NAT10_HUMAN
ID NAT10_HUMAN Reviewed; 1025 AA.
AC Q9H0A0; B4DFD5; E7ESU4; E9PMN9; Q86WK5; Q9C0F4; Q9HA61; Q9NVF2;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=RNA cytidine acetyltransferase {ECO:0000255|HAMAP-Rule:MF_03211, ECO:0000303|PubMed:25411247};
DE EC=2.3.1.- {ECO:0000255|HAMAP-Rule:MF_03211, ECO:0000269|PubMed:25411247, ECO:0000269|PubMed:30449621};
DE AltName: Full=18S rRNA cytosine acetyltransferase {ECO:0000255|HAMAP-Rule:MF_03211, ECO:0000303|PubMed:25653167};
DE AltName: Full=N-acetyltransferase 10 {ECO:0000255|HAMAP-Rule:MF_03211};
DE AltName: Full=N-acetyltransferase-like protein {ECO:0000303|PubMed:14592445};
DE Short=hALP {ECO:0000303|PubMed:14592445};
GN Name=NAT10 {ECO:0000255|HAMAP-Rule:MF_03211};
GN Synonyms=ALP {ECO:0000303|PubMed:14592445, ECO:0000303|PubMed:17631499},
GN KIAA1709 {ECO:0000303|PubMed:11214970};
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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-461.
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-461.
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP HIS-461.
RC TISSUE=Cerebellum, and Mammary gland;
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=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-461.
RC TISSUE=Brain;
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 [MRNA] OF 154-1025, FUNCTION, SUBCELLULAR LOCATION, AND
RP VARIANT HIS-461.
RC TISSUE=Cervix carcinoma;
RX PubMed=14592445; DOI=10.1016/j.bbrc.2003.09.235;
RA Lv J., Liu H., Wang Q., Tang Z., Hou L., Zhang B.;
RT "Molecular cloning of a novel human gene encoding histone
RT acetyltransferase-like protein involved in transcriptional activation of
RT hTERT.";
RL Biochem. Biophys. Res. Commun. 311:506-513(2003).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH SUN1.
RX PubMed=17631499; DOI=10.1074/jbc.m703098200;
RA Chi Y.-H., Haller K., Peloponese J.-M. Jr., Jeang K.-T.;
RT "Histone acetyltransferase hALP and nuclear membrane protein hsSUN1
RT function in de-condensation of mitotic chromosomes.";
RL J. Biol. Chem. 282:27447-27458(2007).
RN [9]
RP FUNCTION, AND INTERACTION WITH TERT.
RX PubMed=18082603; DOI=10.1016/j.molcel.2007.09.023;
RA Fu D., Collins K.;
RT "Purification of human telomerase complexes identifies factors involved in
RT telomerase biogenesis and telomere length regulation.";
RL Mol. Cell 28:773-785(2007).
RN [10]
RP INDUCTION BY GENOTOXIC AGENTS.
RX PubMed=17180247; DOI=10.1007/s11010-006-9390-5;
RA Liu H., Ling Y., Gong Y., Sun Y., Hou L., Zhang B.;
RT "DNA damage induces N-acetyltransferase NAT10 gene expression through
RT transcriptional activation.";
RL Mol. Cell. Biochem. 300:249-258(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-934; SER-984 AND SER-987, AND
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 [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19303003; DOI=10.1016/j.yexcr.2009.03.007;
RA Shen Q., Zheng X., McNutt M.A., Guang L., Sun Y., Wang J., Gong Y., Hou L.,
RA Zhang B.;
RT "NAT10, a nucleolar protein, localizes to the midbody and regulates
RT cytokinesis and acetylation of microtubules.";
RL Exp. Cell Res. 315:1653-1667(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-426, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-716; SER-934; SER-984 AND
RP SER-987, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25411247; DOI=10.1074/jbc.c114.602698;
RA Ito S., Horikawa S., Suzuki T., Kawauchi H., Tanaka Y., Suzuki T.,
RA Suzuki T.;
RT "Human NAT10 is an ATP-dependent RNA acetyltransferase responsible for N4-
RT acetylcytidine formation in 18 S ribosomal RNA (rRNA).";
RL J. Biol. Chem. 289:35724-35730(2014).
RN [16]
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-641.
RX PubMed=24786082; DOI=10.1126/science.1252651;
RA Larrieu D., Britton S., Demir M., Rodriguez R., Jackson S.P.;
RT "Chemical inhibition of NAT10 corrects defects of laminopathic cells.";
RL Science 344:527-532(2014).
RN [17]
RP FUNCTION, INTERACTION WITH THUMPD1, AND SUBCELLULAR LOCATION.
RX PubMed=25653167; DOI=10.1093/nar/gkv075;
RA Sharma S., Langhendries J.L., Watzinger P., Koetter P., Entian K.D.,
RA Lafontaine D.L.;
RT "Yeast Kre33 and human NAT10 are conserved 18S rRNA cytosine
RT acetyltransferases that modify tRNAs assisted by the adaptor
RT Tan1/THUMPD1.";
RL Nucleic Acids Res. 43:2242-2258(2015).
RN [18]
RP FUNCTION.
RX PubMed=26882543; DOI=10.15252/embr.201540505;
RA Liu X., Tan Y., Zhang C., Zhang Y., Zhang L., Ren P., Deng H., Luo J.,
RA Ke Y., Du X.;
RT "NAT10 regulates p53 activation through acetylating p53 at K120 and
RT ubiquitinating Mdm2.";
RL EMBO Rep. 17:349-366(2016).
RN [19]
RP FUNCTION, ACETYLATION AT LYS-426, AND MUTAGENESIS OF LYS-426.
RX PubMed=27993683; DOI=10.1016/j.bbrc.2016.12.092;
RA Cai S., Liu X., Zhang C., Xing B., Du X.;
RT "Autoacetylation of NAT10 is critical for its function in rRNA
RT transcription activation.";
RL Biochem. Biophys. Res. Commun. 483:624-629(2017).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30449621; DOI=10.1016/j.cell.2018.10.030;
RA Arango D., Sturgill D., Alhusaini N., Dillman A.A., Sweet T.J., Hanson G.,
RA Hosogane M., Sinclair W.R., Nanan K.K., Mandler M.D., Fox S.D.,
RA Zengeya T.T., Andresson T., Meier J.L., Coller J., Oberdoerffer S.;
RT "Acetylation of cytidine in mRNA promotes translation efficiency.";
RL Cell 0:0-0(2018).
RN [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=30165671; DOI=10.1093/nar/gky777;
RA Liu X., Cai S., Zhang C., Liu Z., Luo J., Xing B., Du X.;
RT "Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA
RT biogenesis to autophagy upon energy stress.";
RL Nucleic Acids Res. 46:9601-9616(2018).
RN [22]
RP FUNCTION.
RX PubMed=31722219; DOI=10.1016/j.celrep.2019.10.028;
RA Wang T., Zou Y., Huang N., Teng J., Chen J.;
RT "CCDC84 Acetylation Oscillation Regulates Centrosome Duplication by
RT Modulating HsSAS-6 Degradation.";
RL Cell Rep. 29:2078-2091.e5(2019).
RN [23]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-461, AND IDENTIFICATION BY MASS
RP 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).
CC -!- FUNCTION: RNA cytidine acetyltransferase that catalyzes the formation
CC of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs
CC (PubMed:25411247, PubMed:25653167, PubMed:30449621). Catalyzes ac4C
CC modification of a broad range of mRNAs, enhancing mRNA stability and
CC translation (PubMed:30449621). mRNA ac4C modification is frequently
CC present within wobble cytidine sites and promotes translation
CC efficiency (PubMed:30449621). Mediates the formation of ac4C at
CC position 1842 in 18S rRNA (PubMed:25411247). May also catalyze the
CC formation of ac4C at position 1337 in 18S rRNA (By similarity).
CC Required for early nucleolar cleavages of precursor rRNA at sites A0,
CC A1 and A2 during 18S rRNA synthesis (PubMed:25411247, PubMed:25653167).
