ID A0A6I8NJY0_ORNAN Unreviewed; 1130 AA.
AC A0A6I8NJY0;
DT 12-AUG-2020, integrated into UniProtKB/TrEMBL.
DT 12-AUG-2020, sequence version 1.
DT 18-JUN-2025, entry version 23.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 4 {ECO:0000256|ARBA:ARBA00040967};
DE EC=3.4.19.12 {ECO:0000256|ARBA:ARBA00012759};
DE AltName: Full=Deubiquitinating enzyme 4 {ECO:0000256|ARBA:ARBA00042237};
DE AltName: Full=Ubiquitin thioesterase 4 {ECO:0000256|ARBA:ARBA00041731};
DE AltName: Full=Ubiquitin-specific-processing protease 4 {ECO:0000256|ARBA:ARBA00042735};
GN Name=USP4 {ECO:0000313|Ensembl:ENSOANP00000041509.1};
OS Ornithorhynchus anatinus (Duckbill platypus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Monotremata; Ornithorhynchidae; Ornithorhynchus.
OX NCBI_TaxID=9258 {ECO:0000313|Ensembl:ENSOANP00000041509.1, ECO:0000313|Proteomes:UP000002279};
RN [1] {ECO:0000313|Ensembl:ENSOANP00000041509.1, ECO:0000313|Proteomes:UP000002279}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Glennie {ECO:0000313|Ensembl:ENSOANP00000041509.1,
RC ECO:0000313|Proteomes:UP000002279};
RX PubMed=18464734; DOI=10.1038/nature06936;
RA Warren W.C., Hillier L.W., Marshall Graves J.A., Birney E., Ponting C.P.,
RA Grutzner F., Belov K., Miller W., Clarke L., Chinwalla A.T., Yang S.P.,
RA Heger A., Locke D.P., Miethke P., Waters P.D., Veyrunes F., Fulton L.,
RA Fulton B., Graves T., Wallis J., Puente X.S., Lopez-Otin C., Ordonez G.R.,
RA Eichler E.E., Chen L., Cheng Z., Deakin J.E., Alsop A., Thompson K.,
RA Kirby P., Papenfuss A.T., Wakefield M.J., Olender T., Lancet D.,
RA Huttley G.A., Smit A.F., Pask A., Temple-Smith P., Batzer M.A.,
RA Walker J.A., Konkel M.K., Harris R.S., Whittington C.M., Wong E.S.,
RA Gemmell N.J., Buschiazzo E., Vargas Jentzsch I.M., Merkel A., Schmitz J.,
RA Zemann A., Churakov G., Kriegs J.O., Brosius J., Murchison E.P.,
RA Sachidanandam R., Smith C., Hannon G.J., Tsend-Ayush E., McMillan D.,
RA Attenborough R., Rens W., Ferguson-Smith M., Lefevre C.M., Sharp J.A.,
RA Nicholas K.R., Ray D.A., Kube M., Reinhardt R., Pringle T.H., Taylor J.,
RA Jones R.C., Nixon B., Dacheux J.L., Niwa H., Sekita Y., Huang X., Stark A.,
RA Kheradpour P., Kellis M., Flicek P., Chen Y., Webber C., Hardison R.,
RA Nelson J., Hallsworth-Pepin K., Delehaunty K., Markovic C., Minx P.,
RA Feng Y., Kremitzki C., Mitreva M., Glasscock J., Wylie T., Wohldmann P.,
RA Thiru P., Nhan M.N., Pohl C.S., Smith S.M., Hou S., Nefedov M.,
RA de Jong P.J., Renfree M.B., Mardis E.R., Wilson R.K.;
RT "Genome analysis of the platypus reveals unique signatures of evolution.";
RL Nature 453:175-183(2008).
RN [2] {ECO:0000313|Ensembl:ENSOANP00000041509.1}
RP IDENTIFICATION.
RC STRAIN=Glennie {ECO:0000313|Ensembl:ENSOANP00000041509.1};
RG Ensembl;
RL Submitted (MAR-2025) to UniProtKB.
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:0000256|ARBA:ARBA00045453}.
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:0000256|ARBA:ARBA00000707};
CC -!- SUBUNIT: Interacts with RB1 (both dephosphorylated and
CC hypophosphorylated forms). Interacts with RBL1 and RBL2. Interacts with
CC ADORA2A (via cytoplasmic C-terminus); the interaction is direct.
CC Interacts with SART3; recruits USP4 to its substrate PRPF3.
CC {ECO:0000256|ARBA:ARBA00046862}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}.
CC Nucleus {ECO:0000256|ARBA:ARBA00004123}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP4 subfamily.
CC {ECO:0000256|ARBA:ARBA00037971}.
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DR AlphaFoldDB; A0A6I8NJY0; -.
DR Ensembl; ENSOANT00000064982.1; ENSOANP00000041509.1; ENSOANG00000013806.3.
DR GeneTree; ENSGT00940000156645; -.
DR Proteomes; UP000002279; Chromosome X1.
DR Bgee; ENSOANG00000013806; Expressed in heart and 8 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR GO; GO:0016579; P:protein deubiquitination; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd02674; Peptidase_C19R; 1.
DR FunFam; 3.30.2230.10:FF:000003; ubiquitin carboxyl-terminal hydrolase 15 isoform X1; 1.
DR FunFam; 3.90.70.10:FF:000013; ubiquitin carboxyl-terminal hydrolase 15 isoform X1; 1.
DR FunFam; 3.10.20.90:FF:000020; ubiquitin carboxyl-terminal hydrolase 15 isoform X2; 1.
DR FunFam; 3.90.70.10:FF:000047; ubiquitin carboxyl-terminal hydrolase 4 isoform X2; 1.
DR Gene3D; 3.90.70.10; Cysteine proteinases; 2.
DR Gene3D; 3.30.2230.10; DUSP-like; 1.
DR Gene3D; 3.10.20.90; Phosphatidylinositol 3-kinase Catalytic Subunit, Chain A, domain 1; 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; IPR050185; Ub_carboxyl-term_hydrolase.
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 PRINTS; PR01217; PRICHEXTENSN.
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 3: Inferred from homology;
KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Protease {ECO:0000256|ARBA:ARBA00022670};
KW Reference proteome {ECO:0000313|Proteomes:UP000002279};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Thiol protease {ECO:0000256|ARBA:ARBA00022807};
KW Ubl conjugation {ECO:0000256|ARBA:ARBA00022843};
KW Ubl conjugation pathway {ECO:0000256|ARBA:ARBA00022786};
KW Zinc {ECO:0000256|ARBA:ARBA00022833}.
FT DOMAIN 225..336
FT /note="DUSP"
FT /evidence="ECO:0000259|PROSITE:PS51283"
FT DOMAIN 468..1091
FT /note="USP"
FT /evidence="ECO:0000259|PROSITE:PS50235"
FT REGION 9..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1109..1130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..183
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1118..1130
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1130 AA; 126645 MW; 5AF2FE6B1068F67F CRC64;
MVQFFFYPLP LSFLPSPPPS PPPPPPTPPP SPPSNPPPPP PPPPPPPPLP RPAPPASFPV
PSPPPSPPSP PPSPPPSPPS NPPPPPPPPP PPPPLPRPAP PVSFPVPSPP PSPPPSPPSP
LPSPPPSPPS PPPSPPSPPP SPPAPAAPAA PPSPPSLPPP PPPPRCPRLT PPPSPPGPRP
PRSPGRGAGR GRRRRSALCA KRMSGPLRLR LAAEMAEGGG RRGRQDTEAQ KADLGLLLRT
TLQRGAEWYL IDSRWFKQWK KYVGYDSWDM YHVGEQNLYP GPIDNSGLFS DPENQILKDH
LIDELDYVLV PAEAWNKLVN WYGCIEGQQP IVRKVVEHGL FVKHCKVEVY LLELKLCQNS
DPTNLLSCQF SKADTIATIE KEMRRLFNIP DDKETRLWNK YMSNTYEQLN KPDNTIQDAG
LYQGQVLVIE LQNEDGTWPR QTIQSKGSDF SNSYNCLDSG PHTHPGLCGL GNLGNTCFMN
SALQCLSNIA PLTEYFLNDK YEAEINRDNP LGMKGEIAEA FAQLIKQMWS GRNAQVVPRM
FKTQVGRFAP QFSGYQQQDS QELLAFLLDG LHEDLNRVKK KPYLELQDAN GRPDLVVAKE
AWDNHRLRND SVIVDTFHGL FKSTLVCPQC SKISVTFDPF CYLTLPLPLK KDRTMEIFLV
SADPHCRPTQ YRVTVPMMGS VSDLCRSLSK LSGVAIENML VTDVYNHRFH KIFQMSDGLN
HIMPRDDIFV YEVFSSTEDG FECVTFPVYF REKKNRQANT SSGTILYGQP LIISAPKHKL
THDYLYQIIC ERISRYIKYP LMEDSSSHPM ASGTCNGSSG TFEVEEMEHQ NEDREPPTST
VTCSFEGRVE EKLGNDPSRY ISKKITGQMY KKKLFSFSLV NSYGTTDISS LAADGKLLKL
NSRSTVAVDW DSETRSLYYD EQESEAYEKD GSMLQPQKKK KAPVALRDCI GLFTTMETLG
EHDPWYCPYC KKHQQATKKF DLWSLPKILV VHLKRFSYNR YWRDKLDTQV DFPIRNLCMS
EFICDPAAGP YIYDLIAVSN HYGAMGVGHY TAYAKNRLNG KWYYFDDSNV SLASEDQIVT
KAAYVLFYQR RDVEFCRAPS SLPGFSEETL SFQRNREEEG EDDLCSMDTN
//
