Q93009 (UBP7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1102 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, 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. Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. Ref.6 Ref.7 Ref.8 Ref.10 Ref.12 Ref.16 Ref.18 Ref.22
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.7
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. 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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28
Subcellular location	Nucleus. Cytoplasm. Nucleus › PML 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.5 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.9 Ref.13 Ref.17 Ref.19 Ref.20 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.
Biophysicochemical properties	pH dependence: Active from pH 7.0 to 9.5. Ref.7

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Developmental protein Hydrolase Protease Thiol protease
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW protein deubiquitination Inferred from direct assay Ref.12. Source: UniProtKB regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.12. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	PML body Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cysteine-type endopeptidase activity Traceable author statement. Source: ProtInc p53 binding Inferred from direct assay. Source: UniProtKB protein C-terminus binding Inferred from physical interaction Ref.5. Source: UniProtKB transcription factor binding Inferred from physical interaction Ref.12. Source: UniProtKB ubiquitin protein ligase binding Inferred from physical interaction Ref.14. Source: UniProtKB ubiquitin thiolesterase activity Inferred from mutant phenotype Ref.12. Source: UniProtKB ubiquitin-specific protease activity Inferred from direct assay Ref.12. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	10	EBI-302474,EBI-77321
EBNA1	P03211	4	EBI-302474,EBI-996522	From a different organism.
MAL	P21145	3	EBI-302474,EBI-3932027
MDM2	Q00987	13	EBI-302474,EBI-389668
MYD88	Q99836	3	EBI-302474,EBI-447677
SMAD3	P84022	2	EBI-302474,EBI-347161
TBCB	Q99426	2	EBI-302474,EBI-764356
TP53	P04637	10	EBI-302474,EBI-366083
TSPYL5	Q86VY4	4	EBI-302474,EBI-3436472

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1102

1102

Ubiquitin carboxyl-terminal hydrolase 7

PRO_0000080626

Regions

Domain

68 – 195

128

MATH

Region

1 – 208

208

Interaction with TSPYL5

Region

53 – 208

156

Interaction with p53/TP53, MDM2 and EBNA1

Region

70 – 205

136

Necessary for nuclear localization

Region

622 – 801

180

Interaction with ICP0/VMW110

Compositional bias

4 – 10

7

Poly-Gln

Sites

Active site

223

1

Nucleophile

Active site

464

1

Proton acceptor Probable

Amino acid modifications

Modified residue

18

1

Phosphoserine Ref.9 Ref.13 Ref.17 Ref.19 Ref.20

Modified residue

49

1

Phosphoserine Ref.20

Modified residue

54

1

Phosphothreonine Ref.20

Modified residue

595

1

N6-acetyllysine Ref.21

Modified residue

869

1

N6-acetyllysine Ref.21

Modified residue

963

1

Phosphoserine Ref.13 Ref.17

Modified residue

1084

1

N6-acetyllysine Ref.21

Modified residue

1096

1

N6-acetyllysine Ref.21

Cross-link

869

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.13

Experimental info

Mutagenesis

164

1

D → A: Decreased binding to p53/TP53 and MDM2. Ref.28

Mutagenesis

165

1

W → A: Loss of binding to p53/TP53 and MDM2. Ref.28

Mutagenesis

223

1

C → A: Complete loss of activity. Localized in the nucleus and does not inhibit FOXO4-dependent transcriptional activity. Ref.6 Ref.8 Ref.12 Ref.16 Ref.25

Mutagenesis

223

1

C → S: No effect on p53/TP53 and PTEN binding but is defective in deubiquitinating p53/TP53 and PTEN. Ref.6 Ref.8 Ref.12 Ref.16 Ref.25

Mutagenesis

456

1

H → A: Complete loss of activity. Ref.25

Mutagenesis

464

1

H → A: Complete loss of activity. Ref.25

Sequence conflict

201

1

H → I AA sequence Ref.1

Sequence conflict

205

1

W → P AA sequence Ref.1

Sequence conflict

207

1

S → Q AA sequence Ref.1

Sequence conflict

1045

1

M → T in CAA96580. Ref.1

Sequence conflict

1066

1

Q → T AA sequence Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1102

Helix Strand Turn

Details...

Beta strand

67 – 77

11

Helix

78 – 80

3

Beta strand

90 – 92

3

Beta strand

95 – 104

10

Beta strand

114 – 122

9

Beta strand

131 – 140

10

Helix

146 – 148

3

Beta strand

150 – 159

10

Beta strand

164 – 172

9

Helix

173 – 176

4

Turn

179 – 181

3

Beta strand

188 – 197

10

Beta strand

201 – 203

3

Beta strand

210 – 212

3

Helix

223 – 233

11

Helix

236 – 243

8

Turn

252 – 254

3

Helix

256 – 269

14

Helix

277 – 282

6

Helix

287 – 291

5

Helix

296 – 311

16

Turn

315 – 318

4

Helix

319 – 324

6

Beta strand

326 – 337

12

Beta strand

340 – 353

14

Helix

360 – 367

8

Beta strand

371 – 373

3

Helix

375 – 377

3

Beta strand

389 – 397

9

Beta strand

400 – 407

8

Beta strand

409 – 412

4

Turn

413 – 416

4

Beta strand

417 – 420

4

Beta strand

429 – 432

4

Helix

434 – 436

3

Beta strand

437 – 439

3

Beta strand

447 – 459

13

Beta strand

462 – 469

8

Beta strand

473 – 475

3

Beta strand

478 – 481

4

Beta strand

484 – 487

4

Helix

490 – 493

4

Helix

495 – 497

3

Turn

507 – 510

4

Beta strand

511 – 520

10

Helix

521 – 523

3

Helix

524 – 527

4

Helix

533 – 535

3

Helix

538 – 545

8

Helix

547 – 550

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 4, 2008. Version 2. Checksum: F1A5A5C421396E45	FASTA	1,102	128,302
	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
	Isoform 2 (USP7 beta) (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow '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: 9034339] [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: 9130697] [Abstract]
[3]	"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. , 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: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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. , 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].
[5]	"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: 12093161] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 705-1102 (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION WITH ATXN1.
[6]	"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: 11923872] [Abstract] Cited for: FUNCTION, INTERACTION WITH TP53, MUTAGENESIS OF CYS-223.
[7]	"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: 14506283] [Abstract] Cited for: FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, INTERACTION WITH HERPESVIRUS 1 TRANS-ACTING TRANSCRIPTIONAL PROTEIN ICP0/VMW110 AND EBV EBNA1.
[8]	"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: 15053880] [Abstract] Cited for: FUNCTION, INTERACTION WITH MDM2, MUTAGENESIS OF CYS-223.
[9]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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: 16160161] [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: 16845383] [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: 16964248] [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: 17651432] [Abstract] Cited for: SUBUNIT, PHOSPHORYLATION AT SER-18 AND SER-963, UBIQUITINATION AT LYS-869, SUBCELLULAR LOCATION, 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: 18566590] [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: 18768758] [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: 18716620] [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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-963, MASS SPECTROMETRY. 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: 18590780] [Abstract] Cited for: FUNCTION, INTERACTION WITH HERPESVIRUS 1 TRANS-ACTING TRANSCRIPTIONAL PROTEIN ICP0/VMW110, SUBCELLULAR LOCATION, 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: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[20]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-49 AND THR-54, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[21]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-595; LYS-869; LYS-1084 AND LYS-1096, MASS SPECTROMETRY.
[22]	"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: 20153724] [Abstract] Cited for: FUNCTION.
[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: 21269460] [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: 21170034] [Abstract] Cited for: INTERACTION WITH TSPYL5.
[25]	"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: 12507430] [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.
[26]	"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: 15808506] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 54-205 IN COMPLEX WITH EBNA1, INTERACTION WITH EBV EBNA1.
[27]	"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: 16402859] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 43-560 IN COMPLEX WITH TP53 AND MDM2, INTERACTION WITH TP53 AND MDM2.
[28]	"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: 16474402] [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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z72499 mRNA. Translation: CAA96580.1.
AC022167 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85194.1.

IPI

IPI00003965.

RefSeq

NP_003461.2. NM_003470.2.

UniGene

Hs.386939.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NB8	X-ray	2.30	A/B	208-560	[»]
1NBF	X-ray	2.30	A/B/E	208-560	[»]
1YY6	X-ray	1.70	A	54-205	[»]
1YZE	X-ray	2.00	A/B/C	54-205	[»]
2F1W	X-ray	1.65	A	53-206	[»]
2F1X	X-ray	2.30	A/B	53-200	[»]
2F1Y	X-ray	1.70	A	53-198	[»]
2F1Z	X-ray	3.20	A/B	43-560	[»]
2FOJ	X-ray	1.60	A	54-205	[»]
2FOO	X-ray	2.20	A	54-205	[»]
2FOP	X-ray	2.10	A	54-205	[»]
2KVR	NMR	-	A	537-664	[»]
2XXN	X-ray	1.60	A	63-205	[»]
2YLM	X-ray	2.70	A	560-1084	[»]
3MQR	X-ray	1.80	A	54-205	[»]
3MQS	X-ray	2.40	C	54-205	[»]

ProteinModelPortal

Q93009.

SMR

Q93009. Positions 63-664.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29053N.

IntAct

Q93009. 84 interactions.

MINT

MINT-234628.

STRING

Q93009.

Protein family/group databases

MEROPS

C19.016.

PTM databases

PhosphoSite

Q93009.

Polymorphism databases

DMDM

212276477.

Proteomic databases

PRIDE

Q93009.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000344836; ENSP00000343535; ENSG00000187555.

GeneID

7874.

KEGG

hsa:7874.

Organism-specific databases

CTD

7874.

GeneCards

GC16M008907.

H-InvDB

HIX0038590.

HGNC

HGNC:12630. USP7.

HPA

CAB008108.
HPA015641.

MIM

602519. gene.

neXtProt

NX_Q93009.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16583.

GeneTree

ENSGT00600000084170.

HOVERGEN

HBG018029.

OrthoDB

EOG4640B4.

PhylomeDB

Q93009.

Enzyme and pathway databases

Pathway_Interaction_DB

foxopathway. FoxO family signaling.

Gene expression databases

ArrayExpress

Q93009.

Bgee

Q93009.

CleanEx

HS_USP7.

Genevestigator

Q93009.

GermOnline

ENSG00000187555. Homo sapiens.

Family and domain databases

InterPro

IPR002083. MATH.
IPR024729. Pept_C19_dom.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19.
IPR008974. TRAF-like.
[Graphical view]

KO

K11838.

Pfam

PF00917. MATH. 1 hit.
PF00443. UCH. 1 hit.
PF12436. USP7. 1 hit.
[Graphical view]

SMART

SM00061. MATH. 1 hit.
[Graphical view]

SUPFAM

SSF49599. Traf_like. 1 hit.

PROSITE

PS50144. MATH. 1 hit.
PS00972. UCH_2_1. 1 hit.
PS00973. UCH_2_2. 1 hit.
PS50235. UCH_2_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

30332.

SOURCE

Search...

Entry information

Entry name

UBP7_HUMAN

Accession

Primary (citable) accession number: Q93009
Secondary accession number(s): A6NMY8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 4, 2008
Last modified:	January 25, 2012
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.