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Details on Person UniProt:P45974-1 USP5

Class:IdReferenceIsoform:404079
_chainChangeLoginitiator methionine:1 added on Fri February 6 2015;chain:2-858 added on Fri February 6 2015;initiator methionine:1 for 404079 removed on Fri Nov 03 2023;initiator methionine: for 404079 added on Fri Nov 03 2023;initiator methionine: for 404079 removed on Fri Aug 15 2025;initiator methionine:1 for 404079 added on Fri Aug 15 2025
_displayNameUniProt:P45974-1 USP5
_timestamp2025-08-15 21:04:26
chaininitiator methionine:1
chain:2-858
checksumE99CB7CDFA682C65
commentFUNCTION Deubiquitinating enzyme that participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. Affects thereby important cellular signaling pathways such as NF-kappa-B, Wnt/beta-catenin, and cytokine production by regulating ubiquitin-dependent protein degradation. Participates in the activation of the Wnt signaling pathway by promoting FOXM1 deubiquitination and stabilization that induces the recruitment of beta-catenin to Wnt target gene promoter (PubMed:26912724). Regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains (PubMed:29567855). Promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein (PubMed:37534934). Affects T-cell biology by stabilizing the inhibitory receptor on T-cells PDC1 (PubMed:37208329). Acts as a negative regulator of autophagy by regulating ULK1 at both protein and mRNA levels (PubMed:37607937). Acts also as a negative regulator of type I interferon production by simultaneously removing both 'Lys-48'-linked unanchored and 'Lys-63'-linked anchored polyubiquitin chains on the transcription factor IRF3 (PubMed:39761299). Modulates the stability of DNA mismatch repair protein MLH1 and counteracts the effect of the ubiquitin ligase UBR4 (PubMed:39032648). Upon activation by insulin, it gets phosphorylated through mTORC1-mediated phosphorylation to enhance YTHDF1 stability by removing 'Lys-11'-linked polyubiquitination (PubMed:39900921). May also deubiquitinate other substrates such as the calcium channel CACNA1H (By similarity).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).SUBUNIT Homodimer (PubMed:39900921). Interacts with TRIML1.INTERACTION The UBP-type zinc finger domain interacts selectively with an unmodified C-terminus of the proximal ubiquitin. Both UBA domains are involved in polyubiquitin recognition.PTM Ubiquitinated by SMURF1; leading to proteasomal degradation.PTM SUMOylated at Lys-113; SUMOylation affects the interaction with Cav3.2 channels.MISCELLANEOUS The UBP-type zinc finger domain crystallizes as a dimer linked by a disulfide bond between the Cys-195 residues of both molecules, but there is no evidence that the full-length USP5 exists as a dimer.SIMILARITY Belongs to the peptidase C19 family.
created[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
descriptionrecommendedName: Ubiquitin carboxyl-terminal hydrolase 5 ecNumber evidence="13 17"3.4.19.12 alternativeName: Deubiquitinating enzyme 5 alternativeName: Isopeptidase T alternativeName: Ubiquitin thioesterase 5 alternativeName: Ubiquitin-specific-processing protease 5
geneNameUSP5
ISOT
identifierP45974
isoformParent
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Alternative splicing
Cytoplasm
Direct protein sequencing
Disulfide bond
Hydrolase
Isopeptide bond
Metal-binding
Nucleus
Phosphoprotein
Protease
Proteomics identification
Reference proteome
Repeat
Thiol protease
Ubl conjugation
Ubl conjugation pathway
Zinc
Zinc-finger
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameUSP5
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8961074] ENSEMBL:ENSG00000111667 USP5 [Homo sapiens]
secondaryIdentifierUBP5_HUMAN
D3DUS7
D3DUS8
Q96J22
sequenceLength858
species[Species:48887] Homo sapiens
variantIdentifierP45974-1
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No pathways have been reviewed or authored by UniProt:P45974-1 USP5 (404079)