ID   HPA3_YEAST              Reviewed;         161 AA.
AC   P39979; D3DLI4;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   17-FEB-2016, sequence version 2.
DT   27-MAR-2024, entry version 164.
DE   RecName: Full=D-amino-acid N-acetyltransferase HPA3 {ECO:0000303|PubMed:15375647};
DE            Short=DNT;
DE            EC=2.3.1.36 {ECO:0000269|PubMed:15375647};
GN   Name=HPA3 {ECO:0000303|PubMed:10600387};
GN   OrderedLocusNames=YEL066W {ECO:0000312|SGD:S000000792};
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169868;
RA   Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA   Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA   Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA   Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA   Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA   Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA   Botstein D., Davis R.W.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL   Nature 387:78-81(1997).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [3]
RP   FUNCTION, AND ACETYLATION SUBSTRATE.
RX   PubMed=10600387; DOI=10.1006/jmbi.1999.3338;
RA   Angus-Hill M.L., Dutnall R.N., Tafrov S.T., Sternglanz R., Ramakrishnan V.;
RT   "Crystal structure of the histone acetyltransferase Hpa2: a tetrameric
RT   member of the Gcn5-related N-acetyltransferase superfamily.";
RL   J. Mol. Biol. 294:1311-1325(1999).
RN   [4]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [5]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=15375647; DOI=10.1007/s00203-004-0724-y;
RA   Yow G.Y., Uo T., Yoshimura T., Esaki N.;
RT   "D-amino acid N-acetyltransferase of Saccharomyces cerevisiae: a close
RT   homologue of histone acetyltransferase Hpa2p acting exclusively on free D-
RT   amino acids.";
RL   Arch. Microbiol. 182:396-403(2004).
RN   [7]
RP   FUNCTION.
RX   PubMed=16362288; DOI=10.1007/s00203-005-0060-x;
RA   Yow G.Y., Uo T., Yoshimura T., Esaki N.;
RT   "Physiological role of D-amino acid-N-acetyltransferase of Saccharomyces
RT   cerevisiae: detoxification of D-amino acids.";
RL   Arch. Microbiol. 185:39-46(2006).
RN   [8]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [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   [9]
RP   FUNCTION, SUBSTRATE SPECIFICITY, AND IDENTIFICATION OF PROBABLE INITIATION
RP   SITE.
RX   PubMed=23775086; DOI=10.1074/jbc.m113.486274;
RA   Sampath V., Liu B., Tafrov S., Srinivasan M., Rieger R., Chen E.I.,
RA   Sternglanz R.;
RT   "Biochemical characterization of Hpa2 and Hpa3, two small closely related
RT   acetyltransferases from Saccharomyces cerevisiae.";
RL   J. Biol. Chem. 288:21506-21513(2013).
RN   [10]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=31478186; DOI=10.1002/bit.27157;
RA   Liu W., Tang D., Shi R., Lian J., Huang L., Cai J., Xu Z.;
RT   "Efficient production of S-adenosyl-l-methionine from dl-methionine in
RT   metabolic engineered Saccharomyces cerevisiae.";
RL   Biotechnol. Bioeng. 116:3312-3323(2019).
CC   -!- FUNCTION: N-acetyltransferase that acts on a wide range of D-amino
CC       acids (PubMed:15375647). Catalyzes the N-acetylation through an ordered
CC       bi-bi mechanism, in which acetyl-CoA is the first substrate to be bound
CC       and CoA is the last product to be liberated (PubMed:15375647). D-amino
CC       acids are toxic for the cell and their N-acetylation, preceding removal
CC       from cells, plays an important role in detoxification of D-amino acids
CC       (PubMed:10600387, PubMed:16362288, PubMed:31478186). In vitro, capable
CC       of acetylating histone H4 at 'Lys-8' and polyamines like putrescine,
CC       spermidine and spermine (PubMed:23775086).
CC       {ECO:0000269|PubMed:10600387, ECO:0000269|PubMed:15375647,
CC       ECO:0000269|PubMed:16362288, ECO:0000269|PubMed:23775086,
CC       ECO:0000269|PubMed:31478186}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a D-alpha-amino acid + acetyl-CoA = an N-acetyl-D-amino acid +
CC         CoA + H(+); Xref=Rhea:RHEA:20704, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:58496,
CC         ChEBI:CHEBI:59871; EC=2.3.1.36;
CC         Evidence={ECO:0000269|PubMed:15375647, ECO:0000305|PubMed:31478186};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=34 mM for D-Serine {ECO:0000269|PubMed:15375647};
CC         KM=54 mM for D-Alanine {ECO:0000269|PubMed:15375647};
CC         Vmax=22 umol/min/mg enzyme toward D-Serine
CC         {ECO:0000269|PubMed:15375647};
CC         Vmax=18 umol/min/mg enzyme toward D-Alanine
CC         {ECO:0000269|PubMed:15375647};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus
CC       {ECO:0000269|PubMed:14562095}.
