Reviewed, UniProtKB/Swiss-Prot Q9R0P9 (UCHL1_MOUSE)

Names and origin

Protein names

Recommended name:
    Ubiquitin carboxyl-terminal hydrolase isozyme L1
      Short name=UCH-L1
    EC=3.4.19.12
    EC=6.-.-.-
Alternative name(s):
    Ubiquitin thioesterase L1
    Neuron cytoplasmic protein 9.5
    PGP 9.5
      Short name=PGP9.5

Gene names

Name:

Uchl1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	223 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity. Ref.6
Catalytic activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
Subunit structure	Homodimer. Interacts with COPS5 and SNCA By similarity.
Subcellular location	Cytoplasm. Ref.6
Tissue specificity	Expressed in brain, where it is found in neurons but not in oligodendrocytes or astrocytes. Found in the ganglion cell layer and the inner nuclear layer of the retina (at protein level). Expressed in brain and testis. In the brain, expression is at its lowest in replaceable neurons of hippocampus aand olfactory bulb. Highly expressed in senescent pituitary. Ref.6 Ref.1 Ref.2 Ref.7 Ref.8
Post-translational modification	O-glycosylated By similarity.
Disruption phenotype	Mice show sensory ataxia at an early stage, followed by motor ataxia at a later stage. They have reduced levels of monoubiquitin in the nervous system, and increased resistance to retinal ischemia. Ref.6 Ref.1
Miscellaneous	In contrast to UCHL3, does not hydrolyze a peptide bond at the C-terminal glycine of NEDD8 By similarity.
Sequence similarities	Belongs to the peptidase C12 family.
Biophysicochemical properties	Kinetic parameters: KM=116 nM for Ub-AMC

