USP14

USP14
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2AYN, 2AYO
Identifiers
Aliases	USP14, TGT, ubiquitin specific peptidase 14, Ubp6
External IDs	OMIM: 607274; MGI: 1928898; HomoloGene: 3780; GeneCards: USP14; OMA:USP14 - orthologs
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18p11.32 Start 158,383 bp[1] End 214,629 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 A1|18 4.91 cM Start 9,993,066 bp[2] End 10,045,119 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte tibialis anterior muscle deltoid muscle pons thoracic diaphragm trabecular bone trigeminal ganglion lateral nuclear group of thalamus skin of hip spinal ganglia Top expressed in tail of embryo dorsomedial hypothalamic nucleus ventromedial nucleus dentate gyrus of hippocampal formation granule cell epiblast lateral septal nucleus mammillary body lateral hypothalamus superior frontal gyrus maxillary prominence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cysteine-type peptidase activity proteasome binding peptidase activity protein binding thiol-dependent deubiquitinase cysteine-type endopeptidase activity endopeptidase inhibitor activity hydrolase activity tRNA guanylyltransferase activity Cellular component membrane plasma membrane synapse cell surface proteasome complex extracellular exosome cytoplasm cytosol cytoplasmic vesicle nucleus Biological process regulation of proteasomal protein catabolic process regulation of chemotaxis ubiquitin-dependent protein catabolic process proteolysis negative regulation of ER-associated ubiquitin-dependent protein catabolic process chemical synaptic transmission negative regulation of endopeptidase activity protein deubiquitination immune system process innate immune response tRNA 5'-end processing Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9097 59025 Ensembl ENSG00000101557 ENSMUSG00000047879 UniProt P54578 Q9JMA1 RefSeq (mRNA) NM_005151 NM_001037334 NM_001038589 NM_021522 NM_001360884 RefSeq (protein) NP_001032411 NP_005142 NP_001033678 NP_067497 NP_001347813 Location (UCSC) Chr 18: 0.16 – 0.21 Mb Chr 18: 9.99 – 10.05 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ubiquitin-specific protease 14 is an enzyme that in humans is encoded by the USP14 gene.^[5][6]

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.^[6]

Interactions

USP14 has been shown to interact with CXCR4.^[7]

Inhibitors

• IU1 and related compounds ^[8][9]
• VLX1570 (non selective inhibitor of proteasome deubiquitinases)
• Degrasyn (WP1130) (non selective deubiquitinase inhibitor acting at USP9, USP5, USP14, and UCH37)

References

1. GRCh38: Ensembl release 89: ENSG00000101557 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000047879 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Puente XS, Sánchez LM, Overall CM, López-Otín C (Jul 2003). "Human and mouse proteases: a comparative genomic approach". Nat Rev Genet. 4 (7): 544–558. doi:10.1038/nrg1111. PMID 12838346. S2CID 2856065.
6. "Entrez Gene: USP14 ubiquitin specific peptidase 14 (tRNA-guanine transglycosylase)".
7. Mines MA, Goodwin JS, Limbird LE, Cui FF, Fan GH (Feb 2009). "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. doi:10.1074/jbc.M808507200. PMC 2645827. PMID 19106094.
8. Wang F, Ning S, Yu B, Wang Y (2022). "USP14: Structure, Function, and Target Inhibition". Frontiers in Pharmacology. 12 801328. doi:10.3389/fphar.2021.801328. PMC 8766727. PMID 35069211.
9. Lim JJ, Noh S, Kang W, Hyun B, Lee BH, Hyun S (2024). "Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner". Autophagy. 20 (12): 2752–2768. doi:10.1080/15548627.2024.2389607. PMC 11587835. PMID 39113571.

Further reading

• Wilson SM, Bhattacharyya B, Rachel RA, Coppola V, Tessarollo L, Householder DB, et al. (Nov 2002). "Synaptic defects in ataxia mice result from a mutation in Usp14, encoding a ubiquitin-specific protease". Nature Genetics. 32 (3): 420–425. doi:10.1038/ng1006. PMID 12368914. S2CID 23542012.
• D'Andrea A, Pellman D (1999). "Deubiquitinating enzymes: a new class of biological regulators". Crit. Rev. Biochem. Mol. Biol. 33 (5): 337–352. doi:10.1080/10409239891204251. PMID 9827704.
• Deshpande KL, Seubert PH, Tillman DM, Farkas WR, Katze JR (Feb 1996). "Cloning and characterization of cDNA encoding the rabbit tRNA-guanine transglycosylase 60-kilodalton subunit". Arch. Biochem. Biophys. 326 (1): 1–7. doi:10.1006/abbi.1996.0039. PMID 8579355.
• Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, et al. (Oct 2003). "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. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
• Dennehey BK, Gutches DG, McConkey EH, Krauter KS (Mar 2004). "Inversion, duplication, and changes in gene context are associated with human chromosome 18 evolution". Genomics. 83 (3): 493–501. doi:10.1016/j.ygeno.2003.08.017. PMID 14962675.
• Hu M, Li P, Song L, Jeffrey PD, Chenova TA, Wilkinson KD, et al. (Nov 2005). "Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14". EMBO J. 24 (21): 3747–3756. doi:10.1038/sj.emboj.7600832. PMC 1276716. PMID 16211010.
• Shinji S, Naito Z, Ishiwata S, Ishiwata T, Tanaka N, Furukawa K, et al. (Mar 2006). "Ubiquitin-specific protease 14 expression in colorectal cancer is associated with liver and lymph node metastases". Oncol. Rep. 15 (3): 539–543. doi:10.3892/or.15.3.539. PMID 16465409.
• Crimmins S, Jin Y, Wheeler C, Huffman AK, Chapman C, Dobrunz LE, et al. (Nov 2006). "Transgenic rescue of ataxia mice with neuronal-specific expression of ubiquitin-specific protease 14". J. Neurosci. 26 (44): 11423–11431. doi:10.1523/JNEUROSCI.3600-06.2006. PMC 6674543. 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.