CC   -!- PTM: Autoacetylates in an intermolecular reaction.
CC       {ECO:0000305|PubMed:10600387}.
CC   -!- DISRUPTION PHENOTYPE: Sensitive to D-methionine; abolishes the
CC       formation of N-acetyl-D-methionine and leads to the accumulation of D-
CC       methionine in cells when supplemented in the growth medium.
CC       {ECO:0000269|PubMed:31478186}.
CC   -!- MISCELLANEOUS: Present with 1200 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the acetyltransferase family. GNAT subfamily.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB65021.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=DAA07588.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; U18795; AAB65021.1; ALT_INIT; Genomic_DNA.
DR   EMBL; BK006939; DAA07588.1; ALT_INIT; Genomic_DNA.
DR   PIR; S50523; S50523.
DR   RefSeq; NP_010848.1; NM_001178881.1.
DR   AlphaFoldDB; P39979; -.
DR   SMR; P39979; -.
DR   BioGRID; 36663; 54.
DR   DIP; DIP-2063N; -.
DR   IntAct; P39979; 1.
DR   STRING; 4932.YEL066W; -.
DR   iPTMnet; P39979; -.
DR   PaxDb; 4932-YEL066W; -.
DR   PeptideAtlas; P39979; -.
DR   GeneID; 856642; -.
DR   KEGG; sce:YEL066W; -.
DR   AGR; SGD:S000000792; -.
DR   SGD; S000000792; HPA3.
DR   eggNOG; KOG3216; Eukaryota.
DR   HOGENOM; CLU_013985_32_0_1; -.
DR   InParanoid; P39979; -.
DR   OrthoDB; 5232122at2759; -.
DR   BioCyc; YEAST:G3O-30181-MONOMER; -.
DR   BRENDA; 2.3.1.48; 984.
DR   Reactome; R-SCE-351200; Interconversion of polyamines.
DR   SABIO-RK; P39979; -.
DR   BioGRID-ORCS; 856642; 9 hits in 10 CRISPR screens.
DR   PRO; PR:P39979; -.
DR   Proteomes; UP000002311; Chromosome V.
DR   RNAct; P39979; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0047812; F:D-amino-acid N-acetyltransferase activity; IDA:SGD.
DR   GO; GO:0004402; F:histone acetyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008080; F:N-acetyltransferase activity; IDA:SGD.
DR   GO; GO:0070458; P:cellular detoxification of nitrogen compound; IMP:SGD.
DR   GO; GO:0046416; P:D-amino acid metabolic process; IMP:SGD.
DR   GO; GO:0006473; P:protein acetylation; IDA:SGD.
DR   CDD; cd04301; NAT_SF; 1.
DR   Gene3D; 3.40.630.30; -; 1.
DR   InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR   InterPro; IPR000182; GNAT_dom.
DR   PANTHER; PTHR10545:SF29; DIAMINE ACETYLTRANSFERASE 1; 1.
DR   PANTHER; PTHR10545; DIAMINE N-ACETYLTRANSFERASE; 1.
DR   Pfam; PF00583; Acetyltransf_1; 1.
DR   SUPFAM; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1.
DR   PROSITE; PS51186; GNAT; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Acyltransferase; Cytoplasm; Nucleus; Reference proteome;
KW   Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CHAIN           2..161
FT                   /note="D-amino-acid N-acetyltransferase HPA3"
FT                   /id="PRO_0000074634"
FT   DOMAIN          14..161
FT                   /note="N-acetyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT   BINDING         98..111
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:Q06592"
FT   SITE            144
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q06592"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
SQ   SEQUENCE   161 AA;  18814 MW;  2A8DB00521975BDC CRC64;
     MSNEEPEKMV NDRIVVKAIE PKDEEAWNKL WKEYQGFQKT VMPPEVATTT FARFIDPTVK
     LWGALAFDTE TGDAIGFAHY LNHLTSWHVE EVVYMNDLYV TERARVKGVG RKLIEFVYSR
     ADELGTPAVY WVTDHYNHRA QLLYTKVAYK TDKVLYKRNG Y
//