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Molecular function	Hydrolase Ligase Protease Thiol protease
PTM	Glycoprotein Oxidation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	adult walking behavior Inferred from mutant phenotype. Source: MGI axon target recognition Inferred from mutant phenotype. Source: MGI axon transport of mitochondrion Inferred from mutant phenotype. Source: MGI cell proliferation Inferred from mutant phenotype. Source: MGI eating behavior Inferred from genetic interaction. Source: MGI neuromuscular process Inferred from mutant phenotype. Source: MGI protein deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB response to stress Ref.7 Inferred from mutant phenotype. Source: MGI ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	axon Inferred from direct assay. Source: MGI cell soma Inferred from direct assay. Source: MGI cytosol Ref.6 Inferred from direct assay. Source: MGI
Molecular function	cysteine-type endopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB ligase activity Inferred from electronic annotation. Source: UniProtKB-KW omega peptidase activity Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin binding Ref.6 Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin thiolesterase activity Ref.6 Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 223	223	Ubiquitin carboxyl-terminal hydrolase isozyme L1		PRO_0000211058
Regions
	Region	37 – 54	18	Ubiquitin binding Potential
	Region	170 – 178	9	Ubiquitin binding Potential
Sites
	Active site	90	1
	Active site	161	1	By similarity
	Active site	176	1	By similarity
	Site	1	1	Susceptible to oxidation By similarity
	Site	6	1	Susceptible to oxidation By similarity
	Site	12	1	Susceptible to oxidation By similarity
	Site	179	1	Susceptible to oxidation By similarity
	Site	220	1	Susceptible to oxidation By similarity
Experimental info
	Mutagenesis	30	1	D → K: Abolishes enzymatic activity and ubiquitin binding. Ref.6
	Mutagenesis	90	1	C → S: Abolishes enzymatic activity, but does not affect ubiquitin binding. Ref.6
	Sequence conflict	149	1	E → K in AAD51029. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9R0P9-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: F1402BF7B0C077EA	FASTA	223	24,838
	10 20 30 40 50 60 MQLKPMEINP EMLNKVLAKL GVAGQWRFAD VLGLEEETLG SVPSPACALL LLFPLTAQHE 70 80 90 100 110 120 NFRKKQIEEL KGQEVSPKVY FMKQTIGNSC GTIGLIHAVA NNQDKLEFED GSVLKQFLSE 130 140 150 160 170 180 TEKLSPEDRA KCFEKNEAIQ AAHDSVAQEG QCRVDDKVNF HFILFNNVDG HLYELDGRMP 190 200 210 220 FPVNHGASSE DSLLQDAAKV CREFTEREQG EVRFSAVALC KAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice." Saigoh K., Wang Y.-L., Suh J.G., Yamanishi T., Sakai Y., Kiyosawa H., Harada T., Ichihara N., Wakana S., Kikuchi T., Wada K. Nat. Genet. 23:47-51(1999) [PubMed: 10471497] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DISRUPTION PHENOTYPE. Tissue: Brain.
[2]	"Age-related alterations in the protein expression profile of C57BL/6J mouse pituitaries." Marzban G., Grillari J., Reisinger E., Hemetsberger T., Grabherr R., Katinger H. Exp. Gerontol. 37:1451-1460(2002) [PubMed: 12559414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-10, TISSUE SPECIFICITY. Strain: C57BL/6J. Tissue: Pituitary.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Hippocampus.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Retina.
[5]	Lubec G., Kang S.U., Klug S., Yang J.W., Zigmond M. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 20-27; 66-78; 116-123; 136-153 AND 158-199, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Brain and Hippocampus.
[6]	"Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron." Osaka H., Wang Y.-L., Takada K., Takizawa S., Setsuie R., Li H., Sato Y., Nishikawa K., Sun Y.-J., Sakurai M., Harada T., Hara Y., Kimura I., Chiba S., Namikawa K., Kiyama H., Noda M., Aoki S., Wada K. Hum. Mol. Genet. 12:1945-1958(2003) [PubMed: 12913066] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-30 AND CYS-90, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, DISRUPTION PHENOTYPE.
[7]	"Role of ubiquitin carboxy terminal hydrolase-L1 in neural cell apoptosis induced by ischemic retinal injury in vivo." Harada T., Harada C., Wang Y.-L., Osaka H., Amanai K., Tanaka K., Takizawa S., Setsuie R., Sakurai M., Sato Y., Noda M., Wada K. Am. J. Pathol. 164:59-64(2004) [PubMed: 14695319] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Replaceable neurons and neurodegenerative disease share depressed UCHL1 levels." Lombardino A.J., Li X.-C., Hertel M., Nottebohm F. Proc. Natl. Acad. Sci. U.S.A. 102:8036-8041(2005) [PubMed: 15911766] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB025313 mRNA. Translation: BAA84083.1. AF172334 mRNA. Translation: AAD51029.1. AK013729 mRNA. Translation: BAB28976.1. BC039177 mRNA. Translation: AAH39177.1.
IPI	IPI00313962.
RefSeq	NP_035800.2.
UniGene	Mm.29807
3D structure databases
HSSP	HSSP built from PDB template 1UCH based on UniProtKB P15374.
SMR	Q9R0P9. Positions 1-223.
ModBase	Search...
2-D gel databases
REPRODUCTION-2DPAGE	Q9R0P9.
Proteomic databases
PRIDE	Q9R0P9.
Genome annotation databases
Ensembl	ENSMUSG00000029223. Mus musculus. [Contig view]
GeneID	22223.
KEGG	mmu:22223.
Organism-specific databases
MGI	MGI:103149. Uchl1.
Phylogenomic databases
HOVERGEN	Q9R0P9.
OMA	Q9R0P9. CRQFTER.
Enzyme and pathway databases
BRENDA	3.4.19.12. 244.
Gene expression databases
ArrayExpress	Q9R0P9.
Bgee	Q9R0P9.
CleanEx	MM_UCHL1.
GermOnline	ENSMUSG00000029223. Mus musculus.
Family and domain databases
InterPro	IPR001578. Peptidase_C12. [Graphical view]
Gene3D	G3DSA:3.40.532.10. Peptidase_C12. 1 hit.
PANTHER	PTHR10589. Peptidase_C12. 1 hit.
Pfam	PF01088. Peptidase_C12. 1 hit. [Graphical view]
PRINTS	PR00707. UBCTHYDRLASE.
ProDom	PD350662. Peptidase_C12. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00140. UCH_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	302243.
SOURCE	Search...

Entry information

Entry name

UCHL1_MOUSE

Accession

Primary (citable) accession number: Q9R0P9
Secondary accession number(s): Q9R122

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	May 1, 2000
Last modified:	June 16, 2009
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)