CC Catalyzes the formation of ac4C in serine and leucine tRNAs (By
CC similarity). Requires the tRNA-binding adapter protein THUMPD1 for full
CC tRNA acetyltransferase activity but not for 18S rRNA acetylation
CC (PubMed:25653167). In addition to RNA acetyltransferase activity, also
CC able to acetylate lysine residues of proteins, such as histones,
CC microtubules, p53/TP53 and MDM2, in vitro (PubMed:14592445,
CC PubMed:17631499, PubMed:19303003, PubMed:26882543, PubMed:27993683,
CC PubMed:30165671). The relevance of the protein lysine acetyltransferase
CC activity is however unsure in vivo (PubMed:30449621). Activates
CC telomerase activity by stimulating the transcription of TERT, and may
CC also regulate telomerase function by affecting the balance of
CC telomerase subunit assembly, disassembly, and localization
CC (PubMed:14592445, PubMed:18082603). Involved in the regulation of
CC centrosome duplication by acetylating CENATAC during mitosis, promoting
CC SASS6 proteasome degradation (PubMed:31722219).
CC {ECO:0000250|UniProtKB:P53914, ECO:0000269|PubMed:14592445,
CC ECO:0000269|PubMed:17631499, ECO:0000269|PubMed:18082603,
CC ECO:0000269|PubMed:19303003, ECO:0000269|PubMed:25411247,
CC ECO:0000269|PubMed:25653167, ECO:0000269|PubMed:26882543,
CC ECO:0000269|PubMed:27993683, ECO:0000269|PubMed:30165671,
CC ECO:0000269|PubMed:30449621, ECO:0000269|PubMed:31722219}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cytidine in 18S rRNA + acetyl-CoA + ATP + H2O = ADP + an
CC N(4)-acetylcytidine in 18S rRNA + CoA + H(+) + phosphate;
CC Xref=Rhea:RHEA:51424, Rhea:RHEA-COMP:13575, Rhea:RHEA-COMP:13576,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:74900, ChEBI:CHEBI:82748, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03211,
CC ECO:0000269|PubMed:25411247};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cytidine in tRNA + acetyl-CoA + ATP + H2O = ADP + an N(4)-
CC acetylcytidine in tRNA + CoA + H(+) + phosphate;
CC Xref=Rhea:RHEA:53876, Rhea:RHEA-COMP:13670, Rhea:RHEA-COMP:13671,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:74900, ChEBI:CHEBI:82748, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03211};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cytidine in mRNA + acetyl-CoA + ATP + H2O = ADP + an N(4)-
CC acetylcytidine in mRNA + CoA + H(+) + phosphate;
CC Xref=Rhea:RHEA:58480, Rhea:RHEA-COMP:15145, Rhea:RHEA-COMP:15146,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:74900, ChEBI:CHEBI:82748, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:30449621};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58481;
CC Evidence={ECO:0000269|PubMed:30449621};
CC -!- ACTIVITY REGULATION: Specifically inhibited by remodelin (4-[2-(2-
CC cyclopentylidenehydrazinyl)-4-thiazolyl]-benzonitrile,
CC monohydrobromide), a hydrobromide salt molecule (PubMed:24786082).
CC Remodelin can improve nuclear architecture, chromatin organization and
CC fitness of cells from patients suffering from Hutchinson-Gilford
CC progeria syndrome (HGPS); molecular mechanisms explaining the relation
CC between NAT10 activity and nuclear architecture are however unclear
CC (PubMed:24786082). {ECO:0000269|PubMed:24786082}.
CC -!- SUBUNIT: Interacts with THUMPD1 (PubMed:25653167). Interacts with SUN1
CC (via N-terminus) (PubMed:17631499). Interacts with TERT
CC (PubMed:18082603). {ECO:0000255|HAMAP-Rule:MF_03211,
CC ECO:0000269|PubMed:17631499, ECO:0000269|PubMed:18082603,
CC ECO:0000269|PubMed:25653167}.
CC -!- INTERACTION:
CC Q9H0A0; P15880: RPS2; NbExp=2; IntAct=EBI-876527, EBI-443446;
CC Q9H0A0; Q9NXG2: THUMPD1; NbExp=2; IntAct=EBI-876527, EBI-5462248;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000255|HAMAP-
CC Rule:MF_03211, ECO:0000269|PubMed:12429849,
CC ECO:0000269|PubMed:14592445, ECO:0000269|PubMed:19303003,
CC ECO:0000269|PubMed:24786082, ECO:0000269|PubMed:25653167,
CC ECO:0000269|PubMed:30165671}. Midbody {ECO:0000255|HAMAP-Rule:MF_03211,
CC ECO:0000269|PubMed:19303003}. Note=Nucleolar in interphase and
CC redistributes to the perichromosomal layer and to the midbody during
CC telophase. {ECO:0000269|PubMed:19303003}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H0A0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H0A0-2; Sequence=VSP_054018;
CC -!- INDUCTION: Transcriptionally activated by genotoxic agents; possible
CC role in DNA damage and induction of cellular resistance to genotoxic
CC agents. {ECO:0000269|PubMed:17180247}.
