Q6A4J8 (UBP7_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 83. 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||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|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.5 Ref.6
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 By similarity. Interacts with p53/TP53. Interacts with DNMT1 and UHRF1. Ref.1 Ref.6
Nucleus. 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. Ref.5
Expressed at high levels in brain, lung, thymus and testis. Expressed at low levels in the liver. Ref.1
Expressed in embryo at 3.5 and from 7.5 to 10.5 dpc (at protein level).
The C-terminus plays a role in its oligomerization By similarity.
Phosphorylated at positions Ser-19 and Ser-964 By similarity.
Polyneddylated By similarity.
Not sumoylated By similarity.
Polyubiquitinated. Ubiquitinated at Lys-870 By similarity.
Led to early embryonic lethality. Show disorganized germinal layers without the formation of a proamniotic cavity. Many of the surviving cells were trophoblastic giant cells with large nuclei. Ref.5
Belongs to the peptidase C19 family.
Contains 1 MATH domain.
Contains 1 USP domain.
|This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: Q6A4J8-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform 2 (identifier: Q6A4J8-2) |
The sequence of this isoform differs from the canonical sequence as follows:
1-27: MNHQQQQQQQQKAGEQQLSEPEDMEME → MASSTSPPRS...CPWNEGIEYQ
|Isoform 3 (identifier: Q6A4J8-3) |
The sequence of this isoform differs from the canonical sequence as follows:
974-974: E → ECLQ
1094-1103: YLEKAIKIHN → LGLC
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 1103||1103||Ubiquitin carboxyl-terminal hydrolase 7||PRO_0000268006|
|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 Ref.4|
|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|
|Alternative sequence||1 – 27||27||MNHQQ…DMEME → MASSTSPPRSPSGGILTQDT IYFPQSNIISELLPWYLRYT PPEVPSTSVITKFILVNCPW NEGIEYQ in isoform 2.||VSP_021952|
|Alternative sequence||974||1||E → ECLQ in isoform 3.||VSP_021953|
|Alternative sequence||1094 – 1103||10||YLEKAIKIHN → LGLC in isoform 3.||VSP_021954|
|Mutagenesis||224||1||C → S: Loss of p53/TP53-deubiquitinating activity. Ref.1 Ref.6|
|Sequence conflict||162||1||E → K in BAE22671. Ref.2|
|||"Identification and characterization of murine mHAUSP encoding a deubiquitinating enzyme that regulates the status of p53 ubiquitination."|
Lim S.-K., Shin J.-M., Kim Y.-S., Baek K.-H.
Int. J. Oncol. 24:357-364(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TP53, MUTAGENESIS OF CYS-224.
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-545 (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 832-1103.
Tissue: Egg and Stomach.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 214-1103 (ISOFORM 3).
|||"The phagosomal proteome in interferon-gamma-activated macrophages."|
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
|||"Inactivation of HAUSP in vivo modulates p53 function."|
Kon N., Kobayashi Y., Li M., Brooks C.L., Ludwig T., Gu W.
Oncogene 29:1270-1279(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
|||"Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1."|
Qin W., Leonhardt H., Spada F.
J. Cell. Biochem. 112:439-444(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DNMT1 AND UHRF1, MUTAGENESIS OF CYS-224.
|+||Additional computationally mapped references.|
|AF548565 mRNA. Translation: AAQ12339.1.|
AK075830 mRNA. Translation: BAC35992.1.
AK135814 mRNA. Translation: BAE22671.1.
BC100666 mRNA. Translation: AAI00667.1.
|RefSeq||NP_001003918.2. NM_001003918.2. |
3D structure databases
|SMR||Q6A4J8. Positions 64-555, 561-1084. |
Protein-protein interaction databases
|BioGrid||232963. 4 interactions.|
|IntAct||Q6A4J8. 2 interactions.|
Protein family/group databases
Protocols and materials databases
Genome annotation databases
|UCSC||uc007ycx.1. mouse. [Q6A4J8-1]|
|MGI||MGI:2182061. Usp7. |
Gene expression databases
Family and domain databases
|InterPro||IPR002083. MATH. |
|Pfam||PF00917. MATH. 1 hit. |
PF00443. UCH. 1 hit.
PF14533. USP7_C2. 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.
|ChiTaRS||USP7. mouse. |
|Accession||Primary (citable) accession number: Q6A4J8|
Secondary accession number(s): Q3UX92, Q496Y5, Q8BW01
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|