USP13

Summary

USP13 (ubiquitin specific peptidase 13, HGNC:12611) is a protein-coding gene on chromosome 3q26.33, encoding Ubiquitin carboxyl-terminal hydrolase 13 (Q92995). Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression or DNA damage response.

Enables several functions, including BAT3 complex binding activity; peptidase activity; and proteasome binding activity. Involved in several processes, including maintenance of unfolded protein; regulation of DNA-templated transcription; and regulation of catabolic process. Acts upstream of or within protein deubiquitination and protein stabilization. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 8975 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 162 total
• Druggable target: yes
• MANE Select transcript: NM_003940

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12611
Approved symbol	USP13
Name	ubiquitin specific peptidase 13
Location	3q26.33
Locus type	gene with protein product
Status	Approved
Aliases	IsoT-3
Ensembl gene	ENSG00000058056
Ensembl biotype	protein_coding
OMIM	603591
Entrez	8975

Gene structure

Transcript identifiers

Ensembl transcripts: 77 — 31 nonsense_mediated_decay, 27 protein_coding, 16 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000263966, ENST00000482333, ENST00000496897, ENST00000497155, ENST00000497380, ENST00000602704, ENST00000679350, ENST00000679403, ENST00000679407, ENST00000679602, ENST00000679640, ENST00000679660, ENST00000679664, ENST00000679674, ENST00000679694, ENST00000679749, ENST00000679752, ENST00000679768, ENST00000679769, ENST00000679772, ENST00000679783, ENST00000679839, ENST00000679893, ENST00000679954, ENST00000679972, ENST00000680008, ENST00000680031, ENST00000680055, ENST00000680167, ENST00000680217, ENST00000680276, ENST00000680307, ENST00000680308, ENST00000680392, ENST00000680436, ENST00000680477, ENST00000680502, ENST00000680549, ENST00000680567, ENST00000680587, ENST00000680605, ENST00000680651, ENST00000680734, ENST00000680843, ENST00000680853, ENST00000680856, ENST00000680905, ENST00000680930, ENST00000680951, ENST00000681051, ENST00000681064, ENST00000681081, ENST00000681098, ENST00000681109, ENST00000681128, ENST00000681262, ENST00000681299, ENST00000681356, ENST00000681358, ENST00000681362, ENST00000681533, ENST00000681560, ENST00000681561, ENST00000681630, ENST00000681642, ENST00000681649, ENST00000681709, ENST00000681724, ENST00000681736, ENST00000681782, ENST00000681783, ENST00000681836, ENST00000681918, ENST00000867743, ENST00000926429, ENST00000926430, ENST00000960735

RefSeq mRNA: 1 — MANE Select: NM_003940 NM_003940

CCDS: CCDS3235

Canonical transcript exons

ENST00000263966 — 21 exons

Exon	Start	End
ENSE00001056586	179757052	179757078
ENSE00001056590	179752285	179752373
ENSE00001056592	179754732	179754854
ENSE00001056595	179781739	179781823
ENSE00001056597	179761112	179761255
ENSE00001056598	179745043	179745217
ENSE00001056599	179764002	179764168
ENSE00001056600	179765695	179765848
ENSE00001290940	179784048	179789401
ENSE00001823136	179653040	179653393
ENSE00003489582	179740247	179740372
ENSE00003498996	179721402	179721589
ENSE00003505778	179730616	179730709
ENSE00003538105	179742197	179742350
ENSE00003585552	179690241	179690301
ENSE00003594749	179681878	179682003
ENSE00003615292	179701008	179701129
ENSE00003625312	179706934	179707076
ENSE00003645011	179730189	179730260
ENSE00003670104	179719940	179720034
ENSE00003674100	179708773	179708957

