NAA15_HUMAN
ID NAA15_HUMAN Reviewed; 866 AA.
AC Q9BXJ9; D3DNY6; Q52LG9; Q8IWH4; Q8NEV2; Q9H8P6;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=N-alpha-acetyltransferase 15, NatA auxiliary subunit;
DE AltName: Full=Gastric cancer antigen Ga19;
DE AltName: Full=N-terminal acetyltransferase;
DE AltName: Full=NMDA receptor-regulated protein 1;
DE AltName: Full=Protein tubedown-1;
DE AltName: Full=Tbdn100;
GN Name=NAA15; Synonyms=GA19, NARG1, NATH, TBDN100;
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), AND TISSUE SPECIFICITY.
RC TISSUE=Gastric adenocarcinoma;
RX PubMed=12087473; DOI=10.1038/sj.bjc.6600321;
RA Line A., Stengrevics A., Slucka Z., Li G., Jankevics E., Rees R.C.;
RT "Serological identification and expression analysis of gastric cancer-
RT associated genes.";
RL Br. J. Cancer 86:1824-1830(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS
RP SPECTROMETRY, INTERACTION WITH XRCC6 AND XRCC5, AND FUNCTION.
RC TISSUE=Heart, and Osteoblast;
RX PubMed=12145306; DOI=10.1074/jbc.m206482200;
RA Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S., Ornitz D.M.,
RA Towler D.A.;
RT "Regulation of osteocalcin gene expression by a novel Ku antigen
RT transcription factor complex.";
RL J. Biol. Chem. 277:37280-37291(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Thyroid carcinoma;
RX PubMed=12140756; DOI=10.1038/sj.onc.1205687;
RA Fluge O., Bruland O., Akslen L.A., Varhaug J.E., Lillehaug J.R.;
RT "NATH, a novel gene overexpressed in papillary thyroid carcinomas.";
RL Oncogene 21:5056-5068(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12019451;
RA He Y.G., Xie Y.F., Chen Y., Qian W., Lai J.H., Tan D.Y.;
RT "Cloning and analysis of a novel gene encoding N-terminal acetyltransferase
RT subunit.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 34:353-357(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Ovary;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Lymph;
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 [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11687548;
RA Gendron R.L., Good W.V., Adams L.C., Paradis H.;
RT "Suppressed expression of tubedown-1 in retinal neovascularization of
RT proliferative diabetic retinopathy.";
RL Invest. Ophthalmol. Vis. Sci. 42:3000-3007(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP INTERACTION WITH NAA10.
RX PubMed=15496142; DOI=10.1042/bj20041071;
RA Arnesen T., Anderson D., Baldersheim C., Lanotte M., Varhaug J.E.,
RA Lillehaug J.R.;
RT "Identification and characterization of the human ARD1-NATH protein
RT acetyltransferase complex.";
RL Biochem. J. 386:433-443(2005).
RN [11]
RP INTERACTION WITH NAA11.
RX PubMed=16638120; DOI=10.1186/1471-2091-7-13;
RA Arnesen T., Betts M.J., Pendino F., Liberles D.A., Anderson D., Caro J.,
RA Kong X., Varhaug J.E., Lillehaug J.R.;
RT "Characterization of hARD2, a processed hARD1 gene duplicate, encoding a
RT human protein N-alpha-acetyltransferase.";
RL BMC Biochem. 7:13-13(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [13]
RP INTERACTION WITH NAA50.
RX PubMed=16507339; DOI=10.1016/j.gene.2005.12.008;
RA Arnesen T., Anderson D., Torsvik J., Halseth H.B., Varhaug J.E.,
RA Lillehaug J.R.;
RT "Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved
RT component of the NatA protein N-alpha-acetyltransferase complex.";
RL Gene 371:291-295(2006).
RN [14]
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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP NOMENCLATURE.
RX PubMed=19660095; DOI=10.1186/1753-6561-3-s6-s2;
RA Polevoda B., Arnesen T., Sherman F.;
RT "A synopsis of eukaryotic Nalpha-terminal acetyltransferases: nomenclature,
RT subunits and substrates.";
RL BMC Proc. 3:S2-S2(2009).
RN [17]
RP IDENTIFICATION BY 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 [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-262; LYS-735 AND LYS-756, AND
RP IDENTIFICATION BY MASS 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 [19]
RP FUNCTION, IDENTIFICATION IN THE N-TERMINAL ACETYLTRANSFERASE A COMPLEX,
RP IDENTIFICATION IN THE N-TERMINAL ACETYLTRANSFERASE A/HYPK COMPLEX, AND
RP INTERACTION WITH HYPK AND NAA10.
RX PubMed=20154145; DOI=10.1128/mcb.01199-09;
RA Arnesen T., Starheim K.K., Van Damme P., Evjenth R., Dinh H., Betts M.J.,
RA Ryningen A., Vandekerckhove J., Gevaert K., Anderson D.;
RT "The chaperone-like protein HYPK acts together with NatA in cotranslational
RT N-terminal acetylation and prevention of Huntingtin aggregation.";
RL Mol. Cell. Biol. 30:1898-1909(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-856, AND IDENTIFICATION BY
RP 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 [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588 AND SER-856, AND
RP IDENTIFICATION BY 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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-302; SER-537; SER-588 AND
RP SER-855, 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 [25] {ECO:0007744|PDB:6C95, ECO:0007744|PDB:6C9M}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH NAA10 AND HYPK,
RP FUNCTION, IDENTIFICATION IN THE N-TERMINAL ACETYLTRANSFERASE A/HYPK
RP COMPLEX, IDENTIFICATION IN THE N-TERMINAL ACETYLTRANSFERASE E COMPLEX,
RP INTERACTION WITH NAA10; NAA50 AND HYPK, AND MUTAGENESIS OF TYR-834.
RX PubMed=29754825; DOI=10.1016/j.str.2018.04.003;
RA Gottlieb L., Marmorstein R.;
RT "Structure of Human NatA and Its Regulation by the Huntingtin Interacting
RT Protein HYPK.";
RL Structure 26:925-935.e8(2018).
RN [26] {ECO:0007744|PDB:6PPL, ECO:0007744|PDB:6PW9}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.02 ANGSTROMS), FUNCTION, IDENTIFICATION
RP IN THE N-TERMINAL ACETYLTRANSFERASE A COMPLEX, IDENTIFICATION IN THE
RP N-TERMINAL ACETYLTRANSFERASE A/HYPK COMPLEX, IDENTIFICATIONIN THE
RP N-TERMINAL ACETYLTRANSFERASE E COMPLEX, IDENTIFICATION IN THE N-TERMINAL
RP ACETYLTRANSFERASE E/HYPK COMPLEX, INTERACTION WITH NAA10; HYPK AND NAA50,
RP AND MUTAGENESIS OF THR-406 AND LEU-814.
RX PubMed=32042062; DOI=10.1038/s41467-020-14584-7;
RA Deng S., McTiernan N., Wei X., Arnesen T., Marmorstein R.;
RT "Molecular basis for N-terminal acetylation by human NatE and its
RT modulation by HYPK.";
RL Nat. Commun. 11:818-818(2020).
RN [27]
RP INVOLVEMENT IN MRD50, AND VARIANTS MRD50 52-LYS--ILE-866 DEL; ASN-112;
RP 290-GLY--ILE-866 DEL; GLU-450; VAL-475; 565-TYR--ILE-866 DEL;
RP 696-LYS--ILE-866 DEL; 782-ARG--ILE-866 DEL AND 797-ARG--ILE-866 DEL.
RX PubMed=28191889; DOI=10.1038/ng.3792;
RA Stessman H.A., Xiong B., Coe B.P., Wang T., Hoekzema K., Fenckova M.,
RA Kvarnung M., Gerdts J., Trinh S., Cosemans N., Vives L., Lin J.,
RA Turner T.N., Santen G., Ruivenkamp C., Kriek M., van Haeringen A., Aten E.,
RA Friend K., Liebelt J., Barnett C., Haan E., Shaw M., Gecz J.,
RA Anderlid B.M., Nordgren A., Lindstrand A., Schwartz C., Kooy R.F.,
RA Vandeweyer G., Helsmoortel C., Romano C., Alberti A., Vinci M., Avola E.,
RA Giusto S., Courchesne E., Pramparo T., Pierce K., Nalabolu S., Amaral D.G.,
RA Scheffer I.E., Delatycki M.B., Lockhart P.J., Hormozdiari F., Harich B.,
RA Castells-Nobau A., Xia K., Peeters H., Nordenskjoeld M., Schenck A.,
RA Bernier R.A., Eichler E.E.;
RT "Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes
RT with autism and developmental-disability biases.";
RL Nat. Genet. 49:515-526(2017).
