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Protein

Ubiquitin carboxyl-terminal hydrolase isozyme L3

Gene

UCHL3

Organism
Homo sapiens (Human)
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 and is associated with neurogenerative disorders.5 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).3 Publications

Enzyme regulationi

Inhibited by monoubiquitin and diubiquitin.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei95Nucleophile3 Publications1
Active sitei169Proton donorCurated1
Sitei184Important for enzyme activityBy similarity1

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:HS04261-MONOMER.
BRENDAi3.4.19.12. 2681.
ReactomeiR-HSA-5689603. UCH proteinases.
R-HSA-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
SABIO-RKP15374.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:12515. UCHL3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • extracellular exosome Source: UniProtKB
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi33D → A: Decreased interaction with diubiquitin. No accumulation of free diubiquitin. Decreased levels of polyubiquitinated lysozyme. 2 Publications1
Mutagenesisi95C → A: Increased interaction with diubiquitin. 3 Publications1
Mutagenesisi95C → S: Abolishes enzymatic activity. Increased interaction with diubiquitin. 3 Publications1

Organism-specific databases

DisGeNETi7347.
OpenTargetsiENSG00000118939.
PharmGKBiPA37162.

Chemistry databases

ChEMBLiCHEMBL6195.
GuidetoPHARMACOLOGYi2427.

Polymorphism and mutation databases

DMDMi136682.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002110611 – 230Ubiquitin carboxyl-terminal hydrolase isozyme L3Add BLAST230

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei130PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP15374.
MaxQBiP15374.
PaxDbiP15374.
PeptideAtlasiP15374.
PRIDEiP15374.

2D gel databases

OGPiP15374.
REPRODUCTION-2DPAGEIPI00011250.

PTM databases

iPTMnetiP15374.
PhosphoSitePlusiP15374.

Expressioni

Tissue specificityi

Highly expressed in heart, skeletal muscle, and testis.1 Publication

Gene expression databases

BgeeiENSG00000118939.
CleanExiHS_UCHL3.
ExpressionAtlasiP15374. baseline and differential.
GenevisibleiP15374. HS.

Organism-specific databases

HPAiCAB037139.
CAB037208.
HPA019678.

Interactioni

Subunit structurei

Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
SMAD1Q157972EBI-954554,EBI-1567153

GO - Molecular functioni

  • ubiquitin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113194. 87 interactors.
DIPiDIP-29135N.
IntActiP15374. 11 interactors.
MINTiMINT-2863935.
STRINGi9606.ENSP00000366819.

Chemistry databases

BindingDBiP15374.

Structurei

Secondary structure

1230
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi13 – 22Combined sources10
Beta strandi29 – 33Combined sources5
Helixi39 – 42Combined sources4
Beta strandi49 – 57Combined sources9
Helixi60 – 76Combined sources17
Helixi92 – 94Combined sources3
Helixi95 – 105Combined sources11
Helixi106 – 110Combined sources5
Helixi118 – 126Combined sources9
Helixi131 – 139Combined sources9
Helixi142 – 152Combined sources11
Beta strandi155 – 157Combined sources3
Beta strandi168 – 176Combined sources9
Beta strandi179 – 183Combined sources5
Beta strandi187 – 189Combined sources3
Beta strandi191 – 195Combined sources5
Turni198 – 200Combined sources3
Helixi201 – 215Combined sources15
Beta strandi223 – 229Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UCHX-ray1.80A1-230[»]
1XD3X-ray1.45A/C1-230[»]
ProteinModelPortaliP15374.
SMRiP15374.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15374.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni8 – 13Interaction with ubiquitin1 Publication6
Regioni152 – 159Interaction with ubiquitin1 Publication8
Regioni219 – 224Interaction with ubiquitin1 Publication6

Sequence similaritiesi

Belongs to the peptidase C12 family.Curated

Phylogenomic databases

eggNOGiKOG1415. Eukaryota.
ENOG4111HNA. LUCA.
GeneTreeiENSGT00510000046640.
HOGENOMiHOG000182400.
HOVERGENiHBG075483.
InParanoidiP15374.
KOiK05609.
OMAiVYGMEPE.
OrthoDBiEOG091G0LBS.
PhylomeDBiP15374.
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.

P15374-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGQRWLPLE ANPEVTNQFL KQLGLHPNWQ FVDVYGMDPE LLSMVPRPVC
60 70 80 90 100
AVLLLFPITE KYEVFRTEEE EKIKSQGQDV TSSVYFMKQT ISNACGTIGL
110 120 130 140 150
IHAIANNKDK MHFESGSTLK KFLEESVSMS PEERARYLEN YDAIRVTHET
160 170 180 190 200
SAHEGQTEAP SIDEKVDLHF IALVHVDGHL YELDGRKPFP INHGETSDET
210 220 230
LLEDAIEVCK KFMERDPDEL RFNAIALSAA
Length:230
Mass (Da):26,183
Last modified:April 1, 1990 - v1
Checksum:i8ACACE6E1D86FD55
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30496 mRNA. Translation: AAA36791.1.
BT019359 mRNA. Translation: AAV38166.1.
CR456855 mRNA. Translation: CAG33136.1.
AK313665 mRNA. Translation: BAG36417.1.
AL137244 Genomic DNA. Translation: CAI12419.1.
CH471093 Genomic DNA. Translation: EAW80542.1.
BC018125 mRNA. Translation: AAH18125.1.
CCDSiCCDS9453.1.
PIRiA40085.
RefSeqiNP_001257881.1. NM_001270952.1.
NP_005993.1. NM_006002.4.
UniGeneiHs.162241.
Hs.674394.

Genome annotation databases

EnsembliENST00000377595; ENSP00000366819; ENSG00000118939.
GeneIDi7347.
KEGGihsa:7347.
UCSCiuc001vjq.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30496 mRNA. Translation: AAA36791.1.
BT019359 mRNA. Translation: AAV38166.1.
CR456855 mRNA. Translation: CAG33136.1.
AK313665 mRNA. Translation: BAG36417.1.
AL137244 Genomic DNA. Translation: CAI12419.1.
CH471093 Genomic DNA. Translation: EAW80542.1.
BC018125 mRNA. Translation: AAH18125.1.
CCDSiCCDS9453.1.
PIRiA40085.
RefSeqiNP_001257881.1. NM_001270952.1.
NP_005993.1. NM_006002.4.
UniGeneiHs.162241.
Hs.674394.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UCHX-ray1.80A1-230[»]
1XD3X-ray1.45A/C1-230[»]
ProteinModelPortaliP15374.
SMRiP15374.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113194. 87 interactors.
DIPiDIP-29135N.
IntActiP15374. 11 interactors.
MINTiMINT-2863935.
STRINGi9606.ENSP00000366819.

Chemistry databases

BindingDBiP15374.
ChEMBLiCHEMBL6195.
GuidetoPHARMACOLOGYi2427.

Protein family/group databases

MEROPSiC12.003.

PTM databases

iPTMnetiP15374.
PhosphoSitePlusiP15374.

Polymorphism and mutation databases

DMDMi136682.

2D gel databases

OGPiP15374.
REPRODUCTION-2DPAGEIPI00011250.

Proteomic databases

EPDiP15374.
MaxQBiP15374.
PaxDbiP15374.
PeptideAtlasiP15374.
PRIDEiP15374.

Protocols and materials databases

DNASUi7347.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377595; ENSP00000366819; ENSG00000118939.
GeneIDi7347.
KEGGihsa:7347.
UCSCiuc001vjq.5. human.

Organism-specific databases

CTDi7347.
DisGeNETi7347.
GeneCardsiUCHL3.
HGNCiHGNC:12515. UCHL3.
HPAiCAB037139.
CAB037208.
HPA019678.
MIMi603090. gene.
neXtProtiNX_P15374.
OpenTargetsiENSG00000118939.
PharmGKBiPA37162.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1415. Eukaryota.
ENOG4111HNA. LUCA.
GeneTreeiENSGT00510000046640.
HOGENOMiHOG000182400.
HOVERGENiHBG075483.
InParanoidiP15374.
KOiK05609.
OMAiVYGMEPE.
OrthoDBiEOG091G0LBS.
PhylomeDBiP15374.
TreeFamiTF316166.

Enzyme and pathway databases

BioCyciZFISH:HS04261-MONOMER.
BRENDAi3.4.19.12. 2681.
ReactomeiR-HSA-5689603. UCH proteinases.
R-HSA-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
SABIO-RKP15374.

Miscellaneous databases

ChiTaRSiUCHL3. human.
EvolutionaryTraceiP15374.
GeneWikiiUCHL3.
GenomeRNAii7347.
PROiP15374.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118939.
CleanExiHS_UCHL3.
ExpressionAtlasiP15374. baseline and differential.
GenevisibleiP15374. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P15374
Secondary accession number(s): B2R970, Q5TBK8, Q6IBE9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 30, 2016
This is version 168 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Identified as a tumor-specific antigen in colon cancer.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. 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.