USP10

Entrez Summary: N/A
UniProt Summary: Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent 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. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989}.

Pfam Domains GO Terms

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 7/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	1/33
central nervous system	1/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	1/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	2/29
uterus	1/5

Expression Distribution

translesion synthesis
negative regulation of I-kappaB kinase/NF-kappaB signaling
DNA synthesis involved in DNA repair
postreplication repair
thiol-dependent ubiquitinyl hydrolase activity
p53 binding
DNA damage response, signal transduction by p53 class mediator
cysteine-type endopeptidase activity
signal transduction in response to DNA damage
thiol-dependent ubiquitin-specific protease activity
DNA biosynthetic process
signal transduction by p53 class mediator
ion channel binding
cellular response to interleukin-1
response to interleukin-1
regulation of I-kappaB kinase/NF-kappaB signaling
early endosome
autophagy
process utilizing autophagic mechanism
protein deubiquitination
protein modification by small protein removal
regulation of autophagy
negative regulation of intracellular signal transduction
DNA repair
ubiquitin-dependent protein catabolic process
modification-dependent protein catabolic process
modification-dependent macromolecule catabolic process
proteolysis involved in cellular protein catabolic process
protein-containing complex
cellular protein catabolic process
protein catabolic process
DNA metabolic process
cellular response to DNA damage stimulus
regulation of cellular catabolic process
cellular macromolecule catabolic process
protein modification by small protein conjugation or removal
regulation of catabolic process
cellular response to cytokine stimulus
macromolecule catabolic process
organonitrogen compound catabolic process