ID:UBP7_HUMAN DESCRIPTION: RecName: Full=Ubiquitin carboxyl-terminal hydrolase 7; EC=3.4.19.12; AltName: Full=Deubiquitinating enzyme 7; AltName: Full=Herpesvirus-associated ubiquitin-specific protease; AltName: Full=Ubiquitin thioesterase 7; AltName: Full=Ubiquitin-specific-processing protease 7; FUNCTION: Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN and DAXX. 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. 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. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity. 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. 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. Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. 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. Exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C- terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). ENZYME REGULATION: Inhibited by N-ethyl-maleimide (NEM) and divalent cations. Tolerates high concentrations of NaCl but is inhibited at concentrations of 195 mM and higher. BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Active from pH 7.0 to 9.5; SUBUNIT: Monomer. Homodimer. Part of a complex with DAXX, MDM2, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts with MDM2; the interaction is independent of p53/TP53. Interacts with DAXX; the interaction is direct and independent of MDM2 and p53/TP53. Interacts with FOXO4; the interaction is enhanced in presence of hydrogen peroxide and occurs independently of p53/TP53. Interacts with p53/TP53; the interaction is enhanced in response to DNA damage; the interaction is impaired by TSPYL5. Interacts with PTEN; the interaction is direct. Interacts with UBXN6. Interacts with ATXN1 and the strength of interaction is influenced by the length of the poly-Gln region in ATXN1. A weaker interaction seen with mutants having longer poly-Gln regions. Interacts with KIAA1530/UVSSA. Isoform 1 and isoform 2 interact with herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110. Interacts with Epstein-Barr virus EBNA1. EBNA1 shows a 10-fold higher affinity than p53/TP53 and can compete with it for USP7 binding. Binding to ICP0/VMW110 may modulate the substrate specificity or activity of USP7 to stabilize viral proteins. Interacts with MEX3C and antagonizes its ability to degrade mRNA. Interacts with DNMT1 and UHRF1. INTERACTION: Q9UER7:DAXX; NbExp=10; IntAct=EBI-302474, EBI-77321; P03211:EBNA1 (xeno); NbExp=4; IntAct=EBI-302474, EBI-996522; P21145:MAL; NbExp=3; IntAct=EBI-302474, EBI-3932027; Q00987:MDM2; NbExp=13; IntAct=EBI-302474, EBI-389668; Q99836:MYD88; NbExp=3; IntAct=EBI-302474, EBI-447677; P84022:SMAD3; NbExp=2; IntAct=EBI-302474, EBI-347161; Q99426:TBCB; NbExp=2; IntAct=EBI-302474, EBI-764356; P04637:TP53; NbExp=10; IntAct=EBI-302474, EBI-366083; Q86VY4:TSPYL5; NbExp=4; IntAct=EBI-302474, EBI-3436472; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Nucleus, PML body. Note=Present in a minority of ND10 nuclear bodies. Association with ICP0/VMW110 at early times of infection leads to an increased proportion of USP7-containing ND10. Colocalizes with ATXN1 in the nucleus. Colocalized with DAXX in speckled structures. Colocalized with PML and PTEN in promyelocytic leukemia protein (PML) nuclear bodies. TISSUE SPECIFICITY: Widely expressed. Overexpressed in prostate cancer. DOMAIN: The C-terminus plays a role in its oligomerization (By similarity). PTM: Isoform 1: Phosphorylated. Isoform 1 is phosphorylated at positions Ser-18 and Ser-963. Isoform 2: Not phosphorylated. PTM: Isoform 1: Polyneddylated. Isoform 2: Not Polyneddylated. PTM: Isoform 1 and isoform 2: Not sumoylated. PTM: Isoform 1 and isoform 2: Polyubiquitinated by herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110; leading to its subsequent proteasomal degradation. Isoform 1: Ubiquitinated at Lys-869. SIMILARITY: Belongs to the peptidase C19 family. SIMILARITY: Contains 1 MATH domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/USP7ID42773ch16p13.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q93009
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006281 DNA repair GO:0006283 transcription-coupled nucleotide-excision repair GO:0006508 proteolysis GO:0006511 ubiquitin-dependent protein catabolic process GO:0006974 cellular response to DNA damage stimulus GO:0007275 multicellular organism development GO:0010216 maintenance of DNA methylation GO:0016032 viral process GO:0016579 protein deubiquitination GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0035520 monoubiquitinated protein deubiquitination GO:0035616 histone H2B conserved C-terminal lysine deubiquitination GO:0050821 protein stabilization GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0071108 protein K48-linked deubiquitination GO:1901537 positive regulation of DNA demethylation GO:1904353 regulation of telomere capping
