Q4VSI4 (UBP7_RAT) 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
Short name=rHAUSP
Ubiquitin thioesterase 7
Ubiquitin-specific-processing protease 7

Gene names

Name:	Usp7
Synonyms:	Hausp

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1103 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, 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. Nucleus › PML 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.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Molecular function	Developmental protein Hydrolase Protease Thiol protease
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	induction of apoptosis Inferred from direct assay Ref.2. Source: RGD maintenance of DNA methylation Inferred from sequence or structural similarity. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW 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_component	PML 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_function	cysteine-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1103	1103	Ubiquitin carboxyl-terminal hydrolase 7		PRO_0000268007
Regions
	Domain	69 – 196	128	MATH
	Region	1 – 209	209	Interaction with TSPYL5 By similarity
	Region	54 – 209	156	Interaction with p53/TP53 and MDM2 By similarity
	Region	71 – 206	136	Necessary for nuclear localization By similarity
	Compositional bias	4 – 17	14	Gln-rich
Sites
	Active site	224	1	Nucleophile By similarity
	Active site	465	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	19	1	Phosphoserine By similarity
	Modified residue	870	1	N6-acetyllysine By similarity
	Modified residue	964	1	Phosphoserine By similarity
	Modified residue	1085	1	N6-acetyllysine By similarity
	Modified residue	1097	1	N6-acetyllysine By similarity
	Cross-link	870		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Experimental info
	Mutagenesis	224	1	C → S: Loss of p53/TP53-deubiquitinating activity. Ref.1 Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q4VSI4 [UniParc]. Last modified July 5, 2005. Version 1. Checksum: A542C4149E241C7C	FASTA	1,103	128,431
	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

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.
IPI	IPI00372303.
RefSeq	NP_001019961.1. NM_001024790.1.
UniGene	Rn.72721.
3D structure databases
HSSP	HSSP built from PDB template 2F1Z based on UniProtKB Q93009.
ProteinModelPortal	Q4VSI4.
SMR	Q4VSI4. Positions 64-555.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1365534.
STRING	10116.ENSRNOP00000041134.
PTM databases
PhosphoSite	Q4VSI4.
Proteomic databases
PaxDb	Q4VSI4.
PRIDE	Q4VSI4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	360471.
KEGG	rno:360471.
UCSC	RGD:1306915. rat.
Organism-specific databases
CTD	7874.
RGD	1306915. Usp7.
Phylogenomic databases
eggNOG	COG5077.
HOGENOM	HOG000160240.
HOVERGEN	HBG018029.
InParanoid	Q4VSI4.
KO	K11838.
OrthoDB	EOG4640B4.
Gene expression databases
ArrayExpress	Q4VSI4.
Genevestigator	Q4VSI4.
GermOnline	ENSRNOG00000025496. Rattus norvegicus.
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]
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	672877.

Entry information

Entry name

UBP7_RAT

Accession

Primary (citable) accession number: Q4VSI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	July 5, 2005
Last modified:	April 3, 2013
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program