Ubiquitin carboxyl-terminal hydrolase isozyme L3

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Q9JKB1 (UCHL3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 107. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase isozyme L3
Short name=UCH-L3
EC=3.4.19.12

Alternative name(s):
Ubiquitin thioesterase L3

Gene names

Name:

Uchl3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	230 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.12
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).
Enzyme regulation	Inhibited by monoubiquitin and diubiquitin By similarity.
Subunit structure	Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates By similarity.
Subcellular location	Cytoplasm Ref.2 Ref.8.
Tissue specificity	Ubiquitously expressed, with highest levels in brain, liver, heart, thymus, kidney and testis. Highly expressed in the cauda epididymidis, in meiotic pachytene spermatocytes and post-meiotic spematids. In the retina, enriched in the photoreceptor inner segment. Ref.1 Ref.2 Ref.6 Ref.7
Developmental stage	Expressed at E8.5 in structures required for skeletal patterning. Highly expressed at E11, and decreases markedly from E15. Ref.1 Ref.4
Disruption phenotype	Mice have no developmental defects, are fertile, and show normal T-cell differentiation. They have normal anxiety, locomotor behavior, motor function and synaptic transmission, but show defects in spatial learning and working memory. Exhibit stress-related effects with profound apoptosis-mediated germ cell loss and also, prominent retinal degeneration with photoreceptor cell apoptosis and mitochondrial oxidative stress. Mice show reduced capacity for adipocyte differentiation and impaired insulin responses. Ref.5 Ref.6 Ref.7 Ref.10 Ref.11
Sequence similarities	Belongs to the peptidase C12 family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adult walking behavior Inferred from genetic interaction PubMed 11555633. Source: MGI cellular response to insulin stimulus Inferred from direct assay Ref.10. Source: UniProtKB eating behavior Inferred from genetic interaction PubMed 11555633. Source: MGI positive regulation of fat cell differentiation Inferred from direct assay Ref.10. Source: UniProtKB protein catabolic process Inferred from direct assay Ref.12. Source: UniProtKB protein deubiquitination Inferred from sequence alignment Ref.1. Source: MGI retina development in camera-type eye Inferred from mutant phenotype PubMed 21052544. Source: MGI ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW peptidase activity Inferred from direct assay Ref.12. Source: UniProtKB ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 230

230

Ubiquitin carboxyl-terminal hydrolase isozyme L3

PRO_0000211062

Regions

Region

8 – 13

Interaction with ubiquitin By similarity

Region

152 – 159

Interaction with ubiquitin By similarity

Region

219 – 224

Interaction with ubiquitin By similarity

Sites

Active site

Nucleophile By similarity

Active site

169

Proton donor By similarity

Site

184

Important for enzyme activity By similarity

Amino acid modifications

Modified residue

130

Phosphoserine Ref.9

Experimental info

Mutagenesis

C → S: No increase in phosphorylation of AKT1, FOXO1 and INSR. No increased expression of SLC2A1, FABP4 nor ADIPOQ. Impaired formation of large lipid droplets. Ref.10

Sequence conflict

205 – 207

AIE → VIK in AAF64193. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

Q9JKB1 [UniParc].

Last modified September 26, 2001. Version 2.
Checksum: F147991F3ED69AC3
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FASTA

230

26,152

        10         20         30         40         50         60 
MEGQRWLPLE ANPEVTNQFL KQLGLHPNWQ FVDVYGMEPE LLSMVPRPVC AVLLLFPITE 

        70         80         90        100        110        120 
KYEVFRTEEE EKIKSQGQDV TSSVYFMKQT ISNACGTIGL IHAIANNKDK MHFESGSTLK 

       130        140        150        160        170        180 
KFLEESVSMS PEERAKFLEN YDAIRVTHET SAHEGQTEAP SIDEKVDLHF IALVHVDGHL 

       190        200        210        220        230 
YELDGRKPFP INHGKTSDET LLEDAIEVCK KFMERDPDEL RFNAIALSAA

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression and functional analysis of Uch-L3 during mouse development." Kurihara L.J., Semenova E., Levorse J.M., Tilghman S.M. Mol. Cell. Biol. 20:2498-2504(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, TISSUE SPECIFICITY. Strain: Swiss Webster / NIH.
[2]	"Cloning, expression, and mapping of a mouse gene, Uchl4, highly homologous to human and mouse Uchl3." Osawa Y., Wang Y.-L., Osaka H., Aoki S., Wada K. Biochem. Biophys. Res. Commun. 283:627-633(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: C57BL/6J. Tissue: Kidney and Liver.
[3]	"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: Testis.
[4]	"Cleavage of the C-terminus of NEDD8 by UCH-L3." Wada H., Kito K., Caskey L.S., Yeh E.T.H., Kamitani T. Biochem. Biophys. Res. Commun. 251:688-692(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[5]	"Ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory." Wood M.A., Kaplan M.P., Brensinger C.M., Guo W., Abel T. Hippocampus 15:610-621(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"Photoreceptor cell apoptosis in the retinal degeneration of Uchl3-deficient mice." Sano Y., Furuta A., Setsuie R., Kikuchi H., Wang Y.L., Sakurai M., Kwon J., Noda M., Wada K. Am. J. Pathol. 169:132-141(2006) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
[7]	"The new function of two ubiquitin C-terminal hydrolase isozymes as reciprocal modulators of germ cell apoptosis." Kwon J. Exp. Anim. 56:71-77(2007) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
[8]	"The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel." Butterworth M.B., Edinger R.S., Ovaa H., Burg D., Johnson J.P., Frizzell R.A. J. Biol. Chem. 282:37885-37893(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ENAC RECYCLING, SUBCELLULAR LOCATION.
[9]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Ubiquitin carboxyl-terminal hydrolase l3 promotes insulin signaling and adipogenesis." Suzuki M., Setsuie R., Wada K. Endocrinology 150:5230-5239(2009) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION IN ADIPOGENESIS AND INSULIN SIGNALING, MUTAGENESIS OF CYS-95.
[11]	"Skeletal muscles of Uchl3 knockout mice show polyubiquitinated protein accumulation and stress responses." Setsuie R., Suzuki M., Tsuchiya Y., Wada K. Neurochem. Int. 56:911-918(2010) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[12]	"Mutant ubiquitin (UBB(+1)) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3)." Dennissen F.J., Kholod N., Hermes D.J., Kemmerling N., Steinbusch H.W., Dantuma N.P., van Leeuwen F.W. FEBS Lett. 585:2568-2574(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF247358 mRNA. Translation: AAF64193.1. AB033370 mRNA. Translation: BAB20094.1. BC048481 mRNA. Translation: AAH48481.1.
IPI	IPI00311369.
PIR	JC7688.
RefSeq	NP_057932.2. NM_016723.2.
UniGene	Mm.275970.
3D structure databases
ProteinModelPortal	Q9JKB1.
SMR	Q9JKB1. Positions 2-230.
ModBase	Search...
Protein family/group databases
MEROPS	C12.003.
PTM databases
PhosphoSite	Q9JKB1.
2D gel databases
REPRODUCTION-2DPAGE	IPI00311369. Q9JKB1.
Proteomic databases
PaxDb	Q9JKB1.
PRIDE	Q9JKB1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000002289; ENSMUSP00000002289; ENSMUSG00000022111.
GeneID	50933.
KEGG	mmu:50933.
UCSC	uc007uvw.1. mouse.
Organism-specific databases
CTD	7347.
MGI	MGI:1355274. Uchl3.
Phylogenomic databases
eggNOG	NOG327708.
GeneTree	ENSGT00510000046640.
HOGENOM	HOG000182400.
HOVERGEN	HBG075483.
InParanoid	Q9JKB1.
KO	K05609.
OMA	QTEAPNI.
OrthoDB	EOG4HX51V.
Enzyme and pathway databases
BRENDA	3.4.19.12. 3474.
Gene expression databases
Bgee	Q9JKB1.
Genevestigator	Q9JKB1.
GermOnline	ENSMUSG00000022111. 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	Q9JKB1.
NextBio	307977.
SOURCE	Search...

Entry information

Entry name

UCHL3_MOUSE

Accession

Primary (citable) accession number: Q9JKB1
Secondary accession number(s): Q9EQX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	September 26, 2001
Last modified:	April 3, 2013
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

PTM databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents