UBP4_RAT
ID UBP4_RAT Reviewed; 961 AA.
AC B2GUZ1;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 4;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q13107};
DE AltName: Full=Deubiquitinating enzyme 4;
DE AltName: Full=Ubiquitin thioesterase 4;
DE AltName: Full=Ubiquitin-specific-processing protease 4;
GN Name=Usp4;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=16339847; DOI=10.1124/mol.105.015818;
RA Milojevic T., Reiterer V., Stefan E., Korkhov V.M., Dorostkar M.M.,
RA Ducza E., Ogris E., Boehm S., Freissmuth M., Nanoff C.;
RT "The ubiquitin-specific protease Usp4 regulates the cell surface level of
RT the A2A receptor.";
RL Mol. Pharmacol. 69:1083-1094(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-655 AND SER-674, AND
RP IDENTIFICATION BY 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: Deubiquitinating enzyme that removes conjugated ubiquitin
CC from target proteins. Deubiquitinates PDPK1. Deubiquitinates TRIM21.
CC Deubiquitinates receptor ADORA2A which increases the amount of
CC functional receptor at the cell surface. Deubiquitinates HAS2. May
CC regulate mRNA splicing through deubiquitination of the U4 spliceosomal
CC protein PRPF3. This may prevent its recognition by the U5 component
CC PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP. May
CC also play a role in the regulation of quality control in the ER.
CC {ECO:0000250|UniProtKB:Q13107}.
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:0000250|UniProtKB:Q13107};
CC -!- ACTIVITY REGULATION: The completion of the deubiquitinase reaction is
CC mediated by the DUSP and ubiquitin-like 1 domains which promotes the
CC release of ubiquitin from the catalytic site enabling subsequent
CC reactions to occur. {ECO:0000250|UniProtKB:Q13107}.
CC -!- SUBUNIT: Interacts with RB1 (both dephosphorylated and
CC hypophosphorylated forms) (By similarity). Interacts with RBL1 and RBL2
CC (By similarity). Interacts with ADORA2A (via cytoplasmic C-terminus);
CC the interaction is direct. Interacts with SART3; recruits USP4 to its
CC substrate PRPF3 (By similarity). {ECO:0000250|UniProtKB:P35123,
CC ECO:0000250|UniProtKB:Q13107}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P35123,
CC ECO:0000250|UniProtKB:Q13107}. Nucleus {ECO:0000250|UniProtKB:P35123,
CC ECO:0000250|UniProtKB:Q13107}. Note=Shuttles between the nucleus and
CC cytoplasm. Exported to the cytoplasm in a CRM1-dependent manner and
CC recycled back to the nucleus via the importin alpha/beta heterodimeric
CC import receptor. The relative amounts found in the nucleus and
CC cytoplasm vary according to the cell type.
CC {ECO:0000250|UniProtKB:P35123, ECO:0000250|UniProtKB:Q13107}.
CC -!- TISSUE SPECIFICITY: Expressed in hippocampus and striatum (at protein
CC level). {ECO:0000269|PubMed:16339847}.
CC -!- DOMAIN: The DUSP and ubiquitin-like 1 domains promote ubiquitin release
CC and thus enhance USB4 catalytic activity. However, these domains do not
CC bind ubiquitin. {ECO:0000250|UniProtKB:Q13107}.
CC -!- PTM: Monoubiquitinated by TRIM21. Ubiquitination does not lead to its
CC proteasomal degradation. Autodeubiquitinated.
CC {ECO:0000250|UniProtKB:Q13107}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP4 subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC166460; AAI66460.1; -; mRNA.
DR EMBL; CH473954; EDL77177.1; -; Genomic_DNA.
DR RefSeq; NP_001128484.1; NM_001135012.1.
DR AlphaFoldDB; B2GUZ1; -.
DR SMR; B2GUZ1; -.
DR BioGRID; 253348; 1.
DR IntAct; B2GUZ1; 2.
DR STRING; 10116.ENSRNOP00000066449; -.
DR iPTMnet; B2GUZ1; -.
DR PhosphoSitePlus; B2GUZ1; -.
DR jPOST; B2GUZ1; -.
DR PaxDb; B2GUZ1; -.
DR PeptideAtlas; B2GUZ1; -.
DR PRIDE; B2GUZ1; -.
DR Ensembl; ENSRNOT00000083046; ENSRNOP00000071463; ENSRNOG00000054863.
DR GeneID; 290864; -.
DR KEGG; rno:290864; -.
DR CTD; 7375; -.
DR RGD; 1587387; Usp4.
DR eggNOG; KOG1870; Eukaryota.
DR GeneTree; ENSGT00940000156645; -.
DR InParanoid; B2GUZ1; -.
DR OMA; SGTCNEA; -.
DR OrthoDB; 1283205at2759; -.
DR PhylomeDB; B2GUZ1; -.
DR Reactome; R-RNO-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-RNO-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-RNO-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR PRO; PR:B2GUZ1; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Proteomes; UP000234681; Chromosome 8.
DR Bgee; ENSRNOG00000054863; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; B2GUZ1; baseline and differential.
DR Genevisible; B2GUZ1; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0031685; F:adenosine receptor binding; ISO:RGD.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0034394; P:protein localization to cell surface; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0000244; P:spliceosomal tri-snRNP complex assembly; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.2230.10; -; 1.
DR InterPro; IPR035927; DUSP-like_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR006615; Pept_C19_DUSP.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR028135; Ub_USP-typ.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF06337; DUSP; 1.
DR Pfam; PF14836; Ubiquitin_3; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00695; DUSP; 1.
DR SUPFAM; SSF143791; SSF143791; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS51283; DUSP; 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 Cytoplasm; Hydrolase; Metal-binding; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Thiol protease; Ubl conjugation;
KW Ubl conjugation pathway; Zinc.
FT CHAIN 1..961
FT /note="Ubiquitin carboxyl-terminal hydrolase 4"
FT /id="PRO_0000396806"
FT DOMAIN 11..122
FT /note="DUSP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT DOMAIN 142..226
FT /note="Ubiquitin-like 1"
FT /evidence="ECO:0000255"
FT DOMAIN 302..921
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT DOMAIN 483..571
FT /note="Ubiquitin-like 2"
FT /evidence="ECO:0000255"
FT REGION 27..216
FT /note="Necessary for interaction with SART3"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT REGION 219..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 229..295
FT /note="Required for USP4 activation by providing
FT conformational flexibility between the DUSP and catalytic
FT domains"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT REGION 384..386
FT /note="Regulates ubiquitin dissociation"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT REGION 405..407
FT /note="Necessary for interaction with RBL2"
FT /evidence="ECO:0000250|UniProtKB:P35123"
FT REGION 459..463
FT /note="Necessary for interaction with RB1 and RBL2"
FT /evidence="ECO:0000250|UniProtKB:P35123"
FT REGION 485..773
FT /note="Interacts with DUSP and ubiquitin-like 1 domains and
FT is required for USP4 activation"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT REGION 641..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 924..961
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 133..141
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P35123"
FT MOTIF 765..770
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P35123"
FT COMPBIAS 221..257
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 311
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT ACT_SITE 879
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT BINDING 461
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT BINDING 464
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT BINDING 797
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT BINDING 800
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 674
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 679
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35123"
SQ SEQUENCE 961 AA; 108373 MW; D6DD975327451B9F CRC64;
MAEGRGTHER PDVETQKTEL GALMGTTLQR GAQWYLIDSR WFKQWKKYVG FDSWDMYNVG
EHNLFPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPTEA WNKLLNWYGC VEGQQPIVRK
VVEHGLFVKH CKVEVYLLEL KLCENSDPTN VLSCHFSKAD TIATIEKEMR KLFNIPAERE
TRLWNKYMSN TYEQLSKLDN TIQDAGLYQG QVLVIEPQNE DGTWPRQTLQ SKSSTAPSRN
FTTSSKPSAS PYSSMSASLI ANGDSTNSSG MHNSGVSRGG AGFSASYNCQ EPPSPHIQPG
LCGLGNLGNT CFMNSALQCL SNTGPLTEYF LKDEYEAEIN RDNPLGMKGE IAEAYAELIK
QMWSGRDTHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF ILDGLHEDLN RVKKKPYLEP
KDANGRPDAV VAKEAWENHR LRNDSVIVDT FHGLFKSTLV CPECAKVSVT FDPFCYLTLP
LPLKKDRIME VFLVPADPHC RPIQYRVTVP LMGAISDLCE ALSKLSGIAA ENMVVTDVYN
HRFHKIFQMD EGLSHITPRD DIFVYEICTT PMDGSEYITL PVYFREKKSR PSSTSSGAVL
YGQPLLVSVP KHRLTLESLY QAVCERISRY IKQPLPEEFL SSPLEPGACN GSRGSYEGDE
EEMDHQEEGK EQLSEVEESG EDSQGGDPTE TTQKAKGPPR HKRLFTFSLV NSCGTADINS
LATDGKLLKL NSRSTLAIDW DSETRSLYFD EQESEACEKH TSMSQPQKKK KAAIALRECI
ELFTTMETLG EHDPWYCPTC KKHQQATKKF DLWSLPKILV VHLKRFSYNR YWRDKLDTVV
EFPVRALNMS EFVCDRAARP YVYDLIAVSN HYGAMGVGHY TAYAKNRLNG KWYYFDDSSV
SLASEDQIVT KAAYVLFYQR RDDECPSTSS PVSFPGSDGG AKLSSSQQDL GEEEAYTMDT
N
