UBP4_BOVIN
ID UBP4_BOVIN Reviewed; 963 AA.
AC A6QR55;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 03-AUG-2022, entry version 93.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
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 -!- 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}.
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DR EMBL; BC150120; AAI50121.1; -; mRNA.
DR RefSeq; NP_001093789.1; NM_001100319.1.
DR AlphaFoldDB; A6QR55; -.
DR SMR; A6QR55; -.
DR STRING; 9913.ENSBTAP00000015787; -.
DR MEROPS; C19.010; -.
DR PaxDb; A6QR55; -.
DR PRIDE; A6QR55; -.
DR Ensembl; ENSBTAT00000015787; ENSBTAP00000015787; ENSBTAG00000011899.
DR GeneID; 508042; -.
DR KEGG; bta:508042; -.
DR CTD; 7375; -.
DR VEuPathDB; HostDB:ENSBTAG00000011899; -.
DR VGNC; VGNC:36729; USP4.
DR eggNOG; KOG1870; Eukaryota.
DR GeneTree; ENSGT00940000156645; -.
DR HOGENOM; CLU_001060_7_1_1; -.
DR InParanoid; A6QR55; -.
DR OMA; SGTCNEA; -.
DR OrthoDB; 1283205at2759; -.
DR TreeFam; TF106276; -.
DR Proteomes; UP000009136; Chromosome 22.
DR Bgee; ENSBTAG00000011899; Expressed in spermatid and 104 other tissues.
DR ExpressionAtlas; A6QR55; baseline and differential.
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; IEA:Ensembl.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
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 2: Evidence at transcript 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..963
FT /note="Ubiquitin carboxyl-terminal hydrolase 4"
FT /id="PRO_0000301668"
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..923
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..277
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..775
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 634..701
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 930..963
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 767..772
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P35123"
FT COMPBIAS 221..277
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 668..698
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 932..963
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 311
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT ACT_SITE 881
FT /note="Proton acceptor"
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 799
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT BINDING 802
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35123"
FT MOD_RES 680
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35123"
SQ SEQUENCE 963 AA; 108510 MW; 6D132FFE8C371A60 CRC64;
MAEGGGYRER PDAETQKSEL GALMRTTLQR GAQWYLIDSR WFKQWKKYVG FDSWDMYNVG
EHNLYPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPAEA WNKLLNWYGC VEGQQPIVRK
VVEHGLFVKH CKVEVYLLEL KLCENSDPTN VLSCHFSKAD TIATIEKEMR KLFNIPAERE
TRLWNKYMSN TYEQLSKLDN TVQDAGLYQG QVLVIEPQNE DGTWPRQTQQ SKSSTAPSRN
FTTSPKSSAS PYSSVSASPI ANGDSTNTSG MHSSGVSRGG SGFSASYNCQ ESPLTHVQPG
LCGLGNLGNT CFMNSALQCL SNTAPLTDYF LKDEYEAEIN RDNPLGMKGE IAEAYAELIK
QMWSGRDAHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF LLDGLHEDLN RVKKKPYLEL
KDANGRPDAV VAKEAWENHR LRNDSVIVDT FHGLFKSTLV CPECAKVSVT FDPFCYLTLP
LPLKKDRVME IFLVPADPRC RPTQYRVVVP LMGAVSDLCE ALSKLSGIAA ENMVVTDVYN
HRFHKIFQMD EGLNHIMPRD DIFVYEVCST SPDGSECVTL PVYFRERKSR PSSTSTGAVL
YGQPLLVSVP KHKLTLESLY QAVCERISRY IKQPLPDESG SSPLELGACN GSRSGCAGED
EEEMEHQEEG REQLSETEGS GDDEPGSDHG EATQKKNKGR PCPRRLFTFS LVNSYGTADI
NSLATDGKLL KLNSRSTLAI DWDSETRSCY YNEQESETYE KHVSMLQPQK KKKTAVALRD
CIELFTTMET LGEHDPWYCP NCKKHQQATK KFDLWSLPKI LVVHLKRFSY NRYWRDKLDT
VVEFPVRGLN MSEFVCDPSA RPYVYDLIAV SNHYGAMGVG HYTAYAKNKL NGKWYYFDDS
NVSLACEDQI VTKAAYVLFY QRRDDEFHKT PSLSFPGSSD GGARPSSSQQ GTGDDETYSM
DTN
