USP14

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} '''Ubiquitin-specific protease 14''' is an enzyme that in humans is encoded by the ''USP14'' gene.<ref name="Puente_2003">{{cite journal | vauthors = Puente XS, Sánchez LM, Overall CM, López-Otín C | title = Human and mouse proteases: a comparative genomic approach | journal = Nat Rev Genet | volume = 4 | issue = 7 | pages = 544–558 | date = Jul 2003 | pmid = 12838346 | doi = 10.1038/nrg1111 | s2cid = 2856065 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: USP14 ubiquitin specific peptidase 14 (tRNA-guanine transglycosylase) | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=9097 }}</ref>

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.<ref name="entrez" />

== Interactions ==

USP14 has been shown to interact with CXCR4.<ref name="Mines_2009">{{cite journal | vauthors = Mines MA, Goodwin JS, Limbird LE, Cui FF, Fan GH | title = Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK activation | journal = Journal of Biological Chemistry | volume = 284 | issue = 9 | pages = 5742–5752 | date = Feb 2009 | pmid = 19106094 | pmc = 2645827 | doi = 10.1074/jbc.M808507200 | doi-access = free }}</ref>

== Inhibitors == * IU1 and related compounds <ref>{{cite journal | vauthors = Wang F, Ning S, Yu B, Wang Y | title = USP14: Structure, Function, and Target Inhibition | journal = Frontiers in Pharmacology | volume = 12 | date = 2022 | pmid = 35069211 | pmc = 8766727 | doi = 10.3389/fphar.2021.801328 | article-number = 801328 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lim JJ, Noh S, Kang W, Hyun B, Lee BH, Hyun S | title = Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner | journal = Autophagy | volume = 20 | issue = 12 | pages = 2752–2768 | date = 2024 | pmid = 39113571 | doi = 10.1080/15548627.2024.2389607 | pmc = 11587835 }}</ref> * VLX1570 (non selective inhibitor of proteasome deubiquitinases) * Degrasyn (WP1130) (non selective deubiquitinase inhibitor acting at USP9, USP5, USP14, and UCH37)

== References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Wilson SM, Bhattacharyya B, Rachel RA, Coppola V, Tessarollo L, Householder DB, Fletcher CF, Miller RJ, Copeland NG, Jenkins NA | title = Synaptic defects in ataxia mice result from a mutation in Usp14, encoding a ubiquitin-specific protease. | journal = Nature Genetics | volume = 32 | issue = 3 | pages = 420–425 | date = Nov 2002 | pmid = 12368914 | doi = 10.1038/ng1006 | s2cid = 23542012 }} * {{cite journal | vauthors = D'Andrea A, Pellman D | title = Deubiquitinating enzymes: a new class of biological regulators. | journal = Crit. Rev. Biochem. Mol. Biol. | volume = 33 | issue = 5 | pages = 337–352 | year = 1999 | pmid = 9827704 | doi = 10.1080/10409239891204251 }} * {{cite journal | vauthors = Deshpande KL, Seubert PH, Tillman DM, Farkas WR, Katze JR | title = Cloning and characterization of cDNA encoding the rabbit tRNA-guanine transglycosylase 60-kilodalton subunit. | journal = Arch. Biochem. Biophys. | volume = 326 | issue = 1 | pages = 1–7 | date = Feb 1996 | pmid = 8579355 | doi = 10.1006/abbi.1996.0039 }} * {{cite journal | vauthors = Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA | title = Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport. | journal = Exp. Cell Res. | volume = 289 | issue = 2 | pages = 211–221 | date = Oct 2003 | pmid = 14499622 | doi = 10.1016/S0014-4827(03)00261-1 }} * {{cite journal | vauthors = Dennehey BK, Gutches DG, McConkey EH, Krauter KS | title = Inversion, duplication, and changes in gene context are associated with human chromosome 18 evolution. | journal = Genomics | volume = 83 | issue = 3 | pages = 493–501 | date = Mar 2004 | pmid = 14962675 | doi = 10.1016/j.ygeno.2003.08.017 }} * {{cite journal | vauthors = Hu M, Li P, Song L, Jeffrey PD, Chenova TA, Wilkinson KD, Cohen RE, Shi Y | title = Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. | journal = EMBO J. | volume = 24 | issue = 21 | pages = 3747–3756 | date = Nov 2005 | pmid = 16211010 | pmc = 1276716 | doi = 10.1038/sj.emboj.7600832 }} * {{cite journal | vauthors = Shinji S, Naito Z, Ishiwata S, Ishiwata T, Tanaka N, Furukawa K, Suzuki H, Seya T, Matsuda A, Katsuta M, Tajiri T | title = Ubiquitin-specific protease 14 expression in colorectal cancer is associated with liver and lymph node metastases. | journal = Oncol. Rep. | volume = 15 | issue = 3 | pages = 539–543 | date = Mar 2006 | pmid = 16465409 | doi = 10.3892/or.15.3.539 | doi-access = free }} * {{cite journal | vauthors = Crimmins S, Jin Y, Wheeler C, Huffman AK, Chapman C, Dobrunz LE, Levey A, Roth KA, Wilson JA, Wilson SM | title = Transgenic rescue of ataxia mice with neuronal-specific expression of ubiquitin-specific protease 14. | journal = J. Neurosci. | volume = 26 | issue = 44 | pages = 11423–11431 | date = Nov 2006 | pmid = 17079671 | pmc = 6674543 | doi = 10.1523/JNEUROSCI.3600-06.2006 | doi-access = free }} {{refend}}

== External links == * {{PDBe-KB2|P54578|Ubiquitin carboxyl-terminal hydrolase 14}}

Category:Genes on human chromosome 18