NAA50_HUMAN
ID NAA50_HUMAN Reviewed; 169 AA.
AC Q9GZZ1; D3DN74; Q68DQ1;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=N-alpha-acetyltransferase 50 {ECO:0000305};
DE Short=hNaa50p {ECO:0000303|PubMed:19744929, ECO:0000303|PubMed:22311970};
DE EC=2.3.1.258 {ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231, ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
DE AltName: Full=N-acetyltransferase 13;
DE AltName: Full=N-acetyltransferase 5 {ECO:0000303|PubMed:16507339};
DE Short=hNAT5 {ECO:0000303|PubMed:16507339};
DE AltName: Full=N-acetyltransferase san homolog {ECO:0000303|PubMed:16507339};
DE Short=hSAN {ECO:0000303|PubMed:16507339};
DE AltName: Full=N-epsilon-acetyltransferase 50 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:19744929};
DE AltName: Full=NatE catalytic subunit;
GN Name=NAA50 {ECO:0000312|HGNC:HGNC:29533};
GN Synonyms=MAK3 {ECO:0000303|Ref.19}, NAT13,
GN NAT5 {ECO:0000303|PubMed:16507339};
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).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-110, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBUNIT, IDENTIFICATION IN
RP THE N-TERMINAL ACETYLTRANSFERASE E COMPLEX, INTERACTION WITH NAA15 AND
RP NAA11, AND SUBCELLULAR LOCATION.
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-124.
RX PubMed=17502424; DOI=10.1083/jcb.200701043;
RA Hou F., Chu C.W., Kong X., Yokomori K., Zou H.;
RT "The acetyltransferase activity of San stabilizes the mitotic cohesin at
RT the centromeres in a shugoshin-independent manner.";
RL J. Cell Biol. 177:587-597(2007).
RN [8]
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 [9]
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 [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACETYLATION AT
RP LYS-34; LYS-37 AND LYS-140, AND MUTAGENESIS OF 34-LYS--LYS-37; ARG-84;
RP TYR-124 AND LYS-140.
RX PubMed=19744929; DOI=10.1074/jbc.m109.001347;
RA Evjenth R., Hole K., Karlsen O.A., Ziegler M., Arnesen T., Lillehaug J.R.;
RT "Human Naa50p (Nat5/San) displays both protein N alpha- and N epsilon-
RT acetyltransferase activity.";
RL J. Biol. Chem. 284:31122-31129(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-34 AND LYS-37, ACETYLATION [LARGE
RP SCALE ANALYSIS] AT LYS-34 (ISOFORM 2), 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-12, 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 [13]
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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22311970; DOI=10.1074/jbc.m111.326587;
RA Evjenth R.H., Brenner A.K., Thompson P.R., Arnesen T., Froeystein N.A.,
RA Lillehaug J.R.;
RT "Human protein N-terminal acetyltransferase hNaa50p (hNAT5/hSAN) follows
RT ordered sequential catalytic mechanism: combined kinetic and NMR study.";
RL J. Biol. Chem. 287:10081-10088(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-12, AND IDENTIFICATION BY
RP 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 [16]
RP SUBCELLULAR LOCATION.
RX PubMed=25732826; DOI=10.1016/j.celrep.2015.01.053;
RA Aksnes H., Van Damme P., Goris M., Starheim K.K., Marie M., Stoeve S.I.,
RA Hoel C., Kalvik T.V., Hole K., Glomnes N., Furnes C., Ljostveit S.,
RA Ziegler M., Niere M., Gevaert K., Arnesen T.;
RT "An organellar nalpha-acetyltransferase, naa60, acetylates cytosolic N
RT termini of transmembrane proteins and maintains Golgi integrity.";
RL Cell Rep. 10:1362-1374(2015).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-27 AND TYR-124.
RX PubMed=27422821; DOI=10.1074/jbc.m116.737585;
RA Rong Z., Ouyang Z., Magin R.S., Marmorstein R., Yu H.;
RT "Opposing functions of the N-terminal acetyltransferases Naa50 and NatA in
RT sister-chromatid cohesion.";
RL J. Biol. Chem. 291:19079-19091(2016).
RN [18]
RP FUNCTION, IDENTIFICATION IN THE N-TERMINAL ACETYLTRANSFERASE E COMPLEX, AND
RP INTERACTION WITH NAA15.
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 [19] {ECO:0007744|PDB:2OB0, ECO:0007744|PDB:2PSW}
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH COENZYME A.
RG Structural genomics consortium (SGC);
RT "Structure of human MAK3 homolog.";
RL Submitted (JUN-2007) to the PDB data bank.
RN [20] {ECO:0007744|PDB:3TFY}
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH COENZYME A AND
RP SUBSTRATE PEPTIDE, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVE SITE, AND MUTAGENESIS OF PHE-27; PRO-28; VAL-29; TYR-31;
RP PHE-35; TYR-73; HIS-112; TYR-139 AND ILE-142.
RX PubMed=21900231; DOI=10.1074/jbc.m111.282863;
RA Liszczak G., Arnesen T., Marmorstein R.;
RT "Structure of a ternary Naa50p (NAT5/SAN) N-terminal acetyltransferase
RT complex reveals the molecular basis for substrate-specific acetylation.";
RL J. Biol. Chem. 286:37002-37010(2011).
RN [21] {ECO:0007744|PDB:4X5K}
RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) IN COMPLEX WITH COENZYME A AND
RP SUBSTRATE PEPTIDE, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=27484799; DOI=10.1074/jbc.m116.730432;
RA Reddi R., Saddanapu V., Chinthapalli D.K., Sankoju P., Sripadi P.,
RA Addlagatta A.;
RT "Human Naa50 protein displays broad substrate specificity for amino-
RT terminal acetylation: detailed structural and biochemical analysis using
RT tetrapeptide library.";
RL J. Biol. Chem. 291:20530-20538(2016).
RN [22] {ECO:0007744|PDB:6PPL, ECO:0007744|PDB:6PW9}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.02 ANGSTROMS), FUNCTION, IDENTIFICATION
RP IN THE N-TERMINAL ACETYLTRANSFERASE E COMPLEX, IDENTIFICATION IN THE
RP N-TERMINAL ACETYLTRANSFERASE E/HYPK COMPLEX, INTERACTION WITH NAA10 AND
RP NAA15, AND MUTAGENESIS OF GLU-7; ASP-53; TYR-73; MET-75; TYR-138; TYR-139
RP AND ILE-142.
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).
CC -!- FUNCTION: N-alpha-acetyltransferase that acetylates the N-terminus of
CC proteins that retain their initiating methionine (PubMed:19744929,
CC PubMed:22311970, PubMed:21900231, PubMed:27484799). Has a broad
CC substrate specificity: able to acetylate the initiator methionine of
CC most peptides, except for those with a proline in second position
CC (PubMed:27484799). Also displays N-epsilon-acetyltransferase activity
CC by mediating acetylation of the side chain of specific lysines on
CC proteins (PubMed:19744929). Autoacetylates in vivo (PubMed:19744929).
CC The relevance of N-epsilon-acetyltransferase activity is however
CC unclear: able to acetylate H4 in vitro, but this result has not been
CC confirmed in vivo (PubMed:19744929). Component of N-alpha-
CC acetyltransferase complexes containing NAA10 and NAA15, which has N-
CC alpha-acetyltransferase activity (PubMed:16507339, PubMed:29754825,
CC PubMed:27484799, PubMed:32042062). Does not influence the
CC acetyltransferase activity of NAA10 (PubMed:16507339, PubMed:27484799).