CC -!- FUNCTION: Auxillary subunit of N-terminal acetyltransferase complexes
CC which display alpha (N-terminal) acetyltransferase (NAT) activity
CC (PubMed:15496142, PubMed:20154145, PubMed:29754825, PubMed:32042062).
CC The NAT activity may be important for vascular, hematopoietic and
CC neuronal growth and development (PubMed:15496142). Required to control
CC retinal neovascularization in adult ocular endothelial cells
CC (PubMed:11687548). In complex with XRCC6 and XRCC5 (Ku80), up-regulates
CC transcription from the osteocalcin promoter (PubMed:12145306).
CC {ECO:0000269|PubMed:11687548, ECO:0000269|PubMed:12145306,
CC ECO:0000269|PubMed:15496142, ECO:0000269|PubMed:20154145,
CC ECO:0000269|PubMed:29754825, ECO:0000269|PubMed:32042062}.
CC -!- SUBUNIT: Component of the N-terminal acetyltransferase A complex (also
CC called the NatA complex) composed of NAA10 and NAA15 (PubMed:15496142,
CC PubMed:20154145, PubMed:32042062). Within the complex interacts with
CC NAA10 (PubMed:15496142, PubMed:20154145, PubMed:29754825,
CC PubMed:32042062). Component of the N-terminal acetyltransferase A
CC (NatA)/HYPK complex at least composed of NAA10, NAA15 and HYPK, which
CC has N-terminal acetyltransferase activity (PubMed:20154145,
CC PubMed:29754825, PubMed:32042062). In complex with NAA10, interacts
CC with HYPK (PubMed:20154145, PubMed:29754825, PubMed:32042062).
CC Component of the N-terminal acetyltransferase E (NatE) complex at least
CC composed of NAA10, NAA15 and NAA50 (PubMed:29754825, PubMed:32042062).
CC Within the complex interacts with NAA10; the interaction is required
CC for binding to NAA50 (PubMed:29754825, PubMed:32042062). Interacts with
CC NAAT50 (PubMed:16507339, PubMed:29754825, PubMed:32042062). The
CC interaction of the NatA complex with NAA50 reduces the acetylation
CC activity of the NatA complex (PubMed:32042062). Component of the N-
CC terminal acetyltransferase E (NatE)/HYPK complex at least composed of
CC NAA10, NAA15, NAA50 and HYPK (PubMed:32042062). In complex with NAA10
CC interacts with HYPK; the interaction with HYPK reduces the capacity of
CC the NatA complex to interact with NAA50 (PubMed:20154145,
CC PubMed:29754825, PubMed:32042062). Interacts with NAA11
CC (PubMed:16638120). Interacts with XRCC6 and XRCC5 (PubMed:12145306,
CC PubMed:29754825, PubMed:16507339). {ECO:0000269|PubMed:12145306,
CC ECO:0000269|PubMed:15496142, ECO:0000269|PubMed:16507339,
CC ECO:0000269|PubMed:16638120, ECO:0000269|PubMed:20154145,
CC ECO:0000269|PubMed:29754825, ECO:0000269|PubMed:32042062}.
CC -!- INTERACTION:
CC Q9BXJ9; Q9NX55: HYPK; NbExp=5; IntAct=EBI-1042540, EBI-1048743;
CC Q9BXJ9; P41227: NAA10; NbExp=7; IntAct=EBI-1042540, EBI-747693;
CC Q9BXJ9; Q9GZZ1: NAA50; NbExp=3; IntAct=EBI-1042540, EBI-1052523;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Mainly cytoplasmic,
CC nuclear in some cases. Present in the free cytosolic and cytoskeleton-
CC bound polysomes, but not in the membrane-bound polysomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=Q9BXJ9-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q9BXJ9-4; Sequence=VSP_012560, VSP_012561;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in testis and in ocular
CC endothelial cells. Also found in brain (corpus callosum), heart, colon,
CC bone marrow and at lower levels in most adult tissues, including
CC thyroid, liver, pancreas, mammary and salivary glands, lung, ovary,
CC urogenital system and upper gastrointestinal tract. Overexpressed in
CC gastric cancer, in papillary thyroid carcinomas and in a Burkitt
CC lymphoma cell line (Daudi). Specifically suppressed in abnormal
CC proliferating blood vessels in eyes of patients with proliferative
CC diabetic retinopathy. {ECO:0000269|PubMed:11687548,
CC ECO:0000269|PubMed:12087473, ECO:0000269|PubMed:12140756}.
