UCHL3_RAT
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 03-AUG-2022, entry version 126.
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}.
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; 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; Q91Y78; -.
DR PRIDE; Q91Y78; -.
DR GeneID; 498560; -.
DR KEGG; rno:498560; -.
DR CTD; 7347; -.
DR RGD; 1561196; Uchl3.
DR eggNOG; KOG1415; Eukaryota.
DR InParanoid; Q91Y78; -.
DR OrthoDB; 1013351at2759; -.
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:0016579; P:protein deubiquitination; 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 Gene3D; 3.40.532.10; -; 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; PTHR10589; 1.
DR Pfam; PF01088; Peptidase_C12; 1.
DR PRINTS; PR00707; UBCTHYDRLASE.
DR SUPFAM; SSF54001; SSF54001; 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
