Property Summary

NCBI Gene PubMed Count 39
PubMed Score 105.57
PubTator Score 49.53

Knowledge Summary


No data available


  Disease (4)

Disease Target Count P-value
ovarian cancer 8491 1.1e-05
osteosarcoma 7933 3.7e-05
medulloblastoma, large-cell 6234 1.1e-03
astrocytoma 1493 9.7e-03
Disease Target Count Z-score Confidence
Crohn's disease 304 0.0 1.0
Disease Target Count Z-score Confidence
Cancer 2346 0.0 4.0
Disease Target Count Z-score Confidence
Multiple chemical sensitivity 6 3.179 1.6


  Differential Expression (4)

Disease log2 FC p
osteosarcoma -1.072 3.7e-05
astrocytoma 1.200 9.7e-03
medulloblastoma, large-cell -1.200 1.1e-03
ovarian cancer -1.100 1.1e-05

Protein-protein Interaction (1)

Gene RIF (21)

26669864 Results demonstrate that aberrant expression of USP4 contributes to the development and progression of colorectal cancer and reveal a critical mechanism underlying USP4-mediated oncogenic activity.
26455393 findings thus identify USP4 as a novel DNA repair regulator and invoke a model in which ubiquitin adducts regulate USP enzyme interactions and functions.
26387952 USP4 cooperates with CtIP in DNA double-strand break end resection.
26189775 USP4 knockdown in HCT116, a colon cancer cell line, reduced invasion and migration activity.
25821221 USP4 and IL-17 mRNA, but not RORgammat mRNA, were significantly elevated in CD4(+) T cells from patients with rheumatic heart disease
25404403 USP4 requires its N-terminal DUSP-Ubl domain to achieve full catalytic turnover by promoting ubiquitin exchange.
24798342 USP4 overexpression is associated with hepatocellular carcinoma.
23388719 Authors identified USP4 as a new positive regulator for RIG-I that acts through deubiquitinating K48-linked ubiquitin chains and stabilizing RIG-I.
23313255 Data suggest that USP4 down-regulates RIP1 (receptor-interacting serine-threonine kinase 1)-mediated TNFalpha (tumor necrosis factor-alpha) activation and promotes TNFalpha-induced apoptosis via deubiquitination of RIP1 in head/neck carcinoma.
23022198 the interaction with USP4 may regulate the structure and function of the proteasome or the turnover of specific proteasomal substrates.
22706160 Results uncover USP4 as an important determinant for crosstalk between TGF-beta/TGF-beta type I receptor and AKT signalling pathways.
22347420 identify the Ubiquitin-Specific Protease 4 (USP4) as an enzyme that removes ubiquitin from PDK1 in vivo and in vitro and co-localizes with PDK1 at the plasma membrane when the two proteins are overexpressed, indicating direct deubiquitination
22262844 USP4 plays an essential role in negative regulation of the TLR/IL-1R signaling-mediated innate immune response
22029577 USP4 deubiquitinates both TRAF2 and TRAF6 in vivo and in vitro in a deubiquitinase activity-dependent manner and inhibits TNFalpha-induced cancer cell migration.
21931648 Studies indicate that the cylindromatosis/turban tumor syndrome gene (CYLD) ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4).
21331078 Results demonstrate that USP4 serves as a critical control to downregulate TNFalpha-induced NF-kappaB activation through deubiquitinating TAK1.
20307617 Observational study of gene-disease association. (HuGE Navigator)
20141612 modulation of USP4 expression may provide a new means to interfere with canonical Wnt signalling in a variety of physiological and pathological conditions
19367581 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
16472766 Ro52 and UnpEL transregulate each other by ubiquitination and deubiquitination
16316627 These results suggest that UnpEL colocalizes with the unubiquitinated form of Ro52 to the cytoplasmic rod-like structures.

AA Sequence


Text Mined References (43)

PMID Year Title
26669864 2016 Ubiquitin-Specific Protease 4-Mediated Deubiquitination and Stabilization of PRL-3 Is Required for Potentiating Colorectal Oncogenesis.
26455393 2015 USP4 Auto-Deubiquitylation Promotes Homologous Recombination.
26387952 2015 The Deubiquitylating Enzyme USP4 Cooperates with CtIP in DNA Double-Strand Break End Resection.
26189775 2015 Ubiquitin specific protease 4 positively regulates the WNT/?-catenin signaling in colorectal cancer.
25821221 2015 Cutting edge: Ubiquitin-specific protease 4 promotes Th17 cell function under inflammation by deubiquitinating and stabilizing ROR?t.
25404403 2014 The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange.
25082827 2014 A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.
24798342 2014 microRNA-148a dysregulation discriminates poor prognosis of hepatocellular carcinoma in association with USP4 overexpression.
23388719 2013 USP4 positively regulates RIG-I-mediated antiviral response through deubiquitination and stabilization of RIG-I.
23313255 2013 Ubiquitin-specific protease 4 promotes TNF-?-induced apoptosis by deubiquitination of RIP1 in head and neck squamous cell carcinoma.
23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
23022198 2012 The ubiquitin specific protease-4 (USP4) interacts with the S9/Rpn6 subunit of the proteasome.
22706160 2012 USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-? type I receptor.
22347420 2012 Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the master growth factor signaling kinase PDK1.
22262844 2012 Ubiquitin-specific protease 4 mitigates Toll-like/interleukin-1 receptor signaling and regulates innate immune activation.
22029577 2012 Ubiquitin-specific protease 4 (USP4) targets TRAF2 and TRAF6 for deubiquitination and inhibits TNF?-induced cancer cell migration.
22001210 2011 Structural variability of the ubiquitin specific protease DUSP-UBL double domains.
21931648 2011 Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review.
21522127 2011 USP4 inhibits p53 through deubiquitinating and stabilizing ARF-BP1.
21415856 2011 Ubiquitin-specific protease 4 is inhibited by its ubiquitin-like domain.
21331078 2011 USP4 targets TAK1 to downregulate TNF?-induced NF-?B activation.
21269460 2011 Initial characterization of the human central proteome.
20595234 2010 The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome.
20307617 2010 Association analysis of 3p21 with Crohn's disease in a New Zealand population.
20141612 2009 The ubiquitin specific protease 4 (USP4) is a new player in the Wnt signalling pathway.
19367581 2010 Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population.
16641997 2006 The DNA sequence, annotation and analysis of human chromosome 3.
16472766 2006 UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16339847 2006 The ubiquitin-specific protease Usp4 regulates the cell surface level of the A2A receptor.
16316627 2006 Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12838346 2003 Human and mouse proteases: a comparative genomic approach.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11571652 2001 The de-ubiquitinating enzyme Unp interacts with the retinoblastoma protein.
11571651 2001 Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130.
11461834 2001 Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to function.
9827704 1998 Deubiquitinating enzymes: a new class of biological regulators.
9464533 1998 The human UNP locus at 3p21.31 encodes two tissue-selective, cytoplasmic isoforms with deubiquitinating activity that have reduced expression in small cell lung carcinoma cell lines.
8183569 1994 The Unp proto-oncogene encodes a nuclear protein.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
7784062 1995 Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors.