Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q93009 (UBP7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
Ubiquitin thioesterase 7
Ubiquitin-specific-processing protease 7
Gene names
Name:USP7
Synonyms:HAUSP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1102 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. Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. 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.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.16 Ref.18 Ref.21 Ref.25 Ref.27 Ref.28 Ref.30 Ref.31

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).

Enzyme regulation

Inhibited by N-ethyl-maleimide (NEM) and divalent cations. Tolerates high concentrations of NaCl but is inhibited at concentrations of 195 mM and higher. Ref.8

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. Isoform 1 and isoform 2 interact with herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110. Interacts with Epstein-Barr virus EBNA1. EBNA1 shows a 10-fold higher affinity than p53/TP53 and can compete with it for USP7 binding. Binding to ICP0/VMW110 may modulate the substrate specificity or activity of USP7 to stabilize viral proteins. Interacts with MEX3C and antagonizes its ability to degrade mRNA. Interacts with DNMT1 and UHRF1. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.24 Ref.25 Ref.27 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35

Subcellular location

Nucleus. Cytoplasm. NucleusPML body. Note: Present in a minority of ND10 nuclear bodies. Association with ICP0/VMW110 at early times of infection leads to an increased proportion of USP7-containing ND10. Colocalizes with ATXN1 in the nucleus. Colocalized with DAXX in speckled structures. Colocalized with PML and PTEN in promyelocytic leukemia protein (PML) nuclear bodies. Ref.6 Ref.11 Ref.13 Ref.16 Ref.18

Tissue specificity

Widely expressed. Overexpressed in prostate cancer. Ref.16

Domain

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

Post-translational modification

Isoform 1:Phosphorylated. Isoform 1 is phosphorylated at positions Ser-18 and Ser-963. Isoform 2:Not phosphorylated. Ref.13

Isoform 1:Polyneddylated. Isoform 2:Not Polyneddylated.

Isoform 1 and isoform 2:Not sumoylated.

Isoform 1 and isoform 2:Polyubiquitinated by herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110; leading to its subsequent proteasomal degradation. Isoform 1:Ubiquitinated at Lys-869. Ref.10 Ref.13

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 MATH domain.

Contains 1 USP domain.

Biophysicochemical properties

pH dependence:

Active from pH 7.0 to 9.5. Ref.8

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Host-virus interaction
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   Molecular functionDevelopmental protein
Hydrolase
Protease
Thiol protease
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processmaintenance of DNA methylation

Inferred from mutant phenotype Ref.25. Source: UniProtKB

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay PubMed 11279055. Source: UniProtKB

protein deubiquitination

Inferred from direct assay Ref.12Ref.25. Source: UniProtKB

regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.12. Source: UniProtKB

transcription-coupled nucleotide-excision repair

Inferred from mutant phenotype Ref.31. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from direct assay PubMed 11279055. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 11279055Ref.6Ref.12PubMed 20096447. Source: UniProtKB

   Molecular_functioncysteine-type endopeptidase activity

Inferred from mutant phenotype Ref.25. Source: UniProtKB

p53 binding

Inferred from direct assay PubMed 20096447. Source: UniProtKB

protein C-terminus binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 11279055Ref.7Ref.11Ref.25Ref.30Ref.31. Source: UniProtKB

transcription factor binding

Inferred from physical interaction Ref.12. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 11279055Ref.14. Source: UniProtKB

ubiquitin thiolesterase activity

Inferred from direct assay Ref.25. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from direct assay Ref.12Ref.25. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q93009-1)

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: Q93009-2)

Also known as: USP7 beta;

The sequence of this isoform is not available.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q93009-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: MNHQQQQQQQKAGEQQLSEPEDMEM → MAGNHRLGL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11021102Ubiquitin carboxyl-terminal hydrolase 7
PRO_0000080626

Regions

Domain68 – 195128MATH
Domain214 – 521308USP
Region1 – 208208Interaction with TSPYL5
Region53 – 208156Interaction with p53/TP53, MDM2 and EBNA1
Region70 – 205136Necessary for nuclear localization
Region622 – 801180Interaction with ICP0/VMW110
Compositional bias4 – 107Poly-Gln