CC -!- PTM: Acetylation at Lys-426 is required to activation of rRNA
CC transcription (PubMed:27993683). May be autoacetylated; however ability
CC to autoacetylate in vivo requires additional evidences
CC (PubMed:27993683). {ECO:0000269|PubMed:27993683}.
CC -!- SIMILARITY: Belongs to the RNA cytidine acetyltransferase family. NAT10
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03211}.
CC -!- CAUTION: A number of papers have reported some protein lysine
CC acetyltransferase activity in vitro (PubMed:14592445, PubMed:17631499,
CC PubMed:19303003, PubMed:26882543, PubMed:27993683, PubMed:30165671).
CC However, most experiments have been performed in vitro using a protein
CC construct lacking the RNA-binding region at the terminus
CC (PubMed:14592445, PubMed:17631499, PubMed:19303003). Recent evidence
CC suggests that NAT10 mainly acts as a RNA cytidine acetyltransferase in
CC vivo (PubMed:30449621). {ECO:0000269|PubMed:14592445,
CC ECO:0000269|PubMed:17631499, ECO:0000269|PubMed:19303003,
CC ECO:0000269|PubMed:26882543, ECO:0000269|PubMed:27993683,
CC ECO:0000269|PubMed:30165671, ECO:0000269|PubMed:30449621}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO49126.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB21800.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB051496; BAB21800.1; ALT_INIT; mRNA.
DR EMBL; AL136882; CAB66816.1; -; mRNA.
DR EMBL; AK001636; BAA91800.1; -; mRNA.
DR EMBL; AK022241; BAB13995.1; -; mRNA.
DR EMBL; AK294044; BAG57396.1; -; mRNA.
DR EMBL; AC090469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035558; AAH35558.1; -; mRNA.
DR EMBL; AF489535; AAO49126.1; ALT_FRAME; mRNA.
DR CCDS; CCDS44568.1; -. [Q9H0A0-2]
DR CCDS; CCDS7889.1; -. [Q9H0A0-1]
DR RefSeq; NP_001137502.1; NM_001144030.1. [Q9H0A0-2]
DR RefSeq; NP_078938.2; NM_024662.2. [Q9H0A0-1]
DR PDB; 6VLA; NMR; -; A=891-907.
DR PDB; 7MQ8; EM; 3.60 A; NJ/NK=1-1025.
DR PDB; 7MQ9; EM; 3.87 A; NJ/NK=1-1025.
DR PDBsum; 6VLA; -.
DR PDBsum; 7MQ8; -.
DR PDBsum; 7MQ9; -.
DR AlphaFoldDB; Q9H0A0; -.
DR SMR; Q9H0A0; -.
DR BioGRID; 120521; 285.
DR IntAct; Q9H0A0; 90.
DR MINT; Q9H0A0; -.
DR STRING; 9606.ENSP00000257829; -.
DR ChEMBL; CHEMBL4105935; -.
DR GlyGen; Q9H0A0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H0A0; -.
DR MetOSite; Q9H0A0; -.
DR PhosphoSitePlus; Q9H0A0; -.
DR SwissPalm; Q9H0A0; -.
DR BioMuta; NAT10; -.
DR DMDM; 313104140; -.
DR SWISS-2DPAGE; Q9H0A0; -.
DR EPD; Q9H0A0; -.
DR jPOST; Q9H0A0; -.
DR MassIVE; Q9H0A0; -.
DR MaxQB; Q9H0A0; -.
DR PaxDb; Q9H0A0; -.
DR PeptideAtlas; Q9H0A0; -.
DR PRIDE; Q9H0A0; -.
DR ProteomicsDB; 18059; -.
DR ProteomicsDB; 22170; -.
DR ProteomicsDB; 80229; -. [Q9H0A0-1]
DR Antibodypedia; 25804; 228 antibodies from 35 providers.
DR DNASU; 55226; -.
DR Ensembl; ENST00000257829.8; ENSP00000257829.3; ENSG00000135372.10. [Q9H0A0-1]
DR Ensembl; ENST00000531159.6; ENSP00000433011.2; ENSG00000135372.10. [Q9H0A0-2]
DR GeneID; 55226; -.
DR KEGG; hsa:55226; -.
DR MANE-Select; ENST00000257829.8; ENSP00000257829.3; NM_024662.3; NP_078938.3.
DR UCSC; uc001mvk.4; human. [Q9H0A0-1]
DR CTD; 55226; -.
DR DisGeNET; 55226; -.
DR GeneCards; NAT10; -.
DR HGNC; HGNC:29830; NAT10.
DR HPA; ENSG00000135372; Low tissue specificity.
DR MIM; 609221; gene.
DR neXtProt; NX_Q9H0A0; -.
DR OpenTargets; ENSG00000135372; -.
DR PharmGKB; PA143485555; -.
DR VEuPathDB; HostDB:ENSG00000135372; -.
DR eggNOG; KOG2036; Eukaryota.
DR GeneTree; ENSGT00390000009140; -.
DR HOGENOM; CLU_004652_0_0_1; -.
DR InParanoid; Q9H0A0; -.
DR OMA; QDEEFAG; -.
DR OrthoDB; 296129at2759; -.
DR PhylomeDB; Q9H0A0; -.
DR TreeFam; TF300601; -.
DR PathwayCommons; Q9H0A0; -.
DR Reactome; R-HSA-6790901; rRNA modification in the nucleus and cytosol.
DR SignaLink; Q9H0A0; -.
DR BioGRID-ORCS; 55226; 748 hits in 1095 CRISPR screens.
DR ChiTaRS; NAT10; human.
DR GeneWiki; NAT10; -.
DR GenomeRNAi; 55226; -.
DR Pharos; Q9H0A0; Tbio.
DR PRO; PR:Q9H0A0; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H0A0; protein.
DR Bgee; ENSG00000135372; Expressed in sural nerve and 196 other tissues.
DR ExpressionAtlas; Q9H0A0; baseline and differential.
DR Genevisible; Q9H0A0; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0070182; F:DNA polymerase binding; IPI:BHF-UCL.
DR GO; GO:0106162; F:mRNA N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008080; F:N-acetyltransferase activity; EXP:Reactome.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:1990883; F:rRNA cytidine N-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0000049; F:tRNA binding; IBA:GO_Central.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
DR GO; GO:0006473; P:protein acetylation; IDA:UniProtKB.
DR GO; GO:0010824; P:regulation of centrosome duplication; IDA:UniProtKB.
DR GO; GO:1904812; P:rRNA acetylation involved in maturation of SSU-rRNA; IBA:GO_Central.
DR GO; GO:0000154; P:rRNA modification; TAS:Reactome.
DR GO; GO:0051391; P:tRNA acetylation; IEA:UniProtKB-UniRule.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_03211; RNA_acetyltr_Nat10; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR007807; Helicase_dom.
DR InterPro; IPR033688; NAT10.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR032672; TmcA/NAT10/Kre33.
DR InterPro; IPR013562; TmcA_N.
DR InterPro; IPR027992; tRNA_bind_dom.
DR PANTHER; PTHR10925; PTHR10925; 1.
DR Pfam; PF08351; DUF1726; 1.
DR Pfam; PF13718; GNAT_acetyltr_2; 1.
DR Pfam; PF05127; Helicase_RecD; 1.
DR Pfam; PF13725; tRNA_bind_2; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Acyltransferase; Alternative splicing;
KW ATP-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; rRNA processing; Transferase; tRNA processing.
FT CHAIN 1..1025
FT /note="RNA cytidine acetyltransferase"
FT /id="PRO_0000215883"
FT DOMAIN 558..753
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03211"
FT REGION 702..1025
FT /note="Required for localization to the nucleolus and
FT midbody"
FT /evidence="ECO:0000269|PubMed:19303003"
FT REGION 990..1025
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 990..1015
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 287..296
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03211"
FT BINDING 470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03211"
FT BINDING 629..631
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03211"
FT BINDING 636..642
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03211"
FT BINDING 725
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03211"
FT MOD_RES 426
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:27993683,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 716
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 934
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 984
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 987
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..72
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054018"
FT VARIANT 461
FT /note="Y -> H (in dbSNP:rs2957516)"
FT /evidence="ECO:0000269|PubMed:11214970,
FT ECO:0000269|PubMed:11230166, ECO:0000269|PubMed:14592445,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0007744|PubMed:21269460"
FT /id="VAR_059858"
FT VARIANT 983
FT /note="A -> T (in dbSNP:rs36006049)"
FT /id="VAR_061894"
FT MUTAGEN 426
FT /note="K->R: Abolished acetylation."
FT /evidence="ECO:0000269|PubMed:27993683"
FT MUTAGEN 641
FT /note="G->E: Abolished acetyltransferase activity, probably
FT caused by impaired acetyl-CoA binding."
FT /evidence="ECO:0000269|PubMed:24786082"
FT CONFLICT 26
FT /note="F -> L (in Ref. 3; BAA91800)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="T -> A (in Ref. 6; AAO49126)"
FT /evidence="ECO:0000305"
FT CONFLICT 315
FT /note="S -> C (in Ref. 3; BAB13995)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="Y -> C (in Ref. 3; BAG57396)"
FT /evidence="ECO:0000305"
FT CONFLICT 879
FT /note="Q -> R (in Ref. 3; BAB13995)"
FT /evidence="ECO:0000305"
FT CONFLICT 971
FT /note="E -> G (in Ref. 3; BAG57396)"
FT /evidence="ECO:0000305"
FT HELIX 893..906
FT /evidence="ECO:0007829|PDB:6VLA"
SQ SEQUENCE 1025 AA; 115730 MW; 88734933A46EB0EE CRC64;
MHRKKVDNRI RILIENGVAE RQRSLFVVVG DRGKDQVVIL HHMLSKATVK ARPSVLWCYK
KELGFSSHRK KRMRQLQKKI KNGTLNIKQD DPFELFIAAT NIRYCYYNET HKILGNTFGM
CVLQDFEALT PNLLARTVET VEGGGLVVIL LRTMNSLKQL YTVTMDVHSR YRTEAHQDVV
GRFNERFILS LASCKKCLVI DDQLNILPIS SHVATMEALP PQTPDESLGP SDLELRELKE
SLQDTQPVGV LVDCCKTLDQ AKAVLKFIEG ISEKTLRSTV ALTAARGRGK SAALGLAIAG
AVAFGYSNIF VTSPSPDNLH TLFEFVFKGF DALQYQEHLD YEIIQSLNPE FNKAVIRVNV
FREHRQTIQY IHPADAVKLG QAELVVIDEA AAIPLPLVKS LLGPYLVFMA STINGYEGTG
RSLSLKLIQQ LRQQSAQSQV STTAENKTTT TARLASARTL YEVSLQESIR YAPGDAVEKW
LNDLLCLDCL NITRIVSGCP LPEACELYYV NRDTLFCYHK ASEVFLQRLM ALYVASHYKN
SPNDLQMLSD APAHHLFCLL PPVPPTQNAL PEVLAVIQVC LEGEISRQSI LNSLSRGKKA
SGDLIPWTVS EQFQDPDFGG LSGGRVVRIA VHPDYQGMGY GSRALQLLQM YYEGRFPCLE
EKVLETPQEI HTVSSEAVSL LEEVITPRKD LPPLLLKLNE RPAERLDYLG VSYGLTPRLL
KFWKRAGFVP VYLRQTPNDL TGEHSCIMLK TLTDEDEADQ GGWLAAFWKD FRRRFLALLS
YQFSTFSPSL ALNIIQNRNM GKPAQPALSR EELEALFLPY DLKRLEMYSR NMVDYHLIMD
MIPAISRIYF LNQLGDLALS AAQSALLLGI GLQHKSVDQL EKEIELPSGQ LMGLFNRIIR
KVVKLFNEVQ EKAIEEQMVA AKDVVMEPTM KTLSDDLDEA AKEFQEKHKK EVGKLKSMDL
SEYIIRGDDE EWNEVLNKAG PNASIISLKS DKKRKLEAKQ EPKQSKKLKN RETKNKKDMK
LKRKK
