ID UBP14_HUMAN Reviewed; 494 AA. AC P54578; B7Z4N8; J3QRZ5; Q53XY5; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 216. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 14; DE EC=3.4.19.12; DE AltName: Full=Deubiquitinating enzyme 14; DE AltName: Full=Ubiquitin thioesterase 14; DE AltName: Full=Ubiquitin-specific-processing protease 14; GN Name=USP14; Synonyms=TGT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RA Deshpande K.L., Katze J.R.; RT "tRNA-guanine transglycosylase cDNA from human placenta."; RL Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J., RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-308 (ISOFORM 2). RC TISSUE=T-cell; RA Heil O., Ebert L., Hennig S., Henze S., Radelof U., Schneider D., Korn B.; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP INTERACTION WITH FANCC. RX PubMed=14499622; DOI=10.1016/s0014-4827(03)00261-1; RA Reuter T.Y., Medhurst A.L., Waisfisz Q., Zhi Y., Herterich S., Hoehn H., RA Gross H.J., Joenje H., Hoatlin M.E., Mathew C.G., Huber P.A.; RT "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in RT transcription regulation, cell signaling, oxidative metabolism, and RT cellular transport."; RL Exp. Cell Res. 289:211-221(2003). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=T-cell; RX PubMed=19367720; DOI=10.1021/pr800500r; RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.; RT "Phosphorylation analysis of primary human T lymphocytes using sequential RT IMAC and titanium oxide enrichment."; RL J. Proteome Res. 7:5167-5176(2008). RN [9] RP ASSOCIATION WITH THE 26S PROTEASOME, AND FUNCTION. RX PubMed=18162577; DOI=10.1091/mbc.e07-10-1040; RA Koulich E., Li X., DeMartino G.N.; RT "Relative structural and functional roles of multiple deubiquitylating RT proteins associated with mammalian 26S proteasome."; RL Mol. Biol. Cell 19:1072-1082(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP FUNCTION, AND INTERACTION WITH ERN1. RX PubMed=19135427; DOI=10.1016/j.bbrc.2008.12.182; RA Nagai A., Kadowaki H., Maruyama T., Takeda K., Nishitoh H., Ichijo H.; RT "USP14 inhibits ER-associated degradation via interaction with IRE1alpha."; RL Biochem. Biophys. Res. Commun. 379:995-1000(2009). RN [12] RP INTERACTION WITH CXCR4, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19106094; DOI=10.1074/jbc.m808507200; RA Mines M.A., Goodwin J.S., Limbird L.E., Cui F.F., Fan G.H.; RT "Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced RT CXCR4 degradation and chemotaxis but not ERK activation."; RL J. Biol. Chem. 284:5742-5752(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-449, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143 AND THR-235, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-52; SER-143; SER-237; SER-302 RP AND SER-432, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143 AND THR-235, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP FUNCTION, AND INTERACTION WITH TRIM14. RX PubMed=27666593; DOI=10.1016/j.molcel.2016.08.025; RA Chen M., Meng Q., Qin Y., Liang P., Tan P., He L., Zhou Y., Chen Y., RA Huang J., Wang R.F., Cui J.; RT "TRIM14 inhibits cGAS degradation mediated by selective autophagy receptor RT p62 to promote innate immune responses."; RL Mol. Cell 64:105-119(2016). RN [21] RP FUNCTION. RX PubMed=28396413; DOI=10.1073/pnas.1701734114; RA Kuo C.L., Goldberg A.L.; RT "Ubiquitinated proteins promote the association of proteasomes with the RT deubiquitinating enzyme Usp14 and the ubiquitin ligase Ube3c."