ID   ATAT_DANRE              Reviewed;         297 AA.
AC   Q6PH17; Q6NZT0;
DT   30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 115.
DE   RecName: Full=Alpha-tubulin N-acetyltransferase 1 {ECO:0000255|HAMAP-Rule:MF_03130};
DE            Short=Alpha-TAT {ECO:0000255|HAMAP-Rule:MF_03130};
DE            Short=Alpha-TAT1 {ECO:0000255|HAMAP-Rule:MF_03130};
DE            Short=TAT {ECO:0000255|HAMAP-Rule:MF_03130};
DE            EC=2.3.1.108 {ECO:0000255|HAMAP-Rule:MF_03130};
DE   AltName: Full=Acetyltransferase mec-17 homolog {ECO:0000255|HAMAP-Rule:MF_03130};
GN   Name=atat1 {ECO:0000255|HAMAP-Rule:MF_03130}; Synonyms=mec17;
GN   ORFNames=si:ch211-152p11.5, zgc:65893;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Embryo;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20829795; DOI=10.1038/nature09324;
RA   Akella J.S., Wloga D., Kim J., Starostina N.G., Lyons-Abbott S.,
RA   Morrissette N.S., Dougan S.T., Kipreos E.T., Gaertig J.;
RT   "MEC-17 is an alpha-tubulin acetyltransferase.";
RL   Nature 467:218-222(2010).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-188 IN COMPLEX WITH ACETYL-COA,
RP   AND MUTAGENESIS OF GLN-53.
RX   PubMed=23128673; DOI=10.1038/cr.2012.154;
RA   Li W., Zhong C., Li L., Sun B., Wang W., Xu S., Zhang T., Wang C., Bao L.,
RA   Ding J.;
RT   "Molecular basis of the acetyltransferase activity of MEC-17 towards alpha-
RT   tubulin.";
RL   Cell Res. 22:1707-1711(2012).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 1-188 OF WILD-TYPE AND OF MUTANT
RP   ALA-117 IN COMPLEX WITH ACETYL-COA, SUBUNIT, AND MUTAGENESIS OF LEU-45;
RP   ASP-117; ARG-126; SER-131; ASP-151 AND SER-154.
RX   PubMed=23105108; DOI=10.1074/jbc.c112.421222;
RA   Kormendi V., Szyk A., Piszczek G., Roll-Mecak A.;
RT   "Crystal structures of tubulin acetyltransferase reveal a conserved
RT   catalytic core and the plasticity of the essential N terminus.";
RL   J. Biol. Chem. 287:41569-41575(2012).
CC   -!- FUNCTION: Specifically acetylates 'Lys-40' in alpha-tubulin on the
CC       lumenal side of microtubules. Promotes microtubule destabilization and
CC       accelerates microtubule dynamics; this activity may be independent of
CC       acetylation activity. Acetylates alpha-tubulin with a slow enzymatic
CC       rate, due to a catalytic site that is not optimized for acetyl
CC       transfer. Enters the microtubule through each end and diffuses quickly
CC       throughout the lumen of microtubules. Acetylates only long/old
CC       microtubules because of its slow acetylation rate since it does not
CC       have time to act on dynamically unstable microtubules before the enzyme
CC       is released. May be involved in neuron development. Acetylates alpha-
CC       tubulin in neurons, but not in cilia. {ECO:0000255|HAMAP-Rule:MF_03130,
CC       ECO:0000269|PubMed:20829795}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + L-lysyl-[alpha-tubulin] = CoA + H(+) + N(6)-
CC         acetyl-L-lysyl-[alpha-tubulin]; Xref=Rhea:RHEA:15277, Rhea:RHEA-
CC         COMP:11278, Rhea:RHEA-COMP:11279, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC         ChEBI:CHEBI:61930; EC=2.3.1.108; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03130};
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23105108,
CC       ECO:0000269|PubMed:23128673}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03130}.
CC       Membrane, clathrin-coated pit {ECO:0000255|HAMAP-Rule:MF_03130}. Cell
CC       junction, focal adhesion {ECO:0000255|HAMAP-Rule:MF_03130}. Cell
CC       projection, axon {ECO:0000255|HAMAP-Rule:MF_03130}. Cytoplasm,
CC       cytoskeleton {ECO:0000255|HAMAP-Rule:MF_03130}. Cytoplasm,
CC       cytoskeleton, spindle {ECO:0000255|HAMAP-Rule:MF_03130}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6PH17-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6PH17-2; Sequence=VSP_040229;
CC   -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes
CC       developmental defects at 48 hours post-fertilization (hpf), including
CC       cilia curved body shape, short body axis, hydrocephalus, small head and
CC       small eyes. Morphants often do not respond, or have slow startle
CC       response, when probed with a needle, consistent with neuromuscular
CC       defects. {ECO:0000269|PubMed:20829795}.
