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Q6A4J8 (UBP7_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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=mHAUSP
Ubiquitin thioesterase 7
Ubiquitin-specific-processing protease 7
Gene names
Name:Usp7
Synonyms:Hausp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.5 Ref.6

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 By similarity. Interacts with p53/TP53. Interacts with DNMT1 and UHRF1. Ref.1 Ref.6

Subcellular location

Nucleus. 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. Ref.5

Tissue specificity

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

Developmental stage

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

Domain

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

Post-translational modification

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

Polyneddylated By similarity.

Not sumoylated By similarity.

Polyubiquitinated. Ubiquitinated at Lys-870 By similarity.

Disruption phenotype

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

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 MATH domain.

Contains 1 USP domain.

Alternative products

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11031103Ubiquitin carboxyl-terminal hydrolase 7
PRO_0000268006

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 Ref.4
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

Natural variations

Alternative sequence1 – 2727MNHQQ…DMEME → MASSTSPPRSPSGGILTQDT IYFPQSNIISELLPWYLRYT PPEVPSTSVITKFILVNCPW NEGIEYQ in isoform 2.
VSP_021952
Alternative sequence9741E → ECLQ in isoform 3.
VSP_021953
Alternative sequence1094 – 110310YLEKAIKIHN → LGLC in isoform 3.
VSP_021954

Experimental info

Mutagenesis2241C → S: Loss of p53/TP53-deubiquitinating activity. Ref.1 Ref.6
Sequence conflict1621E → K in BAE22671. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 13, 2004. Version 1.
Checksum: 989DFE733F0D961E

FASTA1,103128,475
        10         20         30         40         50         60 
MNHQQQQQQQ QKAGEQQLSE PEDMEMEAGD TDDPPRITQN PVINGNVTLS DGHSNAEEDM 

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

       130        140        150        160        170        180 
QCNAESDSTS WSCHAQAVLK IINYRDDDKS FSRRISHLFF HEENDWGFSN 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 SYIQCKDVDY 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 NEADGNKTMI 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 ELGDKASGRL RLLEIVSYKI IGVHQEDELL 

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

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

      1090       1100 
DHFNKAPKRS RYTYLEKAIK IHN 

« Hide

Isoform 2 [UniParc].

Checksum: 38F6764A2D063600
Show »

FASTA1,143132,749
Isoform 3 [UniParc].

Checksum: 3E5FE589370B8006
Show »

FASTA1,100127,996

References

« Hide 'large scale' references
[1]"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.
[2]"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. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai 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.
Strain: C57BL/6J.
Tissue: Egg and Stomach.
[3]"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).
Strain: C57BL/6.
Tissue: Brain.
[4]"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].
[5]"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.
[6]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF548565 mRNA. Translation: AAQ12339.1.
AK075830 mRNA. Translation: BAC35992.1.
AK135814 mRNA. Translation: BAE22671.1.
BC100666 mRNA. Translation: AAI00667.1.
RefSeqNP_001003918.2. NM_001003918.2.
UniGeneMm.295330.

3D structure databases

ProteinModelPortalQ6A4J8.
SMRQ6A4J8. Positions 64-555, 561-1084.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid232963. 4 interactions.
DIPDIP-38603N.
IntActQ6A4J8. 2 interactions.
MINTMINT-4139284.

Protein family/group databases

MEROPSC19.016.

PTM databases

PhosphoSiteQ6A4J8.

Proteomic databases

PaxDbQ6A4J8.
PRIDEQ6A4J8.

Protocols and materials databases

DNASU252870.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID252870.
KEGGmmu:252870.
UCSCuc007ycx.1. mouse. [Q6A4J8-1]

Organism-specific databases

CTD7874.
MGIMGI:2182061. Usp7.

Phylogenomic databases

eggNOGCOG5077.
HOGENOMHOG000160240.
HOVERGENHBG018029.
KOK11838.
PhylomeDBQ6A4J8.

Gene expression databases

CleanExMM_USP7.
GenevestigatorQ6A4J8.

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

ChiTaRSUSP7. mouse.
NextBio387363.
PROQ6A4J8.
SOURCESearch...

Entry information

Entry nameUBP7_MOUSE
AccessionPrimary (citable) accession number: Q6A4J8
Secondary accession number(s): Q3UX92, Q496Y5, Q8BW01
Entry history
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: September 13, 2004
Last modified: April 16, 2014
This is version 80 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot