UBP7_RAT
ID UBP7_RAT Reviewed; 1103 AA.
AC Q4VSI4;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 7;
DE EC=3.4.19.12 {ECO:0000269|PubMed:16111684, ECO:0000269|PubMed:16328052};
DE AltName: Full=Deubiquitinating enzyme 7;
DE AltName: Full=Herpesvirus-associated ubiquitin-specific protease;
DE Short=rHAUSP;
DE AltName: Full=Ubiquitin thioesterase 7;
DE AltName: Full=Ubiquitin-specific-processing protease 7;
GN Name=Usp7; Synonyms=Hausp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TISSUE
RP SPECIFICITY, MUTAGENESIS OF CYS-224, POLYUBIQUITINATION, AND
RP POLYNEDDYLATION.
RC TISSUE=Testis;
RX PubMed=16111684; DOI=10.1016/j.febslet.2005.07.048;
RA Lee H.-J., Kim M.-S., Kim Y.-K., Oh Y.-K., Baek K.-H.;
RT "HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated,
RT polyneddylated, and dimerized.";
RL FEBS Lett. 579:4867-4872(2005).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, UBIQUITINATION, AND MUTAGENESIS OF CYS-224.
RC TISSUE=Testis;
RX PubMed=16328052;
RA Baek K.H., Lee H.J., Kim M.S., Kim Y.S., Seong M., Lee E.J., Lee M.Y.;
RT "Molecular cloning of rHAUSP encoding a deubiquitinating enzyme in rat
RT testis.";
RL Oncol. Rep. 15:173-177(2006).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Hydrolase that deubiquitinates target proteins such as FOXO4,
CC KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX
CC (PubMed:16111684, PubMed:16328052). Together with DAXX, prevents MDM2
CC self-ubiquitination and enhances the E3 ligase activity of MDM2 towards
CC p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal
CC degradation (By similarity). Deubiquitinates p53/TP53, preventing
CC degradation of p53/TP53, and enhances p53/TP53-dependent transcription
CC regulation, cell growth repression and apoptosis (By similarity).
CC Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even
CC in the presence of excess MDM2, and also induces p53/TP53-dependent
CC cell growth repression and apoptosis (By similarity). Deubiquitination
CC of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53
CC and inhibits FOXO4-induced transcriptional activity. In association
CC with DAXX, is involved in the deubiquitination and translocation of
CC PTEN from the nucleus to the cytoplasm, both processes that are
CC counteracted by PML (By similarity). Deubiquitinates KMT2E preventing
CC KMT2E proteasomal-mediated degradation (By similarity). Involved in
CC cell proliferation during early embryonic development (By similarity).
CC Involved in transcription-coupled nucleotide excision repair (TC-NER)
CC in response to UV damage: recruited to DNA damage sites following
CC interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6,
CC preventing UV-induced degradation of ERCC6 (By similarity). Involved in
CC maintenance of DNA methylation via its interaction with UHRF1 and
CC DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1,
CC preventing their degradation and promoting DNA methylation by DNMT1 (By
CC similarity). Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4
CC recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the
CC repair of alkylated DNA lesions (By similarity). Acts as a chromatin
CC regulator via its association with the Polycomb group (PcG)
CC multiprotein PRC1-like complex; may act by deubiquitinating components
CC of the PRC1-like complex (By similarity). Able to mediate
CC deubiquitination of histone H2B; it is however unsure whether this
CC activity takes place in vivo (By similarity). Exhibits a preference
CC towards 'Lys-48'-linked ubiquitin chains. Increases regulatory T-cells
CC (Treg) suppressive capacity by deubiquitinating and stabilizing
CC transcription factor FOXP3 which is crucial for Treg cell function (By
CC similarity). Plays a role in the maintenance of the circadian clock
CC periodicity via deubiquitination and stabilization of the CRY1 and CRY2
CC proteins (By similarity). Deubiquitinates REST, thereby stabilizing
CC REST and promoting the maintenance of neural progenitor cells (By
CC similarity). Deubiquitinates SIRT7, inhibiting SIRT7 histone
CC deacetylase activity and regulating gluconeogenesis (By similarity).
CC {ECO:0000250|UniProtKB:Q93009, ECO:0000269|PubMed:16111684,
CC ECO:0000269|PubMed:16328052}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:16111684,
CC ECO:0000269|PubMed:16328052};
CC -!- SUBUNIT: Monomer. Homodimer (PubMed:16111684). Part of a complex with
CC DAXX, MDM2, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and
CC USP7. Interacts with MDM2; the interaction is independent of p53/TP53.
CC Interacts with DAXX; the interaction is direct and independent of MDM2
CC and p53/TP53. Component of a complex composed of KMT2E, OGT and USP7;
CC the complex stabilizes KMT2E, preventing KMT2E ubiquitination and
CC proteosomal-mediated degradation (By similarity). Interacts (via MATH
CC domain) with KMT2E (By similarity). Interacts with OGT (By similarity).
CC Interacts with FOXO4; the interaction is enhanced in presence of
CC hydrogen peroxide and occurs independently of p53/TP53. Interacts with
CC p53/TP53; the interaction is enhanced in response to DNA damage; the
CC interaction is impaired by TSPYL5. Interacts with PTEN; the interaction
CC is direct. Interacts with ATXN1 and the strength of interaction is
CC influenced by the length of the poly-Gln region in ATXN1. A weaker
CC interaction seen with mutants having longer poly-Gln regions. Interacts
CC with KIAA1530/UVSSA. Interacts with MEX3C and antagonizes its ability
CC to degrade mRNA. Interacts with DNMT1 and UHRF1. Interacts with FOXP3.
CC Interacts (via MATH domain) with RNF220 (By similarity). Associated
CC component of the Polycomb group (PcG) multiprotein PRC1-like complex
CC (By similarity). Interacts with EPOP (By similarity). Interacts with
CC OTUD4 and USP9X; the interaction is direct (By similarity). Interacts
CC with CRY2 (By similarity). Interacts with REST (By similarity).
CC Interacts with ERCC6 (By similarity). {ECO:0000250|UniProtKB:Q6A4J8,
CC ECO:0000250|UniProtKB:Q93009, ECO:0000269|PubMed:16111684}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q93009}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q93009}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:Q93009}. Chromosome
CC {ECO:0000250|UniProtKB:Q93009}. Note=Present in a minority of ND10
CC nuclear bodies. Association with ICP0/VMW110 at early times of
CC infection leads to an increased proportion of USP7-containing ND10.
CC Colocalizes with ATXN1 in the nucleus. Colocalized with DAXX in
CC speckled structures. Colocalized with PML and PTEN in promyelocytic
CC leukemia protein (PML) nuclear bodies. {ECO:0000250|UniProtKB:Q93009}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in the testis, spleen and brain.
CC Weakly expressed in the stomach, small intestine, skeletal muscle and
CC uterus. {ECO:0000269|PubMed:16111684}.
CC -!- DOMAIN: The C-terminus plays a role in its oligomerization.
CC -!- PTM: Polyneddylated. {ECO:0000269|PubMed:16111684}.
CC -!- PTM: Not sumoylated. {ECO:0000250}.
CC -!- PTM: Ubiquitinated at Lys-870 (By similarity). Polyubiquitinated.
CC {ECO:0000250|UniProtKB:Q93009, ECO:0000269|PubMed:16111684,
CC ECO:0000269|PubMed:16328052}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AY641530; AAT68666.1; -; mRNA.
DR RefSeq; NP_001019961.1; NM_001024790.1.
DR AlphaFoldDB; Q4VSI4; -.
DR BMRB; Q4VSI4; -.
DR SMR; Q4VSI4; -.
DR BioGRID; 261960; 2.
DR MINT; Q4VSI4; -.
DR STRING; 10116.ENSRNOP00000041134; -.
DR MEROPS; C19.016; -.
DR iPTMnet; Q4VSI4; -.
DR PhosphoSitePlus; Q4VSI4; -.
DR jPOST; Q4VSI4; -.
DR PaxDb; Q4VSI4; -.
DR PRIDE; Q4VSI4; -.
DR GeneID; 360471; -.
DR KEGG; rno:360471; -.
DR UCSC; RGD:1306915; rat.
DR CTD; 7874; -.
DR RGD; 1306915; Usp7.
DR eggNOG; KOG1863; Eukaryota.
DR InParanoid; Q4VSI4; -.
DR OrthoDB; 77113at2759; -.
DR PhylomeDB; Q4VSI4; -.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-RNO-6782135; Dual incision in TC-NER.
DR Reactome; R-RNO-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-RNO-6804757; Regulation of TP53 Degradation.
DR Reactome; R-RNO-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-RNO-8948747; Regulation of PTEN localization.
DR PRO; PR:Q4VSI4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0001741; C:XY body; ISO:RGD.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0101005; F:deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0002039; F:p53 binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0035616; P:histone H2B conserved C-terminal lysine deubiquitination; ISS:UniProtKB.
DR GO; GO:0010216; P:maintenance of DNA methylation; ISS:UniProtKB.
DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISO:RGD.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
DR GO; GO:1901537; P:positive regulation of DNA demethylation; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:RGD.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0006111; P:regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:RGD.
