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Protein

Ubiquitin carboxyl-terminal hydrolase 7

Gene

Usp7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN and DAXX (PubMed:21268065, PubMed:14719112, PubMed:19946331). 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, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (By similarity). 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 (By similarity). 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. Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222).By similarity4 Publications

Catalytic activityi

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).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei224NucleophilePROSITE-ProRule annotation2 Publications1
Active sitei465Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • p53 binding Source: MGI
  • protein C-terminus binding Source: MGI
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • transcription factor binding Source: MGI
  • ubiquitin protein ligase binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Protease, Thiol protease

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Protein family/group databases

MEROPSiC19.016.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 7 (EC:3.4.19.122 Publications)
Alternative name(s):
Deubiquitinating enzyme 7
Herpesvirus-associated ubiquitin-specific protease
Short name:
mHAUSP
Ubiquitin thioesterase 7
Ubiquitin-specific-processing protease 7
Gene namesi
Name:Usp7
Synonyms:Hausp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:2182061. Usp7.

Subcellular locationi

  • Nucleus 1 Publication
  • Cytoplasm By similarity
  • NucleusPML 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).By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • nuclear body Source: MGI
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
  • XY body Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi224C → S: Loss of p53/TP53-deubiquitinating activity. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002680061 – 1103Ubiquitin carboxyl-terminal hydrolase 7Add BLAST1103

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19PhosphoserineCombined sources1
Modified residuei50PhosphoserineCombined sources1
Modified residuei54PhosphoserineCombined sources1
Modified residuei870N6-acetyllysine; alternateBy similarity1
Cross-linki870Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki870Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei964PhosphoserineBy similarity1
Modified residuei1085N6-acetyllysineBy similarity1
Modified residuei1097N6-acetyllysineBy similarity1

Post-translational modificationi

Polyneddylated.By similarity
Not sumoylated.By similarity
Polyubiquitinated. Ubiquitinated at Lys-870 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ6A4J8.
PaxDbiQ6A4J8.
PeptideAtlasiQ6A4J8.
PRIDEiQ6A4J8.

PTM databases

iPTMnetiQ6A4J8.
PhosphoSitePlusiQ6A4J8.

Expressioni

Tissue specificityi

Expressed at high levels in brain, lung, thymus and testis. Expressed at low levels in the liver.1 Publication

Developmental stagei

Expressed in embryo at 3.5 and from 7.5 to 10.5 dpc (at protein level).

Gene expression databases

CleanExiMM_USP7.

Interactioni

Subunit structurei

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 DNMT1 and UHRF1. Interacts with FOXP3 (By similarity). Interacts (via MATH domain) with RNF220 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi232963. 7 interactors.
DIPiDIP-38603N.
IntActiQ6A4J8. 4 interactors.
MINTiMINT-4139284.
STRINGi10090.ENSMUSP00000124093.

Structurei

3D structure databases

ProteinModelPortaliQ6A4J8.
SMRiQ6A4J8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini69 – 196MATHPROSITE-ProRule annotationAdd BLAST128
Domaini215 – 522USPAdd BLAST308

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 209Interaction with TSPYL5By similarityAdd BLAST209
Regioni54 – 209Interaction with p53/TP53 and MDM2By similarityAdd BLAST156
Regioni71 – 206Necessary for nuclear localizationBy similarityAdd BLAST136

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 17Gln-richAdd BLAST14

Domaini

The C-terminus plays a role in its oligomerization.By similarity

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 1 MATH domain.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiKOG1863. Eukaryota.
COG5077. LUCA.
HOGENOMiHOG000160240.
HOVERGENiHBG018029.
InParanoidiQ6A4J8.
KOiK11838.
PhylomeDBiQ6A4J8.