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E3404-E3413(2017). RN [22] RP FUNCTION, INTERACTION WITH TRIM14, AND SUBCELLULAR LOCATION. RX PubMed=35145029; DOI=10.1073/pnas.2113454119; RA Liu D., Zhao Z., She Y., Zhang L., Chen X., Ma L., Cui J.; RT "TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to RT epigenetically regulate inflammation."; RL Proc. Natl. Acad. Sci. U.S.A. 119:0-0(2022). RN [23] RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 91-494, CATALYTIC ACTIVITY, AND RP ACTIVE SITE. RX PubMed=16211010; DOI=10.1038/sj.emboj.7600832; RA Hu M., Li P., Song L., Jeffrey P.D., Chenova T.A., Wilkinson K.D., RA Cohen R.E., Shi Y.; RT "Structure and mechanisms of the proteasome-associated deubiquitinating RT enzyme USP14."; RL EMBO J. 24:3747-3756(2005). CC -!- FUNCTION: Proteasome-associated deubiquitinase which releases ubiquitin CC from the proteasome targeted ubiquitinated proteins (PubMed:35145029). CC Ensures the regeneration of ubiquitin at the proteasome CC (PubMed:18162577, PubMed:28396413). Is a reversibly associated subunit CC of the proteasome and a large fraction of proteasome-free protein CC exists within the cell (PubMed:18162577). Required for the degradation CC of the chemokine receptor CXCR4 which is critical for CXCL12-induced CC cell chemotaxis (PubMed:19106094). Serves also as a physiological CC inhibitor of endoplasmic reticulum-associated degradation (ERAD) under CC the non-stressed condition by inhibiting the degradation of unfolded CC endoplasmic reticulum proteins via interaction with ERN1 CC (PubMed:19135427). Indispensable for synaptic development and function CC at neuromuscular junctions (NMJs) (By similarity). Plays a role in the CC innate immune defense against viruses by stabilizing the viral DNA CC sensor CGAS and thus inhibiting its autophagic degradation CC (PubMed:27666593). Inhibits OPTN-mediated selective autophagic CC degradation of KDM4D and thereby negatively regulates H3K9me2 and CC H3K9me3 (PubMed:35145029). {ECO:0000250|UniProtKB:Q9JMA1, CC ECO:0000269|PubMed:18162577, ECO:0000269|PubMed:19106094, CC ECO:0000269|PubMed:19135427, ECO:0000269|PubMed:27666593, CC ECO:0000269|PubMed:28396413, ECO:0000269|PubMed:35145029}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:16211010}; CC -!- SUBUNIT: Homodimer (Potential). Associates with the 26S proteasome. CC Interacts with FANCC, CXCR4 and ERN1. Interacts with TRIM14; this CC interaction recruits USP14 to cleave ubiquitin chains of CGAS and KDM4D CC (PubMed:27666593, PubMed:35145029). {ECO:0000269|PubMed:14499622, CC ECO:0000269|PubMed:19106094, ECO:0000269|PubMed:19135427, CC ECO:0000269|PubMed:27666593, ECO:0000269|PubMed:35145029, ECO:0000305}. CC -!- INTERACTION: CC P54578; Q08209: PPP3CA; NbExp=3; IntAct=EBI-1048016, EBI-352922; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19106094}. Cell CC membrane {ECO:0000269|PubMed:19106094}; Peripheral membrane protein CC {ECO:0000269|PubMed:19106094}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P54578-1; Sequence=Displayed; CC Name=2; CC IsoId=P54578-2; Sequence=VSP_047343; CC Name=3; CC IsoId=P54578-3; Sequence=VSP_057292; CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP14/UBP6 subfamily. CC {ECO:0000305}. CC -!