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.6444 / max 476.5108, expressed in 1743 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39943	12.8260	1703
39941	2.9886	1270
39944	1.2701	653
39942	0.3150	168
39945	0.1932	63
39946	0.0515	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.37	gold quality
gluteal muscle	UBERON:0002000	99.36	gold quality
biceps brachii	UBERON:0001507	99.34	gold quality
diaphragm	UBERON:0001103	99.29	gold quality
deltoid	UBERON:0001476	99.24	gold quality
vastus lateralis	UBERON:0001379	99.17	gold quality
tibialis anterior	UBERON:0001385	99.17	gold quality
quadriceps femoris	UBERON:0001377	99.13	gold quality
triceps brachii	UBERON:0001509	99.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.05	gold quality
skeletal muscle tissue	UBERON:0001134	98.99	gold quality
heart right ventricle	UBERON:0002080	98.33	gold quality
left ventricle myocardium	UBERON:0006566	98.33	gold quality
body of tongue	UBERON:0011876	98.27	gold quality
muscle organ	UBERON:0001630	97.53	gold quality
myocardium	UBERON:0002349	97.53	gold quality
skeletal muscle organ	UBERON:0014892	97.53	gold quality
gastrocnemius	UBERON:0001388	97.28	gold quality
muscle tissue	UBERON:0002385	97.12	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.87	gold quality
muscle of leg	UBERON:0001383	96.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.68	gold quality
secondary oocyte	CL:0000655	96.67	gold quality
cartilage tissue	UBERON:0002418	94.34	gold quality
tongue	UBERON:0001723	92.42	gold quality
oocyte	CL:0000023	91.27	gold quality
cardiac ventricle	UBERON:0002082	91.19	gold quality
heart left ventricle	UBERON:0002084	90.96	gold quality
vena cava	UBERON:0004087	90.05	gold quality
adrenal tissue	UBERON:0018303	89.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

242 targeting USP13, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631

Literature-anchored findings (GeneRIF, showing 38)

