Biology:USP14
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Ubiquitin-specific protease 14 is an enzyme that in humans is encoded by the USP14 gene.[1][2]
This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. Mice with a mutation that results in reduced expression of the ortholog of this protein are retarded for growth, develop severe tremors by 2 to 3 weeks of age followed by hindlimb paralysis and death by 6 to 10 weeks of age. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[2]
Interactions
USP14 has been shown to interact with CXCR4.[3]
Inhibitors
- IU1 and related compounds [4][5]
- VLX1570 (non selective inhibitor of proteasome deubiquitinases)
- Degrasyn (WP1130) (non selective deubiquitinase inhibitor acting at USP9, USP5, USP14, and UCH37)
References
- ↑ "Human and mouse proteases: a comparative genomic approach". Nat Rev Genet 4 (7): 544–558. Jul 2003. doi:10.1038/nrg1111. PMID 12838346.
- ↑ 2.0 2.1 "Entrez Gene: USP14 ubiquitin specific peptidase 14 (tRNA-guanine transglycosylase)". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=9097.
- ↑ "Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK activation". Journal of Biological Chemistry 284 (9): 5742–5752. Feb 2009. doi:10.1074/jbc.M808507200. PMID 19106094.
- ↑ "USP14: Structure, Function, and Target Inhibition". Frontiers in Pharmacology 12. 2022. doi:10.3389/fphar.2021.801328. PMID 35069211.
- ↑ "Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner". Autophagy 20 (12): 2752–2768. 2024. doi:10.1080/15548627.2024.2389607. PMID 39113571.
Further reading
- "Synaptic defects in ataxia mice result from a mutation in Usp14, encoding a ubiquitin-specific protease.". Nature Genetics 32 (3): 420–425. Nov 2002. doi:10.1038/ng1006. PMID 12368914.
- "Deubiquitinating enzymes: a new class of biological regulators.". Crit. Rev. Biochem. Mol. Biol. 33 (5): 337–352. 1999. doi:10.1080/10409239891204251. PMID 9827704.
- "Cloning and characterization of cDNA encoding the rabbit tRNA-guanine transglycosylase 60-kilodalton subunit.". Arch. Biochem. Biophys. 326 (1): 1–7. Feb 1996. doi:10.1006/abbi.1996.0039. PMID 8579355.
- "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport.". Exp. Cell Res. 289 (2): 211–221. Oct 2003. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
- "Inversion, duplication, and changes in gene context are associated with human chromosome 18 evolution.". Genomics 83 (3): 493–501. Mar 2004. doi:10.1016/j.ygeno.2003.08.017. PMID 14962675.
- "Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14.". EMBO J. 24 (21): 3747–3756. Nov 2005. doi:10.1038/sj.emboj.7600832. PMID 16211010.
- "Ubiquitin-specific protease 14 expression in colorectal cancer is associated with liver and lymph node metastases.". Oncol. Rep. 15 (3): 539–543. Mar 2006. doi:10.3892/or.15.3.539. PMID 16465409.
- "Transgenic rescue of ataxia mice with neuronal-specific expression of ubiquitin-specific protease 14.". J. Neurosci. 26 (44): 11423–11431. Nov 2006. doi:10.1523/JNEUROSCI.3600-06.2006. PMID 17079671.
External links
- Overview of all the structural information available in the PDB for UniProt: P54578 (Ubiquitin carboxyl-terminal hydrolase 14) at the PDBe-KB.
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