Sites

Active site2231Nucleophile
Active site4641Proton acceptor Probable

Amino acid modifications

Modified residue181Phosphoserine Ref.13 Ref.17 Ref.22 Ref.26
Modified residue8691N6-acetyllysine; alternate Ref.20
Modified residue9631Phosphoserine Ref.13 Ref.17
Modified residue10841N6-acetyllysine Ref.20
Modified residue10961N6-acetyllysine Ref.20
Cross-link869Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate Ref.13

Natural variations

Alternative sequence1 – 2525MNHQQ…EDMEM → MAGNHRLGL in isoform 3.
VSP_054884

Experimental info

Mutagenesis1641D → A: Decreased binding to p53/TP53 and MDM2. Ref.35
Mutagenesis1651W → A: Loss of binding to p53/TP53 and MDM2. Ref.35
Mutagenesis2231C → A: Complete loss of activity. Localized in the nucleus and does not inhibit FOXO4-dependent transcriptional activity. Ref.7 Ref.9 Ref.12 Ref.16 Ref.25 Ref.27 Ref.32
Mutagenesis2231C → S: No effect on p53/TP53 and PTEN binding but is defective in deubiquitinating p53/TP53 and PTEN. Ref.7 Ref.9 Ref.12 Ref.16 Ref.25 Ref.27 Ref.32
Mutagenesis4561H → A: Complete loss of activity. Ref.32
Mutagenesis4641H → A: Complete loss of activity. Ref.32
Sequence conflict2011H → I AA sequence Ref.1
Sequence conflict2051W → P AA sequence Ref.1
Sequence conflict2071S → Q AA sequence Ref.1
Sequence conflict10451M → T in CAA96580. Ref.1
Sequence conflict10661Q → T AA sequence Ref.1

Secondary structure

........................................................................................................................................................................................................... 1102
Helix Strand Turn

Details...

Sequences

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

Last modified November 4, 2008. Version 2.
Checksum: F1A5A5C421396E45

FASTA1,102128,302
        10         20         30         40         50         60 
MNHQQQQQQQ KAGEQQLSEP EDMEMEAGDT DDPPRITQNP VINGNVALSD GHNTAEEDME 

        70         80         90        100        110        120 
DDTSWRSEAT FQFTVERFSR LSESVLSPPC FVRNLPWKIM VMPRFYPDRP HQKSVGFFLQ 

       130        140        150        160        170        180 
CNAESDSTSW SCHAQAVLKI INYRDDEKSF SRRISHLFFH KENDWGFSNF MAWSEVTDPE 

       190        200        210        220        230        240 
KGFIDDDKVT FEVFVQADAP HGVAWDSKKH TGYVGLKNQG ATCYMNSLLQ TLFFTNQLRK 

       250        260        270        280        290        300 
AVYMMPTEGD DSSKSVPLAL QRVFYELQHS DKPVGTKKLT KSFGWETLDS FMQHDVQELC 

       310        320        330        340        350        360 
RVLLDNVENK MKGTCVEGTI PKLFRGKMVS YIQCKEVDYR SDRREDYYDI QLSIKGKKNI 

       370        380        390        400        410        420 
FESFVDYVAV EQLDGDNKYD AGEHGLQEAE KGVKFLTLPP VLHLQLMRFM YDPQTDQNIK 

       430        440        450        460        470        480 
INDRFEFPEQ LPLDEFLQKT DPKDPANYIL HAVLVHSGDN HGGHYVVYLN PKGDGKWCKF 

       490        500        510        520        530        540 
DDDVVSRCTK EEAIEHNYGG HDDDLSVRHC TNAYMLVYIR ESKLSEVLQA VTDHDIPQQL 

       550        560        570        580        590        600 
VERLQEEKRI EAQKRKERQE AHLYMQVQIV AEDQFCGHQG NDMYDEEKVK YTVFKVLKNS 

       610        620        630        640        650        660 
SLAEFVQSLS QTMGFPQDQI RLWPMQARSN GTKRPAMLDN EADGNKTMIE LSDNENPWTI 

       670        680        690        700        710        720 
FLETVDPELA ASGATLPKFD KDHDVMLFLK MYDPKTRSLN YCGHIYTPIS CKIRDLLPVM 

       730        740        750        760        770        780 
CDRAGFIQDT SLILYEEVKP NLTERIQDYD VSLDKALDEL MDGDIIVFQK DDPENDNSEL 