- CAUTION: Was originally thought to be a guanine tRNA- CC ribosyltransferase. {ECO:0000305, ECO:0000305|Ref.1}. CC -!- SEQUENCE CAUTION: CC Sequence=CR976282; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U30888; AAB60365.1; -; mRNA. DR EMBL; BT007183; AAP35847.1; -; mRNA. DR EMBL; AK297605; BAH12624.1; -; mRNA. DR EMBL; AP000845; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003556; AAH03556.1; -; mRNA. DR EMBL; CR976282; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS32780.1; -. [P54578-1] DR CCDS; CCDS32781.1; -. [P54578-2] DR PIR; G01932; G01932. DR RefSeq; NP_001032411.1; NM_001037334.1. [P54578-2] DR RefSeq; NP_005142.1; NM_005151.3. [P54578-1] DR PDB; 2AYN; X-ray; 3.20 A; A/B/C=91-494. DR PDB; 2AYO; X-ray; 3.50 A; A=91-494. DR PDB; 5GJQ; EM; 4.50 A; x=1-494. DR PDB; 6IIK; X-ray; 1.97 A; A/B=96-494. DR PDB; 6IIL; X-ray; 2.20 A; A/B=96-494. DR PDB; 6IIM; X-ray; 2.21 A; A/B=96-494. DR PDB; 6IIN; X-ray; 2.53 A; A/B=101-485. DR PDB; 6LVS; X-ray; 2.73 A; A/B/C/D/E/F=92-494. DR PDB; 7W37; EM; 3.00 A; x=1-494. DR PDB; 7W38; EM; 3.10 A; x=1-494. DR PDB; 7W39; EM; 3.20 A; x=1-494. DR PDB; 7W3A; EM; 3.50 A; x=1-494. DR PDB; 7W3B; EM; 3.60 A; x=1-494. DR PDB; 7W3C; EM; 3.40 A; x=1-494. DR PDB; 7W3F; EM; 3.30 A; x=1-494. DR PDB; 7W3G; EM; 3.20 A; x=1-494. DR PDB; 7W3H; EM; 3.20 A; x=1-494. DR PDB; 7W3I; EM; 3.50 A; x=1-494. DR PDB; 7W3J; EM; 3.50 A; x=1-494. DR PDB; 7W3K; EM; 3.60 A; x=1-494. DR PDB; 7W3M; EM; 3.50 A; x=1-494. DR PDBsum; 2AYN; -. DR PDBsum; 2AYO; -. DR PDBsum; 5GJQ; -. DR PDBsum; 6IIK; -. DR PDBsum; 6IIL; -. DR PDBsum; 6IIM; -. DR PDBsum; 6IIN; -. DR PDBsum; 6LVS; -. DR PDBsum; 7W37; -. DR PDBsum; 7W38; -. DR PDBsum; 7W39; -. DR PDBsum; 7W3A; -. DR PDBsum; 7W3B; -. DR PDBsum; 7W3C; -. DR PDBsum; 7W3F; -. DR PDBsum; 7W3G; -. DR PDBsum; 7W3H; -. DR PDBsum; 7W3I; -. DR PDBsum; 7W3J; -. DR PDBsum; 7W3K; -. DR PDBsum; 7W3M; -. DR AlphaFoldDB; P54578; -. DR BMRB; P54578; -. DR EMDB; EMD-32272; -. DR EMDB; EMD-32273; -. DR EMDB; EMD-32274; -. DR EMDB; EMD-32275; -. DR EMDB; EMD-32276; -. DR EMDB; EMD-32277; -. DR EMDB; EMD-32278; -. DR EMDB; EMD-32279; -. DR EMDB; EMD-32280; -. DR EMDB; EMD-32281; -. DR EMDB; EMD-32282; -. DR EMDB; EMD-32283; -. DR EMDB; EMD-32284; -. DR EMDB; EMD-9511; -. DR SMR; P54578; -. DR BioGRID; 114551; 502. DR IntAct; P54578; 51. DR MINT; P54578; -. DR STRING; 9606.ENSP00000261601; -. DR BindingDB; P54578; -. DR ChEMBL; CHEMBL1293295; -. DR DrugBank; DB12695; Phenethyl Isothiocyanate. DR GuidetoPHARMACOLOGY; 2429; -. DR MEROPS; C19.015; -. DR GlyCosmos; P54578; 2 sites, 1 glycan. DR GlyGen; P54578; 10 sites, 1 O-linked glycan (10 sites). DR iPTMnet; P54578; -. DR MetOSite; P54578; -. DR PhosphoSitePlus; P54578; -. DR SwissPalm; P54578; -. DR BioMuta; USP14; -. DR DMDM; 1729927; -. DR OGP; P54578; -. DR EPD; P54578; -. DR jPOST; P54578; -. DR MassIVE; P54578; -. DR MaxQB; P54578; -. DR PaxDb; 9606-ENSP00000261601; -. DR PeptideAtlas; P54578; -. DR ProteomicsDB; 56687; -. [P54578-1] DR ProteomicsDB; 6620; -. DR Pumba; P54578; -. DR Antibodypedia; 676; 356 antibodies from 35 providers. DR DNASU; 9097; -. DR Ensembl; ENST00000261601.8; ENSP00000261601.6; ENSG00000101557.15. [P54578-1] DR Ensembl; ENST00000400266.7; ENSP00000383125.3; ENSG00000101557.15. [P54578-3] DR Ensembl; ENST00000582707.5; ENSP00000464447.1; ENSG00000101557.15. [P54578-2] DR GeneID; 9097; -. DR