CC However, it negatively regulates the N-alpha-acetyltransferase activity
CC of the N-terminal acetyltransferase A complex (also called the NatA
CC complex) (PubMed:32042062). The multiprotein complexes probably
CC constitute the major contributor for N-terminal acetylation at the
CC ribosome exit tunnel, with NAA10 acetylating all amino termini that are
CC devoid of methionine and NAA50 acetylating other peptides
CC (PubMed:16507339, PubMed:27484799). Required for sister chromatid
CC cohesion during mitosis by promoting binding of CDCA5/sororin to
CC cohesin: may act by counteracting the function of NAA10
CC (PubMed:17502424, PubMed:27422821). {ECO:0000269|PubMed:16507339,
CC ECO:0000269|PubMed:17502424, ECO:0000269|PubMed:19744929,
CC ECO:0000269|PubMed:21900231, ECO:0000269|PubMed:22311970,
CC ECO:0000269|PubMed:27422821, ECO:0000269|PubMed:27484799,
CC ECO:0000269|PubMed:29754825, ECO:0000269|PubMed:32042062}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N-terminal L-methionyl-L-alanyl-[protein] = CoA +
CC H(+) + N-terminal N(alpha)-acetyl-L-methionyl-L-alanyl-[protein];
CC Xref=Rhea:RHEA:50564, Rhea:RHEA-COMP:12726, Rhea:RHEA-COMP:12727,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:133398, ChEBI:CHEBI:133399; EC=2.3.1.258;
CC Evidence={ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231,
CC ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N-terminal L-methionyl-L-seryl-[protein] = CoA +
CC H(+) + N-terminal N(alpha)-acetyl-L-methionyl-L-seryl-[protein];
CC Xref=Rhea:RHEA:50568, Rhea:RHEA-COMP:12728, Rhea:RHEA-COMP:12729,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:133400, ChEBI:CHEBI:133401; EC=2.3.1.258;
CC Evidence={ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231,
CC ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N-terminal L-methionyl-L-valyl-[protein] = CoA +
CC H(+) + N-terminal N(alpha)-acetyl-L-methionyl-L-valyl-[protein];
CC Xref=Rhea:RHEA:50572, Rhea:RHEA-COMP:12730, Rhea:RHEA-COMP:12731,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:133402, ChEBI:CHEBI:133403; EC=2.3.1.258;
CC Evidence={ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231,
CC ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N-terminal L-methionyl-L-threonyl-[protein] = CoA
CC + H(+) + N-terminal N(alpha)-acetyl-L-methionyl-L-threonyl-[protein];
CC Xref=Rhea:RHEA:50576, Rhea:RHEA-COMP:12732, Rhea:RHEA-COMP:12733,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:133404, ChEBI:CHEBI:133405; EC=2.3.1.258;
CC Evidence={ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231,
CC ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N-terminal L-methionyl-L-lysyl-[protein] = CoA +
CC H(+) + N-terminal N(alpha)-acetyl-L-methionyl-L-lysyl-[protein];
CC Xref=Rhea:RHEA:50580, Rhea:RHEA-COMP:12734, Rhea:RHEA-COMP:12735,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:133406, ChEBI:CHEBI:133407; EC=2.3.1.258;
CC Evidence={ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231,
CC ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N-terminal L-methionyl-L-leucyl-[protein] = CoA +
CC H(+) + N-terminal N(alpha)-acetyl-L-methionyl-L-leucyl-[protein];
CC Xref=Rhea:RHEA:50520, Rhea:RHEA-COMP:12711, Rhea:RHEA-COMP:12712,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:133377, ChEBI:CHEBI:133378; EC=2.3.1.258;
CC Evidence={ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231,
CC ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N-terminal L-methionyl-L-phenylalanyl-[protein] =
CC CoA + H(+) + N-terminal N(alpha)-acetyl-L-methionyl-L-phenylalanyl-
CC [protein]; Xref=Rhea:RHEA:50528, Rhea:RHEA-COMP:12715, Rhea:RHEA-
CC COMP:12716, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:133382, ChEBI:CHEBI:133383; EC=2.3.1.258;
CC Evidence={ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231,
CC ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + N-terminal L-methionyl-L-tyrosyl-[protein] = CoA
CC + H(+) + N-terminal N(alpha)-acetyl-L-methionyl-L-tyrosyl-[protein];
CC Xref=Rhea:RHEA:50532, Rhea:RHEA-COMP:12717, Rhea:RHEA-COMP:12718,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:133384, ChEBI:CHEBI:133385; EC=2.3.1.258;
CC Evidence={ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:21900231,
CC ECO:0000269|PubMed:22311970, ECO:0000269|PubMed:27484799};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=132.6 uM for M-A-A-A peptide {ECO:0000269|PubMed:27484799};
CC KM=126.1 uM for L-A-A-A peptide {ECO:0000269|PubMed:27484799};
CC KM=5 uM for Acetyl-CoA {ECO:0000269|PubMed:22311970};
CC KM=79 uM for M-L-G-P-E peptide {ECO:0000269|PubMed:19744929};
CC KM=91 uM for M-L-D-P-E peptide {ECO:0000269|PubMed:19744929};
CC KM=185 uM for M-I-G-P-E peptide {ECO:0000269|PubMed:19744929};
CC KM=190 uM for M-L-A-L-I peptide {ECO:0000269|PubMed:19744929};
CC KM=320 uM for M-L-G-T-G peptide {ECO:0000269|PubMed:19744929};
CC KM=416 uM for M-L-G-T-E peptide {ECO:0000269|PubMed:19744929};
CC KM=460 uM for M-L-R-P-E peptide {ECO:0000269|PubMed:19744929};
CC KM=478 uM for M-L-L-P-E peptide {ECO:0000269|PubMed:19744929};
CC KM=3734 uM for M-F-G-P-E peptide {ECO:0000269|PubMed:19744929};
CC Note=kcat is 7.2 min(-1) with M-L-G-P-E peptide. kcat is 7.2 min(-1)
CC with M-L-D-P-E peptide. kcat is 10.9 min(-1) with M-I-G-P-E peptide.
CC kcat is 6.8 min(-1) with M-L-A-L-I peptide. kcat is 2.3 min(-1) with
CC M-L-G-T-G peptide. kcat is 5.6 min(-1) with M-L-G-T-E peptide.
CC {ECO:0000269|PubMed:19744929};
CC pH dependence:
CC Optimum pH is 7.5-8.0. {ECO:0000269|PubMed:21900231};
CC -!- SUBUNIT: Component of the N-terminal acetyltransferase E (NatE) complex
CC at least composed of NAA10, NAA15 and NAA50 (PubMed:16507339,
CC PubMed:29754825, PubMed:32042062). Interacts with NAA10
CC (PubMed:16507339, PubMed:32042062). Interacts with NAA15
CC (PubMed:16507339, PubMed:29754825, PubMed:32042062). Predominantly
CC interacts with NAA15 in the N-terminal acetyltransferase A complex
CC (NatA complex); the interactions reduce the acetylation activity of the
CC NatA complex (PubMed:16507339, 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). Within the complex
CC interacts with NAA15 (PubMed:32042062). Its capacity to interact with
CC the NatA complex is reduced by HYPK (PubMed:32042062). Interacts with
CC NAA35 (By similarity). {ECO:0000250|UniProtKB:Q6PGB6,
CC ECO:0000269|PubMed:16507339, ECO:0000269|PubMed:29754825,
CC ECO:0000269|PubMed:32042062}.
CC -!- INTERACTION:
CC Q9GZZ1; O14503: BHLHE40; NbExp=6; IntAct=EBI-1052523, EBI-711810;
CC Q9GZZ1; Q6NYC1: JMJD6; NbExp=6; IntAct=EBI-1052523, EBI-8464037;
CC Q9GZZ1; P41227: NAA10; NbExp=3; IntAct=EBI-1052523, EBI-747693;
CC Q9GZZ1; Q9BXJ9: NAA15; NbExp=3; IntAct=EBI-1052523, EBI-1042540;
CC Q9GZZ1; P32243-2: OTX2; NbExp=3; IntAct=EBI-1052523, EBI-9087860;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16507339,
CC ECO:0000269|PubMed:17502424, ECO:0000269|PubMed:25732826,
CC ECO:0000269|PubMed:27422821}. Nucleus {ECO:0000269|PubMed:25732826}.
CC Note=Localizes to the cytoplasm in interphase cells (PubMed:17502424).
CC {ECO:0000269|PubMed:17502424}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9GZZ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9GZZ1-2; Sequence=VSP_024747;
CC -!- SIMILARITY: Belongs to the acetyltransferase family. GNAT subfamily.
CC {ECO:0000305}.
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DR EMBL; AK023090; BAB14397.1; -; mRNA.
DR EMBL; AK023256; BAB14490.1; -; mRNA.
DR EMBL; CR749314; CAH18169.1; -; mRNA.
DR EMBL; CH471052; EAW79629.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79630.1; -; Genomic_DNA.
DR EMBL; BC012731; AAH12731.1; -; mRNA.
DR CCDS; CCDS2975.1; -. [Q9GZZ1-1]
DR RefSeq; NP_079422.1; NM_025146.3. [Q9GZZ1-1]
DR PDB; 2OB0; X-ray; 1.80 A; A/B/C=2-169.
DR PDB; 2PSW; X-ray; 2.10 A; A/B/C=2-169.
DR PDB; 3TFY; X-ray; 2.75 A; A/B/C=1-169.
DR PDB; 4X5K; X-ray; 2.49 A; A=1-169.
DR PDB; 6PPL; EM; 3.02 A; A=1-169.
DR PDB; 6PW9; EM; 4.03 A; A=1-169.
DR PDB; 6WF3; X-ray; 2.29 A; A/B/C/D/E/F=1-169.
DR PDB; 6WF5; X-ray; 2.04 A; A/B=1-169.
DR PDB; 6WFG; X-ray; 2.16 A; A/C/E=1-169.
DR PDB; 6WFK; X-ray; 1.87 A; A/B/C=1-169.
DR PDB; 6WFN; X-ray; 1.07 A; A=1-169.
DR PDB; 6WFO; X-ray; 1.85 A; A/B/C=1-169.
DR PDBsum; 2OB0; -.
DR PDBsum; 2PSW; -.
DR PDBsum; 3TFY; -.
DR PDBsum; 4X5K; -.
DR PDBsum; 6PPL; -.
DR PDBsum; 6PW9; -.
DR PDBsum; 6WF3; -.
DR PDBsum; 6WF5; -.
DR PDBsum; 6WFG; -.
DR PDBsum; 6WFK; -.
DR PDBsum; 6WFN; -.
DR PDBsum; 6WFO; -.
DR AlphaFoldDB; Q9GZZ1; -.
DR BMRB; Q9GZZ1; -.
DR SMR; Q9GZZ1; -.
DR BioGRID; 123185; 108.
DR IntAct; Q9GZZ1; 27.
DR MINT; Q9GZZ1; -.
DR STRING; 9606.ENSP00000240922; -.
DR BindingDB; Q9GZZ1; -.
DR ChEMBL; CHEMBL4630854; -.
DR GlyGen; Q9GZZ1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9GZZ1; -.
DR PhosphoSitePlus; Q9GZZ1; -.
DR SwissPalm; Q9GZZ1; -.
DR BioMuta; NAA50; -.
DR DMDM; 74733509; -.
DR EPD; Q9GZZ1; -.
DR jPOST; Q9GZZ1; -.
DR MassIVE; Q9GZZ1; -.
DR MaxQB; Q9GZZ1; -.
DR PaxDb; Q9GZZ1; -.
DR PeptideAtlas; Q9GZZ1; -.
DR PRIDE; Q9GZZ1; -.
DR ProteomicsDB; 80182; -. [Q9GZZ1-1]
DR ProteomicsDB; 80183; -. [Q9GZZ1-2]
DR Antibodypedia; 32596; 167 antibodies from 27 providers.
DR DNASU; 80218; -.
DR Ensembl; ENST00000240922.8; ENSP00000240922.2; ENSG00000121579.14. [Q9GZZ1-1]
DR GeneID; 80218; -.
DR KEGG; hsa:80218; -.
DR MANE-Select; ENST00000240922.8; ENSP00000240922.2; NM_025146.4; NP_079422.1.
DR UCSC; uc003ean.3; human. [Q9GZZ1-1]
DR CTD; 80218; -.
DR DisGeNET; 80218; -.
DR GeneCards; NAA50; -.
DR HGNC; HGNC:29533; NAA50.
DR HPA; ENSG00000121579; Tissue enhanced (skeletal).
DR MIM; 610834; gene.
DR neXtProt; NX_Q9GZZ1; -.
DR OpenTargets; ENSG00000121579; -.
DR PharmGKB; PA165697846; -.
DR VEuPathDB; HostDB:ENSG00000121579; -.
DR eggNOG; KOG3138; Eukaryota.
DR GeneTree; ENSGT00390000009110; -.
DR InParanoid; Q9GZZ1; -.
DR OMA; IVETKEH; -.
DR OrthoDB; 1536763at2759; -.
DR PhylomeDB; Q9GZZ1; -.
DR TreeFam; TF314841; -.
DR BioCyc; MetaCyc:ENSG00000121579-MON; -.
DR BRENDA; 2.3.1.258; 2681.
DR PathwayCommons; Q9GZZ1; -.
DR SignaLink; Q9GZZ1; -.
DR BioGRID-ORCS; 80218; 778 hits in 1085 CRISPR screens.
DR ChiTaRS; NAA50; human.
DR EvolutionaryTrace; Q9GZZ1; -.
DR GenomeRNAi; 80218; -.
DR Pharos; Q9GZZ1; Tchem.
DR PRO; PR:Q9GZZ1; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9GZZ1; protein.
DR Bgee; ENSG00000121579; Expressed in skeletal muscle tissue of rectus abdominis and 211 other tissues.
DR ExpressionAtlas; Q9GZZ1; baseline and differential.
DR Genevisible; Q9GZZ1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031415; C:NatA complex; IDA:GO_Central.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0010485; F:H4 histone acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008080; F:N-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0004596; F:peptide alpha-N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0052858; F:peptidyl-lysine acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0034087; P:establishment of mitotic sister chromatid cohesion; IDA:UniProtKB.
DR GO; GO:0016573; P:histone acetylation; IBA:GO_Central.
DR GO; GO:0007064; P:mitotic sister chromatid cohesion; IBA:GO_Central.
DR GO; GO:0071962; P:mitotic sister chromatid cohesion, centromeric; IDA:UniProtKB.
DR GO; GO:0006474; P:N-terminal protein amino acid acetylation; IDA:UniProtKB.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR Pfam; PF00583; Acetyltransf_1; 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 Cytoplasm; Nucleus; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..169
FT /note="N-alpha-acetyltransferase 50"
FT /id="PRO_0000284902"
FT DOMAIN 6..155
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT ACT_SITE 73
FT /evidence="ECO:0000269|PubMed:21900231"
FT ACT_SITE 112
FT /evidence="ECO:0000269|PubMed:21900231"
FT BINDING 31
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:27484799, ECO:0007744|PDB:3TFY,
FT ECO:0007744|PDB:4X5K"
FT BINDING 75
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:27484799, ECO:0007744|PDB:3TFY,
FT ECO:0007744|PDB:4X5K"
FT BINDING 77..90
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:27484799, ECO:0000269|Ref.19,
FT ECO:0007744|PDB:2PSW, ECO:0007744|PDB:3TFY,
FT ECO:0007744|PDB:4X5K"
FT BINDING 117..126
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:27484799, ECO:0000269|Ref.19,
FT ECO:0007744|PDB:2PSW, ECO:0007744|PDB:3TFY,
FT ECO:0007744|PDB:4X5K"
FT BINDING 138..141
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:27484799, ECO:0007744|PDB:3TFY,
FT ECO:0007744|PDB:4X5K"
FT MOD_RES 12
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 34
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19744929,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 37
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19744929,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 110
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 140
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19744929"
FT VAR_SEQ 35..122
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_024747"
FT MUTAGEN 7
FT /note="E->A: Restores the acetylation activity of the NatA
FT complex."
FT /evidence="ECO:0000269|PubMed:32042062"
FT MUTAGEN 27
FT /note="F->A: Abolishes N-alpha-acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:27422821"
FT MUTAGEN 28
FT /note="P->A: Strongly decreased N-alpha-acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:21900231"
FT MUTAGEN 29
FT /note="V->A: Strongly decreased N-alpha-acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:21900231"
FT MUTAGEN 31
FT /note="Y->A: Abolishes N-alpha-acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:21900231"
FT MUTAGEN 34..37
FT /note="KFYK->AFYA: Decreased acetylation; when associated
FT with A-140."
FT /evidence="ECO:0000269|PubMed:19744929"
FT MUTAGEN 35
FT /note="F->A: Abolishes N-alpha-acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:21900231"
FT MUTAGEN 53
FT /note="D->A: Restores the acetylation activity of the NatA
FT complex."
FT /evidence="ECO:0000269|PubMed:32042062"
FT MUTAGEN 73
FT /note="Y->A,F: Abolishes N-alpha-acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:32042062"
FT MUTAGEN 75
FT /note="M->A: Reduces N-alpha-acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:32042062"
FT MUTAGEN 84
FT /note="R->A: Strongly decreased N-alpha-acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:19744929"
FT MUTAGEN 112
FT /note="H->A,F: Abolishes N-alpha-acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:21900231"
FT MUTAGEN 124
FT /note="Y->F: Strongly decreased N-alpha-acetyltransferase
FT activity. Impaired sister chromatid cohesion during
FT mitosis."
FT /evidence="ECO:0000269|PubMed:17502424,
FT ECO:0000269|PubMed:19744929, ECO:0000269|PubMed:27422821"
FT MUTAGEN 138
FT /note="Y->A: Abolishes N-alpha-acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:32042062"
FT MUTAGEN 139
FT /note="Y->A: Abolishes N-alpha-acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:32042062"
FT MUTAGEN 140
FT /note="K->A: Decreased acetylation; when associated with
FT 34-A-A-37."
FT /evidence="ECO:0000269|PubMed:19744929"
FT MUTAGEN 142
FT /note="I->A: Reduces N-alpha-acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:21900231,
FT ECO:0000269|PubMed:32042062"
FT STRAND 6..10
FT /evidence="ECO:0007829|PDB:6WFN"
FT TURN 13..15
FT /evidence="ECO:0007829|PDB:6WFN"
FT HELIX 16..26
FT /evidence="ECO:0007829|PDB:6WFN"
FT HELIX 33..39
FT /evidence="ECO:0007829|PDB:6WFN"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 54..66
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 69..79
FT /evidence="ECO:0007829|PDB:6WFN"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:6WFN"
FT HELIX 88..103
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:6WFN"
FT HELIX 118..125
FT /evidence="ECO:0007829|PDB:6WFN"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 140..144
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:6WFN"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6WF5"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:2OB0"
FT MOD_RES Q9GZZ1-2:34
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
SQ SEQUENCE 169 AA; 19398 MW; 153A8021B74655CC CRC64;
MKGSRIELGD VTPHNIKQLK RLNQVIFPVS YNDKFYKDVL EVGELAKLAY FNDIAVGAVC
CRVDHSQNQK RLYIMTLGCL APYRRLGIGT KMLNHVLNIC EKDGTFDNIY LHVQISNESA
IDFYRKFGFE IIETKKNYYK RIEPADAHVL QKNLKVPSGQ NADVQKTDN
