DegronMD - Q93009(USP7)

FUNCTION: Hydrolase that deubiquitinates target proteins such as FOXO4, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148, PubMed:25865756, PubMed:26678539, PubMed:28655758). Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation (PubMed:15053880, PubMed:16845383, PubMed:18566590, PubMed:20153724). Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:25283148). Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis (PubMed:11923872). Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity (PubMed:16964248). In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML (PubMed:18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation (PubMed:26678539). Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6 (PubMed:22466611, PubMed:22466612). Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1 (PubMed:21745816, PubMed:22411829). Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). 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 (PubMed:20601937). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (PubMed:20601937). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains (PubMed:22689415). Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222). Plays a role in the maintenance of the circadian clock periodicity via deubiquitination and stabilization of the CRY1 and CRY2 proteins (PubMed:27123980). Deubiquitinates REST, thereby stabilizing REST and promoting the maintenance of neural progenitor cells (PubMed:21258371). Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity and regulating gluconeogenesis (PubMed:28655758). {ECO:0000269|PubMed:11923872, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:20153724, ECO:0000269|PubMed:20601937, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148, ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28655758}.; FUNCTION: (Microbial infection) Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. {ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:16160161, ECO:0000269|PubMed:18590780}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P740L	TCGA-06-5416	GBM	TCGA	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.25
p.P740L	TCGA-BF-AAP7	SKCM	TCGA	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.25
p.R723G	TCGA-B5-A3FA	UCEC	TCGA	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.0833
p.D729Y	TCGA-BK-A6W3	UCEC	TCGA	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.25
p.R723I	TCGA-D3-A3C8	SKCM	TCGA	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.0833
p.R723I	DO47636	SKCM	ICGC	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.0833
p.Y735C	TCGA-VQ-A91D	STAD	TCGA	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation altering degron motif	0.8198
p.R730S	DO25444	LUAD	ICGC	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation blocking phosphorylation signal	0.7222
p.V735M	DO38328	STAD	ICGC	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation altering degron motif	0.7208
p.Q728L	SIDM00032	Bladder Carcinoma	GDSC	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.2222
p.Q728L	ACH-000839	Bladder Cancer	CCLE	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.2222
p.Q728L	SCaBER	urinary tract	COSMIC	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.2222
p.M745L	SHP-77	lung	COSMIC	LILYEE	LIG_APCC_ABBA_1	732:737	Mutation rewiring degron network	0.1111

DegronMD: protein-targeted degradation, mutation and drug response to degrons

USP7

UniProt ID: Q93009

Entrez ID: 7874

Protein name: Ubiquitin carboxyl-terminal hydrolase 7 (EC 3.4.19.12) (Deubiquitinating enzyme 7) (Herpesvirus-associated ubiquitin-specific protease) (Ubiquitin thioesterase 7) (Ubiquitin-specific-processing protease 7)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for USP7 in