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Protein

Ubiquitin carboxyl-terminal hydrolase isozyme L5

Gene

UCHL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • proteasome binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processDNA damage, DNA recombination, DNA repair, Transcription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000116750.13
HGNCiHGNC:19678 UCHL5
MIMi610667 gene
neXtProtiNX_Q9Y5K5

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, 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
ProteomicsDBi86430
86431 [Q9Y5K5-2]
86432 [Q9Y5K5-3]
86433 [Q9Y5K5-4]

PTM databases

iPTMnetiQ9Y5K5
PhosphoSitePlusiQ9Y5K5

Expressioni

Gene expression databases

BgeeiENSG00000116750
CleanExiHS_UCHL5
ExpressionAtlasiQ9Y5K5 baseline and differential
GenevisibleiQ9Y5K5 HS

Organism-specific databases

HPAiHPA005908
HPA006069
HPA075383

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

Show more details

Protein-protein interaction databases

BioGridi119509, 223 interactors
ComplexPortaliCPX-846 INO80 chromatin remodeling complex
DIPiDIP-42671N
IntActiQ9Y5K5, 66 interactors
MINTiQ9Y5K5
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 – 244Combined sources18
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
InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001578 Peptidase_C12_UCH
IPR036959 Peptidase_C12_UCH_sf
IPR017390 Ubiquitinyl_hydrolase_UCH37
IPR033837 UCH37
PANTHERiPTHR10589 PTHR10589, 1 hit
PfamiView protein in Pfam
PF01088 Peptidase_C12, 1 hit
PIRSFiPIRSF038120 Ubiquitinyl_hydrolase_UCH37, 1 hit
PRINTSiPR00707 UBCTHYDRLASE
SUPFAMiSSF54001 SSF54001, 1 hit

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 → F2 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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiUCHL5_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5K5
Secondary accession number(s): Q5LJA6
, Q5LJA7, Q8TBS4, Q96BJ9, Q9H1W5, Q9P0I3, Q9UQN2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 30, 2006
Last modified: June 20, 2018
This is version 163 of the entry and version 3 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

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