ID UBP4_PONAB Reviewed; 963 AA.
AC Q5RCD3;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 24-JAN-2024, entry version 91.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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.
CC Deubiquitinates RHEB in response to EGF signaling, promoting mTORC1
CC signaling. May regulate mRNA splicing through deubiquitination of the
CC U4 spliceosomal protein PRPF3. This may prevent its recognition by the
CC U5 component PRPF8 thereby destabilizing interactions within the
CC U4/U6.U5 snRNP. May also play a role in the regulation of quality
CC control in the ER. {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: Phosphorylated at Ser-445 by PKB/AKT1 in response to EGF stimulus,
CC promoting its ability deubiquitinate RHEB.
CC {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; CR858339; CAH90574.1; -; mRNA.
DR RefSeq; NP_001125307.1; NM_001131835.1.
DR AlphaFoldDB; Q5RCD3; -.
DR SMR; Q5RCD3; -.
DR STRING; 9601.ENSPPYP00000015523; -.
DR MEROPS; C19.010; -.
DR GeneID; 100172206; -.
DR KEGG; pon:100172206; -.
DR CTD; 7375; -.
DR eggNOG; KOG1870; Eukaryota.
DR InParanoid; Q5RCD3; -.
DR OrthoDB; 5474185at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
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:1904263; P:positive regulation of TORC1 signaling; 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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0000244; P:spliceosomal tri-snRNP complex assembly; ISS:UniProtKB.
DR CDD; cd02674; Peptidase_C19R; 1.
DR Gene3D; 3.90.70.10; Cysteine proteinases; 2.
DR Gene3D; 3.30.2230.10; DUSP-like; 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 PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR PANTHER; PTHR21646:SF45; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 4; 1.
DR Pfam; PF06337; DUSP; 1.
DR Pfam; PF14836; Ubiquitin_3; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00695; DUSP; 1.
DR SUPFAM; SSF54001; Cysteine proteinases; 1.
DR SUPFAM; SSF143791; DUSP-like; 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_0000301667"
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 220..255
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 637..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 928..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..255
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 930..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 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13107"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B2GUZ1"
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; 108318 MW; 818FB26F04B5AD2D CRC64;
MAEGGGCRER PDAETQKSEL GALMRTTLQR GAQWYLIDSR WFKQWKKYVG FGSWDMYNVG
EHNLFPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPTEA WNKLLNWYGC VEGQQPIVRK
VVEHGLFVKH CKVEVYLLEL KLCENSDPTN VLSCHFSKAD TIATIEKEMR KLFNIPAERE
ARLWNKYMSN TYEQLSKLDN TVQDAGLYLG QVLVIEPQNE DGTWPRQTLQ SKSSTAPSRN
FTTSPKSSAS PYSSVSDSLI ANGDSTSTCG MHSSGVSRGG SGFSASYNCQ EPPSSHIQPG
LCGLGNLGNT CFMNSALQCL SNTAPLTDYF LKDEYEAEIN RDNPLGMKGE IAEAYAELIK
QMWSGRDAHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF LLDGLHEDLN RVKKKPYLEL
KDANGRPDVV VAKEAWENHR LRNDSVIVDT FHGLFKSTLV CPECAKVSVT FDPFCYLTLP
LPLKKDRVME VFLVPADPHC RPTQYRVTVP LMGAVSDLCE ALSRLSGIAA ENMVVADVYN
HRFHKIFQMD EGLNHIMPRD DIFVYEVCST SVDGSECVTL PVYFRERKSR PSSTSSASAL
YGQPLLLSVP KHKLTLESLY QAVCDRISRY VKQPLPDEFG SSPLEPGACN GSRNSCEGED
EEEMEHQEEG KEQLSETEGS GEDEPGSDPS ETTQKKIKGQ PCPKRLFTFS LVNSYGTADI
NSLAADGKLL KLNSRSTLAM DWDSETRSLY YDEQESEAYE KHVSMLQPQK KKKTTVALRD
CIELFTTMET LGEHDPWYCP NCKKHQQATK KSDLWSLPKI LVVHLKRFSY NRYWRDKLDT
VVEFPIRGLN MSEFVCNLSA RPYVYDLIAV SNHYGAMGVG HYTAYAKNKL NGKWYYFDDS
NVSLASEDQI VTKAAYVLFY QRRDDEFYKT PSLSSSGSSD GGTRPSSSQQ GLGDDEACSM
DTN
//
