Q4VSI4 (UBP7_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 66. History...
Names and origin
|Protein names||Recommended name:|
Ubiquitin carboxyl-terminal hydrolase 7
Deubiquitinating enzyme 7
Herpesvirus-associated ubiquitin-specific protease
Ubiquitin thioesterase 7
Ubiquitin-specific-processing protease 7
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||1103 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. 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. Ref.1 Ref.2
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).
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. Interacts with MEX3C and antagonizes its ability to degrade mRNA. Interacts with DNMT1 and UHRF1 By similarity. Ref.1
Nucleus By similarity. Cytoplasm By similarity. Nucleus › PML body By similarity. Note: Present in a minority of ND10 nuclear bodies. Colocalizes with ATXN1 in the nucleus. Colocalized with DAXX in speckled structures. Colocalized with PML and PTEN in promyelocytic leukemia protein (PML) nuclear bodies By similarity.
Strongly expressed in the testis, spleen and brain. Weakly expressed in the stomach, small intestine, skeletal muscle and uterus. Ref.1
The C-terminus plays a role in its oligomerization.
Phosphorylated at positions Ser-19 and Ser-964 By similarity.
Not sumoylated By similarity.
Belongs to the peptidase C19 family.
Contains 1 MATH domain.
Contains 1 USP domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 1103||1103||Ubiquitin carboxyl-terminal hydrolase 7||PRO_0000268007|
|Domain||69 – 196||128||MATH|
|Domain||215 – 522||308||USP|
|Region||1 – 209||209||Interaction with TSPYL5 By similarity|
|Region||54 – 209||156||Interaction with p53/TP53 and MDM2 By similarity|
|Region||71 – 206||136||Necessary for nuclear localization By similarity|
|Compositional bias||4 – 17||14||Gln-rich|
|Active site||224||1||Nucleophile By similarity|
|Active site||465||1||Proton acceptor By similarity|
Amino acid modifications
|Modified residue||19||1||Phosphoserine By similarity|
|Modified residue||870||1||N6-acetyllysine; alternate By similarity|
|Modified residue||964||1||Phosphoserine By similarity|
|Modified residue||1085||1||N6-acetyllysine By similarity|
|Modified residue||1097||1||N6-acetyllysine By similarity|
|Cross-link||870||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity|
|Mutagenesis||224||1||C → S: Loss of p53/TP53-deubiquitinating activity. Ref.1 Ref.2|
|||"HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated, and dimerized."|
Lee H.-J., Kim M.-S., Kim Y.-K., Oh Y.-K., Baek K.-H.
FEBS Lett. 579:4867-4872(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-224, POLYUBIQUITINATION, POLYNEDDYLATION.
|||"Molecular cloning of rHAUSP encoding a deubiquitinating enzyme in rat testis."|
Baek K.H., Lee H.J., Kim M.S., Kim Y.S., Seong M., Lee E.J., Lee M.Y.
Oncol. Rep. 15:173-177(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION, MUTAGENESIS OF CYS-224.
|+||Additional computationally mapped references.|
|AY641530 mRNA. Translation: AAT68666.1.|
|RefSeq||NP_001019961.1. NM_001024790.1. |
3D structure databases
|SMR||Q4VSI4. Positions 64-555. |
Protein-protein interaction databases
|BioGrid||261960. 4 interactions.|
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:1306915. rat. |
|RGD||1306915. Usp7. |
Gene expression databases
Family and domain databases
|InterPro||IPR002083. MATH. |
|Pfam||PF00917. MATH. 1 hit. |
PF00443. UCH. 1 hit.
PF12436. USP7_ICP0_bdg. 1 hit.
|SMART||SM00061. MATH. 1 hit. |
|SUPFAM||SSF49599. SSF49599. 1 hit. |
|PROSITE||PS50144. MATH. 1 hit. |
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
|Accession||Primary (citable) accession number: Q4VSI4|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|