UCHL1_MONDO
ID UCHL1_MONDO Reviewed; 223 AA.
AC P50103; F7APK9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L1;
DE Short=UCH-L1;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:P09936};
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 Monodelphis domestica (Gray short-tailed opossum).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Didelphimorphia; Didelphidae; Monodelphis.
OX NCBI_TaxID=13616;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=8522974; DOI=10.1046/j.1471-4159.1996.66010035.x;
RA Mann D.A., Trowern A.R., Lavender F.L., Whittaker P.A., Thompson R.J.;
RT "Identification of evolutionary conserved regulatory sequences in the 5'
RT untranscribed region of the neural-specific ubiquitin C-terminal hydrolase
RT (PGP9.5) gene.";
RL J. Neurochem. 66:35-46(1996).
CC -!- FUNCTION: Ubiquitin-protein hydrolase involved both in the processing
CC of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a
CC thiol protease that recognizes and hydrolyzes a peptide bond at the C-
CC terminal glycine of ubiquitin (By similarity). Also binds to free
CC monoubiquitin and may prevent its degradation in lysosomes (By
CC similarity). The homodimer may have ATP-independent ubiquitin ligase
CC activity (By similarity). {ECO:0000250|UniProtKB:P09936,
CC 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 and SNCA (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum membrane
CC {ECO:0000250}; Lipid-anchor {ECO:0000250}.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
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}.
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; U32208; AAA89059.1; -; Genomic_DNA.
DR RefSeq; XP_001365417.1; XM_001365380.4.
DR AlphaFoldDB; P50103; -.
DR SMR; P50103; -.
DR STRING; 13616.ENSMODP00000025726; -.
DR MEROPS; C12.001; -.
DR PRIDE; P50103; -.
DR Ensembl; ENSMODT00000026186; ENSMODP00000025726; ENSMODG00000020568.
DR GeneID; 100015629; -.
DR KEGG; mdo:100015629; -.
DR CTD; 7345; -.
DR eggNOG; KOG1415; Eukaryota.
DR GeneTree; ENSGT00940000157306; -.
DR HOGENOM; CLU_054406_2_0_1; -.
DR InParanoid; P50103; -.
DR OMA; HACGLIA; -.
DR OrthoDB; 1013351at2759; -.
DR TreeFam; TF316166; -.
DR Proteomes; UP000002280; Chromosome 5.
DR Bgee; ENSMODG00000020568; Expressed in spinal cord and 21 other tissues.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044306; C:neuron projection terminus; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:Ensembl.
DR GO; GO:0016874; F:ligase activity; IEA:InterPro.
DR GO; GO:0008242; F:omega peptidase activity; IEA:Ensembl.
DR GO; GO:0043130; F:ubiquitin binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0007412; P:axon target recognition; IEA:Ensembl.
DR GO; GO:0019896; P:axonal transport of mitochondrion; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0042755; P:eating behavior; IEA:Ensembl.
DR GO; GO:0002176; P:male germ cell proliferation; IEA:Ensembl.
DR GO; GO:0055001; P:muscle cell development; IEA:Ensembl.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
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 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 3: Inferred from homology;
KW Cytoplasm; Endoplasmic reticulum; Glycoprotein; Hydrolase; Lipoprotein;
KW Membrane; Phosphoprotein; Prenylation; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..223
FT /note="Ubiquitin carboxyl-terminal hydrolase isozyme L1"
FT /id="PRO_0000211057"
FT PROPEP 221..223
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421570"
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:0000250|UniProtKB:Q00981"
FT LIPID 220
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P09936"
SQ SEQUENCE 223 AA; 24767 MW; 5EC27BD80CADF896 CRC64;
MQLKPMEINP EMLNKVLTRL GVGGDWKFVD VLGLEEDVLG TVPAPACALL LLFPLTAQHE
NFRKKQIEEL KGQEVSPKVY FMKQTVGNSC GTIGLIHAVA NNQDKLNFDD GSVLKQFISE
TAKLSPEDRA KCFEKNEAIQ AAHDAVAQEG QCRVDDEVNF HFILFNNVDG HLYELDGRMP
FPINHGSNSD ESVLKGAAEI CRQFTEREEG EVRFSAVALC KCA