       790        800        810        820        830        840 
PTAKEYFRDL YHRVDVIFCD KTIPNDPGFV VTLSNRMNYF QVAKTVAQRL NTDPMLLQFF 

       850        860        870        880        890        900 
KSQGYRDGPG NPLRHNYEGT LRDLLQFFKP RQPKKLYYQQ LKMKITDFEN RRSFKCIWLN 

       910        920        930        940        950        960 
SQFREEEITL YPDKHGCVRD LLEECKKAVE LGEKASGKLR LLEIVSYKII GVHQEDELLE 

       970        980        990       1000       1010       1020 
CLSPATSRTF RIEEIPLDQV DIDKENEMLV TVAHFHKEVF GTFGIPFLLR IHQGEHFREV 

      1030       1040       1050       1060       1070       1080 
MKRIQSLLDI QEKEFEKFKF AIVMMGRHQY INEDEYEVNL KDFEPQPGNM SHPRPWLGLD 

      1090       1100 
HFNKAPKRSR YTYLEKAIKI HN 

« Hide

Isoform 2 (USP7 beta) (Sequence not available).
Isoform 3 [UniParc].

Checksum: 0CC92229880D2E2B
Show »

FASTA1,086126,269

References

« Hide 'large scale' references
[1]"A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein."
Everett R.D., Meredith M., Orr A., Cross A., Kathoria M., Parkinson J.
EMBO J. 16:566-577(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
Tissue: Mammary cancer.
[2]Erratum
Everett R.D., Meredith M., Orr A., Cross A., Kathoria M., Parkinson J.
EMBO J. 16:1519-1530(1997) [PubMed] [Europe PMC] [Abstract]
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Testis.
[4]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 gene product."
Hong S., Kim S.J., Ka S., Choi I., Kang S.
Mol. Cell. Neurosci. 20:298-306(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 705-1102 (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION WITH ATXN1.
[7]"Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization."
Li M., Chen D., Shiloh A., Luo J., Nikolaev A.Y., Qin J., Gu W.
Nature 416:648-653(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TP53, MUTAGENESIS OF CYS-223.
[8]"Protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP."
Holowaty M.N., Sheng Y., Nguyen T., Arrowsmith C., Frappier L.
J. Biol. Chem. 278:47753-47761(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, INTERACTION WITH HERPESVIRUS 1 TRANS-ACTING TRANSCRIPTIONAL PROTEIN ICP0/VMW110 AND EBV EBNA1.
[9]"A dynamic role of HAUSP in the p53-Mdm2 pathway."
Li M., Brooks C.L., Kon N., Gu W.
Mol. Cell 13:879-886(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MDM2, MUTAGENESIS OF CYS-223.
[10]"Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7."
Boutell C., Canning M., Orr A., Everett R.D.
J. Virol. 79:12342-12354(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION, INTERACTION WITH HERPESVIRUS 1 TRANS-ACTING TRANSCRIPTIONAL PROTEIN ICP0/VMW110.
[11]"Critical role for Daxx in regulating Mdm2."
Tang J., Qu L.K., Zhang J., Wang W., Michaelson J.S., Degenhardt Y.Y., El-Deiry W.S., Yang X.
Nat. Cell Biol. 8:855-862(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH DAXX AND MDM2, INTERACTION WITH DAXX, SUBCELLULAR LOCATION.
[12]"FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP."
van der Horst A., de Vries-Smits A.M., Brenkman A.B., van Triest M.H., van den Broek N., Colland F., Maurice M.M., Burgering B.M.
Nat. Cell Biol. 8:1064-1073(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH FOXO4, MUTAGENESIS OF CYS-223.
[13]"Biochemical characterization of USP7 reveals post-translational modification sites and structural requirements for substrate processing and subcellular localization."
Fernandez-Montalvan A., Bouwmeester T., Joberty G., Mader R., Mahnke M., Pierrat B., Schlaeppi J.M., Worpenberg S., Gerhartz B.
FEBS J. 274:4256-4270(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, PHOSPHORYLATION AT SER-18 AND SER-963, UBIQUITINATION AT LYS-869, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[14]"The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex."
Song M.S., Song S.J., Kim S.Y., Oh H.J., Lim D.S.
EMBO J. 27:1863-1874(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH DAXX; RASSF1 AND MDM2, INTERACTION WITH DAXX AND MDM2.
[15]"AAA ATPase p97 and adaptor UBXD1 suppress MDM2 ubiquitination and degradation and promote constitutive p53 turnover."
Zweitzig D.R., Shcherbik N., Haines D.S.
Mol. Biol. Cell 19:5029-5029(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBXN6.
[16]"The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network."
Song M.S., Salmena L., Carracedo A., Egia A., Lo-Coco F., Teruya-Feldstein J., Pandolfi P.P.
Nature 455:813-817(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PTEN, MUTAGENESIS OF CYS-223, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[17]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-963, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"Identification of a novel higher molecular weight isoform of USP7/HAUSP that interacts with the Herpes simplex virus type-1 immediate early protein ICP0."
Antrobus R., Boutell C.
Virus Res. 137:64-71(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HERPESVIRUS 1 TRANS-ACTING TRANSCRIPTIONAL PROTEIN ICP0/VMW110, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, ALTERNATIVE SPLICING (ISOFORM 2).