DR GO; GO:1905279; P:regulation of retrograde transport, endosome to Golgi; ISO:RGD.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 2.60.210.10; -; 1.
DR InterPro; IPR002083; MATH/TRAF_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR008974; TRAF-like.
DR InterPro; IPR024729; USP7_ICP0-binding_dom.
DR InterPro; IPR029346; USP_C.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00917; MATH; 1.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF14533; USP7_C2; 1.
DR Pfam; PF12436; USP7_ICP0_bdg; 1.
DR SMART; SM00061; MATH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50144; MATH; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Biological rhythms; Chromosome; Cytoplasm;
KW Developmental protein; DNA damage; DNA repair; Hydrolase; Isopeptide bond;
KW Nucleus; Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1103
FT /note="Ubiquitin carboxyl-terminal hydrolase 7"
FT /id="PRO_0000268007"
FT DOMAIN 69..196
FT /note="MATH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT DOMAIN 215..522
FT /note="USP"
FT REGION 1..209
FT /note="Interaction with TSPYL5"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 54..209
FT /note="Interaction with p53/TP53 and MDM2"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT REGION 71..206
FT /note="Necessary for nuclear localization"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 224
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093,
FT ECO:0000269|PubMed:16111684, ECO:0000269|PubMed:16328052"
FT ACT_SITE 465
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6A4J8"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6A4J8"
FT MOD_RES 870
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT MOD_RES 964
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT MOD_RES 1085
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT MOD_RES 1097
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT CROSSLNK 870
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT CROSSLNK 870
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT CROSSLNK 883
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q93009"
FT MUTAGEN 224
FT /note="C->S: Loss of p53/TP53-deubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:16111684,
FT ECO:0000269|PubMed:16328052"
SQ SEQUENCE 1103 AA; 128431 MW; A542C4149E241C7C CRC64;
MNHQQQQQQQ QKAGEQQLSE PEDMEMEAGD TDDPPRITQN PVINGNVALS DGHSNAEEDM
EDDTSWRSEA TFQFTVERFS RLSESVLSPP CFVRNLPWKI MVMPRFYPDR PHQKSVGFFL
QCNAESDSTS WSCHAQAVLK IINYRDDDKS FSRRISHLFF HKENDWGFSN FMAWSEVTDP
EKGFIDDDKV TFEVFVQADA PHGVAWDSKK HTGYVGLKNQ GATCYMNSLL QTLFFTNQLR
KAVYMMPTEG DDSSKSVPLA LQRVFYELQH SDKPVGTKKL TKSFGWETLD SFMQHDVQEL
CRVLLDNVEN KMKGTCVEGT IPKLFRGKMV SYIQCKEVDY RSDRREDYYD IQLSIKGKKN
IFESFVDYVA VEQLDGDNKY DAGEHGLQEA EKGVKFLTLP PVLHLQLMRF MYDPQTDQNI
KINDRFEFPE QLPLDEFLQK TDPKDPANYI LHAVLVHSGD NHGGHYVVYL NPKGDGKWCK
FDDDVVSRCT KEEAIEHNYG GHDDDLSVRH CTNAYMLVYI RESKLSEVLQ AVTDHDIPQQ
LVERLQEEKR IEAQKRKERQ EAHLYMQVQI VAEDQFCGHQ GNDMYDEEKV RYTVFKVLKN
SSLAEFVQSL SQTMGFPQDQ IRLWPMQARS NGTKRPAMLD NEADGSKTMI ELSDNENPWT
IFLETVDPEL AASGATLPKF DKDHDVMLFL KMYDPKTRSL NYCGHIYTPI SCKIRDLLPV
MCDRAGFIQD TSLILYEEVK PNLTERIQDY DVSLDKALDE LMDGDIIVFQ KDDPENDNSE
LPTAKEYFRD LYHRVDVIFC DKTIPNDPGF VVTLSNRMNY FQVAKTVAQR LNTDPMLLQF
FKSQGYRDGP GNPLRHNYEG TLRDLLQFFK PRQPKKLYYQ QLKMKITDFE NRRSFKCIWL
NSQFREEEIT LYPDKHGCVR DLLEECKKAV ELGDEASGRL RLLEIVSYKI IGVHQEDELL
ECLSPATSRT FRIEEIPLDQ VNIDKENEML ITVAHFHKEV FGTFGIPFLL RIHQGEHFRE
VMKRIQSLLD IQEKEFEKFK FAIVMMGRHQ YINEDEYEVN LKDFEPQPGN MSHPRPWLGL
DHFNKAPKRS RYTYLEKAIK IHN
