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Q4VSI4 (UBP7_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 66. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Usp7
Synonyms:Hausp
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1103 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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).

Subunit structure

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

Subcellular location

Nucleus By similarity. 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.

Tissue specificity

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

Domain

The C-terminus plays a role in its oligomerization.

Post-translational modification

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

Polyneddylated.

Not sumoylated By similarity.

Ubiquitinated at Lys-870 By similarity. Polyubiquitinated. Ref.1 Ref.2

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 MATH domain.

Contains 1 USP domain.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Molecular functionDevelopmental protein
Hydrolase
Protease
Thiol protease
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmaintenance of DNA methylation

Inferred from sequence or structural similarity. Source: UniProtKB

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of apoptotic process

Inferred from direct assay Ref.2. Source: RGD

protein deubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein stability

Inferred from direct assay Ref.1. Source: RGD

regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription-coupled nucleotide-excision repair

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functioncysteine-type endopeptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.1. Source: RGD

ubiquitin thiolesterase activity

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11031103Ubiquitin carboxyl-terminal hydrolase 7
PRO_0000268007

Regions

Domain69 – 196128MATH
Domain215 – 522308USP
Region1 – 209209Interaction with TSPYL5 By similarity
Region54 – 209156Interaction with p53/TP53 and MDM2 By similarity
Region71 – 206136Necessary for nuclear localization By similarity
Compositional bias4 – 1714Gln-rich

Sites

Active site2241Nucleophile By similarity
Active site4651Proton acceptor By similarity

Amino acid modifications

Modified residue191Phosphoserine By similarity
Modified residue8701N6-acetyllysine; alternate By similarity
Modified residue9641Phosphoserine By similarity
Modified residue10851N6-acetyllysine By similarity
Modified residue10971N6-acetyllysine By similarity
Cross-link870Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity

Experimental info

Mutagenesis2241C → S: Loss of p53/TP53-deubiquitinating activity. Ref.1 Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q4VSI4 [UniParc].

Last modified July 5, 2005. Version 1.
Checksum: A542C4149E241C7C

FASTA1,103128,431
        10         20         30         40         50         60 
MNHQQQQQQQ QKAGEQQLSE PEDMEMEAGD TDDPPRITQN PVINGNVALS DGHSNAEEDM 

        70         80         90        100        110        120 
EDDTSWRSEA TFQFTVERFS RLSESVLSPP CFVRNLPWKI MVMPRFYPDR PHQKSVGFFL 

       130        140        150        160        170        180 
QCNAESDSTS WSCHAQAVLK IINYRDDDKS FSRRISHLFF HKENDWGFSN FMAWSEVTDP 

       190        200        210        220        230        240 
EKGFIDDDKV TFEVFVQADA PHGVAWDSKK HTGYVGLKNQ GATCYMNSLL QTLFFTNQLR 

       250        260        270        280        290        300 
KAVYMMPTEG DDSSKSVPLA LQRVFYELQH SDKPVGTKKL TKSFGWETLD SFMQHDVQEL 

       310        320        330        340        350        360 
CRVLLDNVEN KMKGTCVEGT IPKLFRGKMV SYIQCKEVDY RSDRREDYYD IQLSIKGKKN 

       370        380        390        400        410        420 
IFESFVDYVA VEQLDGDNKY DAGEHGLQEA EKGVKFLTLP PVLHLQLMRF MYDPQTDQNI 

       430        440        450        460        470        480 
KINDRFEFPE QLPLDEFLQK TDPKDPANYI LHAVLVHSGD NHGGHYVVYL NPKGDGKWCK 

       490        500        510        520        530        540 
FDDDVVSRCT KEEAIEHNYG GHDDDLSVRH CTNAYMLVYI RESKLSEVLQ AVTDHDIPQQ 

       550        560        570        580        590        600 
LVERLQEEKR IEAQKRKERQ EAHLYMQVQI VAEDQFCGHQ GNDMYDEEKV RYTVFKVLKN 

       610        620        630        640        650        660 
SSLAEFVQSL SQTMGFPQDQ IRLWPMQARS NGTKRPAMLD NEADGSKTMI ELSDNENPWT 

       670        680        690        700        710        720 
IFLETVDPEL AASGATLPKF DKDHDVMLFL KMYDPKTRSL NYCGHIYTPI SCKIRDLLPV 

       730        740        750        760        770        780 
MCDRAGFIQD TSLILYEEVK PNLTERIQDY DVSLDKALDE LMDGDIIVFQ KDDPENDNSE 

       790        800        810        820        830        840 
LPTAKEYFRD LYHRVDVIFC DKTIPNDPGF VVTLSNRMNY FQVAKTVAQR LNTDPMLLQF 

       850        860        870        880        890        900 
FKSQGYRDGP GNPLRHNYEG TLRDLLQFFK PRQPKKLYYQ QLKMKITDFE NRRSFKCIWL 

       910        920        930        940        950        960 
NSQFREEEIT LYPDKHGCVR DLLEECKKAV ELGDEASGRL RLLEIVSYKI IGVHQEDELL 

       970        980        990       1000       1010       1020 
ECLSPATSRT FRIEEIPLDQ VNIDKENEML ITVAHFHKEV FGTFGIPFLL RIHQGEHFRE 

      1030       1040       1050       1060       1070       1080 
VMKRIQSLLD IQEKEFEKFK FAIVMMGRHQ YINEDEYEVN LKDFEPQPGN MSHPRPWLGL 

      1090       1100 
DHFNKAPKRS RYTYLEKAIK IHN 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY641530 mRNA. Translation: AAT68666.1.
RefSeqNP_001019961.1. NM_001024790.1.
UniGeneRn.72721.

3D structure databases

ProteinModelPortalQ4VSI4.
SMRQ4VSI4. Positions 64-555.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid261960. 4 interactions.
MINTMINT-1365534.
STRING10116.ENSRNOP00000041134.

PTM databases

PhosphoSiteQ4VSI4.

Proteomic databases

PaxDbQ4VSI4.
PRIDEQ4VSI4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID360471.
KEGGrno:360471.
UCSCRGD:1306915. rat.

Organism-specific databases

CTD7874.
RGD1306915. Usp7.

Phylogenomic databases

eggNOGCOG5077.
HOGENOMHOG000160240.
HOVERGENHBG018029.
InParanoidQ4VSI4.
KOK11838.
PhylomeDBQ4VSI4.

Gene expression databases

GenevestigatorQ4VSI4.

Family and domain databases

InterProIPR002083. MATH.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR008974. TRAF-like.
IPR028889. UCH/PAN2.
IPR024729. USP7_ICP0-binding_dom.
[Graphical view]
PfamPF00917. MATH. 1 hit.
PF00443. UCH. 1 hit.
PF12436. USP7_ICP0_bdg. 1 hit.
[Graphical view]
SMARTSM00061. MATH. 1 hit.
[Graphical view]
SUPFAMSSF49599. SSF49599. 1 hit.
PROSITEPS50144. MATH. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio672877.
PROQ4VSI4.

Entry information

Entry nameUBP7_RAT
AccessionPrimary (citable) accession number: Q4VSI4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: July 5, 2005
Last modified: April 16, 2014
This is version 66 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries