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Protein

Ubiquitin carboxyl-terminal hydrolase isozyme L3

Gene

Uchl3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.6 Publications

Catalytic activityi

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 regulationi

Inhibited by monoubiquitin and diubiquitin.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei95 – 951NucleophilePROSITE-ProRule annotation
Active sitei169 – 1691Proton donorPROSITE-ProRule annotation
Sitei184 – 1841Important for enzyme activityBy similarity

GO - Molecular functioni

  1. peptidase activity Source: UniProtKB
  2. ubiquitin binding Source: MGI
  3. ubiquitin-specific protease activity Source: InterPro

GO - Biological processi

  1. adult walking behavior Source: MGI
  2. cellular response to insulin stimulus Source: UniProtKB
  3. eating behavior Source: MGI
  4. positive regulation of fat cell differentiation Source: UniProtKB
  5. protein catabolic process Source: UniProtKB
  6. protein deubiquitination Source: MGI
  7. retina development in camera-type eye Source: MGI
  8. ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi3.4.19.12. 3474.

Protein family/group databases

MEROPSiC12.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase isozyme L3 (EC:3.4.19.12)
Short name:
UCH-L3
Alternative name(s):
Ubiquitin thioesterase L3
Gene namesi
Name:Uchl3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1355274. Uchl3.

Subcellular locationi

Cytoplasm 2 Publications

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. extracellular vesicular exosome Source: MGI
  3. nucleoplasm Source: MGI
  4. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

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.5 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi95 – 951C → S: No increase in phosphorylation of AKT1, FOXO1 and INSR. No increased expression of SLC2A1, FABP4 nor ADIPOQ. Impaired formation of large lipid droplets. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 230230Ubiquitin carboxyl-terminal hydrolase isozyme L3PRO_0000211062Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei130 – 1301PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9JKB1.
PaxDbiQ9JKB1.
PRIDEiQ9JKB1.

2D gel databases

REPRODUCTION-2DPAGEIPI00311369.
Q9JKB1.

PTM databases

PhosphoSiteiQ9JKB1.

Expressioni

Tissue specificityi

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.4 Publications

Developmental stagei

Expressed at E8.5 in structures required for skeletal patterning. Highly expressed at E11, and decreases markedly from E15.2 Publications

Gene expression databases

BgeeiQ9JKB1.
GenevestigatoriQ9JKB1.

Interactioni

Subunit structurei

Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates.By similarity

Protein-protein interaction databases

BioGridi206165. 1 interaction.
IntActiQ9JKB1. 2 interactions.
MINTiMINT-1856010.

Structurei

3D structure databases

ProteinModelPortaliQ9JKB1.
SMRiQ9JKB1. Positions 2-230.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni8 – 136Interaction with ubiquitinBy similarity
Regioni152 – 1598Interaction with ubiquitinBy similarity
Regioni219 – 2246Interaction with ubiquitinBy similarity

Sequence similaritiesi

Belongs to the peptidase C12 family.Curated

Phylogenomic databases

eggNOGiNOG327708.
GeneTreeiENSGT00510000046640.
HOGENOMiHOG000182400.
HOVERGENiHBG075483.
InParanoidiQ9JKB1.
KOiK05609.
OMAiVYGMEPE.
OrthoDBiEOG7S7SFK.
PhylomeDBiQ9JKB1.
TreeFamiTF316166.

Family and domain databases

Gene3Di3.40.532.10. 1 hit.
InterProiIPR001578. Peptidase_C12_UCH.
[Graphical view]
PANTHERiPTHR10589. PTHR10589. 1 hit.
PfamiPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PRINTSiPR00707. UBCTHYDRLASE.
PROSITEiPS00140. UCH_1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9JKB1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGQRWLPLE ANPEVTNQFL KQLGLHPNWQ FVDVYGMEPE LLSMVPRPVC
60 70 80 90 100
AVLLLFPITE KYEVFRTEEE EKIKSQGQDV TSSVYFMKQT ISNACGTIGL
110 120 130 140 150
IHAIANNKDK MHFESGSTLK KFLEESVSMS PEERAKFLEN YDAIRVTHET
160 170 180 190 200
SAHEGQTEAP SIDEKVDLHF IALVHVDGHL YELDGRKPFP INHGKTSDET
210 220 230
LLEDAIEVCK KFMERDPDEL RFNAIALSAA
Length:230
Mass (Da):26,152
Last modified:September 26, 2001 - v2
Checksum:iF147991F3ED69AC3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti205 – 2073AIE → VIK in AAF64193 (PubMed:10713173).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF247358 mRNA. Translation: AAF64193.1.
AB033370 mRNA. Translation: BAB20094.1.
BC048481 mRNA. Translation: AAH48481.1.
CCDSiCCDS27313.1.
PIRiJC7688.
RefSeqiNP_057932.2. NM_016723.2.
UniGeneiMm.275970.

Genome annotation databases

EnsembliENSMUST00000002289; ENSMUSP00000002289; ENSMUSG00000022111.
GeneIDi50933.
KEGGimmu:50933.
UCSCiuc007uvw.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF247358 mRNA. Translation: AAF64193.1.
AB033370 mRNA. Translation: BAB20094.1.
BC048481 mRNA. Translation: AAH48481.1.
CCDSiCCDS27313.1.
PIRiJC7688.
RefSeqiNP_057932.2. NM_016723.2.
UniGeneiMm.275970.

3D structure databases

ProteinModelPortaliQ9JKB1.
SMRiQ9JKB1. Positions 2-230.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi206165. 1 interaction.
IntActiQ9JKB1. 2 interactions.
MINTiMINT-1856010.

Chemistry

BindingDBiQ9JKB1.

Protein family/group databases

MEROPSiC12.003.

PTM databases

PhosphoSiteiQ9JKB1.

2D gel databases

REPRODUCTION-2DPAGEIPI00311369.
Q9JKB1.

Proteomic databases

MaxQBiQ9JKB1.
PaxDbiQ9JKB1.
PRIDEiQ9JKB1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000002289; ENSMUSP00000002289; ENSMUSG00000022111.
GeneIDi50933.
KEGGimmu:50933.
UCSCiuc007uvw.1. mouse.

Organism-specific databases

CTDi7347.
MGIiMGI:1355274. Uchl3.

Phylogenomic databases

eggNOGiNOG327708.
GeneTreeiENSGT00510000046640.
HOGENOMiHOG000182400.
HOVERGENiHBG075483.
InParanoidiQ9JKB1.
KOiK05609.
OMAiVYGMEPE.
OrthoDBiEOG7S7SFK.
PhylomeDBiQ9JKB1.
TreeFamiTF316166.

Enzyme and pathway databases

BRENDAi3.4.19.12. 3474.

Miscellaneous databases

NextBioi307977.
PROiQ9JKB1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JKB1.
GenevestigatoriQ9JKB1.

Family and domain databases

Gene3Di3.40.532.10. 1 hit.
InterProiIPR001578. Peptidase_C12_UCH.
[Graphical view]
PANTHERiPTHR10589. PTHR10589. 1 hit.
PfamiPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PRINTSiPR00707. UBCTHYDRLASE.
PROSITEiPS00140. UCH_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1999) [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(2000) [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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  4. 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(2004) [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(2005) [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(2006) [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(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ENAC RECYCLING, SUBCELLULAR LOCATION.
  9. "Ubiquitin carboxyl-terminal hydrolase l3 promotes insulin signaling and adipogenesis."
    Suzuki M., Setsuie R., Wada K.
    Endocrinology 150:5230-5239(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION IN ADIPOGENESIS AND INSULIN SIGNALING, MUTAGENESIS OF CYS-95.
  10. "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(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  11. "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(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiUCHL3_MOUSE
AccessioniPrimary (citable) accession number: Q9JKB1
Secondary accession number(s): Q9EQX7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: September 26, 2001
Last modified: March 4, 2015
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.