Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9JKB1 (UCHL3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length230 AA.
Sequence statusComplete.
Protein existenceEvidence 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.9 Ref.11

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.9 Ref.10

Sequence similarities

Belongs to the peptidase C12 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 230230Ubiquitin carboxyl-terminal hydrolase isozyme L3
PRO_0000211062

Regions

Region8 – 136Interaction with ubiquitin By similarity
Region152 – 1598Interaction with ubiquitin By similarity
Region219 – 2246Interaction with ubiquitin By similarity

Sites

Active site951Nucleophile By similarity
Active site1691Proton donor By similarity
Site1841Important for enzyme activity By similarity

Amino acid modifications

Modified residue1301Phosphoserine By similarity

Experimental info

Mutagenesis951C → 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.9
Sequence conflict205 – 2073AIE → VIK in AAF64193. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9JKB1 [UniParc].

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

FASTA23026,152
        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' 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]"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.
[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(2010) [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(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.
CCDSCCDS27313.1.
PIRJC7688.
RefSeqNP_057932.2. NM_016723.2.
UniGeneMm.275970.

3D structure databases

ProteinModelPortalQ9JKB1.
SMRQ9JKB1. Positions 2-230.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid206165. 1 interaction.
IntActQ9JKB1. 2 interactions.
MINTMINT-1856010.

Chemistry

BindingDBQ9JKB1.

Protein family/group databases

MEROPSC12.003.

PTM databases

PhosphoSiteQ9JKB1.

2D gel databases

REPRODUCTION-2DPAGEIPI00311369.
Q9JKB1.

Proteomic databases

MaxQBQ9JKB1.
PaxDbQ9JKB1.
PRIDEQ9JKB1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000002289; ENSMUSP00000002289; ENSMUSG00000022111.
GeneID50933.
KEGGmmu:50933.
UCSCuc007uvw.1. mouse.

Organism-specific databases

CTD7347.
MGIMGI:1355274. Uchl3.

Phylogenomic databases

eggNOGNOG327708.
GeneTreeENSGT00510000046640.
HOGENOMHOG000182400.
HOVERGENHBG075483.
InParanoidQ9JKB1.
KOK05609.
OrthoDBEOG7S7SFK.
PhylomeDBQ9JKB1.
TreeFamTF316166.

Enzyme and pathway databases

BRENDA3.4.19.12. 3474.

Gene expression databases

BgeeQ9JKB1.
GenevestigatorQ9JKB1.

Family and domain databases

Gene3D3.40.532.10. 1 hit.
InterProIPR001578. Peptidase_C12_UCH.
[Graphical view]
PANTHERPTHR10589. PTHR10589. 1 hit.
PfamPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PRINTSPR00707. UBCTHYDRLASE.
PROSITEPS00140. UCH_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio307977.
PROQ9JKB1.
SOURCESearch...

Entry information

Entry nameUCHL3_MOUSE
AccessionPrimary (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: July 9, 2014
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

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