• study identifies a new layer of Siah2 regulation mediated by USP13 binding to ubiquitinated Siah2 protein with a concomitant inhibitory effect on its activity under normoxia (PMID:21659512)
• Through deubiquitination, USP13 stabilizes and upregulates MITF protein levels. (PMID:21811243)
• USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. (PMID:21962518)
• to our knowledge, USP13 is the first deubiquitinating enzymes identified to modulate STAT1 and play a role in the antiviral activity of IFN against DEN-2 replication. (PMID:23940278)
• USP13 is a tumour-suppressing protein that functions through deubiquitylation and stabilization of PTEN. (PMID:24270891)
• The authors identify USP13 as a gp78-associated deubiquitinase that eliminates ubiquitin conjugates from Ubl4A to maintain the functionality of Bag6. (PMID:24424410)
• Down-regulation of USP13 mediates PTEN protein loss and fibroblast phenotypic change, and thereby plays a crucial role in idiopathic pulmonary fibrosis pathogenesis. (PMID:26453058)
• our results demonstrate that AR can promote melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signal and targeting this newly identified signal with AR degradation enhancer ASC-J9 may help us to better suppress the melanoma metastasis. (PMID:27869170)
• These results reveal an important metabolism-centric role of USP13, which may lead to potential therapeutics targeting USP13 in ovarian cancers. (PMID:27892457)
• USP13 and FBXL14 play opposing roles in the regulation of glioma stem cells (GSCs) through reversible ubiquitination of c-Myc. (PMID:27923907)
• in the samples of 293T cell lines after the overexpression of USP13 and USP13 C345S, vinculin exhibited an increased expression, suggesting that it may be a candidate substrate of USP13. (PMID:28498477)
• USP13 is a regulator of DNA repair.USP13 regulates RAP80-BRCA1 complex foci formation.The role of USP13 in the neoplasm drug resistance. (PMID:28569838)
• Deubiquitinating enzyme 13 (USP13) regulates myeloid cell leukemia sequence 1 protein (MCL1) stability in lung and ovarian cancer cells. (PMID:29335437)
• As unanchored ubiquitin chains are preferred substrates for USP5, we suggest that USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains. (PMID:29567855)
• We found that USP13 independently regulates parkin and alpha-synuclein ubiquitination in models of alpha-synucleinopathies. USP13 shRNA knockdown increases alpha-synuclein ubiquitination and clearance, in a parkin-independent manner..These studies provide novel evidence of USP13 effects on parkin and alpha-synuclein metabolism and suggest that USP13 is a potential therapeutic target in the alpha-synucleinopathies (PMID:30329047)
• Downregulation of USP13 dramatically inhibited A549. (PMID:30986623)
• the present study demonstrates the tumor suppressor role of USP13 in BC and the potential regulatory loop network of NF-kB/USP13/PTEN. USP13 has been identified to be a target of miR-130b/301b and a downstream effector of NF-kB. (PMID:31200745)
• Ubiquitin Specific Protease 13 Regulates Tau Accumulation and Clearance in Models of Alzheimer’s Disease. (PMID:31594232)
• Auto-ubiquitination of NEDD4-1 Recruits USP13 to Facilitate Autophagy through Deubiquitinating VPS34. (PMID:32101753)
• Potent USP10/13 antagonist spautin-1 suppresses melanoma growth via ROS-mediated DNA damage and exhibits synergy with cisplatin. (PMID:32129945)
• Knockdown of ubiquitin-specific peptidase 13 inhibits cell growth of hepatocellular carcinoma by reducing c-Myc expression. (PMID:32255563)
• Molecular profiling of immune cell-enriched Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacting protein USP13. (PMID:32735883)
• USP13 interacts with cohesin and regulates its ubiquitination in human cells. (PMID:33334891)
• USP13 regulates the replication stress response by deubiquitinating TopBP1. (PMID:33592542)
• The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer. (PMID:33627786)
• SARS-CoV-2 non-structural protein 13 (nsp13) hijacks host deubiquitinase USP13 and counteracts host antiviral immune response. (PMID:33707416)
• Identification of targets of JS-K against HBV-positive human hepatocellular carcinoma HepG2.2.15 cells with iTRAQ proteomics. (PMID:34001947)
• Inhibition of ubiquitin-specific protease 13-mediated degradation of Raf1 kinase by Spautin-1 has opposing effects in naive and primed pluripotent stem cells. (PMID:34688658)
• USP13 genetics and expression in a family with thyroid cancer. (PMID:35583846)
• USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer. (PMID:36037364)
• ncRNA-mediated overexpression of ubiquitin-specific proteinase 13 contributes to the progression of prostate cancer via modulating AR signaling, DNA damage repair and immune infiltration. (PMID:36564767)
• USP13 regulates HMGB1 stability and secretion through its deubiquitinase activity. (PMID:36585612)
• USP13 promotes breast cancer metastasis through FBXL14-induced Twist1 ubiquitination. (PMID:36732432)
• Deubiquitinase USP13 regulates glycolytic reprogramming and progression in osteosarcoma by stabilizing METTL3/m[6]A/ATG5 axis. (PMID:37151889)
• USP13 deubiquitinates and stabilizes cyclin D1 to promote gastric cancer cell cycle progression and cell proliferation. (PMID:37311811)
• USP13 deubiquitinates p62/SQSTM1 to induce autophagy and Nrf2 release for activating antioxidant response genes. (PMID:37776917)
• Oncogenic KRAS effector USP13 promotes metastasis in non-small cell lung cancer through deubiquitinating beta-catenin. (PMID:38043062)
• USP13 drives lung squamous cell carcinoma by switching lung club cell lineage plasticity. (PMID:38093367)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp13	ENSDARG00000079198
mus_musculus	Usp13	ENSMUSG00000056900
rattus_norvegicus	Usp13	ENSRNOG00000030639

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242), USP32 (ENSG00000170832)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 13 — Q92995 (reviewed: Q92995)

Alternative names: Deubiquitinating enzyme 13, Isopeptidase T-3, Ubiquitin thioesterase 13, Ubiquitin-specific-processing protease 13