CC -!- PTM: Cleaved by caspases during apoptosis, resulting in a stable 35 kDa
CC fragment.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 50,
CC with behavioral abnormalities (MRD50) [MIM:617787]: A disorder
CC characterized by significantly below average general intellectual
CC functioning associated with impairments in adaptive behavior and
CC manifested during the developmental period.
CC {ECO:0000269|PubMed:28191889}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH39818.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AY039242; AAK68661.1; -; mRNA.
DR EMBL; AY112670; AAM48746.1; -; mRNA.
DR EMBL; AJ314788; CAC43228.1; -; mRNA.
DR EMBL; AF327722; AAK15707.1; -; mRNA.
DR EMBL; AK023402; BAB14562.1; -; mRNA.
DR EMBL; AC097376; AAY40950.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05119.1; -; Genomic_DNA.
DR EMBL; BC039818; AAH39818.1; ALT_SEQ; mRNA.
DR EMBL; BC093928; AAH93928.1; -; mRNA.
DR EMBL; BC104806; AAI04807.1; -; mRNA.
DR CCDS; CCDS43270.1; -. [Q9BXJ9-1]
DR RefSeq; NP_476516.1; NM_057175.4. [Q9BXJ9-1]
DR PDB; 6C95; X-ray; 3.15 A; A=1-866.
DR PDB; 6C9M; X-ray; 2.80 A; A/C=1-866.
DR PDB; 6PPL; EM; 3.02 A; B=1-866.
DR PDB; 6PW9; EM; 4.03 A; B=1-866.
DR PDBsum; 6C95; -.
DR PDBsum; 6C9M; -.
DR PDBsum; 6PPL; -.
DR PDBsum; 6PW9; -.
DR AlphaFoldDB; Q9BXJ9; -.
DR SMR; Q9BXJ9; -.
DR BioGRID; 123146; 114.
DR ComplexPortal; CPX-6271; NatA N-alpha-acetyltransferase complex, NAA10-NAA15 variant.
DR ComplexPortal; CPX-6273; NatA N-alpha-acetyltransferase complex, NAA11-NAA15 variant.
DR CORUM; Q9BXJ9; -.
DR IntAct; Q9BXJ9; 41.
DR MINT; Q9BXJ9; -.
DR STRING; 9606.ENSP00000296543; -.
DR GlyGen; Q9BXJ9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BXJ9; -.
DR MetOSite; Q9BXJ9; -.
DR PhosphoSitePlus; Q9BXJ9; -.
DR SwissPalm; Q9BXJ9; -.
DR BioMuta; NAA15; -.
DR DMDM; 57012969; -.
DR EPD; Q9BXJ9; -.
DR jPOST; Q9BXJ9; -.
DR MassIVE; Q9BXJ9; -.
DR MaxQB; Q9BXJ9; -.
DR PaxDb; Q9BXJ9; -.
DR PeptideAtlas; Q9BXJ9; -.
DR PRIDE; Q9BXJ9; -.
DR ProteomicsDB; 79443; -. [Q9BXJ9-1]
DR ProteomicsDB; 79444; -. [Q9BXJ9-4]
DR Antibodypedia; 7371; 238 antibodies from 29 providers.
DR DNASU; 80155; -.
DR Ensembl; ENST00000296543.10; ENSP00000296543.4; ENSG00000164134.13. [Q9BXJ9-1]
DR GeneID; 80155; -.
DR KEGG; hsa:80155; -.
DR MANE-Select; ENST00000296543.10; ENSP00000296543.4; NM_057175.5; NP_476516.1.
DR UCSC; uc003ihu.2; human. [Q9BXJ9-1]
DR CTD; 80155; -.
DR DisGeNET; 80155; -.
DR GeneCards; NAA15; -.
DR HGNC; HGNC:30782; NAA15.
DR HPA; ENSG00000164134; Low tissue specificity.
DR MalaCards; NAA15; -.
DR MIM; 608000; gene.
DR MIM; 617787; phenotype.
DR neXtProt; NX_Q9BXJ9; -.
DR OpenTargets; ENSG00000164134; -.
DR PharmGKB; PA165664293; -.
DR VEuPathDB; HostDB:ENSG00000164134; -.
DR eggNOG; KOG1156; Eukaryota.
DR GeneTree; ENSGT00950000183174; -.
DR InParanoid; Q9BXJ9; -.
DR OMA; WQEDQFD; -.
DR PhylomeDB; Q9BXJ9; -.
DR TreeFam; TF106301; -.
DR BioCyc; MetaCyc:ENSG00000164134-MON; -.
DR BRENDA; 2.3.1.255; 2681.
DR BRENDA; 2.3.1.258; 2681.
DR PathwayCommons; Q9BXJ9; -.
DR SignaLink; Q9BXJ9; -.
DR SIGNOR; Q9BXJ9; -.
DR BioGRID-ORCS; 80155; 732 hits in 1086 CRISPR screens.
DR ChiTaRS; NAA15; human.
DR GeneWiki; NARG1; -.
DR GenomeRNAi; 80155; -.
DR Pharos; Q9BXJ9; Tbio.
DR PRO; PR:Q9BXJ9; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9BXJ9; protein.
DR Bgee; ENSG00000164134; Expressed in calcaneal tendon and 197 other tissues.
DR ExpressionAtlas; Q9BXJ9; baseline and differential.
DR Genevisible; Q9BXJ9; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0031415; C:NatA complex; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0017196; P:N-terminal peptidyl-methionine acetylation; IBA:GO_Central.
DR GO; GO:0006474; P:N-terminal protein amino acid acetylation; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR InterPro; IPR021183; NatA_aux_su.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF12569; NARP1; 1.
DR Pfam; PF13181; TPR_8; 1.
DR PIRSF; PIRSF000422; N-terminal-AcTrfase-A_aux_su; 1.
DR SMART; SM00028; TPR; 6.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50005; TPR; 5.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Angiogenesis; Cytoplasm;
KW Developmental protein; Differentiation; Disease variant;
KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; TPR repeat; Transcription; Transcription regulation.
FT CHAIN 1..866
FT /note="N-alpha-acetyltransferase 15, NatA auxiliary
FT subunit"
FT /id="PRO_0000106294"
FT REPEAT 46..79
FT /note="TPR 1"
FT REPEAT 80..113
FT /note="TPR 2"
FT REPEAT 148..184
FT /note="TPR 3"
FT REPEAT 224..257
FT /note="TPR 4"
FT REPEAT 374..407
FT /note="TPR 5"
FT REPEAT 409..441
FT /note="TPR 6"
FT REPEAT 485..518
FT /note="TPR 7"
FT REPEAT 672..705
FT /note="TPR 8"
FT REGION 500..866
FT /note="Interaction with HYPK"
FT /evidence="ECO:0000269|PubMed:20154145"
FT REGION 575..642
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 612..629
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOD_RES 262
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 537
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 735
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 756
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 855
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 856
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT VAR_SEQ 514..525
FT /note="HFIEITDDQFDF -> KSLMTSLTFIHTV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012560"
FT VAR_SEQ 526..866
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012561"
FT VARIANT 52..866
FT /note="Missing (in MRD50)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080534"
FT VARIANT 112
FT /note="D -> N (in MRD50; unknown pathological significance;
FT dbSNP:rs889543097)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080535"
FT VARIANT 290..866
FT /note="Missing (in MRD50)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080536"
FT VARIANT 450
FT /note="K -> E (in MRD50; unknown pathological significance;
FT dbSNP:rs1436993876)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080537"
FT VARIANT 475
FT /note="A -> V (in MRD50; unknown pathological significance;
FT dbSNP:rs202204424)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080538"
FT VARIANT 565..866
FT /note="Missing (in MRD50)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080539"
FT VARIANT 696..866
FT /note="Missing (in MRD50)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080540"
FT VARIANT 782..866
FT /note="Missing (in MRD50)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080541"
FT VARIANT 797..866
FT /note="Missing (in MRD50)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080542"
FT MUTAGEN 406
FT /note="T->Y: Reduces binding to NAA50, but increases
FT binding to HYPK. Reduces catalytic activity of the NatA
FT complex while retaining the interaction with NAA10."
FT /evidence="ECO:0000269|PubMed:32042062"
FT MUTAGEN 814
FT /note="L->P: Reduces binding to HYPK, increases binding to
FT NAA50. Increases catalytic activity of the NatA complex
FT while retaining the interaction with NAA10."
FT /evidence="ECO:0000269|PubMed:32042062"
FT MUTAGEN 834
FT /note="Y->F,A: Reduces NatA complex stability and reduces
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:29754825"
FT CONFLICT 425
FT /note="K -> R (in Ref. 2; AAM48746)"
FT /evidence="ECO:0000305"
FT HELIX 8..22
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 26..38
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 46..58
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 80..92
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 96..109
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 114..126
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 130..143
FT /evidence="ECO:0007829|PDB:6C9M"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:6C95"
FT HELIX 148..161
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 164..180
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 186..202
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 206..216
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 223..236
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 240..253
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 258..268
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 273..286
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 297..300
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 304..320
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 325..329
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 330..334
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 336..355
FT /evidence="ECO:0007829|PDB:6C9M"
FT STRAND 356..360
FT /evidence="ECO:0007829|PDB:6C9M"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:6C95"
FT HELIX 370..386
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 390..403
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 408..420
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 424..437
FT /evidence="ECO:0007829|PDB:6C9M"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:6C95"
FT HELIX 442..454
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 458..465
FT /evidence="ECO:0007829|PDB:6C9M"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:6C9M"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 475..481
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 485..497
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 501..520
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 521..524
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 525..532
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 535..546
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 547..550
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 552..570
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 644..648
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 653..667
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 672..684
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 688..701
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 706..721
FT /evidence="ECO:0007829|PDB:6C9M"
FT STRAND 724..726
FT /evidence="ECO:0007829|PDB:6PPL"
FT HELIX 728..740
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 747..757
FT /evidence="ECO:0007829|PDB:6C9M"
FT TURN 758..760
FT /evidence="ECO:0007829|PDB:6C95"
FT HELIX 762..775
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 777..779
FT /evidence="ECO:0007829|PDB:6C95"
FT HELIX 780..787
FT /evidence="ECO:0007829|PDB:6C9M"
FT STRAND 794..796
FT /evidence="ECO:0007829|PDB:6PPL"
FT HELIX 799..810
FT /evidence="ECO:0007829|PDB:6C9M"
FT STRAND 812..814
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 818..829
FT /evidence="ECO:0007829|PDB:6C9M"
FT HELIX 836..838
FT /evidence="ECO:0007829|PDB:6C95"
SQ SEQUENCE 866 AA; 101272 MW; 6B4BA23B99D99121 CRC64;
MPAVSLPPKE NALFKRILRC YEHKQYRNGL KFCKQILSNP KFAEHGETLA MKGLTLNCLG
KKEEAYELVR RGLRNDLKSH VCWHVYGLLQ RSDKKYDEAI KCYRNALKWD KDNLQILRDL
SLLQIQMRDL EGYRETRYQL LQLRPAQRAS WIGYAIAYHL LEDYEMAAKI LEEFRKTQQT
SPDKVDYEYS ELLLYQNQVL REAGLYREAL EHLCTYEKQI CDKLAVEETK GELLLQLCRL
EDAADVYRGL QERNPENWAY YKGLEKALKP ANMLERLKIY EEAWTKYPRG LVPRRLPLNF
LSGEKFKECL DKFLRMNFSK GCPPVFNTLR SLYKDKEKVA IIEELVVGYE TSLKSCRLFN
PNDDGKEEPP TTLLWVQYYL AQHYDKIGQP SIALEYINTA IESTPTLIEL FLVKAKIYKH
AGNIKEAARW MDEAQALDTA DRFINSKCAK YMLKANLIKE AEEMCSKFTR EGTSAVENLN
EMQCMWFQTE CAQAYKAMNK FGEALKKCHE IERHFIEITD DQFDFHTYCM RKITLRSYVD
LLKLEDVLRQ HPFYFKAARI AIEIYLKLHD NPLTDENKEH EADTANMSDK ELKKLRNKQR
RAQKKAQIEE EKKNAEKEKQ QRNQKKKKDD DDEEIGGPKE ELIPEKLAKV ETPLEEAIKF
LTPLKNLVKN KIETHLFAFE IYFRKEKFLL MLQSVKRAFA IDSSHPWLHE CMIRLFNTAV
CESKDLSDTV RTVLKQEMNR LFGATNPKNF NETFLKRNSD SLPHRLSAAK MVYYLDPSSQ
KRAIELATTL DESLTNRNLQ TCMEVLEALY DGSLGDCKEA AEIYRANCHK LFPYALAFMP
PGYEEDMKIT VNGDSSAEAE ELANEI