Family and domain databases

InterProiIPR002083. MATH/TRAF_dom.
IPR001394. Peptidase_C19_UCH.
IPR008974. TRAF-like.
IPR024729. USP7_ICP0-binding_dom.
IPR029346. USP_C.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00917. MATH. 1 hit.
PF00443. UCH. 1 hit.
PF14533. USP7_C2. 1 hit.
PF12436. USP7_ICP0_bdg. 1 hit.
[Graphical view]
SMARTiSM00061. MATH. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50144. MATH. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6A4J8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MNHQQQQQQQ QKAGEQQLSE PEDMEMEAGD TDDPPRITQN PVINGNVTLS
60 70 80 90 100
DGHSNAEEDM EDDTSWRSEA TFQFTVERFS RLSESVLSPP CFVRNLPWKI
110 120 130 140 150
MVMPRFYPDR PHQKSVGFFL QCNAESDSTS WSCHAQAVLK IINYRDDDKS
160 170 180 190 200
FSRRISHLFF HEENDWGFSN FMAWSEVTDP EKGFIDDDKV TFEVFVQADA
210 220 230 240 250
PHGVAWDSKK HTGYVGLKNQ GATCYMNSLL QTLFFTNQLR KAVYMMPTEG
260 270 280 290 300
DDSSKSVPLA LQRVFYELQH SDKPVGTKKL TKSFGWETLD SFMQHDVQEL
310 320 330 340 350
CRVLLDNVEN KMKGTCVEGT IPKLFRGKMV SYIQCKDVDY RSDRREDYYD
360 370 380 390 400
IQLSIKGKKN IFESFVDYVA VEQLDGDNKY DAGEHGLQEA EKGVKFLTLP
410 420 430 440 450
PVLHLQLMRF MYDPQTDQNI KINDRFEFPE QLPLDEFLQK TDPKDPANYI
460 470 480 490 500
LHAVLVHSGD NHGGHYVVYL NPKGDGKWCK FDDDVVSRCT KEEAIEHNYG
510 520 530 540 550
GHDDDLSVRH CTNAYMLVYI RESKLSEVLQ AVTDHDIPQQ LVERLQEEKR
560 570 580 590 600
IEAQKRKERQ EAHLYMQVQI VAEDQFCGHQ GNDMYDEEKV RYTVFKVLKN
610 620 630 640 650
SSLAEFVQSL SQTMGFPQDQ IRLWPMQARS NGTKRPAMLD NEADGNKTMI
660 670 680 690 700
ELSDNENPWT IFLETVDPEL AASGATLPKF DKDHDVMLFL KMYDPKTRSL
710 720 730 740 750
NYCGHIYTPI SCKIRDLLPV MCDRAGFIQD TSLILYEEVK PNLTERIQDY
760 770 780 790 800
DVSLDKALDE LMDGDIIVFQ KDDPENDNSE LPTAKEYFRD LYHRVDVIFC
810 820 830 840 850
DKTIPNDPGF VVTLSNRMNY FQVAKTVAQR LNTDPMLLQF FKSQGYRDGP
860 870 880 890 900
GNPLRHNYEG TLRDLLQFFK PRQPKKLYYQ QLKMKITDFE NRRSFKCIWL
910 920 930 940 950
NSQFREEEIT LYPDKHGCVR DLLEECKKAV ELGDKASGRL RLLEIVSYKI
960 970 980 990 1000
IGVHQEDELL ECLSPATSRT FRIEEIPLDQ VDIDKENEML ITVAHFHKEV
1010 1020 1030 1040 1050
FGTFGIPFLL RIHQGEHFRE VMKRIQSLLD IQEKEFEKFK FAIVMMGRHQ
1060 1070 1080 1090 1100
YINEDEYEVN LKDFEPQPGN MSHPRPWLGL DHFNKAPKRS RYTYLEKAIK

IHN
Length:1,103
Mass (Da):128,475
Last modified:September 13, 2004 - v1
Checksum:i989DFE733F0D961E
GO
Isoform 2 (identifier: Q6A4J8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MNHQQQQQQQQKAGEQQLSEPEDMEME → MASSTSPPRS...CPWNEGIEYQ