[19]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-869; LYS-1084 AND LYS-1096, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Daxx is reciprocally regulated by Mdm2 and Hausp."
Tang J., Qu L., Pang M., Yang X.
Biochem. Biophys. Res. Commun. 393:542-545(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[22]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"TSPYL5 suppresses p53 levels and function by physical interaction with USP7."
Epping M.T., Meijer L.A., Krijgsman O., Bos J.L., Pandolfi P.P., Bernards R.
Nat. Cell Biol. 13:102-108(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TSPYL5.
[25]"The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1 and regulates the stability of UHRF1."
Felle M., Joppien S., Nemeth A., Diermeier S., Thalhammer V., Dobner T., Kremmer E., Kappler R., Langst G.
Nucleic Acids Res. 39:8355-8365(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DNMT1 AND UHRF1, MUTAGENESIS OF CYS-223.
[26]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"M phase phosphorylation of the epigenetic regulator UHRF1 regulates its physical association with the deubiquitylase USP7 and stability."
Ma H., Chen H., Guo X., Wang Z., Sowa M.E., Zheng L., Hu S., Zeng P., Guo R., Diao J., Lan F., Harper J.W., Shi Y.G., Xu Y., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 109:4828-4833(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UHRF1, MUTAGENESIS OF CYS-223.
[28]"Profiling ubiquitin linkage specificities of deubiquitinating enzymes with branched ubiquitin isopeptide probes."
Iphofer A., Kummer A., Nimtz M., Ritter A., Arnold T., Frank R., van den Heuvel J., Kessler B.M., Jansch L., Franke R.
ChemBioChem 13:1416-1420(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, LINKAGE SPECIFICITY.
[29]"The RNA-binding E3 ubiquitin ligase MEX-3C links ubiquitination with MHC-I mRNA degradation."
Cano F., Bye H., Duncan L.M., Buchet-Poyau K., Billaud M., Wills M.R., Lehner P.J.
EMBO J. 31:3596-3606(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEX3C.
[30]"UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair."
Schwertman P., Lagarou A., Dekkers D.H., Raams A., van der Hoek A.C., Laffeber C., Hoeijmakers J.H., Demmers J.A., Fousteri M., Vermeulen W., Marteijn J.A.
Nat. Genet. 44:598-602(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UVSSA.
[31]"Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair."
Zhang X., Horibata K., Saijo M., Ishigami C., Ukai A., Kanno S.I., Tahara H., Neilan E.G., Honma M., Nohmi T., Yasui A., Tanaka K.
Nat. Genet. 44:593-597(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UVSSA.
[32]"Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde."
Hu M., Li P., Li M., Li W., Yao T., Wu J.-W., Gu W., Cohen R.E., Shi Y.
Cell 111:1041-1054(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 208-560 IN COMPLEX WITH UBIQUITIN, MUTAGENESIS OF CYS-223; HIS-456 AND HIS-464, INTERACTION WITH TP53.
[33]"Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization."
Saridakis V., Sheng Y., Sarkari F., Holowaty M.N., Shire K., Nguyen T., Zhang R.G., Liao J., Lee W., Edwards A.M., Arrowsmith C.H., Frappier L.
Mol. Cell 18:25-36(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 54-205 IN COMPLEX WITH EBNA1, INTERACTION WITH EBV EBNA1.
[34]"Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway."
Hu M., Gu L., Li M., Jeffrey P.D., Gu W., Shi Y.
PLoS Biol. 4:228-239(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 43-560 IN COMPLEX WITH TP53 AND MDM2, INTERACTION WITH TP53 AND MDM2.
[35]"Molecular recognition of p53 and MDM2 by USP7/HAUSP."
Sheng Y., Saridakis V., Sarkari F., Duan S., Wu T., Arrowsmith C.H., Frappier L.
Nat. Struct. Mol. Biol. 13:285-291(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 54-205 IN COMPLEX WITH TP53 AND MDM2, INTERACTION WITH TP53 AND MDM2, MUTAGENESIS OF ASP-164 AND TRP-165.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z72499 mRNA. Translation: CAA96580.1.
AK302771 mRNA. Translation: BAH13801.1.
AC022167 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85194.1.
CCDSCCDS32385.1. [Q93009-1]
RefSeqNP_003461.2. NM_003470.2. [Q93009-1]
UniGeneHs.386939.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NB8X-ray2.30A/B208-560[»]
1NBFX-ray2.30A/B/E208-560[»]
1YY6X-ray1.70A54-204[»]
1YZEX-ray2.00A/B/C54-205[»]
2F1WX-ray1.65A53-206[»]
2F1XX-ray2.30A/B53-200[»]
2F1YX-ray1.70A53-198[»]
2F1ZX-ray3.20A/B43-560[»]
2FOJX-ray1.60A54-205[»]
2FOOX-ray2.20A54-205[»]
2FOPX-ray2.10A54-205[»]
2KVRNMR-A537-664[»]
2XXNX-ray1.60A63-205[»]
2YLMX-ray2.70A560-1084[»]
3MQRX-ray1.80A54-205[»]
3MQSX-ray2.40C54-205[»]
4JJQX-ray1.95A54-205[»]
4KG9X-ray1.70A54-205[»]
4M5WX-ray2.24A207-560[»]
4M5XX-ray2.19A/B207-560[»]
4PYZX-ray2.84A/B537-793[»]
ProteinModelPortalQ93009.
SMRQ93009. Positions 63-554, 560-1083.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113622. 199 interactions.
DIPDIP-29053N.
IntActQ93009. 104 interactions.
MINTMINT-234628.
STRING9606.ENSP00000343535.

