USP11

Summary

USP11 (ubiquitin specific peptidase 11, HGNC:12609) is a protein-coding gene on chromosome Xp11.3, encoding Ubiquitin carboxyl-terminal hydrolase 11 (P51784). Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains.

Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23

Source: NCBI Gene 8237 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 186 total — 2 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001371072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12609
Approved symbol	USP11
Name	ubiquitin specific peptidase 11
Location	Xp11.3
Locus type	gene with protein product
Status	Approved
Aliases	UHX1
Ensembl gene	ENSG00000102226
Ensembl biotype	protein_coding
OMIM	300050
Entrez	8237

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 23 protein_coding, 8 retained_intron

ENST00000218348, ENST00000377078, ENST00000377080, ENST00000377107, ENST00000467378, ENST00000469080, ENST00000478596, ENST00000480104, ENST00000488848, ENST00000489030, ENST00000489111, ENST00000497179, ENST00000866792, ENST00000866793, ENST00000866794, ENST00000866795, ENST00000866796, ENST00000866797, ENST00000866798, ENST00000866799, ENST00000866800, ENST00000866801, ENST00000866802, ENST00000866803, ENST00000933738, ENST00000933739, ENST00000970026, ENST00000970027, ENST00000970028, ENST00000970029, ENST00000970030

RefSeq mRNA: 1 — MANE Select: NM_001371072 NM_001371072

CCDS: CCDS14277

Canonical transcript exons

ENST00000377107 — 21 exons

Exon	Start	End
ENSE00000669296	47247072	47247221
ENSE00000669297	47247304	47247419
ENSE00000669299	47247611	47247699
ENSE00000669301	47247793	47248328
ENSE00001858001	47233009	47233219
ENSE00003491638	47242439	47242522
ENSE00003497270	47244682	47244924
ENSE00003539575	47240774	47240876
ENSE00003541302	47245370	47245482
ENSE00003562213	47243396	47243602
ENSE00003605335	47242626	47242720
ENSE00003608329	47244498	47244550
ENSE00003609475	47242082	47242306
ENSE00003614483	47240305	47240450
ENSE00003635445	47241541	47241699
ENSE00003643058	47239351	47239481
ENSE00003650277	47245016	47245086
ENSE00003662919	47241277	47241450
ENSE00003662979	47240587	47240648
ENSE00003671380	47239790	47239907
ENSE00003689412	47239070	47239179

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.6906 / max 746.3879, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196197	47.3826	1815
196198	1.2856	736
196199	1.0224	514

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.95	gold quality
middle temporal gyrus	UBERON:0002771	98.84	gold quality
pituitary gland	UBERON:0000007	98.77	gold quality
adenohypophysis	UBERON:0002196	98.76	gold quality
entorhinal cortex	UBERON:0002728	98.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.72	gold quality
postcentral gyrus	UBERON:0002581	98.70	gold quality
parietal lobe	UBERON:0001872	98.68	gold quality
superior frontal gyrus	UBERON:0002661	98.66	gold quality
nucleus accumbens	UBERON:0001882	98.56	gold quality
cerebellar hemisphere	UBERON:0002245	98.54	gold quality
cerebellar cortex	UBERON:0002129	98.53	gold quality
frontal cortex	UBERON:0001870	98.45	gold quality
frontal lobe	UBERON:0016525	98.45	gold quality
cerebellum	UBERON:0002037	98.37	gold quality
neocortex	UBERON:0001950	98.35	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.35	gold quality
temporal lobe	UBERON:0001871	98.26	gold quality
cingulate cortex	UBERON:0003027	98.26	gold quality
anterior cingulate cortex	UBERON:0009835	98.24	gold quality
cerebral cortex	UBERON:0000956	98.17	gold quality
hypothalamus	UBERON:0001898	98.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.12	gold quality
left ovary	UBERON:0002119	98.09	gold quality
forebrain	UBERON:0001890	98.08	gold quality
ganglionic eminence	UBERON:0004023	98.08	gold quality
telencephalon	UBERON:0001893	98.05	gold quality
ventral tegmental area	UBERON:0002691	98.05	gold quality
lateral globus pallidus	UBERON:0002476	98.04	gold quality
caudate nucleus	UBERON:0001873	98.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	6.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting USP11, 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-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-3664-5P	96.74	66.56	770
HSA-MIR-3918	96.13	64.65	1300