All UniProt accessions (48): Q92995, A0A0A6YZ17, A0A7P0T849, A0A7P0T859, A0A7P0T863, A0A7P0T873, A0A7P0T8B2, A0A7P0T8G3, A0A7P0T8S4, A0A7P0T8Y7, A0A7P0T949, A0A7P0T979, A0A7P0T9F2, A0A7P0T9H6, A0A7P0T9J2, A0A7P0T9N7, A0A7P0T9Q1, A0A7P0T9S5, A0A7P0T9V0, A0A7P0T9X0, A0A7P0TA93, A0A7P0TA96, A0A7P0TAC6, A0A7P0TAJ4, A0A7P0TAJ9, A0A7P0TAM7, A0A7P0TAN6, A0A7P0TAP9, A0A7P0TAU4, A0A7P0TAV8, A0A7P0TB18, A0A7P0TB48, A0A7P0TB69, A0A7P0TB82, A0A7P0TB92, A0A7P0TBA7, A0A7P0TBD6, A0A7P0TBG5, A0A7P0TBN7, A0A7P0Z460, A0A7P0Z496, A0A7P0Z4C0, A0A7P0Z4J7, A0A7P0Z4M1, A0A7P0Z4P4, A0A7P0Z4R3, H7C502, H7C5J3

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression or DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Alternatively, forms with NEDD4 a deubiquitination complex, which subsequently stabilizes VPS34 to promote autophagy. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Regulates the cell cycle progression by stabilizing cell cycle proteins such as SKP2 and AURKB. In addition, plays an important role in maintaining genomic stability and in DNA replication checkpoint activation via regulation of RAP80 and TOPBP1. Deubiquitinates the multifunctional protein HMGB1 and subsequently drives its nucleocytoplasmic localization and its secretion. Positively regulates type I and type II interferon signalings by deubiquitinating STAT1 but negatively regulates antiviral response by deubiquitinating STING1.

Subunit / interactions. Interacts with UFD1. Interacts (via UBA domains) with SIAH2 (when ubiquitinated). Interacts with BAG6; the interaction is direct and may mediate UBL4A deubiquitination. Interacts (via UBA 2 domain) with AMFR; the interaction is direct. Interacts with UBL4A; may be indirect via BAG6. Interacts with NEDD4.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in ovary and testes.

Post-translational modifications. Phosphorylated by AURKB at Ser-114; leading to stabilization of cell cycle proteins such as SKP2 and AURKB, but not MCL1.

Activity regulation. Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes. The weak deubiquitinase activity in vitro suggests the existence of some mechanism that activates the enzyme.

Domain organisation. The UBP-type zinc finger has lost its ability to bind ubiquitin and USP13 is not activated by unanchored ubiquitin. Swapping with the UBP-type zinc finger from USP5 restores ability to bind unanchored ubiquitin and subsequent activation of the protein. The UBA domains mediate binding to ubiquitin.

Similarity. Belongs to the peptidase C19 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92995-1	1	yes
Q92995-2	2

RefSeq proteins (1): NP_003931* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR001607	Znf_UBP	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR015940	UBA	Domain
IPR016652	Ubiquitinyl_hydrolase	Family
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR041432	UBP13_Znf-UBP_var	Domain
IPR050185	Ub_carboxyl-term_hydrolase	Family

Pfam: PF00443, PF00627, PF02148, PF17807

UniProt features (50 total): helix 10, mutagenesis site 8, strand 8, sequence conflict 5, binding site 4, domain 3, turn 3, modified residue 2, cross-link 2, active site 2, chain 1, splice variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2L80	SOLUTION NMR
2LBC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92995-F1	77.80	0.37

Functional residue map

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

Catalytic / active sites (2): 345 (nucleophile); 823 (proton acceptor)

Ligand- & substrate-binding residues (4): 244; 211; 214; 231

Post-translational modifications (4): 114, 122, 311, 405

Mutagenesis-validated functional residues (8):

Position	Phenotype
221	does not abolish ability to stabilize siah2.
233	does not abolish ability to stabilize siah2.
273	impairs ability to stabilize siah2.
345	abolishes deubiquitinating activity. does not abolish ability to stabilize siah2. does not abolish ability to stabilize
664	impairs ability to stabilize siah2 and stat1. abolishes ability to stabilize siah2 and stat1; when associated with e-739
739	impairs ability to stabilize siah2 and stat1. abolishes ability to stabilize siah2 and stat1; when associated with e-664
814	does not abolish ability to stabilize siah2; when associated with a-345 and a-823.
823	does not abolish ability to stabilize siah2; when associated with a-345 and a-814.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases
R-HSA-8948751	Regulation of PTEN stability and activity

