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Protein

Ubiquitin carboxyl-terminal hydrolase 7

Gene

Usp7

Organism
Rattus norvegicus (Rat)
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. 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. 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).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei224 – 2241NucleophilePROSITE-ProRule annotation
Active sitei465 – 4651Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: UniProtKB
  2. protein homodimerization activity Source: RGD
  3. ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

  1. histone deubiquitination Source: GO_Central
  2. maintenance of DNA methylation Source: UniProtKB
  3. multicellular organismal development Source: UniProtKB-KW
  4. positive regulation of apoptotic process Source: RGD
  5. proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  6. protein deubiquitination Source: UniProtKB
  7. regulation of proteasomal protein catabolic process Source: GO_Central
  8. regulation of protein stability Source: RGD
  9. regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  10. regulation of transcription, DNA-templated Source: GO_Central
  11. transcription-coupled nucleotide-excision repair Source: UniProtKB
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:3.4.19.12)
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1306915. Usp7.

Subcellular locationi

  1. Nucleus By similarity
  2. Cytoplasm By similarity
  3. NucleusPML body By similarity

  4. 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

  1. cytoplasm Source: GO_Central
  2. nucleus Source: UniProtKB
  3. PML body Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi224 – 2241C → S: Loss of p53/TP53-deubiquitinating activity. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11031103Ubiquitin carboxyl-terminal hydrolase 7PRO_0000268007Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191PhosphoserineBy similarity
Modified residuei870 – 8701N6-acetyllysine; alternateBy similarity
Cross-linki870 – 870Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei964 – 9641PhosphoserineBy similarity
Modified residuei1085 – 10851N6-acetyllysineBy similarity
Modified residuei1097 – 10971N6-acetyllysineBy similarity

Post-translational modificationi

Phosphorylated at positions Ser-19 and Ser-964.By similarity
Polyneddylated.
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

PhosphoSiteiQ4VSI4.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevestigatoriQ4VSI4.

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

Protein-protein interaction databases

BioGridi261960. 4 interactions.
MINTiMINT-1365534.
STRINGi10116.ENSRNOP00000041134.

Structurei

3D structure databases

ProteinModelPortaliQ4VSI4.
SMRiQ4VSI4. Positions 64-555.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini69 – 196128MATHPROSITE-ProRule annotationAdd
BLAST
Domaini215 – 522308USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 209209Interaction with TSPYL5By similarityAdd
BLAST
Regioni54 – 209156Interaction with p53/TP53 and MDM2By similarityAdd
BLAST
Regioni71 – 206136Necessary for nuclear localizationBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi4 – 1714Gln-richAdd
BLAST

Domaini

The C-terminus plays a role in its oligomerization.

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5077.
HOGENOMiHOG000160240.
HOVERGENiHBG018029.
InParanoidiQ4VSI4.
KOiK11838.
PhylomeDBiQ4VSI4.

Family and domain databases

InterProiIPR002083. MATH.
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]

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliQ4VSI4.
SMRiQ4VSI4. Positions 64-555.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi261960. 4 interactions.
MINTiMINT-1365534.
STRINGi10116.ENSRNOP00000041134.

Protein family/group databases

MEROPSiC19.016.

PTM databases

PhosphoSiteiQ4VSI4.

Proteomic databases

PaxDbiQ4VSI4.
PRIDEiQ4VSI4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi360471.
KEGGirno:360471.
UCSCiRGD:1306915. rat.

Organism-specific databases

CTDi7874.
RGDi1306915. Usp7.

Phylogenomic databases

eggNOGiCOG5077.
HOGENOMiHOG000160240.
HOVERGENiHBG018029.
InParanoidiQ4VSI4.
KOiK11838.
PhylomeDBiQ4VSI4.

Miscellaneous databases

NextBioi672877.
PROiQ4VSI4.

Gene expression databases

GenevestigatoriQ4VSI4.

Family and domain databases

InterProiIPR002083. MATH.
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...

Publicationsi

  1. "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.
    Tissue: Testis.
  2. "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.
    Tissue: Testis.

Entry informationi

Entry nameiUBP7_RAT
AccessioniPrimary (citable) accession number: Q4VSI4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: July 5, 2005
Last modified: April 1, 2015
This is version 73 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. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.