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Protein

Ubiquitin carboxyl-terminal hydrolase isozyme L3

Gene

UCHL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

Identified as a tumor-specific antigen in colon cancer.

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

  • NEDD8-specific protease activity Source: Reactome
  • peptidase activity Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB
  • ubiquitin binding Source: UniProtKB

GO - Biological processi

  • post-translational protein modification Source: Reactome
  • protein catabolic process Source: UniProtKB
  • protein deubiquitination Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: InterPro

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway

Enzyme and pathway databases

BRENDAi3.4.19.12 2681
ReactomeiR-HSA-5689603 UCH proteinases
R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-8951664 Neddylation
SABIO-RKiP15374

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

EuPathDBiHostDB:ENSG00000118939.17
HGNCiHGNC:12515 UCHL3
MIMi603090 gene
neXtProtiNX_P15374

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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-2DPAGEiIPI00011250

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, 90 interactors
DIPiDIP-29135N
IntActiP15374, 12 interactors
MINTiP15374
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
InterProiView protein in InterPro
IPR001578 Peptidase_C12_UCH
IPR036959 Peptidase_C12_UCH_sf
PANTHERiPTHR10589 PTHR10589, 1 hit
PfamiView protein in Pfam
PF01088 Peptidase_C12, 1 hit
PRINTSiPR00707 UBCTHYDRLASE
PROSITEiView protein in PROSITE
PS00140 UCH_1, 1 hit

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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiUCHL3_HUMAN
AccessioniPrimary (citable) accession number: P15374
Secondary accession number(s): B2R970, Q5TBK8, Q6IBE9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: May 23, 2018
This is version 180 of the entry and version 1 of the sequence. See 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

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

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