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Protein

Ubiquitin carboxyl-terminal hydrolase 7

Gene

Usp7

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:16111684, PubMed:16328052). 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 (By similarity). 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 (By similarity). 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 (By similarity). Deubiquitinates KMT2E preventing KMT2E proteasomal-mediated degradation (By similarity). Involved in cell proliferation during early embryonic development (By similarity). 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 (By similarity). Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (By similarity). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (By similarity). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (By similarity). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing transcription factor FOXP3 which is crucial for Treg cell function (By similarity).By similarity2 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

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Hydrolase, Protease, Thiol protease
Biological processDNA 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:
rHAUSP
Ubiquitin thioesterase 7
Ubiquitin-specific-processing protease 7
Gene namesi
Name:Usp7
Synonyms:Hausp
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1306915 Usp7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

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_00002680071 – 1103Ubiquitin carboxyl-terminal hydrolase 7Add BLAST1103

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19PhosphoserineCombined sources1
Modified residuei50PhosphoserineBy similarity1
Modified residuei54PhosphoserineBy similarity1
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
Cross-linki883Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei964PhosphoserineBy similarity1
Modified residuei1085N6-acetyllysineBy similarity1
Modified residuei1097N6-acetyllysineBy similarity1

Post-translational modificationi

Polyneddylated.1 Publication
Not sumoylated.By similarity
Ubiquitinated at Lys-870 (By similarity). Polyubiquitinated.By similarity2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ4VSI4
PRIDEiQ4VSI4

PTM databases

iPTMnetiQ4VSI4
PhosphoSitePlusiQ4VSI4

Expressioni

Tissue specificityi

Strongly expressed in the testis, spleen and brain. Weakly expressed in the stomach, small intestine, skeletal muscle and uterus.1 Publication

Interactioni

Subunit structurei

Monomer. Homodimer (PubMed:16111684). 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. Component of a complex composed of KMT2E, OGT and USP7; the complex stabilizes KMT2E, preventing KMT2E ubiquitination and proteosomal-mediated degradation (By similarity). Interacts (via MATH domain) with KMT2E (By similarity). Interacts with OGT (By similarity). 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 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. Interacts with FOXP3. Interacts (via MATH domain) with RNF220 (By similarity). Associated component of the Polycomb group (PcG) multiprotein PRC1-like complex (By similarity). Interacts with EPOP (By similarity). Interacts with OTUD4 and USP9X; the interaction is direct (By similarity).By similarity1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

BioGridi261960, 2 interactors
MINTiQ4VSI4
STRINGi10116.ENSRNOP00000041134

Structurei

3D structure databases

ProteinModelPortaliQ4VSI4
SMRiQ4VSI4
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.

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Phylogenomic databases

eggNOGiKOG1863 Eukaryota
COG5077 LUCA
HOGENOMiHOG000160240
HOVERGENiHBG018029
InParanoidiQ4VSI4
KOiK11838
PhylomeDBiQ4VSI4

Family and domain databases

Gene3Di2.60.210.10, 1 hit
InterProiView protein in InterPro
IPR002083 MATH/TRAF_dom
IPR001394 Peptidase_C19_UCH
IPR008974 TRAF-like
IPR024729 USP7_ICP0-binding_dom
IPR029346 USP_C
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00917 MATH, 1 hit
PF00443 UCH, 1 hit
PF14533 USP7_C2, 1 hit
PF12436 USP7_ICP0_bdg, 1 hit
SMARTiView protein in SMART
SM00061 MATH, 1 hit
SUPFAMiSSF49599 SSF49599, 1 hit
PROSITEiView protein in PROSITE
PS50144 MATH, 1 hit
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequencei

Sequence statusi: Complete.

Q4VSI4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNHQQQQQQQ QKAGEQQLSE PEDMEMEAGD TDDPPRITQN PVINGNVALS
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 HKENDWGFSN 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 SYIQCKEVDY 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 NEADGSKTMI
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 ELGDEASGRL RLLEIVSYKI
960 970 980 990 1000
IGVHQEDELL ECLSPATSRT FRIEEIPLDQ VNIDKENEML 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):128,431
Last modified:July 5, 2005 - v1
Checksum:iA542C4149E241C7C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY641530 mRNA Translation: AAT68666.1
RefSeqiNP_001019961.1, NM_001024790.1
UniGeneiRn.72721

Genome annotation databases

GeneIDi360471
KEGGirno:360471
UCSCiRGD:1306915 rat

Similar proteinsi

Entry informationi

Entry nameiUBP7_RAT
AccessioniPrimary (citable) accession number: Q4VSI4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: July 5, 2005
Last modified: May 23, 2018
This is version 99 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

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