Literature-anchored findings (GeneRIF, showing 40)

• structural and functional characterization of the USP11 deubiquitinating enzyme (PMID:12084015)
• Results suggest that BRCA2 expression levels are regulated by ubiquitination in response to DNA damage and that USP11 participates in DNA damage repair functions within the BRCA2 pathway independently of BRCA2 deubiquitination. (PMID:15314155)
• the ectopic expression of IKKalpha into cells silenced for USP11 restores p53 expression, demonstrating that USP11 functions as an upstream regulator of an IKKalpha-p53 signaling pathway. (PMID:17897950)
• USP11 plays an important role in regulating the levels of E7 protein and subsequently affects the biological function of E7 as well as its contribution to cell transformation by HPV-16E7. (PMID:18408009)
• Ubiquitin specific protease 11 protein plays an important role in maintaining a delicate balance in TNFalpha-mediated inflammatory responses by being a part of Yin-Yang regulatory mechanism. (PMID:19874889)
• Ablation of either USP7 or USP11 in primary human fibroblasts results in de-repression of the INK4a tumour suppressor accompanied by loss of Polycomb repressive complex 1 binding at the locus and a senescence-like proliferative arrest. (PMID:20601937)
• USP11 augments TGFbeta signalling by deubiquitylating ALK5. (PMID:22773947)
• USP-11 is not a predictor of a pCR after anthracycline-taxane-containing NST for breast cancer. Low USP-11 expression was independently correlated with better survival outcomes. (PMID:23337751)
• PML degradation mechanism through Notch/Hey1-induced repression of USP11 involved in brain tumour pathogenesis (PMID:24487962)
• Our data support a model whereby USP11 domains outside the catalytic core domain serve as protein interaction or trafficking modules rather than a direct regulatory function of the proteolytic activity. (PMID:24724799)
• USP11 is a novel regulator of p53, which is required for p53 activation in response to DNA damage (PMID:25471832)
• novel insight into cross-talk between ubiquitin and SUMO and uncover USP11 and RNF4 as a balanced SUMO-targeted ubiquitin ligase/protease pair with a role in the DDR. (PMID:25969536)
• These findings elucidate deeply and extensively the mechanism of RNF8/RNF168 and USP11 to maintain the proper status of ubiquitylation gammaH2AX to repair double strand breaks. (PMID:26507658)
• High USP11 expression is associated with cancer. (PMID:26919101)
• USP11 may contribute to the pathogenesis of pulmonary fibrosis by stabilization of TbetaRII and promotion of TGFbeta-1 signaling. (PMID:27853171)
• We demonstrated that, while depletion of XIAP attenuates cell transformation, elevated USP11 significantly promotes the tumor colony formation through stabilization of XIAP. (PMID:28040451)
• USP11 depletion suppresses cell proliferation and wound healing in lung epithelial cells, and these effects are reversed by E2F1 and PEG10 overexpression. (PMID:28992046)
• show that USP11 is associated with the mitotic spindle, does not regulate SAC inactivation, but controls ubiquitination of RAE1 at the mitotic spindle, hereby functionally modulating its interaction with Nuclear Mitotic Apparatus protein (NuMA) (PMID:29293652)
• FASN-induced S6 kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in diffuse large B-cell lymphoma. (PMID:29483509)
• Studied ubiquitin specific peptidase 11 (USP11) expression in hepatocellular carcinoma in clinical samples, in vivo and in vitro; found USP11 upregulated HCC cell invasion, migration ability and results suggest USP11 promotes HCC tumor invasion through inducing angiogenesis. (PMID:29545598)
• These findings reveal an important mechanism by which p21 can be stabilized by direct deubiquitylation, and they pinpoint a crucial role of the USP11-p21 axis in regulating cell-cycle progression and DNA damage responses. (PMID:29666278)
• modulating USP11 expression altered the stability of TGFb receptor type II (TGFBR2) and TGFb downstream signaling in human breast cancer cells. Together, these data suggest that deubiquitination of TGFBR2 by USP11 effectively spares TGFBR2 from proteasomal degradation to promote EMT and metastasis (PMID:29724812)
• A crystal structure of a USP11-peptide complex revealed a previously unknown binding site in USP11’s noncatalytic ubiquitin-like region. (PMID:30373771)
• Study results revealed that USP11 promoted epithelialtomesenchymal transition in ovarian cancer by deubiquitinating Snail, and USP11 may be a novel therapeutic target for ovarian cancer treatment. (PMID:30569152)
• USP11 is involved in chromatin condensation, genomic stability, and cell survival. Together, these observations indicate that USP11 is a chromatin modifier critically involved in DNA damage response and the maintenance of genomic stability. (PMID:31504778)
• USP11 activated the ERK/MAPK signaling pathway by stabilizing PPP1CA during the development of CRC. (PMID:31521612)
• Unveiling the genetic etiology of primary ciliary dyskinesia: When standard genetic approach is not enough. (PMID:31835165)
• TRIM32/USP11 Balances ARID1A Stability and the Oncogenic/Tumor-Suppressive Status of Squamous Cell Carcinoma. (PMID:31914402)
• CRL4(DCAF8) and USP11 oppositely regulate the stability of myeloid leukemia factors (MLFs). (PMID:32703400)
• A Functional Genomic Screen Identifies the Deubiquitinase USP11 as a Novel Transcriptional Regulator of ERalpha in Breast Cancer. (PMID:33004351)
• The regulation of NONO by USP11 via deubiquitination is linked to the proliferation of melanoma cells. (PMID:33369124)
• The deubiquitinase USP11 regulates cell proliferation and ferroptotic cell death via stabilization of NRF2 USP11 deubiquitinates and stabilizes NRF2. (PMID:33531626)
• USP11 mediates repair of DNA-protein cross-links by deubiquitinating SPRTN metalloprotease. (PMID:33567341)
• Circ_DOCK1 regulates USP11 through miR-132-3p to control colorectal cancer progression. (PMID:33685455)
• The E2F1/USP11 positive feedback loop promotes hepatocellular carcinoma metastasis and inhibits autophagy by activating ERK/mTOR pathway. (PMID:34044068)
• USP11 degrades KLF4 via its deubiquitinase activity in liver diseases. (PMID:34114341)
• The deubiquitinase USP11 promotes ovarian cancer chemoresistance by stabilizing BIP. (PMID:34257276)
• Inhibition of USP11 sensitizes gastric cancer to chemotherapy via suppressing RhoA and Ras-mediated signaling pathways. (PMID:34332125)
• USP11 controls R-loops by regulating senataxin proteostasis. (PMID:34526504)
• The deubiquitinase USP11 is a versatile and conserved regulator of autophagy. (PMID:34600886)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp11	ENSDARG00000076303
mus_musculus	Usp11	ENSMUSG00000031066
rattus_norvegicus	Cdk16	ENSRNOG00000008578