MSigDB gene sets: 224 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, AP1_01, GOBP_REGULATION_OF_AUTOPHAGY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, WONG_PROTEASOME_GENE_MODULE, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, chr3q26, CAGCTG_AP4_Q5, PUJANA_CHEK2_PCC_NETWORK, GOBP_PIGMENTATION

GO Biological Process (15): regulation of DNA-templated transcription (GO:0006355), proteolysis (GO:0006508), autophagy (GO:0006914), cell population proliferation (GO:0008283), regulation of autophagy (GO:0010506), protein deubiquitination (GO:0016579), melanocyte differentiation (GO:0030318), regulation of protein stability (GO:0031647), protein K29-linked deubiquitination (GO:0035523), obsolete maintenance of unfolded protein (GO:0036506), protein K6-linked deubiquitination (GO:0044313), protein stabilization (GO:0050821), protein K63-linked deubiquitination (GO:0070536), positive regulation of ERAD pathway (GO:1904294), positive regulation of proteasomal protein catabolic process (GO:1901800)

GO Molecular Function (15): cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), zinc ion binding (GO:0008270), ubiquitin protein ligase binding (GO:0031625), ubiquitin binding (GO:0043130), ubiquitin-like protein ligase binding (GO:0044389), protein-folding chaperone binding (GO:0051087), proteasome binding (GO:0070628), BAT3 complex binding (GO:1904288), K48-linked deubiquitinase activity (GO:1990380), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Deubiquitination	1
PTEN Regulation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein deubiquitination	3
cellular anatomical structure	3
cysteine-type peptidase activity	2
deubiquitinase activity	2
protein-containing complex binding	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein metabolic process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cellular process	1
autophagy	1
regulation of catabolic process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
pigment cell differentiation	1
regulation of biological quality	1
regulation of protein stability	1
ERAD pathway	1
positive regulation of proteasomal protein catabolic process	1
regulation of ERAD pathway	1
positive regulation of response to endoplasmic reticulum stress	1
proteasomal protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
endopeptidase activity	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-like protein binding	1
enzyme binding	1
protein binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1373 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP13	USP22	Q9UPT9	838
USP13	AMFR	P26442	791
USP13	YOD1	Q5VVQ6	780
USP13	USP25	Q9UHP3	775
USP13	USP14	P54578	742
USP13	UFD1	Q92890	742
USP13	USP7	Q93009	725
USP13	ZUP1	Q96AP4	724
USP13	USP19	O94966	723
USP13	ATXN3	P54252	716
USP13	FAF2	Q96CS3	711
USP13	BECN1	Q14457	694
USP13	NPLOC4	Q8TAT6	689
USP13	ATXN3L	Q9H3M9	687
USP13	USP39	Q53GS9	671

IntAct

65 interactions, top by confidence:

A	B	Type	Score
RAD21	SMC1A	psi-mi:“MI:0914”(association)	0.930
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
USP13	rep	psi-mi:“MI:0915”(physical association)	0.670
USP4	PRPF3	psi-mi:“MI:0914”(association)	0.640
DAZAP2	USP13	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	USP13	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	USP13	psi-mi:“MI:0915”(physical association)	0.560
SMC1A	PDS5B	psi-mi:“MI:0914”(association)	0.530
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
TRIM63	USP13	psi-mi:“MI:0915”(physical association)	0.510
TRIM55	USP13	psi-mi:“MI:0915”(physical association)	0.510
PTEN	USP13	psi-mi:“MI:0915”(physical association)	0.400
USP13		psi-mi:“MI:0915”(physical association)	0.400
USP13	USP5	psi-mi:“MI:0915”(physical association)	0.400
TRPC4	USP13	psi-mi:“MI:0915”(physical association)	0.400
USP13	ENTREP1	psi-mi:“MI:0915”(physical association)	0.370
USP13	LAPTM5	psi-mi:“MI:0915”(physical association)	0.370
Smc3	PDS5B	psi-mi:“MI:0914”(association)	0.350
Smc1a	PDS5B	psi-mi:“MI:0914”(association)	0.350
SMC3	NEURL4	psi-mi:“MI:0914”(association)	0.350
SYNCRIP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350

BioGRID (240): USP13 (Affinity Capture-RNA), USP13 (Reconstituted Complex), VCP (Reconstituted Complex), VCP (Affinity Capture-Western), AMFR (Affinity Capture-Western), USP13 (Reconstituted Complex), BAG6 (Affinity Capture-Western), UBL4A (Affinity Capture-Western), BAG6 (Reconstituted Complex), USP13 (Reconstituted Complex), USP13 (Reconstituted Complex), GET4 (Affinity Capture-Western), USP13 (Affinity Capture-Western), UBL4A (Biochemical Activity), USP13 (Affinity Capture-MS)

ESM2 similar proteins: A1CEK7, A1D8E4, A1DE13, A1DFN6, A1Z7K9, A2QW83, A2QY22, A4RF51, A5DAD0, A8Q2R5, E1BMF7, E1BY77, F1QFS9, G0SAK8, P0C581, P0CQ08, P0CQ09, P0CR22, P0CR23, P11637, P25635, Q00784, Q09798, Q0CJU7, Q0CW42, Q0UNC6, Q0UPL5, Q1E5T3, Q1E873, Q2GSV2, Q2UBU2, Q2ULU6, Q4IBR4, Q4PGM6, Q4U3U3, Q4U3U5, Q4WHP6, Q4WLI5, Q4WTC4, Q4WWE9

Diamond homologs: A6QR55, E1BMF7, E1BY77, F1QFS9, F6V6I0, F6Z5C0, P45974, P54201, P56399, Q04323, Q11119, Q13107, Q2HJE4, Q32KW2, Q3V0C5, Q499N6, Q5BKP2, Q5R407, Q5RCD3, Q6GL77, Q6GLV4, Q6IP50, Q6NXA9, Q86UV5, Q8C2S0, Q8L6Y1, Q8R5H1, Q922Y1, Q92995, Q949Y0, Q9R085, Q9Y4E8, E2RK09, F1N5V1, F1SRY5, P34547, P39538, Q0V9G5, Q5XGZ2, Q6NTR6

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
USP13	“up-regulates quantity by stabilization”	BECN1	deubiquitination
BECN1	“up-regulates quantity by stabilization”	USP13	deubiquitination
USP13	“up-regulates activity”	UBL4A	deubiquitination
CLK3	“up-regulates activity”	USP13	phosphorylation
USP13	“up-regulates quantity by stabilization”	MYC	deubiquitination
USP13	“up-regulates quantity by stabilization”	ATG5	deubiquitination
METTL3	“up-regulates quantity by stabilization”	USP13	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein stability	5	11.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	123
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4290 predictions. Top by Δscore:

Variant	Effect	Δscore
3:179653394:G:GG	donor_gain	1.0000
3:179681876:A:AG	acceptor_gain	1.0000
3:179681877:G:GG	acceptor_gain	1.0000
3:179681877:GA:G	acceptor_gain	1.0000
3:179701134:G:GG	donor_gain	1.0000
3:179706929:TATA:T	acceptor_loss	1.0000
3:179706931:TAGGT:T	acceptor_loss	1.0000
3:179707073:CAAG:C	donor_loss	1.0000
3:179707074:AAGG:A	donor_loss	1.0000
3:179707075:AGGTG:A	donor_loss	1.0000
3:179707076:GGT:G	donor_loss	1.0000
3:179707078:T:G	donor_loss	1.0000
3:179708771:A:AG	acceptor_gain	1.0000
3:179708771:AGT:A	acceptor_gain	1.0000
3:179708772:G:GG	acceptor_gain	1.0000
3:179708772:GTG:G	acceptor_gain	1.0000
3:179720032:GGG:G	donor_gain	1.0000
3:179720033:GGG:G	donor_gain	1.0000
3:179721585:AGAGC:A	donor_gain	1.0000
3:179721586:GAGC:G	donor_gain	1.0000
3:179721586:GAGCG:G	donor_gain	1.0000
3:179721587:AGC:A	donor_gain	1.0000
3:179721588:GC:G	donor_gain	1.0000
3:179721588:GCG:G	donor_gain	1.0000
3:179721590:G:GG	donor_gain	1.0000
3:179730184:TCTA:T	acceptor_loss	1.0000
3:179730185:CTA:C	acceptor_loss	1.0000
3:179730188:GGTAT:G	acceptor_gain	1.0000
3:179730256:CAGAT:C	donor_gain	1.0000
3:179730257:AGAT:A	donor_gain	1.0000

