
CHEMBL5562787	IC50	10500 nM
CHEMBL5523454	IC50	13300 nM
CHEMBL5560170	IC50	14500 nM
CHEMBL5558678	IC50	15400 nM
CHEMBL5523517	IC50	22300 nM
CHEMBL5269090	IC50	25000 nM
CHEMBL4089822	IC50	25400 nM
CHEMBL5568379	IC50	29100 nM
CHEMBL3410535	IC50	32600 nM
Cholic Acid	EC50	45000 nM
CHEMBL5184337	IC50	50000 nM
LCAGLY	IC50	138000 nM
CHEMBL1230155	IC50	1.3e+06 nM

ChEMBL bioactivities

3401 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.20	Potency	6.3	nM	CHEMBL1395605
8.10	Potency	7.9	nM	CHEMBL1437213
7.80	Potency	15.8	nM	CHEMBL1323897
7.70	Potency	20	nM	CHEMBL1314723
7.50	Potency	31.6	nM	CHEMBL1608984
7.50	Potency	31.6	nM	CHEMBL1475207
7.40	Potency	39.8	nM	CHEMBL1394223
7.00	Potency	100	nM	CHEMBL1575586
6.90	Potency	125.9	nM	CHEMBL1367789
6.80	Potency	158.5	nM	CHEMBL1559404
6.80	Potency	158.5	nM	CHEMBL489943
6.70	Potency	199.5	nM	CHEMBL374632
6.70	Potency	199.5	nM	CHEMBL1465204
6.60	IC50	250	nM	CHEMBL5556193
6.60	Potency	251.2	nM	CHEMBL1558999
6.60	Potency	251.2	nM	CHEMBL1597805
6.60	Potency	251.2	nM	CHEMBL1306484
6.60	Potency	251.2	nM	CHEMBL1364519
6.60	Potency	251.2	nM	CHEMBL1338051
6.60	Potency	251.2	nM	CHEMBL1484120
6.60	Potency	251.2	nM	CHEMBL1474503
6.55	Potency	281.8	nM	CHEMBL1560196
6.50	Potency	316.2	nM	CHEMBL3197156
6.50	Potency	316.2	nM	IODOQUINOL
6.50	Potency	316.2	nM	CHEMBL1475686
6.50	Potency	316.2	nM	CHEMBL1524600
6.40	Potency	398.1	nM	CHEMBL1447663
6.40	Potency	398.1	nM	CHEMBL1379269
6.40	Potency	398.1	nM	CHEMBL1477247
6.40	Potency	398.1	nM	CHEMBL1593545
6.40	Potency	398.1	nM	CHEMBL1724937
6.35	Potency	446.7	nM	CHEMBL1583747
6.30	Potency	501.2	nM	CHEMBL1341658
6.30	Potency	501.2	nM	CHEMBL1361346
6.30	Potency	501.2	nM	CHEMBL576544
6.30	Potency	501.2	nM	CHEMBL416615
6.30	Potency	501.2	nM	CHEMBL1460582
6.30	Potency	501.2	nM	CHEMBL1471583
6.30	Potency	501.2	nM	CHEMBL1441649
6.30	Potency	501.2	nM	CHEMBL1304690
6.30	Potency	501.2	nM	ACRISORCIN
6.30	Potency	501.2	nM	CHEMBL1599155
6.30	Potency	501.2	nM	CHEMBL1325932
6.30	Potency	501.2	nM	CHEMBL1326155
6.30	Potency	501.2	nM	CHEMBL1515885
6.30	Potency	501.2	nM	CHEMBL1341609
6.30	Potency	501.2	nM	CHEMBL1487321
6.25	Potency	562.3	nM	CHEMBL1583734
6.20	Potency	631	nM	CHEMBL1558420
6.20	Potency	631	nM	CHEMBL1334796

