Q9R0P9 (UCHL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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):
Neuron cytoplasmic protein 9.5
PGP 9.5
Short name=PGP9.5
Ubiquitin thioesterase L1

Gene names

Name:

Uchl1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	223 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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	Monomer. Homodimer. Interacts with COPS5 and SNCA By similarity.
Subcellular location	Cytoplasm. Endoplasmic reticulum membrane; Lipid-anchor By similarity 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.1 Ref.2 Ref.6 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.1 Ref.6
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 Ref.6

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Endoplasmic reticulum Membrane
Molecular function	Hydrolase Ligase Protease Thiol protease
PTM	Glycoprotein Lipoprotein Oxidation Prenylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adult walking behavior Inferred from mutant phenotype PubMed 11555633PubMed 3340629. Source: MGI axon target recognition Inferred from mutant phenotype PubMed 8474599. Source: MGI axon transport of mitochondrion Inferred from mutant phenotype PubMed 2558488. Source: MGI cell proliferation Inferred from mutant phenotype PubMed 12638230. Source: MGI eating behavior Inferred from genetic interaction PubMed 11555633. Source: MGI muscle fiber development Inferred from genetic interaction PubMed 8007658. Source: MGI negative regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara neuromuscular process Inferred from mutant phenotype PubMed 3340629PubMed 7555927. Source: MGI protein deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB response to stress Inferred from mutant phenotype Ref.7. Source: MGI sensory perception of pain Inferred from electronic annotation. Source: Compara ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from direct assay PubMed 11466438PubMed 12074562PubMed 12107488PubMed 12866128PubMed 14973275PubMed 21606356PubMed 8896700. Source: MGI cytosol Inferred from direct assay Ref.6. Source: MGI endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell neuronal cell body Inferred from direct assay PubMed 11549719. Source: MGI nucleus Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: Compara
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 Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin thiolesterase activity Inferred from direct assay Ref.6. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 220	220	Ubiquitin carboxyl-terminal hydrolase isozyme L1		PRO_0000211058
	Propeptide	221 – 223	3	Removed in mature form By similarity		PRO_0000414313
Regions
	Region	5 – 10	6	Interaction with ubiquitin By similarity
	Region	151 – 156	6	Interaction with ubiquitin By similarity
	Region	211 – 216	6	Interaction with ubiquitin By similarity
Sites
	Active site	90	1	Nucleophile Probable
	Active site	161	1	Proton donor 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	176	1	Important for enzyme activity By similarity
	Site	179	1	Susceptible to oxidation By similarity
	Site	220	1	Susceptible to oxidation By similarity
Amino acid modifications
	Lipidation	220	1	S-farnesyl cysteine 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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. NM_011670.2.
UniGene	Mm.29807.
3D structure databases
ProteinModelPortal	Q9R0P9.
SMR	Q9R0P9. Positions 1-223.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9R0P9. 2 interactions.
STRING	10090.ENSMUSP00000031131.
Protein family/group databases
MEROPS	C12.001.
PTM databases
PhosphoSite	Q9R0P9.
2D gel databases
REPRODUCTION-2DPAGE	IPI00313962. Q9R0P9.
UCD-2DPAGE	Q9R0P9.
Proteomic databases
PaxDb	Q9R0P9.
PRIDE	Q9R0P9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000031131; ENSMUSP00000031131; ENSMUSG00000029223.
GeneID	22223.
KEGG	mmu:22223.
UCSC	uc008xpf.2. mouse.
Organism-specific databases
CTD	7345.
MGI	MGI:103149. Uchl1.
Phylogenomic databases
eggNOG	NOG327708.
GeneTree	ENSGT00510000046640.
HOVERGEN	HBG075483.
InParanoid	Q9R0P9.
KO	K05611.
OMA	SAKICRQ.
OrthoDB	EOG4RJG2F.
Enzyme and pathway databases
BRENDA	3.4.19.12. 3474.
Gene expression databases
Bgee	Q9R0P9.
CleanEx	MM_UCHL1.
Genevestigator	Q9R0P9.
GermOnline	ENSMUSG00000029223. Mus musculus.
Family and domain databases
Gene3D	3.40.532.10. 1 hit.
InterPro	IPR001578. Peptidase_C12. [Graphical view]
PANTHER	PTHR10589. PTHR10589. 1 hit.
Pfam	PF01088. Peptidase_C12. 1 hit. [Graphical view]
PRINTS	PR00707. UBCTHYDRLASE.
PROSITE	PS00140. UCH_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9R0P9.
ChiTaRS	UCHL1. mouse.
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:	April 3, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program