LP895331 - Sequence 195 from Patent EP3253886. Z72499 - H.sapiens mRNA for herpesvirus associated ubiquitin-specific protease (HAUSP). BC166690 - Synthetic construct Homo sapiens clone IMAGE:100066416, MGC:195553 ubiquitin specific peptidase 7 (herpes virus-associated) (USP7) mRNA, encodes complete protein. AK302481 - Homo sapiens cDNA FLJ50426 complete cds, highly similar to Ubiquitin carboxyl-terminal hydrolase 7 (EC 3.1.2.15). JD450579 - Sequence 431603 from Patent EP1572962. AY376241 - Homo sapiens ubiquitin-specific protease 7 isoform mRNA, partial cds. AK302771 - Homo sapiens cDNA FLJ53593 complete cds, highly similar to Ubiquitin carboxyl-terminal hydrolase 7 (EC 3.1.2.15). AK316441 - Homo sapiens cDNA, FLJ79340 complete cds, highly similar to Ubiquitin carboxyl-terminal hydrolase 7 (EC 3.1.2.15). AK302912 - Homo sapiens cDNA FLJ50427 complete cds, highly similar to Ubiquitin carboxyl-terminal hydrolase 7 (EC3.1.2.15). JD022610 - Sequence 3634 from Patent EP1572962. JD032760 - Sequence 13784 from Patent EP1572962. AK302872 - Homo sapiens cDNA FLJ52374 complete cds, highly similar to Ubiquitin carboxyl-terminal hydrolase 7 (EC 3.1.2.15). DQ576601 - Homo sapiens piRNA piR-44713, complete sequence. JD076228 - Sequence 57252 from Patent EP1572962. JD191901 - Sequence 172925 from Patent EP1572962. JD458350 - Sequence 439374 from Patent EP1572962. JD458450 - Sequence 439474 from Patent EP1572962. JD458486 - Sequence 439510 from Patent EP1572962. JD458498 - Sequence 439522 from Patent EP1572962. JD271292 - Sequence 252316 from Patent EP1572962. JD458514 - Sequence 439538 from Patent EP1572962. JD056228 - Sequence 37252 from Patent EP1572962. JD458513 - Sequence 439537 from Patent EP1572962. JD056229 - Sequence 37253 from Patent EP1572962. JD054749 - Sequence 35773 from Patent EP1572962. JD389863 - Sequence 370887 from Patent EP1572962. JD458455 - Sequence 439479 from Patent EP1572962. JD458499 - Sequence 439523 from Patent EP1572962. JD271286 - Sequence 252310 from Patent EP1572962. JD271285 - Sequence 252309 from Patent EP1572962. JD416741 - Sequence 397765 from Patent EP1572962. DL492192 - Novel nucleic acids. JD178440 - Sequence 159464 from Patent EP1572962. DL491898 - Novel nucleic acids. DL490461 - Novel nucleic acids.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q93009 (Reactome details) participates in the following event(s):
R-HSA-3222072 DAXX binds Ub-MDM2 and USP7 R-HSA-3215295 USP7 deubiquitinates MDM2 R-HSA-6782004 Assembly of the pre-incision complex in TC-NER R-HSA-5689950 USP7 deubiquitinates TP53,MDM2,MDM4,FOXO4, PTEN R-HSA-3215310 USP7 deubiquitinates TP53 and counteracts MDM2 R-HSA-6807118 USP7 deubiquitinates monoubiquitinated PTEN R-HSA-6782069 UVSSA:USP7 deubiquitinates ERCC6 R-HSA-6782131 RNA Pol II backtracking in TC-NER R-HSA-6782138 ERCC5 and RPA bind TC-NER site R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-6782204 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-HSA-8853503 UCHL3,USP7,USP9X cleaves RPS27A yielding ubiquitin R-HSA-8853514 UCHL3,USP7,USP9X cleaves UBA52 yielding ubiquitin R-HSA-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER R-HSA-6804757 Regulation of TP53 Degradation R-HSA-6781823 Formation of TC-NER Pre-Incision Complex R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-5689880 Ub-specific processing proteases R-HSA-6806003 Regulation of TP53 Expression and Degradation R-HSA-8948747 Regulation of PTEN localization R-HSA-6782135 Dual incision in TC-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-5696398 Nucleotide Excision Repair R-HSA-5688426 Deubiquitination R-HSA-5633007 Regulation of TP53 Activity R-HSA-6807070 PTEN Regulation R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes R-HSA-73894 DNA Repair R-HSA-597592 Post-translational protein modification R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-1257604 PIP3 activates AKT signaling R-HSA-8852135 Protein ubiquitination R-HSA-392499 Metabolism of proteins R-HSA-212436 Generic Transcription Pathway R-HSA-9006925 Intracellular signaling by second messengers R-HSA-73857 RNA Polymerase II Transcription R-HSA-162582 Signal Transduction R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
