UCHL1_RAT
ID UCHL1_RAT Reviewed; 223 AA.
AC Q00981; Q6P9V8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L1;
DE Short=UCH-L1 {ECO:0000250|UniProtKB:P09936};
DE EC=3.4.19.12;
DE AltName: Full=Neuron cytoplasmic protein 9.5;
DE AltName: Full=PGP 9.5;
DE Short=PGP9.5;
DE AltName: Full=Ubiquitin thioesterase L1;
DE Flags: Precursor;
GN Name=Uchl1;
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 TISSUE=Brain;
RX PubMed=1331034; DOI=10.1093/oxfordjournals.jbchem.a123860;
RA Kajimoto Y., Hashimoto T., Shirai Y., Nishino N., Kuno T., Tanaka C.;
RT "cDNA cloning and tissue distribution of a rat ubiquitin carboxyl-terminal
RT hydrolase PGP9.5.";
RL J. Biochem. 112:28-32(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 20-27; 84-123 AND 132-199, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Spinal cord;
RA Lubec G., Boddul S., Afjehi-Sadat L., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [4]
RP GLYCOSYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11739622; DOI=10.1046/j.1471-4159.2001.00655.x;
RA Cole R.N., Hart G.W.;
RT "Cytosolic O-glycosylation is abundant in nerve terminals.";
RL J. Neurochem. 79:1080-1089(2001).
RN [5]
RP INTERACTION WITH SNCA.
RX PubMed=12408865; DOI=10.1016/s0092-8674(02)01012-7;
RA Liu Y., Fallon L., Lashuel H.A., Liu Z., Lansbury P.T. Jr.;
RT "The UCH-L1 gene encodes two opposing enzymatic activities that affect
RT alpha-synuclein degradation and Parkinson's disease susceptibility.";
RL Cell 111:209-218(2002).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, 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: Ubiquitin-protein hydrolase involved both in the processing
CC of ubiquitin precursors and of ubiquitinated proteins (By similarity).
CC This enzyme is a thiol protease that recognizes and hydrolyzes a
CC peptide bond at the C-terminal glycine of ubiquitin (By similarity).
CC Also binds to free monoubiquitin and may prevent its degradation in
CC lysosomes (By similarity). The homodimer may have ATP-independent
CC ubiquitin ligase activity (By similarity).
CC {ECO:0000250|UniProtKB:P09936, ECO:0000250|UniProtKB:Q9R0P9}.
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:P09936};
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with COPS5 (By similarity).
CC Interacts with SNCA. {ECO:0000250, ECO:0000269|PubMed:12408865}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum membrane
CC {ECO:0000250}; Lipid-anchor {ECO:0000250}.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:11739622}.
CC -!- MISCELLANEOUS: In contrast to UCHL3, does not hydrolyze a peptide bond
CC at the C-terminal glycine of NEDD8. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C12 family. {ECO:0000305}.
CC -!- CAUTION: The homodimer may have ATP-independent ubiquitin ligase
CC activity. However, in another study, UCHL1 was shown to lack ubiquitin
CC ligase activity. {ECO:0000250|UniProtKB:P09936}.
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DR EMBL; D10699; BAA01541.1; -; mRNA.
DR EMBL; BC060573; AAH60573.1; -; mRNA.
DR PIR; JX0222; JX0222.
DR RefSeq; NP_058933.2; NM_017237.3.
DR AlphaFoldDB; Q00981; -.
DR SMR; Q00981; -.
DR BioGRID; 248179; 5.
DR IntAct; Q00981; 2.
DR STRING; 10116.ENSRNOP00000003248; -.
DR MEROPS; C12.001; -.
DR iPTMnet; Q00981; -.
DR PhosphoSitePlus; Q00981; -.
DR SwissPalm; Q00981; -.
DR World-2DPAGE; 0004:Q00981; -.
DR jPOST; Q00981; -.
DR PaxDb; Q00981; -.
DR PRIDE; Q00981; -.
DR Ensembl; ENSRNOT00000094226; ENSRNOP00000086461; ENSRNOG00000002343.
DR GeneID; 29545; -.
DR KEGG; rno:29545; -.
DR UCSC; RGD:3928; rat.
DR CTD; 7345; -.
DR RGD; 3928; Uchl1.
DR eggNOG; KOG1415; Eukaryota.
DR GeneTree; ENSGT00940000157306; -.
DR HOGENOM; CLU_054406_2_0_1; -.
DR InParanoid; Q00981; -.
DR OMA; HACGLIA; -.
DR OrthoDB; 1013351at2759; -.
DR PhylomeDB; Q00981; -.
DR BRENDA; 3.4.19.12; 5301.
DR Reactome; R-RNO-5689603; UCH proteinases.
DR PRO; PR:Q00981; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000002343; Expressed in frontal cortex and 20 other tissues.
DR Genevisible; Q00981; RN.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044306; C:neuron projection terminus; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0031694; F:alpha-2A adrenergic receptor binding; ISO:RGD.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0016874; F:ligase activity; IEA:InterPro.
DR GO; GO:0008242; F:omega peptidase activity; ISO:RGD.
DR GO; GO:0043130; F:ubiquitin binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0007628; P:adult walking behavior; ISO:RGD.
DR GO; GO:0007412; P:axon target recognition; ISO:RGD.
DR GO; GO:0019896; P:axonal transport of mitochondrion; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0042755; P:eating behavior; ISO:RGD.
DR GO; GO:0002176; P:male germ cell proliferation; IEA:Ensembl.
DR GO; GO:0055001; P:muscle cell development; ISO:RGD.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0050905; P:neuromuscular process; ISO:RGD.
DR GO; GO:0016579; P:protein deubiquitination; ISO:RGD.
DR GO; GO:0002931; P:response to ischemia; ISO:RGD.
DR GO; GO:0019233; P:sensory perception of pain; IDA:RGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:RGD.
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 InterPro; IPR030297; UCHL1.
DR PANTHER; PTHR10589; PTHR10589; 1.
DR PANTHER; PTHR10589:SF19; PTHR10589:SF19; 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; Endoplasmic reticulum; Glycoprotein;
KW Hydrolase; Lipoprotein; Membrane; Phosphoprotein; Prenylation; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..220
FT /note="Ubiquitin carboxyl-terminal hydrolase isozyme L1"
FT /id="PRO_0000211060"
FT PROPEP 221..223
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000414315"
FT REGION 5..10
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT REGION 211..216
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT ACT_SITE 90
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10091"
FT ACT_SITE 161
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10091"
FT SITE 176
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 220
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT CONFLICT 38
FT /note="T -> I (in Ref. 1; BAA01541)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="I -> M (in Ref. 1; BAA01541)"
FT /evidence="ECO:0000305"
FT CONFLICT 105..107
FT /note="KLE -> NLG (in Ref. 1; BAA01541)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 223 AA; 24838 MW; F1402BF7B0C077EA CRC64;
MQLKPMEINP EMLNKVLAKL GVAGQWRFAD VLGLEEETLG SVPSPACALL LLFPLTAQHE
NFRKKQIEEL KGQEVSPKVY FMKQTIGNSC GTIGLIHAVA NNQDKLEFED GSVLKQFLSE
TEKLSPEDRA KCFEKNEAIQ AAHDSVAQEG QCRVDDKVNF HFILFNNVDG HLYELDGRMP
FPVNHGASSE DSLLQDAAKV CREFTEREQG EVRFSAVALC KAA
