ID   UCHL3_RAT               Reviewed;         230 AA.
AC   Q91Y78;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 130.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L3;
DE            Short=UCH-L3;
DE            EC=3.4.19.12 {ECO:0000250|UniProtKB:P15374};
DE   AltName: Full=Ubiquitin thioesterase L3;
GN   Name=Uchl3;
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].
RC   STRAIN=Wistar; TISSUE=Brain, and Liver;
RA   Osawa Y.;
RT   "Cloning of rat UCHL3.";
RL   Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 166-186, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA   Lubec G., Chen W.-Q.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, 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: Deubiquitinating enzyme (DUB) that controls levels of
CC       cellular ubiquitin through processing of ubiquitin precursors and
CC       ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a
CC       peptide bond at the C-terminal glycine of either ubiquitin or NEDD8.
CC       Has a 10-fold preference for Arg and Lys at position P3, and exhibits a
CC       preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates
CC       ENAC in apical compartments, thereby regulating apical membrane
CC       recycling. Indirectly increases the phosphorylation of IGFIR, AKT and
CC       FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis.
CC       Required for stress-response retinal, skeletal muscle and germ cell
CC       maintenance. May be involved in working memory. Can hydrolyze UBB(+1),
CC       a mutated form of ubiquitin which is not effectively degraded by the
CC       proteasome (By similarity). {ECO:0000250}.
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:P15374};
CC   -!- ACTIVITY REGULATION: Inhibited by monoubiquitin and diubiquitin.
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Preferentially binds diubiquitin; the interaction does not
CC       hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity
CC       on other substrates. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase C12 family. {ECO:0000305}.
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DR   EMBL; AB043959; BAB47136.1; -; mRNA.
DR   RefSeq; NP_001103635.1; NM_001110165.1.
DR   AlphaFoldDB; Q91Y78; -.
DR   BMRB; Q91Y78; -.
DR   SMR; Q91Y78; -.
DR   STRING; 10116.ENSRNOP00000012842; -.
DR   MEROPS; C12.003; -.
DR   iPTMnet; Q91Y78; -.
DR   PhosphoSitePlus; Q91Y78; -.
DR   SwissPalm; Q91Y78; -.
DR   jPOST; Q91Y78; -.
DR   PaxDb; 10116-ENSRNOP00000012842; -.
DR   Ensembl; ENSRNOT00055012563; ENSRNOP00055009983; ENSRNOG00055007508.
DR   Ensembl; ENSRNOT00060025720; ENSRNOP00060020545; ENSRNOG00060014959.
DR   Ensembl; ENSRNOT00065011136; ENSRNOP00065008141; ENSRNOG00065007054.
DR   GeneID; 498560; -.
DR   KEGG; rno:498560; -.
DR   AGR; RGD:1561196; -.
DR   CTD; 7347; -.
DR   RGD; 1561196; Uchl3.
DR   eggNOG; KOG1415; Eukaryota.
DR   InParanoid; Q91Y78; -.
DR   OrthoDB; 179179at2759; -.
DR   PhylomeDB; Q91Y78; -.
DR   Reactome; R-RNO-5689603; UCH proteinases.
DR   Reactome; R-RNO-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR   Reactome; R-RNO-8951664; Neddylation.
DR   PRO; PR:Q91Y78; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:RGD.
DR   GO; GO:0101005; F:deubiquitinase activity; ISO:RGD.
DR   GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR   GO; GO:0043130; F:ubiquitin binding; ISO:RGD.
DR   GO; GO:0007628; P:adult walking behavior; ISO:RGD.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
DR   GO; GO:0042755; P:eating behavior; ISO:RGD.
DR   GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
DR   GO; GO:0030163; P:protein catabolic process; ISO:RGD.
DR   GO; GO:0060041; P:retina development in camera-type eye; ISO:RGD.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR   CDD; cd09616; Peptidase_C12_UCH_L1_L3; 1.
DR   Gene3D; 3.40.532.10; Peptidase C12, ubiquitin carboxyl-terminal hydrolase; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001578; Peptidase_C12_UCH.
DR   InterPro; IPR036959; Peptidase_C12_UCH_sf.
DR   PANTHER; PTHR10589; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR10589:SF24; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE ISOZYME L3; 1.
DR   Pfam; PF01088; Peptidase_C12; 1.
DR   PRINTS; PR00707; UBCTHYDRLASE.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00140; UCH_1; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Direct protein sequencing; Hydrolase; Phosphoprotein; Protease;
KW   Reference proteome; Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..230
FT                   /note="Ubiquitin carboxyl-terminal hydrolase isozyme L3"
FT                   /id="PRO_0000211063"
FT   REGION          8..13
FT                   /note="Interaction with ubiquitin"
FT                   /evidence="ECO:0000250|UniProtKB:P15374"
FT   REGION          152..159
FT                   /note="Interaction with ubiquitin. Crossover loop which
FT                   restricts access of large ubiquitin adducts to the active
FT                   site"
FT                   /evidence="ECO:0000250|UniProtKB:P15374"
FT   REGION          219..224
FT                   /note="Interaction with ubiquitin"
FT                   /evidence="ECO:0000250|UniProtKB:P15374"
FT   ACT_SITE        95
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10091"
FT   ACT_SITE        169
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10091"
FT   SITE            184
FT                   /note="Important for enzyme activity"
FT                   /evidence="ECO:0000250|UniProtKB:P09936"
FT   MOD_RES         130
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
SQ   SEQUENCE   230 AA;  26124 MW;  C793BEFEEB926F10 CRC64;
     MEGQRWLPLE ANPEVTNQFL KQLGLHPNWQ FVDVYGMEPE LLSMVPRPVC AVLLLFPITE
     KYEVFRTEEE EKIKSQGQDV TSSVYFMKQT ISNACGTIGL IHAIANNKDK MHFESGSALK
     KFLEESVAMS PEERARHLEN YDAIRVTHET SAHEGQTEAP SIDEKVDLHF IALVHVDGHL
     YELDGRKPFP INHGKTSDET LLEDAIEVCK KFMERDPDEL RFNAIALSAA
//