USP6
USP6 (Ubiquitin carboxyl-terminal hydrolase 6) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Breast cancer, Hepatocellular carcinoma and 5 more.
Overview
Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyses its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity.
Open Targets scores its association with cancer at 0.74 (direct and indirect evidence; datatypes literature 0.78, animal model 0.53, genetic association 0.00, somatic mutation 0.96). IntOGen calls it a driver in 8 cohorts (5 activating, 0 loss-of-function), covering Acute Myeloid Leukaemia, Basal Cell Carcinoma, Invasive Breast Carcinoma, Colorectal Adenocarcinoma, Hepatocellular Carcinoma, Lung Squamous Cell Carcinoma and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · USP6 (Ubiquitin carboxyl-terminal hydrolase 6) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Breast cancer, Hepatocellular carcinoma and 5 more.
- 1 · What it is
USP6 (Ubiquitin carboxyl-terminal hydrolase 6) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Breast cancer, Hepatocellular carcinoma and 5 more.
- 2 · What goes wrong in cancer
Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyses its own deubiquitination.
- 3 · How drugs use it
No product in this corpus aims at USP6 yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:12629 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P35125 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000129204 (association with cancer (MONDO_0004992) 0.74; per-cancer scores at or above 0.5: colorectal cancer 0.59, melanoma 0.56, sarcoma 0.53, skin cancer 0.57, breast cancer 0.51, lung cancer 0.54 (GraphQL API, CC0)); IntOGen USP6 (driver in 8 cohorts (Act 5, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyses its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localisation of ARF6 and selectively regulates ARF6-dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation. May act as a GTPase-activating protein for RAB3A. Location: Cell membrane; Cytoplasm; Endosome (UniProt). Locus 17p13.2 (HGNC).
- Colorectal cancer: Open Targets association 0.59 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD)
- Breast cancer: Open Targets association 0.51 with breast cancer (MONDO_0007254); IntOGen driver in 1 cohort (BRCA)
- Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)
- Prostate cancer: IntOGen driver in 1 cohort (PRAD)
- Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898)
- Lung cancer: Open Targets association 0.54 with lung cancer (MONDO_0008903)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 5 cohorts; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"USP6" OR ABSTRACT:"USP6" OR TITLE:"ubiquitin specific peptidase 6" OR ABSTRACT:"ubiquitin specific peptidase 6" OR TITLE:"Ubiquitin carboxyl-terminal hydrolase 6" OR ABSTRACT:"Ubiquitin carboxyl-terminal hydrolase 6" OR TITLE:"Tre-2" OR ABSTRACT:"Tre-2" OR TITLE:"TRE17" OR ABSTRACT:"TRE17" OR TITLE:"Tre2" OR ABSTRACT:"Tre2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about USP6, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetCLTCL1
Shares Lung cancer (all types), Skin cancer (all types), Hepatocellular carcinoma, Breast cancer (all types).
- TargetCACNA1D
Shares Lung cancer (all types), Skin cancer (all types), Sarcomas (soft tissue, bone, GIST), Hepatocellular carcinoma.
- TargetAFF4
Shares Lung cancer (all types), Skin cancer (all types), Hepatocellular carcinoma, Breast cancer (all types).
- TargetCAMTA1
Shares Lung cancer (all types), Skin cancer (all types), Sarcomas (soft tissue, bone, GIST), Breast cancer (all types).
- TargetAFDN
Shares Lung cancer (all types), Skin cancer (all types), Breast cancer (all types), IntOGen.
- TargetATP2B3
Shares Lung cancer (all types), Skin cancer (all types), Breast cancer (all types), IntOGen.
- TargetETV5
Shares Lung cancer (all types), Skin cancer (all types), Breast cancer (all types), Acute myeloid leukaemia.
- TargetETV1
Shares Lung cancer (all types), Sarcomas (soft tissue, bone, GIST), Breast cancer (all types), IntOGen.