Chemistry

ChEMBLCHEMBL2157850.

Protein family/group databases

MEROPSC19.016.

PTM databases

PhosphoSiteQ93009.

Polymorphism databases

DMDM212276477.

Proteomic databases

MaxQBQ93009.
PaxDbQ93009.
PRIDEQ93009.

Protocols and materials databases

DNASU7874.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344836; ENSP00000343535; ENSG00000187555. [Q93009-1]
ENST00000381886; ENSP00000371310; ENSG00000187555.
GeneID7874.
KEGGhsa:7874.
UCSCuc002czl.2. human. [Q93009-1]

Organism-specific databases

CTD7874.
GeneCardsGC16M008985.
H-InvDBHIX0038590.
HGNCHGNC:12630. USP7.
HPACAB008108.
HPA015641.
MIM602519. gene.
neXtProtNX_Q93009.
PharmGKBPA37255.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5077.
HOGENOMHOG000160240.
HOVERGENHBG018029.
KOK11838.
OMAAMSDGHN.
OrthoDBEOG75B84G.
PhylomeDBQ93009.
TreeFamTF105667.

Enzyme and pathway databases

SignaLinkQ93009.

Gene expression databases

ArrayExpressQ93009.
BgeeQ93009.
CleanExHS_USP7.
GenevestigatorQ93009.

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.
IPR029346. USP_C.
[Graphical view]
PfamPF00917. MATH. 1 hit.
PF00443. UCH. 1 hit.
PF14533. USP7_C2. 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

EvolutionaryTraceQ93009.
GeneWikiUSP7.
GenomeRNAi7874.
NextBio30332.
PROQ93009.
SOURCESearch...

Entry information

Entry nameUBP7_HUMAN
AccessionPrimary (citable) accession number: Q93009
Secondary accession number(s): A6NMY8, B7Z815, H0Y3G8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 4, 2008
Last modified: July 9, 2014
This is version 157 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM