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Protein

Ubiquitin carboxyl-terminal hydrolase isozyme L5

Gene

UCHL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1.2 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

Activated by ADRM1. Inhibited by interaction with NFRKB.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei88NucleophileCurated1
Active sitei164Proton donorBy similarity1
Sitei179Important for enzyme activityBy similarity1

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • proteasome binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

DNA damage, DNA recombination, DNA repair, Transcription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:HS04047-MONOMER.
BRENDAi3.4.19.12. 2681.
ReactomeiR-HSA-2173788. Downregulation of TGF-beta receptor signaling.
R-HSA-5689603. UCH proteinases.
SignaLinkiQ9Y5K5.
SIGNORiQ9Y5K5.

Protein family/group databases

MEROPSiC12.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase isozyme L5 (EC:3.4.19.12)
Short name:
UCH-L5
Alternative name(s):
Ubiquitin C-terminal hydrolase UCH37
Ubiquitin thioesterase L5
Gene namesi
Name:UCHL5
Synonyms:UCH37
ORF Names:AD-019, CGI-70
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:19678. UCHL5.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • cytosolic proteasome complex Source: Ensembl
  • Ino80 complex Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus, Proteasome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi88C → A: Abolishes enzymatic activity. 1 Publication1

Organism-specific databases

DisGeNETi51377.
OpenTargetsiENSG00000116750.
PharmGKBiPA134916228.

Chemistry databases

ChEMBLiCHEMBL3407316.

Polymorphism and mutation databases

BioMutaiUCHL5.
DMDMi108936023.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002110661 – 329Ubiquitin carboxyl-terminal hydrolase isozyme L5Add BLAST329

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei47N6-succinyllysineBy similarity1
Modified residuei158N6-acetyllysineCombined sources1
Modified residuei289N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9Y5K5.
PaxDbiQ9Y5K5.
PeptideAtlasiQ9Y5K5.
PRIDEiQ9Y5K5.

PTM databases

iPTMnetiQ9Y5K5.
PhosphoSitePlusiQ9Y5K5.

Expressioni

Gene expression databases

BgeeiENSG00000116750.
CleanExiHS_UCHL5.
ExpressionAtlasiQ9Y5K5. baseline and differential.
GenevisibleiQ9Y5K5. HS.

Organism-specific databases

HPAiHPA005908.
HPA006069.

Interactioni

Subunit structurei

Component of the 19S (PA700) regulatory complex of the 26S proteasome. Interacts with ADRM1 and NFRKB; in vitro ADRM1 and NFRKB compete for interaction with UCHL5. Component of the INO80 complex; specifically part of a complex module associated with N-terminus of INO80.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ACTR8Q9H9813EBI-1051183,EBI-769597
ADRM1Q1618620EBI-1051183,EBI-954387
INO80EQ8NBZ07EBI-1051183,EBI-769401
NFRKBQ6P4R812EBI-1051183,EBI-2511210
PSMA6P609004EBI-1051183,EBI-357793
PSMD2Q132005EBI-1051183,EBI-357648
PSMD4P550365EBI-1051183,EBI-359318
TFPTP0C1Z63EBI-1051183,EBI-1245626
ZBED1O960063EBI-1051183,EBI-740037

GO - Molecular functioni

  • proteasome binding Source: UniProtKB

Protein-protein interaction databases

BioGridi119509. 218 interactors.
DIPiDIP-42671N.
IntActiQ9Y5K5. 64 interactors.
MINTiMINT-2823912.
STRINGi9606.ENSP00000356425.

Chemistry databases

BindingDBiQ9Y5K5.

Structurei

Secondary structure

1329
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi15 – 24Combined sources10
Beta strandi28 – 34Combined sources7
Turni40 – 46Combined sources7
Beta strandi48 – 56Combined sources9
Beta strandi65 – 68Combined sources4
Helixi72 – 75Combined sources4
Helixi85 – 87Combined sources3
Helixi88 – 98Combined sources11
Helixi109 – 118Combined sources10
Helixi123 – 131Combined sources9
Helixi134 – 142Combined sources9
Helixi159 – 162Combined sources4
Beta strandi163 – 171Combined sources9
Beta strandi174 – 178Combined sources5
Beta strandi182 – 184Combined sources3
Beta strandi186 – 190Combined sources5
Beta strandi193 – 195Combined sources3
Helixi197 – 213Combined sources17
Beta strandi218 – 225Combined sources8
Helixi227 – 243Combined sources17
Helixi255 – 289Combined sources35
Helixi293 – 305Combined sources13
Helixi309 – 318Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A7SX-ray2.20A1-228[»]
3IHRX-ray2.95A1-329[»]
3RIIX-ray2.00A/B1-228[»]
3RISX-ray2.40A/B/C/D1-240[»]
3TB3X-ray2.30A/B1-227[»]
4UELX-ray2.30A1-329[»]
4UEMX-ray2.82A1-329[»]
4UF5X-ray3.70A1-329[»]
4UF6X-ray3.69A/D/G/J1-329[»]
4WLPX-ray3.10A5-322[»]
ProteinModelPortaliQ9Y5K5.
SMRiQ9Y5K5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y5K5.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni313 – 329Interaction with ADRM1Add BLAST17

Sequence similaritiesi

Belongs to the peptidase C12 family.Curated

Phylogenomic databases

eggNOGiKOG2778. Eukaryota.
ENOG410XP0P. LUCA.
GeneTreeiENSGT00510000046560.
HOVERGENiHBG056021.
InParanoidiQ9Y5K5.
KOiK05610.
PhylomeDBiQ9Y5K5.
TreeFamiTF313976.

Family and domain databases

CDDicd02255. Peptidase_C12. 1 hit.
Gene3Di3.40.532.10. 1 hit.
InterProiIPR001578. Peptidase_C12_UCH.
IPR017390. Ubiquitinyl_hydrolase_UCH37.
IPR033837. UCH37.
[Graphical view]
PANTHERiPTHR10589. PTHR10589. 1 hit.
PfamiPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PIRSFiPIRSF038120. Ubiquitinyl_hydrolase_UCH37. 1 hit.
PRINTSiPR00707. UBCTHYDRLASE.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9Y5K5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTGNAGEWCL MESDPGVFTE LIKGFGCRGA QVEEIWSLEP ENFEKLKPVH
60 70 80 90 100
GLIFLFKWQP GEEPAGSVVQ DSRLDTIFFA KQVINNACAT QAIVSVLLNC
110 120 130 140 150
THQDVHLGET LSEFKEFSQS FDAAMKGLAL SNSDVIRQVH NSFARQQMFE
160 170 180 190 200
FDTKTSAKEE DAFHFVSYVP VNGRLYELDG LREGPIDLGA CNQDDWISAV
210 220 230 240 250
RPVIEKRIQK YSEGEIRFNL MAIVSDRKMI YEQKIAELQR QLAEEEPMDT
260 270 280 290 300
DQGNSMLSAI QSEVAKNQML IEEEVQKLKR YKIENIRRKH NYLPFIMELL
310 320
KTLAEHQQLI PLVEKAKEKQ NAKKAQETK
Length:329
Mass (Da):37,607
Last modified:May 30, 2006 - v3
Checksum:iDF307347D48C9D0F
GO
Isoform 2 (identifier: Q9Y5K5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     246-246: Missing.
     316-329: AKEKQNAKKAQETK → GK

Show »
Length:316
Mass (Da):36,079
Checksum:i2552C52F2CFC1E9C
GO
Isoform 3 (identifier: Q9Y5K5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     246-246: Missing.

Show »
Length:328
Mass (Da):37,478
Checksum:i2ECFB3AB11D07E72
GO
Isoform 4 (identifier: Q9Y5K5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     246-246: Missing.
     316-329: AKEKQNAKKAQETK → FEKHFEKTLLGK

Note: No experimental confirmation available.
Show »
Length:326
Mass (Da):37,353
Checksum:iA3570094A7EC96CB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6G → V in AAD34065 (PubMed:10810093).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011613197I → F.2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005253246Missing in isoform 2, isoform 3 and isoform 4. 4 Publications1
Alternative sequenceiVSP_005254316 – 329AKEKQ…AQETK → GK in isoform 2. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_017062316 – 329AKEKQ…AQETK → FEKHFEKTLLGK in isoform 4. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF147717 mRNA. Translation: AAD31528.1.
AF151828 mRNA. Translation: AAD34065.1.
AF157320 mRNA. Translation: AAF67486.1.
BT006790 mRNA. Translation: AAP35436.1.
AL136370 Genomic DNA. Translation: CAI10829.1.
AL136370 Genomic DNA. Translation: CAI10830.1.
AL136370 Genomic DNA. Translation: CAI10831.1.
AL136370 Genomic DNA. Translation: CAI10833.1.
BC015521 mRNA. Translation: AAH15521.1.
BC025369 mRNA. Translation: AAH25369.1.
CCDSiCCDS1378.1. [Q9Y5K5-1]
CCDS55668.1. [Q9Y5K5-3]
CCDS55669.1. [Q9Y5K5-2]
CCDS55670.1. [Q9Y5K5-4]
RefSeqiNP_001186190.1. NM_001199261.1. [Q9Y5K5-3]
NP_001186191.1. NM_001199262.1. [Q9Y5K5-4]
NP_001186192.1. NM_001199263.1. [Q9Y5K5-2]
NP_057068.1. NM_015984.3. [Q9Y5K5-1]
UniGeneiHs.145469.

Genome annotation databases

EnsembliENST00000367448; ENSP00000356418; ENSG00000116750. [Q9Y5K5-4]
ENST00000367449; ENSP00000356419; ENSG00000116750. [Q9Y5K5-2]
ENST00000367454; ENSP00000356424; ENSG00000116750. [Q9Y5K5-3]
ENST00000367455; ENSP00000356425; ENSG00000116750. [Q9Y5K5-1]
GeneIDi51377.
KEGGihsa:51377.
UCSCiuc001gsm.4. human. [Q9Y5K5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF147717 mRNA. Translation: AAD31528.1.
AF151828 mRNA. Translation: AAD34065.1.
AF157320 mRNA. Translation: AAF67486.1.
BT006790 mRNA. Translation: AAP35436.1.
AL136370 Genomic DNA. Translation: CAI10829.1.
AL136370 Genomic DNA. Translation: CAI10830.1.
AL136370 Genomic DNA. Translation: CAI10831.1.
AL136370 Genomic DNA. Translation: CAI10833.1.
BC015521 mRNA. Translation: AAH15521.1.
BC025369 mRNA. Translation: AAH25369.1.
CCDSiCCDS1378.1. [Q9Y5K5-1]
CCDS55668.1. [Q9Y5K5-3]
CCDS55669.1. [Q9Y5K5-2]
CCDS55670.1. [Q9Y5K5-4]
RefSeqiNP_001186190.1. NM_001199261.1. [Q9Y5K5-3]
NP_001186191.1. NM_001199262.1. [Q9Y5K5-4]
NP_001186192.1. NM_001199263.1. [Q9Y5K5-2]
NP_057068.1. NM_015984.3. [Q9Y5K5-1]
UniGeneiHs.145469.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3A7SX-ray2.20A1-228[»]
3IHRX-ray2.95A1-329[»]
3RIIX-ray2.00A/B1-228[»]
3RISX-ray2.40A/B/C/D1-240[»]
3TB3X-ray2.30A/B1-227[»]
4UELX-ray2.30A1-329[»]
4UEMX-ray2.82A1-329[»]
4UF5X-ray3.70A1-329[»]
4UF6X-ray3.69A/D/G/J1-329[»]
4WLPX-ray3.10A5-322[»]
ProteinModelPortaliQ9Y5K5.
SMRiQ9Y5K5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119509. 218 interactors.
DIPiDIP-42671N.
IntActiQ9Y5K5. 64 interactors.
MINTiMINT-2823912.
STRINGi9606.ENSP00000356425.