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), 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 11 — P51784 (reviewed: P51784)

Alternative names: Deubiquitinating enzyme 11, Ubiquitin thioesterase 11, Ubiquitin-specific-processing protease 11

All UniProt accessions (4): P51784, C9JBP8, G5E9A6, Q5JXD3

UniProt curated annotations — full annotation on UniProt →

Function. Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains. Inhibits the degradation of target proteins by the proteasome. Cleaves preferentially ‘Lys-6’ and ‘Lys-63’-linked ubiquitin chains. Has lower activity with ‘Lys-11’ and ‘Lys-33’-linked ubiquitin chains, and extremely low activity with ‘Lys-27’, ‘Lys-29’ and ‘Lys-48’-linked ubiquitin chains (in vitro). Plays a role in the regulation of pathways leading to NF-kappa-B activation. Plays a role in the regulation of DNA repair after double-stranded DNA breaks. Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex. Promotes cell proliferation by deubiquitinating phosphorylated E2F1.

Subunit / interactions. Monomer. Associated component of the Polycomb group (PcG) multiprotein PRC1-like complex. Interacts with RANBP9/RANBPM. Interacts with BRCA2. Interacts with CHUK/IKKA. Interacts with NFKBIA. Interacts with SPRY3, RAE1, MYCBP2/PAM, and KCTD6. (Microbial infection) Interacts with papilloma virus protein 16E7.

Subcellular location. Nucleus. Cytoplasm. Chromosome.

Similarity. Belongs to the peptidase C19 family.

RefSeq proteins (1): NP_001358001* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR006615	Pept_C19_DUSP	Domain
IPR018200	USP_CS	Conserved_site
IPR028135	Ub_USP-typ	Domain
IPR028889	USP	Domain
IPR029346	USP_C	Domain
IPR035927	DUSP-like_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050185	Ub_carboxyl-term_hydrolase	Family

Pfam: PF00443, PF06337, PF14533, PF14836

UniProt features (80 total): strand 27, helix 20, turn 8, sequence conflict 7, compositionally biased region 4, modified residue 4, region of interest 4, domain 2, active site 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5OK6	X-RAY DIFFRACTION	1.3
8OYP	X-RAY DIFFRACTION	2.44
4MEL	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51784-F1	79.22	0.55

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): 318 (nucleophile); 888 (proton acceptor)

Post-translational modifications (4): 245, 648, 733, 948

Mutagenesis-validated functional residues (1):

Position	Phenotype
318	loss of deubiquitinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 151 (showing top): KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, HSIAO_HOUSEKEEPING_GENES, WONG_PROTEASOME_GENE_MODULE, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, MAYBURD_RESPONSE_TO_L663536_UP, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, TIEN_INTESTINE_PROBIOTICS_24HR_UP, MORF_PDPK1, MORF_IKBKG, DANG_BOUND_BY_MYC, MODULE_20, GCGSCMNTTT_UNKNOWN, MORF_MYST2, GOBP_PROTEOLYSIS

GO Biological Process (2): proteolysis (GO:0006508), protein deubiquitination (GO:0016579)

GO Molecular Function (7): transcription corepressor binding (GO:0001222), cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), 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), chromosome (GO:0005694), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chaperonin-mediated protein folding	1
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cysteine-type peptidase activity	2
protein metabolic process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
transcription coregulator binding	1
endopeptidase activity	1
deubiquitinase 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
intracellular membraneless organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP11	BRCA2	P51587	871
USP11	USP7	Q93009	815
USP11	TP53BP1	Q12888	755
USP11	RAD51	Q06609	720
USP11	ZUP1	Q96AP4	719
USP11	USP5	P45974	652
USP11	OTUD5	Q96G74	630
USP11	BRCA1	P38398	626
USP11	USP13	Q92995	620
USP11	UCHL5	Q9Y5K5	598
USP11	OTUB1	Q96FW1	596
USP11	USP28	Q96RU2	588
USP11	MYSM1	Q5VVJ2	582
USP11	PPP1CA	P08129	558
USP11	PCGF2	P35227	550

IntAct

173 interactions, top by confidence:

A	B	Type	Score
BMI1	CBX7	psi-mi:“MI:0914”(association)	0.940
BMI1	CBX4	psi-mi:“MI:0914”(association)	0.900
ARRDC1	WWP2	psi-mi:“MI:0914”(association)	0.850
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.790
COPRS	PRMT5	psi-mi:“MI:0914”(association)	0.770
STK11	HSP90AA1	psi-mi:“MI:0914”(association)	0.740
TDP1	XRCC1	psi-mi:“MI:0914”(association)	0.670
ORAI1	USP11	psi-mi:“MI:0915”(physical association)	0.650
ORAI1	USP11	psi-mi:“MI:0407”(direct interaction)	0.650
USP11	BMI1	psi-mi:“MI:0915”(physical association)	0.650
BMI1	USP11	psi-mi:“MI:0915”(physical association)	0.650
USP7	BMI1	psi-mi:“MI:0914”(association)	0.650
USP11	BMI1	psi-mi:“MI:0407”(direct interaction)	0.650
PTP4A2	PTP4A3	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
MRPS27	MRPS14	psi-mi:“MI:0914”(association)	0.640
RAB11A	CHML	psi-mi:“MI:2364”(proximity)	0.610
PCGF2	USP11	psi-mi:“MI:0915”(physical association)	0.590
USP11	CBX8	psi-mi:“MI:0915”(physical association)	0.590
RNF2	USP11	psi-mi:“MI:0915”(physical association)	0.590
RNF2	USP11	psi-mi:“MI:0914”(association)	0.590
CBX8	USP11	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (769): USP11 (Affinity Capture-RNA), USP11 (Affinity Capture-RNA), TP53 (Affinity Capture-Western), TP53 (Biochemical Activity), USP11 (Affinity Capture-MS), USP11 (Affinity Capture-MS), USP11 (Affinity Capture-MS), USP11 (Affinity Capture-MS), TRIM27 (Affinity Capture-MS), TCEB2 (Affinity Capture-MS), UBA1 (Affinity Capture-MS), MOGS (Affinity Capture-MS), SEMA3B (Affinity Capture-MS), USP7 (Affinity Capture-MS), USP11 (Affinity Capture-MS)