PubChem BioAssay actives

35 with measured affinity, of 150 total; 30 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
N-(2-bromophenyl)-3-(6-fluoro-1,3-dioxo-4H-isoquinolin-2-yl)propanamide	2069636: Inhibition of USP2 (unknown origin) incubated for 20 mins followed by substrate addition by fluorescence based high-throughput assay	ic50	0.2500	uM
2,3-bis(butylsulfonylmethyl)benzo[g]quinoxaline-5,10-dione	2069640: Inhibition of USP2 (unknown origin) using Di-Ub IQF K48-4 as substrate preincubated for 10 mins followed by substrate addition by high-throughput assay	ic50	0.8000	uM
4-methoxy-2-[(4-phenylphenyl)sulfonylamino]-N-(5-phenyl-1,3,4-thiadiazol-2-yl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	0.8000	uM
4-methoxy-2-[[4-(5-methylthiophen-2-yl)phenyl]sulfonylamino]-N-(4-phenyl-1,3-thiazol-2-yl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	0.8900	uM
2-[(4-methylphenyl)sulfonylamino]-N-(4-phenyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide	1930821: Inhibition of human USP2 using Di-Ub IQF as substrate incubated for 15 mins by K63-2 assay	ic50	1.1000	uM
2-[(4-phenylphenyl)sulfonylamino]-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-4-(trifluoromethyl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	1.3000	uM
N-(1,3-benzothiazol-2-yl)-2-[(4-phenylphenyl)sulfonylamino]-4-(trifluoromethyl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	1.4000	uM
4-methoxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-2-[[3-(trifluoromethyl)phenyl]sulfonylamino]benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	1.5000	uM
2-[(4-phenylphenyl)sulfonylamino]-N-(4-phenyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	1.6000	uM
2-[(4-bromophenyl)sulfonylamino]-4-methoxy-N-(4-phenyl-1,3-thiazol-2-yl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	3.2000	uM
(4R)-4-[(5R,8R,9S,10S,13R,14S,17R)-3-methoxycarbonyl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	1802687: Di-UB K63-2 Hydrolysis Assay from Article 10.1016/j.chembiol.2017.03.002: “Lithocholic Acid Hydroxyamide Destabilizes Cyclin D1 and Induces G0/G1 Arrest by Inhibiting Deubiquitinase USP2a.”	ic50	3.3000	uM
2-(naphthalen-1-ylsulfonylamino)-N-(4-phenyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	3.3000	uM
2-[[2-[(5-thiophen-2-yl-1,2-oxazol-3-yl)methoxy]acetyl]amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide	1383944: Inhibition of human USP2a (258 to 605 residues) expressed in Escherichia coli BL21(DE3) using Ub-AMC as substrate incubated for 30 mins measured at 30 secs interval by fluorescence assay	ic50	3.3000	uM
4-methoxy-N-(4-phenyl-1,3-thiazol-2-yl)-2-[[2-(trifluoromethyl)phenyl]sulfonylamino]benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	3.4000	uM
(4R)-N-hydroxy-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanamide	1802687: Di-UB K63-2 Hydrolysis Assay from Article 10.1016/j.chembiol.2017.03.002: “Lithocholic Acid Hydroxyamide Destabilizes Cyclin D1 and Induces G0/G1 Arrest by Inhibiting Deubiquitinase USP2a.”	ic50	3.7000	uM
2-[2-chloro-6-fluoro-3-[(3R)-1-methylpyrrolidin-3-yl]oxyphenyl]benzo[f][1,3]benzoxazole-4,9-dione	1857650: Inhibition of USP2 (unknown origin) using Ub-Rho measured after 0.5 to 3 hrs	ic50	3.8000	uM
4-methoxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-2-(pyridin-3-ylsulfonylamino)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	3.8000	uM
2-[(4-fluorophenyl)sulfonylamino]-4-methoxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	4.4000	uM
4-methoxy-2-[[4-(4-methyl-3-pyridinyl)phenyl]sulfonylamino]-N-(4-phenyl-1,3-thiazol-2-yl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	4.6000	uM
2-pyridin-3-ylbenzo[f][1,3]benzoxazole-4,9-dione	1857650: Inhibition of USP2 (unknown origin) using Ub-Rho measured after 0.5 to 3 hrs	ic50	5.1000	uM