KEGG; hsa:9097; -. DR MANE-Select; ENST00000261601.8; ENSP00000261601.6; NM_005151.4; NP_005142.1. DR UCSC; uc002kkf.2; human. [P54578-1] DR AGR; HGNC:12612; -. DR CTD; 9097; -. DR DisGeNET; 9097; -. DR GeneCards; USP14; -. DR HGNC; HGNC:12612; USP14. DR HPA; ENSG00000101557; Low tissue specificity. DR MIM; 607274; gene. DR neXtProt; NX_P54578; -. DR OpenTargets; ENSG00000101557; -. DR PharmGKB; PA37238; -. DR VEuPathDB; HostDB:ENSG00000101557; -. DR eggNOG; KOG1872; Eukaryota. DR GeneTree; ENSGT00390000009615; -. DR InParanoid; P54578; -. DR OMA; FKSDAEY; -. DR OrthoDB; 160664at2759; -. DR PhylomeDB; P54578; -. DR TreeFam; TF314494; -. DR PathwayCommons; P54578; -. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-9758274; Regulation of NF-kappa B signaling. DR SignaLink; P54578; -. DR SIGNOR; P54578; -. DR BioGRID-ORCS; 9097; 100 hits in 1167 CRISPR screens. DR ChiTaRS; USP14; human. DR EvolutionaryTrace; P54578; -. DR GeneWiki; USP14; -. DR GenomeRNAi; 9097; -. DR Pharos; P54578; Tchem. DR PRO; PR:P54578; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; P54578; Protein. DR Bgee; ENSG00000101557; Expressed in secondary oocyte and 221 other cell types or tissues. DR ExpressionAtlas; P54578; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProt. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW. DR GO; GO:0045202; C:synapse; IEA:Ensembl. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc. DR GO; GO:0101005; F:deubiquitinase activity; IMP:ParkinsonsUK-UCL. DR GO; GO:0004866; F:endopeptidase inhibitor activity; IMP:UniProtKB. DR GO; GO:0061578; F:K63-linked deubiquitinase activity; EXP:Reactome. DR GO; GO:0070628; F:proteasome binding; IDA:UniProtKB. DR GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:1904293; P:negative regulation of ERAD pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:InterPro. DR GO; GO:0016579; P:protein deubiquitination; IDA:FlyBase. DR GO; GO:0050920; P:regulation of chemotaxis; IMP:UniProtKB. DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB. DR CDD; cd02657; Peptidase_C19A; 1. DR CDD; cd16104; Ubl_USP14_like; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR001394; Peptidase_C19_UCH. DR InterPro; IPR000626; Ubiquitin-like_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR InterPro; IPR019954; Ubiquitin_CS. DR InterPro; IPR044635; UBP14-like. DR InterPro; IPR018200; USP_CS. DR InterPro; IPR028889; USP_dom. DR PANTHER; PTHR43982; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR43982:SF1; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 14; 1. DR Pfam; PF00443; UCH; 1. DR SMART; SM00213; UBQ; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS00299; UBIQUITIN_1; 1. DR PROSITE; PS50053; UBIQUITIN_2; 1. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. DR Genevisible; P54578; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; Cytoplasm; KW Hydrolase; Immunity; Innate immunity; Membrane; Phosphoprotein; Protease; KW Proteasome; Reference proteome; Thiol protease; Ubl conjugation pathway. FT CHAIN 1..494 FT /note="Ubiquitin carboxyl-terminal hydrolase 14" FT /id="PRO_0000080636" FT DOMAIN 4..80 FT /note="Ubiquitin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214" FT DOMAIN 105..483 FT /note="USP" FT ACT_SITE 114 FT /note="Nucleophile" FT /evidence="ECO:0000305|PubMed:16211010" FT ACT_SITE 435 