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, A5PMR2, A5PN09, A6NNY8, A6QNM7, A7Z056, B1AY13, B1WBD7, D2HBJ8, D6RBM5, E1C213, E7F6T8, E9Q9U0, F6Z5C0, F8VPU6, F8VPZ3, M9PD06, O00507, O22207, O60079, O74442, O94269, O94966, O96612, P0C7I0, P0C8Z3, P0CAQ1, P35125, P39538, P40453, P51784, P53874, P55824, P70398, Q01988, Q09738, Q0V9G5, Q28CN3, Q2HJE4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
USP11	“up-regulates activity”	EEF1A1	deubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 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
SUMOylation of DNA methylation proteins	7	41.2×	5e-08
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	7	18.4×	1e-05
Regulation of PTEN gene transcription	11	17.2×	2e-08
SUMOylation of transcription cofactors	7	14.9×	4e-05
SUMOylation of RNA binding proteins	7	14.6×	4e-05
PTEN Regulation	7	14.0×	5e-05
Transcriptional Regulation by E2F6	5	12.8×	2e-03
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	9	11.6×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	7	14.4×	2e-04
autophagosome assembly	7	10.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	58
Likely benign	10
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
402175	NC_000023.11:g.47240362G>A	Likely pathogenic
635007	NC_000023.11:g.47242504G>A	Likely pathogenic

SpliceAI

2591 predictions. Top by Δscore:

Variant	Effect	Δscore
X:47239060:T:TA	acceptor_gain	1.0000
X:47239061:G:A	acceptor_gain	1.0000
X:47239337:C:G	acceptor_gain	1.0000
X:47239341:C:A	acceptor_gain	1.0000
X:47239346:CACA:C	acceptor_loss	1.0000
X:47239347:ACAG:A	acceptor_loss	1.0000
X:47239348:CA:C	acceptor_loss	1.0000
X:47239349:A:AG	acceptor_gain	1.0000
X:47239350:G:GA	acceptor_gain	1.0000
X:47239350:GAT:G	acceptor_gain	1.0000
X:47239350:GATGA:G	acceptor_gain	1.0000
X:47239785:TACA:T	acceptor_loss	1.0000
X:47239788:A:AG	acceptor_gain	1.0000
X:47239789:G:GA	acceptor_gain	1.0000
X:47239789:G:GC	acceptor_loss	1.0000
X:47239903:TATTG:T	donor_gain	1.0000
X:47239907:GGTGA:G	donor_loss	1.0000
X:47239908:G:GC	donor_loss	1.0000
X:47239908:G:GG	donor_gain	1.0000
X:47239909:TGAG:T	donor_loss	1.0000
X:47240580:A:AG	acceptor_gain	1.0000
X:47240581:A:G	acceptor_gain	1.0000
X:47240583:CCAG:C	acceptor_loss	1.0000
X:47240585:A:AG	acceptor_gain	1.0000
X:47240585:AGTT:A	acceptor_gain	1.0000
X:47240586:G:GA	acceptor_gain	1.0000
X:47240586:GT:G	acceptor_gain	1.0000
X:47240586:GTT:G	acceptor_gain	1.0000
X:47240586:GTTG:G	acceptor_gain	1.0000
X:47240644:GTCAT:G	donor_gain	1.0000