N-(4-phenyl-1,3-thiazol-2-yl)-2-(thiophen-2-ylsulfonylamino)-4-(trifluoromethyl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	5.5000	uM
N-(5-phenyl-1,3,4-thiadiazol-2-yl)-2-(pyridin-3-ylsulfonylamino)-4-(trifluoromethyl)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	5.5000	uM
(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-acetyloxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	2069637: Inhibition of human USP2A (258 to 605 residues) expressed in Escherichia coli BL21 (DE3) using Ub-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay	ic50	5.8000	uM
4-methoxy-N-(4-phenyl-1,3-thiazol-2-yl)-2-(thiophen-2-ylsulfonylamino)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	5.9000	uM
2-[2-chloro-5-[(3R)-1-methylpyrrolidin-3-yl]oxyphenyl]benzo[f][1,3]benzoxazole-4,9-dione	1857650: Inhibition of USP2 (unknown origin) using Ub-Rho measured after 0.5 to 3 hrs	ic50	6.2000	uM
4-methoxy-N-(4-phenyl-1,3-thiazol-2-yl)-2-(pyridin-3-ylsulfonylamino)benzamide	2069590: Inhibition of USP2 (267 to 599 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using ubiquitin-rhodamine-110 as substrate preincubated with compound for 30 mins followed by substrate addition measured after 30 mins by fluorometric assay	ic50	6.4000	uM
(2,6-diamino-5-thiocyanato-3-pyridinyl) thiocyanate	1925871: Inhibition of USP2 (unknown origin)	ec50	7.2000	uM
(4R)-N-(cyanomethyl)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanamide	1802686: Ub-AMC-Hydrolysis Assay from Article 10.1016/j.chembiol.2017.03.002: “Lithocholic Acid Hydroxyamide Destabilizes Cyclin D1 and Induces G0/G1 Arrest by Inhibiting Deubiquitinase USP2a.”	ic50	7.4000	uM
2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide	1383944: Inhibition of human USP2a (258 to 605 residues) expressed in Escherichia coli BL21(DE3) using Ub-AMC as substrate incubated for 30 mins measured at 30 secs interval by fluorescence assay	ic50	8.7000	uM
(4R)-N-hydroxy-4-[(3R,5R,8R,9R,10S,13R,14R,17R)-3-hydroxy-8,10,13-trimethyl-1,2,3,4,5,6,7,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanamide	1558721: Inhibition of USP2 (unknown origin) using Ub-AMC substrate	ic50	9.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	3
Valproic Acid	decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
CB-5083	decreases reaction, increases reaction, increases ubiquitination	1
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression, affects cotreatment	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Amiodarone	increases expression	1
Amphotericin B	increases expression	1
Arsenic	decreases reaction, increases ubiquitination, increases reaction	1
Atrazine	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

49 unique, capped per target: 41 binding, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613927	Functional	PUBCHEM_BIOASSAY: qHTS Validation Assay for Inhibitors of Ubiquitin-specific Protease USP2a Using CHOP2 as the Reporter. (Class of assay: confirmatory) [Related pubchem assays: 2281 (Summary of qHTS Assay for Inhibitors of Ubiquitin-specifi	PubChem BioAssay data set
CHEMBL2163012	Binding	Inhibition of USP2 expressed in Escherichia coli BL21(DE3) by Ub-CHOP reporter assay	Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7 and USP47. — *ACS Med Chem Lett*

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9VI	Ubigene HEK293 USP2 KO	Transformed cell line	Female
CVCL_E0SL	Ubigene HeLa USP2 KO	Cancer cell line	Female
CVCL_TW70	HAP1 USP2 (-) 1	Cancer cell line	Male
CVCL_TW71	HAP1 USP2 (-) 2	Cancer cell line	Male
CVCL_XU89	HAP1 USP2 (-) 3	Cancer cell line	Male
CVCL_XU90	HAP1 USP2 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

2 trials:

NCT	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for USP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.