AlphaMissense

5741 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:179653370:T:C	C49R	1.000
3:179681904:C:G	C65W	1.000
3:179706943:G:C	A163P	1.000
3:179761145:T:C	L661P	1.000
3:179761175:G:A	C671Y	1.000
3:179761176:T:G	C671W	1.000
3:179761183:G:C	A674P	1.000
3:179761184:C:A	A674D	1.000
3:179653338:C:A	P38H	0.999
3:179653371:G:A	C49Y	0.999
3:179653372:C:G	C49W	0.999
3:179653379:T:C	S52P	0.999
3:179681890:G:A	G61R	0.999
3:179681890:G:C	G61R	0.999
3:179681891:G:A	G61E	0.999
3:179681900:T:A	V64E	0.999
3:179681902:T:C	C65R	0.999
3:179681903:G:A	C65Y	0.999
3:179681903:G:T	C65F	0.999
3:179681939:T:A	V77D	0.999
3:179681972:T:A	V88E	0.999
3:179681974:T:G	Y89D	0.999
3:179681984:T:C	L92P	0.999
3:179701068:T:A	L139H	0.999
3:179701068:T:C	L139P	0.999
3:179701071:T:A	V140D	0.999
3:179701119:T:C	L156S	0.999
3:179701122:C:A	P157Q	0.999
3:179701122:C:G	P157R	0.999
3:179706944:C:A	A163D	0.999

dbSNP variants (sampled 300 via entrez): RS1000014533 (3:179753611 C>A,G,T), RS1000017305 (3:179772164 C>T), RS1000037880 (3:179729716 C>T), RS1000044421 (3:179709063 GC>G), RS1000046939 (3:179771689 T>G), RS1000048222 (3:179663334 G>A,C), RS1000083561 (3:179755450 A>G), RS1000113740 (3:179657414 A>C), RS1000198942 (3:179777394 T>A,G), RS1000201983 (3:179689581 C>G), RS1000214986 (3:179783982 G>T), RS1000241992 (3:179760697 T>C), RS1000250835 (3:179730461 T>G), RS1000287259 (3:179683776 T>A), RS1000290717 (3:179742114 A>T)

Disease associations

OMIM: gene MIM:603591 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3407324 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.22	IC50	600	nM	CHEMBL2391504
6.16	IC50	700	nM	CHEMBL2391504
6.16	IC50	690	nM	CHEMBL2391504

PubChem BioAssay actives

3 with measured affinity, of 6 total; 1 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
6-fluoro-N-[(4-fluorophenyl)methyl]quinazolin-4-amine	1195684: Inhibition of USP13 (unknown origin) by Ub-AMC assay	ic50	0.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
lead acetate	affects cotreatment, increases expression	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
zinc protoporphyrin	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
tamibarotene	decreases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	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	affects cotreatment, decreases expression	1
bisphenol S	increases methylation	1
NSC 689534	affects binding, decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3412295	Binding	Inhibition of USP13 (unknown origin) by Ub-AMC assay	Inhibiting the deubiquitinating enzymes (DUBs). — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 telomerase immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3KU	N/Tert-1 USP13	Telomerase immortalized cell line	Male
CVCL_TW55	HAP1 USP13 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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