AlphaMissense

6063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:47240855:C:G	C318W	1.000
X:47240856:T:C	F319L	1.000
X:47240858:C:A	F319L	1.000
X:47240858:C:G	F319L	1.000
X:47242128:C:T	S452F	1.000
X:47242175:T:C	C468R	1.000
X:47242452:T:A	V516D	1.000
X:47242491:T:C	L529P	1.000
X:47242642:T:A	V545D	1.000
X:47242644:T:C	F546L	1.000
X:47242646:C:A	F546L	1.000
X:47242646:C:G	F546L	1.000
X:47242654:G:C	R549P	1.000
X:47242657:T:C	F550S	1.000
X:47242716:T:C	F570L	1.000
X:47242718:C:A	F570L	1.000
X:47242718:C:G	F570L	1.000
X:47243458:T:A	V592D	1.000
X:47243467:G:C	R595P	1.000
X:47243520:T:C	F613L	1.000
X:47243522:T:A	F613L	1.000
X:47243522:T:G	F613L	1.000
X:47243523:G:A	G614R	1.000
X:47243523:G:C	G614R	1.000
X:47243524:G:A	G614E	1.000
X:47243524:G:T	G614V	1.000
X:47243529:C:A	P616T	1.000
X:47243529:C:T	P616S	1.000
X:47243530:C:A	P616H	1.000
X:47243530:C:G	P616R	1.000

dbSNP variants (sampled 300 via entrez): RS1000063232 (X:47237794 G>A), RS1000115141 (X:47238129 C>T), RS1000562980 (X:47236044 G>A), RS1000617503 (X:47246680 A>G), RS1000733154 (X:47246207 C>T), RS1000995488 (X:47235609 C>T), RS1001120579 (X:47240632 G>A,T), RS1001379357 (X:47237160 T>C), RS1001904120 (X:47232059 A>G), RS1002272877 (X:47232704 G>A), RS1002856992 (X:47234595 A>G), RS1002874514 (X:47235104 T>C), RS1002948046 (X:47242836 C>T), RS1003119471 (X:47244365 C>A,T), RS1003392081 (X:47233006 C>T)

Disease associations

OMIM: gene MIM:300050 | disease phenotypes: MIM:211400

GenCC curated gene-disease

Mondo (1): bronchiectasis (MONDO:0004822)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001987	Bronchiectasis	C08.127.384

