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Details on Person UniProt:P45974 USP5
| Class:Id | ReferenceGeneProduct:66828 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-858 added on Fri February 6 2015;initiator methionine:1 for 66828 removed on Fri Nov 03 2023;initiator methionine: for 66828 added on Fri Nov 03 2023;initiator methionine: for 66828 removed on Fri Aug 15 2025;initiator methionine:1 for 66828 added on Fri Aug 15 2025 |
| _displayName | UniProt:P45974 USP5 |
| _timestamp | 2025-08-15 21:04:26 |
| chain | initiator methionine:1 chain:2-858 |
| checksum | E99CB7CDFA682C65 |
| comment | FUNCTION 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. |
| description | recommendedName: 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 |
| geneName | USP5 ISOT |
| identifier | P45974 |
| isSequenceChanged | FALSE |
| keyword | 3D-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 |
| name | USP5 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8961074] ENSEMBL:ENSG00000111667 USP5 [Homo sapiens] |
| secondaryIdentifier | UBP5_HUMAN D3DUS7 D3DUS8 Q96J22 |
| sequenceLength | 858 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:155497] UniProt:P45974-2 USP5 [Homo sapiens] [ReferenceIsoform:404079] UniProt:P45974-1 USP5 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:5690104] USP5 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8961203] USP5 [extracellular region] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P45974 USP5 (66828)