Show »
Length:1,143
Mass (Da):132,749
Checksum:i38F6764A2D063600
GO
Isoform 3 (identifier: Q6A4J8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     974-974: E → ECLQ
     1094-1103: YLEKAIKIHN → LGLC

Show »
Length:1,100
Mass (Da):127,996
Checksum:i3E5FE589370B8006
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti162E → K in BAE22671 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0219521 – 27MNHQQ…DMEME → MASSTSPPRSPSGGILTQDT IYFPQSNIISELLPWYLRYT PPEVPSTSVITKFILVNCPW NEGIEYQ in isoform 2. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_021953974E → ECLQ in isoform 3. 1 Publication1
Alternative sequenceiVSP_0219541094 – 1103YLEKAIKIHN → LGLC in isoform 3. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF548565 mRNA. Translation: AAQ12339.1.
AK075830 mRNA. Translation: BAC35992.1.
AK135814 mRNA. Translation: BAE22671.1.
BC100666 mRNA. Translation: AAI00667.1.
CCDSiCCDS49755.1. [Q6A4J8-1]
RefSeqiNP_001003918.2. NM_001003918.2.
UniGeneiMm.295330.

Genome annotation databases

GeneIDi252870.
KEGGimmu:252870.
UCSCiuc007ycx.1. mouse. [Q6A4J8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF548565 mRNA. Translation: AAQ12339.1.
AK075830 mRNA. Translation: BAC35992.1.
AK135814 mRNA. Translation: BAE22671.1.
BC100666 mRNA. Translation: AAI00667.1.
CCDSiCCDS49755.1. [Q6A4J8-1]
RefSeqiNP_001003918.2. NM_001003918.2.
UniGeneiMm.295330.

3D structure databases

ProteinModelPortaliQ6A4J8.
SMRiQ6A4J8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi232963. 7 interactors.
DIPiDIP-38603N.
IntActiQ6A4J8. 4 interactors.
MINTiMINT-4139284.
STRINGi10090.ENSMUSP00000124093.

Protein family/group databases

MEROPSiC19.016.

PTM databases

iPTMnetiQ6A4J8.
PhosphoSitePlusiQ6A4J8.

Proteomic databases

EPDiQ6A4J8.
PaxDbiQ6A4J8.
PeptideAtlasiQ6A4J8.
PRIDEiQ6A4J8.

Protocols and materials databases

DNASUi252870.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi252870.
KEGGimmu:252870.
UCSCiuc007ycx.1. mouse. [Q6A4J8-1]

Organism-specific databases

CTDi7874.
MGIiMGI:2182061. Usp7.

Phylogenomic databases

eggNOGiKOG1863. Eukaryota.
COG5077. LUCA.
HOGENOMiHOG000160240.
HOVERGENiHBG018029.
InParanoidiQ6A4J8.
KOiK11838.
PhylomeDBiQ6A4J8.

Miscellaneous databases

ChiTaRSiUsp7. mouse.
PROiQ6A4J8.
SOURCEiSearch...

Gene expression databases

CleanExiMM_USP7.

Family and domain databases

InterProiIPR002083. MATH/TRAF_dom.
IPR001394. Peptidase_C19_UCH.
IPR008974. TRAF-like.
IPR024729. USP7_ICP0-binding_dom.
IPR029346. USP_C.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00917. MATH. 1 hit.
PF00443. UCH. 1 hit.
PF14533. USP7_C2. 1 hit.
PF12436. USP7_ICP0_bdg. 1 hit.
[Graphical view]
SMARTiSM00061. MATH. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50144. MATH. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP7_MOUSE
AccessioniPrimary (citable) accession number: Q6A4J8
Secondary accession number(s): Q3UX92, Q496Y5, Q8BW01
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: September 13, 2004
Last modified: November 2, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.