USP15

Gene Information

Official Symbol: USP15
Official Name: ubiquitin specific peptidase 15
Aliases and Previous Symbols: N/A
Entrez ID: 9958
UniProt: Q9Y4E8
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: N/A
UniProt Summary: Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:21947082, PubMed:22344298, PubMed:24852371, PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF- beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys- 48'-linked polyubiquitin chains, protecting them against proteasomal degradation. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF- kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). {ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:17318178, ECO:0000269|PubMed:19576224, ECO:0000269|PubMed:19826004, ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24526689, ECO:0000269|PubMed:24852371, ECO:0000269|PubMed:27368102}.

Pfam Domains GO Terms

CRISPR Data

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

Screen	Score
Rifampicin 1μM R00 exp31	1.75
Hydroxyurea 15μM R06 exp289	1.8
Mitomycin-C 0.06μM R08 exp503	1.84
42°C R08 exp539	2.08
Resveratrol 16μM R03 exp147	2.12
LLY-283 2.6μM R06 exp290	2.19
TRAIL 50ng/ml R00 exp36	2.58
TRAIL 5ng/ml R00 exp35	2.6
Etoposide 1μM R00 exp19	2.74

Global Fraction of Cell Lines Where Essential: 0/739

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	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
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	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 8548
Expression level (log2 read counts): 6.79

Expression Distribution

UCH
DUSP

ubiquitin modification-dependent histone binding
histone H2B conserved C-terminal lysine deubiquitination
monoubiquitinated protein deubiquitination
pathway-restricted SMAD protein phosphorylation
histone deubiquitination
transforming growth factor beta receptor binding
SMAD binding
thiol-dependent ubiquitinyl hydrolase activity
BMP signaling pathway
cysteine-type endopeptidase activity
transforming growth factor beta receptor signaling pathway
response to BMP
cellular response to BMP stimulus
thiol-dependent ubiquitin-specific protease activity
cellular response to transforming growth factor beta stimulus
response to transforming growth factor beta
transmembrane receptor protein serine/threonine kinase signaling pathway
protein deubiquitination
protein modification by small protein removal
histone modification
covalent chromatin modification
cellular response to growth factor stimulus
ubiquitin-dependent protein catabolic process
response to growth factor
modification-dependent protein catabolic process
modification-dependent macromolecule catabolic process
proteolysis involved in cellular protein catabolic process
cellular protein catabolic process
protein catabolic process
chromatin organization
enzyme linked receptor protein signaling pathway
cellular macromolecule catabolic process
protein phosphorylation
protein modification by small protein conjugation or removal
macromolecule catabolic process
organonitrogen compound catabolic process
chromosome organization
identical protein binding
cellular response to endogenous stimulus
mitochondrion