UCHL1_MOUSE
ID UCHL1_MOUSE Reviewed; 223 AA.
AC Q9R0P9; Q9R122;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L1;
DE Short=UCH-L1;
DE EC=3.4.19.12 {ECO:0000269|PubMed:12913066};
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RC TISSUE=Brain;
RX PubMed=10471497; DOI=10.1038/12647;
RA Saigoh K., Wang Y.-L., Suh J.G., Yamanishi T., Sakai Y., Kiyosawa H.,
RA Harada T., Ichihara N., Wakana S., Kikuchi T., Wada K.;
RT "Intragenic deletion in the gene encoding ubiquitin carboxy-terminal
RT hydrolase in gad mice.";
RL Nat. Genet. 23:47-51(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-10, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Pituitary;
RX PubMed=12559414; DOI=10.1016/s0531-5565(02)00117-1;
RA Marzban G., Grillari J., Reisinger E., Hemetsberger T., Grabherr R.,
RA Katinger H.;
RT "Age-related alterations in the protein expression profile of C57BL/6J
RT mouse pituitaries.";
RL Exp. Gerontol. 37:1451-1460(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
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 [5]
RP PROTEIN SEQUENCE OF 20-27; 66-78; 116-123; 136-153 AND 158-199, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus;
RA Lubec G., Kang S.U., Klug S., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-30 AND CYS-90.
RX PubMed=12913066; DOI=10.1093/hmg/ddg211;
RA Osaka H., Wang Y.-L., Takada K., Takizawa S., Setsuie R., Li H., Sato Y.,
RA Nishikawa K., Sun Y.-J., Sakurai M., Harada T., Hara Y., Kimura I.,
RA Chiba S., Namikawa K., Kiyama H., Noda M., Aoki S., Wada K.;
RT "Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes
RT monoubiquitin in neuron.";
RL Hum. Mol. Genet. 12:1945-1958(2003).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=14695319; DOI=10.1016/s0002-9440(10)63096-9;
RA Harada T., Harada C., Wang Y.-L., Osaka H., Amanai K., Tanaka K.,
RA Takizawa S., Setsuie R., Sakurai M., Sato Y., Noda M., Wada K.;
RT "Role of ubiquitin carboxy terminal hydrolase-L1 in neural cell apoptosis
RT induced by ischemic retinal injury in vivo.";
RL Am. J. Pathol. 164:59-64(2004).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=15911766; DOI=10.1073/pnas.0503239102;
RA Lombardino A.J., Li X.-C., Hertel M., Nottebohm F.;
RT "Replaceable neurons and neurodegenerative disease share depressed UCHL1
RT levels.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8036-8041(2005).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Liver, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Ubiquitin-protein hydrolase involved both in the processing
CC of ubiquitin precursors and of ubiquitinated proteins (Probable). This
CC enzyme is a thiol protease that recognizes and hydrolyzes a peptide
CC bond at the C-terminal glycine of ubiquitin (PubMed:12913066). Also
CC binds to free monoubiquitin and may prevent its degradation in
CC lysosomes (PubMed:12913066). The homodimer may have ATP-independent
CC ubiquitin ligase activity (By similarity).
CC {ECO:0000250|UniProtKB:P09936, ECO:0000269|PubMed:12913066,
CC ECO:0000305|PubMed:12913066}.
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:0000269|PubMed:12913066};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=116 nM for Ub-AMC {ECO:0000269|PubMed:12913066};
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with COPS5 and SNCA (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12913066}.
CC Endoplasmic reticulum membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, where it is found in neurons
CC but not in oligodendrocytes or astrocytes. Found in the ganglion cell
CC layer and the inner nuclear layer of the retina (at protein level).
CC Expressed in brain and testis. In the brain, expression is at its
CC lowest in replaceable neurons of hippocampus and olfactory bulb. Highly
CC expressed in senescent pituitary. {ECO:0000269|PubMed:10471497,
CC ECO:0000269|PubMed:12559414, ECO:0000269|PubMed:12913066,
CC ECO:0000269|PubMed:14695319, ECO:0000269|PubMed:15911766}.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice show sensory ataxia at an early stage,
CC followed by motor ataxia at a later stage. They have reduced levels of
CC monoubiquitin in the nervous system, and increased resistance to
CC retinal ischemia. {ECO:0000269|PubMed:10471497,
CC ECO:0000269|PubMed:12913066}.
