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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)DescriptionActionsGraphical viewLength
Active sitei95NucleophilePROSITE-ProRule annotation1
Active sitei169Proton donorPROSITE-ProRule annotation1
Sitei184Important for enzyme activityBy similarity1

GO - Molecular functioni

  • peptidase activity Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: GO_Central
  • ubiquitin binding Source: MGI
  • ubiquitinyl hydrolase activity Source: MGI

GO - Biological processi

  • adult walking behavior Source: MGI
  • cellular response to insulin stimulus Source: UniProtKB
  • eating behavior Source: MGI
  • positive regulation of fat cell differentiation Source: UniProtKB
  • protein catabolic process Source: UniProtKB
  • protein deubiquitination Source: MGI
  • retina development in camera-type eye Source: MGI
  • 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.
ReactomeiR-MMU-5689603. UCH proteinases.
R-MMU-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1355274. Uchl3.

Subcellular locationi

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Mutagenesisi95C → 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 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002110621 – 230Ubiquitin carboxyl-terminal hydrolase isozyme L3Add BLAST230

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei130PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9JKB1.
MaxQBiQ9JKB1.
PaxDbiQ9JKB1.
PeptideAtlasiQ9JKB1.
PRIDEiQ9JKB1.

2D gel databases

REPRODUCTION-2DPAGEIPI00311369.
Q9JKB1.

PTM databases

iPTMnetiQ9JKB1.
PhosphoSitePlusiQ9JKB1.

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

BgeeiENSMUSG00000022111.
GenevisibleiQ9JKB1. MM.

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi206165. 2 interactors.
IntActiQ9JKB1. 2 interactors.
MINTiMINT-1856010.
STRINGi10090.ENSMUSP00000002289.

Chemistry databases

BindingDBiQ9JKB1.

Structurei

3D structure databases

ProteinModelPortaliQ9JKB1.
SMRiQ9JKB1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni8 – 13Interaction with ubiquitinBy similarity6
Regioni152 – 159Interaction with ubiquitinBy similarity8
Regioni219 – 224Interaction with ubiquitinBy similarity6

Sequence similaritiesi

Belongs to the peptidase C12 family.Curated

Phylogenomic databases

eggNOGiKOG1415. Eukaryota.
ENOG4111HNA. LUCA.
GeneTreeiENSGT00510000046640.
HOGENOMiHOG000182400.
HOVERGENiHBG075483.
InParanoidiQ9JKB1.
KOiK05609.
OMAiVYGMEPE.
OrthoDBiEOG091G0LBS.
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)DescriptionActionsGraphical viewLength
Sequence conflicti205 – 207AIE → VIK in AAF64193 (PubMed:10713173).Curated3

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi206165. 2 interactors.
IntActiQ9JKB1. 2 interactors.
MINTiMINT-1856010.
STRINGi10090.ENSMUSP00000002289.

Chemistry databases

BindingDBiQ9JKB1.

Protein family/group databases

MEROPSiC12.003.

PTM databases

iPTMnetiQ9JKB1.
PhosphoSitePlusiQ9JKB1.

2D gel databases

REPRODUCTION-2DPAGEIPI00311369.
Q9JKB1.

Proteomic databases

EPDiQ9JKB1.
MaxQBiQ9JKB1.
PaxDbiQ9JKB1.
PeptideAtlasiQ9JKB1.
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

eggNOGiKOG1415. Eukaryota.
ENOG4111HNA. LUCA.
GeneTreeiENSGT00510000046640.
HOGENOMiHOG000182400.
HOVERGENiHBG075483.
InParanoidiQ9JKB1.
KOiK05609.
OMAiVYGMEPE.
OrthoDBiEOG091G0LBS.
PhylomeDBiQ9JKB1.
TreeFamiTF316166.

Enzyme and pathway databases

BRENDAi3.4.19.12. 3474.
ReactomeiR-MMU-5689603. UCH proteinases.
R-MMU-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.

Miscellaneous databases

PROiQ9JKB1.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022111.
GenevisibleiQ9JKB1. MM.

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...

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: November 30, 2016
This is version 137 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

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 one 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.