Chemistry databases

BindingDBiQ9Y5K5.
ChEMBLiCHEMBL3407316.

Protein family/group databases

MEROPSiC12.005.

PTM databases

iPTMnetiQ9Y5K5.
PhosphoSitePlusiQ9Y5K5.

Polymorphism and mutation databases

BioMutaiUCHL5.
DMDMi108936023.

Proteomic databases

EPDiQ9Y5K5.
PaxDbiQ9Y5K5.
PeptideAtlasiQ9Y5K5.
PRIDEiQ9Y5K5.

Protocols and materials databases

DNASUi51377.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367448; ENSP00000356418; ENSG00000116750. [Q9Y5K5-4]
ENST00000367449; ENSP00000356419; ENSG00000116750. [Q9Y5K5-2]
ENST00000367454; ENSP00000356424; ENSG00000116750. [Q9Y5K5-3]
ENST00000367455; ENSP00000356425; ENSG00000116750. [Q9Y5K5-1]
GeneIDi51377.
KEGGihsa:51377.
UCSCiuc001gsm.4. human. [Q9Y5K5-1]

Organism-specific databases

CTDi51377.
DisGeNETi51377.
GeneCardsiUCHL5.
HGNCiHGNC:19678. UCHL5.
HPAiHPA005908.
HPA006069.
MIMi610667. gene.
neXtProtiNX_Q9Y5K5.
OpenTargetsiENSG00000116750.
PharmGKBiPA134916228.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2778. Eukaryota.
ENOG410XP0P. LUCA.
GeneTreeiENSGT00510000046560.
HOVERGENiHBG056021.
InParanoidiQ9Y5K5.
KOiK05610.
PhylomeDBiQ9Y5K5.
TreeFamiTF313976.

Enzyme and pathway databases

BioCyciZFISH:HS04047-MONOMER.
BRENDAi3.4.19.12. 2681.
ReactomeiR-HSA-2173788. Downregulation of TGF-beta receptor signaling.
R-HSA-5689603. UCH proteinases.
SignaLinkiQ9Y5K5.
SIGNORiQ9Y5K5.

Miscellaneous databases

ChiTaRSiUCHL5. human.
EvolutionaryTraceiQ9Y5K5.
GeneWikiiUbiquitin_carboxyl-terminal_hydrolase_L5.
GenomeRNAii51377.
PROiQ9Y5K5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000116750.
CleanExiHS_UCHL5.
ExpressionAtlasiQ9Y5K5. baseline and differential.
GenevisibleiQ9Y5K5. HS.

Family and domain databases

CDDicd02255. Peptidase_C12. 1 hit.
Gene3Di3.40.532.10. 1 hit.
InterProiIPR001578. Peptidase_C12_UCH.
IPR017390. Ubiquitinyl_hydrolase_UCH37.
IPR033837. UCH37.
[Graphical view]
PANTHERiPTHR10589. PTHR10589. 1 hit.
PfamiPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PIRSFiPIRSF038120. Ubiquitinyl_hydrolase_UCH37. 1 hit.
PRINTSiPR00707. UBCTHYDRLASE.
ProtoNetiSearch...

Entry informationi

Entry nameiUCHL5_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5K5
Secondary accession number(s): Q5LJA6
, Q5LJA7, Q8TBS4, Q96BJ9, Q9H1W5, Q9P0I3, Q9UQN2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 30, 2006
Last modified: November 30, 2016
This is version 152 of the entry and version 3 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.