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; AB025313; BAA84083.1; -; mRNA.
DR EMBL; AF172334; AAD51029.1; -; mRNA.
DR EMBL; AK013729; BAB28976.1; -; mRNA.
DR EMBL; BC039177; AAH39177.1; -; mRNA.
DR CCDS; CCDS19315.1; -.
DR RefSeq; NP_035800.2; NM_011670.2.
DR AlphaFoldDB; Q9R0P9; -.
DR SMR; Q9R0P9; -.
DR BioGRID; 204423; 27.
DR IntAct; Q9R0P9; 8.
DR MINT; Q9R0P9; -.
DR STRING; 10090.ENSMUSP00000031131; -.
DR BindingDB; Q9R0P9; -.
DR MEROPS; C12.001; -.
DR iPTMnet; Q9R0P9; -.
DR PhosphoSitePlus; Q9R0P9; -.
DR SwissPalm; Q9R0P9; -.
DR REPRODUCTION-2DPAGE; IPI00313962; -.
DR REPRODUCTION-2DPAGE; Q9R0P9; -.
DR UCD-2DPAGE; Q9R0P9; -.
DR EPD; Q9R0P9; -.
DR MaxQB; Q9R0P9; -.
DR PaxDb; Q9R0P9; -.
DR PeptideAtlas; Q9R0P9; -.
DR PRIDE; Q9R0P9; -.
DR ProteomicsDB; 298189; -.
DR Antibodypedia; 1062; 2211 antibodies from 52 providers.
DR DNASU; 22223; -.
DR Ensembl; ENSMUST00000031131; ENSMUSP00000031131; ENSMUSG00000029223.
DR GeneID; 22223; -.
DR KEGG; mmu:22223; -.
DR UCSC; uc008xpf.2; mouse.
DR CTD; 7345; -.
DR MGI; MGI:103149; Uchl1.
DR VEuPathDB; HostDB:ENSMUSG00000029223; -.
DR eggNOG; KOG1415; Eukaryota.
DR GeneTree; ENSGT00940000157306; -.
DR HOGENOM; CLU_054406_2_0_1; -.
DR InParanoid; Q9R0P9; -.
DR OMA; HACGLIA; -.
DR OrthoDB; 1013351at2759; -.
DR PhylomeDB; Q9R0P9; -.
DR TreeFam; TF316166; -.
DR BRENDA; 3.4.19.12; 3474.
DR Reactome; R-MMU-5689603; UCH proteinases.
DR BioGRID-ORCS; 22223; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Uchl1; mouse.
DR PRO; PR:Q9R0P9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9R0P9; protein.
DR Bgee; ENSMUSG00000029223; Expressed in superior cervical ganglion and 238 other tissues.
DR Genevisible; Q9R0P9; MM.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0044306; C:neuron projection terminus; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0031694; F:alpha-2A adrenergic receptor binding; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:MGI.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:InterPro.
DR GO; GO:0008242; F:omega peptidase activity; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR GO; GO:0007412; P:axon target recognition; IMP:MGI.
DR GO; GO:0019896; P:axonal transport of mitochondrion; IMP:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0042755; P:eating behavior; IGI:MGI.
DR GO; GO:0002176; P:male germ cell proliferation; IMP:MGI.
DR GO; GO:0055001; P:muscle cell development; IGI:MGI.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0050905; P:neuromuscular process; IMP:MGI.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; IMP:MGI.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:MGI.
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_0000211058"
FT PROPEP 221..223
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000414313"
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:0000305"
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"
FT MUTAGEN 30
FT /note="D->K: Abolishes enzymatic activity and ubiquitin
FT binding."
FT /evidence="ECO:0000269|PubMed:12913066"
FT MUTAGEN 90
FT /note="C->S: Abolishes enzymatic activity, but does not
FT affect ubiquitin binding."
FT /evidence="ECO:0000269|PubMed:12913066"
FT CONFLICT 149
FT /note="E -> K (in Ref. 2; AAD51029)"
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