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630820 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, decreases methylation, affects cotreatment	6
bisphenol A	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	affects localization, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cisplatin	increases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4605979	Binding	Inhibition of USP11 (unknown origin)	Discovery of Potent, Selective, and Orally Bioavailable Inhibitors of USP7 with In Vivo Antitumor Activity. — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6BD	HyCyte HEK293 KO-hUSP11	Transformed cell line	Female
CVCL_D6CK	HyCyte SH-SY5Y KO-hUSP11	Cancer cell line	Female
CVCL_D8DA	Ubigene A-549 USP11 KO	Cancer cell line	Male
CVCL_KU16	HeLa SilenciX USP11	Cancer cell line	Female
CVCL_TW49	HAP1 USP11 (-) 1	Cancer cell line	Male
CVCL_TW50	HAP1 USP11 (-) 2	Cancer cell line	Male
CVCL_TW51	HAP1 USP11 (-) 3	Cancer cell line	Male
CVCL_TW52	HAP1 USP11 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00749866	PHASE4	COMPLETED	Long Term Nebulised Gentamicin in Patients With Bronchiectasis
NCT00816309	PHASE4	COMPLETED	Is Regular Chest Physiotherapy an Effective Treatment in Severe, Non Cystic Fibrosis Bronchiectasis?
NCT00868075	PHASE4	COMPLETED	Pulmonary Rehabilitation in Non Cystic Fibrosis Bronchiectasis
NCT01299181	PHASE4	COMPLETED	A Trial of Atorvastatin as an Anti-Inflammatory Agent in Non-Cystic Fibrosis Bronchiectasis
NCT01299194	PHASE4	COMPLETED	Atorvastatin in Bronchiectasis in Patients With Pseudomonas Aeruginosa
NCT01677403	PHASE4	UNKNOWN	A Study to Access Safety and Efficacy of Nebulized Tobramycin in Patients With Bronchiectasis
NCT01684683	PHASE4	COMPLETED	The Effect of Theophylline in the Treatment of Bronchiectasis
NCT01769898	PHASE4	COMPLETED	The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis
NCT02047773	PHASE4	COMPLETED	Bacterial Load Guided Therapy for Severe Bronchiectasis Exacerbations
NCT02107274	PHASE4	COMPLETED	Efficacy of Azithromycin in Treatment of Bronchiectasis
NCT02507843	PHASE4	UNKNOWN	Vitamin D as an Adjunctive Treatment in Patients With Non-Cystic Fibrosis Bronchiectasis
NCT02509091	PHASE4	UNKNOWN	Therapy of Bronchoalveolar Lavage and Local Amikacin Injection in Patients With Acute Exacerbation of Bronchiectasis
NCT02546297	PHASE4	UNKNOWN	Comparisons of Inhaled LAMA or LAMA+LABA or ICS+LABA for COPD With Bronchiectasis
NCT02782312	PHASE4	COMPLETED	Salmeterol-Fluticasone Combined Inhaled Therapy for Non-cystic Fibrosis Bronchiectasis
NCT03147443	PHASE4	UNKNOWN	Evaluating the Effects of Traditional Chinese Medicine by N-of-1 Trials
NCT03262142	PHASE4	TERMINATED	Targeted AntiBiotics for Chronic Pulmonary Diseases
NCT03737617	PHASE4	WITHDRAWN	Immunoglobulin Replacement Therapy for Immunoglobulin G Subclass 2 Deficient Patients With Bronchiectasis
NCT04601792	PHASE4	UNKNOWN	A Series of N-of-1 Trials of Traditional Chinese Medicine Based on Bayesian Method
NCT04765033	PHASE4	COMPLETED	Trial on The Efficacy of Hypertonic Saline on Non-CF CSLD.
NCT06035055	PHASE4	UNKNOWN	Ceftolozane/Tazobactam Continuous Infusion for Infective Exacerbations of Cystic Fibrosis and Bronchiectasis
NCT06242795	PHASE4	RECRUITING	Hypertonic Saline in NCFB
NCT06551337	PHASE4	RECRUITING	Vitamin D Replacement in Bronchiectasis
NCT07114120	PHASE4	RECRUITING	Clinical Study on the Treatment of Stable Bronchiectasis With Bailing Capsules Combined With Guben Kechuan Granules
NCT07283497	PHASE4	RECRUITING	Itraconazole Therapy In Bronchiectasis With Airway Mold
NCT07608328	PHASE4	NOT_YET_RECRUITING	Azithromycin to Modify Bronchiectasis Exacerbation Risk
NCT00105183	PHASE3	COMPLETED	EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection
NCT00277537	PHASE3	COMPLETED	Safety and Efficacy of Bronchitol in Bronchiectasis
NCT00415350	PHASE3	COMPLETED	Bronchiectasis and Long Term Azithromycin Treatment
NCT00484263	PHASE3	COMPLETED	The Long Term Effect of Inhaled Hypertonic Saline (6%) in Patients With Non Cystic Fibrosis Bronchiectasis
NCT00669331	PHASE3	COMPLETED	Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis
NCT01270074	PHASE3	COMPLETED	Prevention of Bronchiectasis in Infants With Cystic Fibrosis
NCT01313624	PHASE3	COMPLETED	Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis
NCT01314716	PHASE3	COMPLETED	Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis
NCT01764841	PHASE3	COMPLETED	Ciprofloxacin Dry Powder for Inhalation in Non-cystic Fibrosis Bronchiectasis (Non-CF BE)
NCT02106832	PHASE3	COMPLETED	Ciprofloxacin Dry Powder for Inhalation (DPI) in Non-cystic Fibrosis Bronchiectasis (Non-CF BE)
NCT03443531	PHASE3	UNKNOWN	Effects of Traditional Chinese Medicine on Bronchiectasis Patients
NCT03846570	PHASE3	TERMINATED	Formoterol-beclomethasone in Patients With Bronchiectasis: a Randomized Controlled Trial
NCT04122547	PHASE3	COMPLETED	Efficacy of Roflumilast on Exacerbations in Patients With Non-cystic Fibrosis Bronchiectasis
NCT04140214	PHASE3	COMPLETED	Randomised Open Label Trial of Hypertonic Saline and Carbocisteine in Bronchiectasis (CLEAR)
NCT04616924	PHASE3	TERMINATED	RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex Disease