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT MOD_RES 52 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 143 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19367720, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 148 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JMA1" FT MOD_RES 235 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:24275569" FT MOD_RES 237 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 302 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 432 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 449 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 55..65 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057292" FT VAR_SEQ 66..100 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_047343" FT STRAND 110..112 FT /evidence="ECO:0007829|PDB:6IIL" FT HELIX 114..124 FT /evidence="ECO:0007829|PDB:6IIK" FT HELIX 127..135 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 142..144 FT /evidence="ECO:0007829|PDB:6LVS" FT HELIX 147..165 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 167..170 FT /evidence="ECO:0007829|PDB:6IIK" FT HELIX 173..182 FT /evidence="ECO:0007829|PDB:6IIK" FT HELIX 184..187 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 191..193 FT /evidence="ECO:0007829|PDB:6LVS" FT HELIX 200..214 FT /evidence="ECO:0007829|PDB:6IIK" FT HELIX 242..247 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 249..259 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 266..273 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 275..278 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 280..282 FT /evidence="ECO:0007829|PDB:2AYN" FT HELIX 286..293 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 295..302 FT /evidence="ECO:0007829|PDB:6IIK" FT TURN 303..306 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 307..319 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 321..329 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 331..334 FT /evidence="ECO:0007829|PDB:6LVS" FT TURN 335..338 FT /evidence="ECO:0007829|PDB:6LVS" FT STRAND 339..342 FT /evidence="ECO:0007829|PDB:6LVS" FT STRAND 351..354 FT /evidence="ECO:0007829|PDB:6IIK" FT HELIX 356..358 FT /evidence="ECO:0007829|PDB:6IIK" FT HELIX 361..376 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 404..406 FT /evidence="ECO:0007829|PDB:6LVS" FT TURN 409..412 FT /evidence="ECO:0007829|PDB:2AYN" FT STRAND 414..429 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 435..443 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 446..451 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 454..458 FT /evidence="ECO:0007829|PDB:6IIK" FT HELIX 460..464 FT /evidence="ECO:0007829|PDB:6IIK" FT HELIX 465..467 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 469..472 FT /evidence="ECO:0007829|PDB:6IIK" FT STRAND 474..482 FT /evidence="ECO:0007829|PDB:6IIK" SQ SEQUENCE 494 AA; 56069 MW; E6D4679A86E9DF00 CRC64; MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN IKIKNGMTLL MMGSADALPE EPSAKTVFVE DMTEEQLASA MELPCGLTNL GNTCYMNATV QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH MAFPQFAEKG EQGQYLQQDA NECWIQMMRV LQQKLEAIED DSVKETDSSS ASAATPSKKK SLIDQFFGVE FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDMYELCT PELQEKMVSF RSKFKDLEDK KVNQQPNTSD KKSSPQKEVK YEPFSFADDI GSNNCGYYDL QAVLTHQGRS SSSGHYVSWV KRKQDEWIKF DDDKVSIVTP EDILRLSGGG DWHIAYVLLY GPRRVEIMEE ESEQ //