CC   -!- SIMILARITY: Belongs to the acetyltransferase ATAT1 family.
CC       {ECO:0000255|HAMAP-Rule:MF_03130}.
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DR   EMBL; BX511233; CAM56330.1; -; Genomic_DNA.
DR   EMBL; BC056749; AAH56749.1; -; mRNA.
DR   EMBL; BC065981; AAH65981.1; -; mRNA.
DR   RefSeq; NP_001315192.1; NM_001328263.1. [Q6PH17-1]
DR   RefSeq; NP_001315193.1; NM_001328264.1.
DR   RefSeq; NP_998423.1; NM_213258.2. [Q6PH17-2]
DR   PDB; 4H6U; X-ray; 2.45 A; A/B=1-188.
DR   PDB; 4H6Z; X-ray; 2.70 A; A/B=1-186.
DR   PDB; 4HKF; X-ray; 1.70 A; A=1-188.
DR   PDB; 4YRH; X-ray; 2.86 A; A/B=2-185.
DR   PDBsum; 4H6U; -.
DR   PDBsum; 4H6Z; -.
DR   PDBsum; 4HKF; -.
DR   PDBsum; 4YRH; -.
DR   AlphaFoldDB; Q6PH17; -.
DR   SMR; Q6PH17; -.
DR   STRING; 7955.ENSDARP00000049367; -.
DR   PaxDb; 7955-ENSDARP00000049367; -.
DR   DNASU; 406389; -.
DR   GeneID; 406389; -.
DR   KEGG; dre:406389; -.
DR   AGR; ZFIN:ZDB-GENE-040426-2120; -.
DR   CTD; 79969; -.
DR   ZFIN; ZDB-GENE-040426-2120; atat1.
DR   eggNOG; KOG4601; Eukaryota.
DR   HOGENOM; CLU_949825_0_0_1; -.
DR   InParanoid; Q6PH17; -.
DR   OrthoDB; 125820at2759; -.
DR   PhylomeDB; Q6PH17; -.
DR   TreeFam; TF315643; -.
DR   PRO; PR:Q6PH17; -.
DR   Proteomes; UP000000437; Chromosome 19.
DR   Bgee; ENSDARG00000004472; Expressed in head and 17 other cell types or tissues.
DR   ExpressionAtlas; Q6PH17; baseline and differential.
DR   GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR   GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005874; C:microtubule; IEA:InterPro.
DR   GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR   GO; GO:0004468; F:lysine N-acetyltransferase activity, acting on acetyl phosphate as donor; ISS:UniProtKB.
DR   GO; GO:0019799; F:tubulin N-acetyltransferase activity; IMP:UniProtKB.
DR   GO; GO:0071929; P:alpha-tubulin acetylation; ISS:UniProtKB.
DR   GO; GO:0048666; P:neuron development; IEA:UniProtKB-UniRule.
DR   GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IEA:UniProtKB-UniRule.
DR   Gene3D; 3.40.630.30; -; 1.
DR   Gene3D; 6.20.370.120; -; 1.
DR   HAMAP; MF_03130; mec17; 1.
DR   InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR   InterPro; IPR038746; Atat.
DR   InterPro; IPR007965; GNAT_ATAT.
DR   PANTHER; PTHR12327:SF0; ALPHA-TUBULIN N-ACETYLTRANSFERASE 1; 1.
DR   PANTHER; PTHR12327; UNCHARACTERIZED; 1.
DR   Pfam; PF05301; Acetyltransf_16; 1.
DR   SUPFAM; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1.
DR   PROSITE; PS51730; GNAT_ATAT; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acyltransferase; Alternative splicing; Cell junction;
KW   Cell projection; Coated pit; Cytoplasm; Cytoskeleton; Membrane;
KW   Reference proteome; Transferase.
FT   CHAIN           1..297
FT                   /note="Alpha-tubulin N-acetyltransferase 1"
FT                   /id="PRO_0000402067"
FT   DOMAIN          1..184
FT                   /note="N-acetyltransferase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03130"
FT   REGION          226..297
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        226..240
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        265..297
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         118..131
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03130,
FT                   ECO:0000269|PubMed:23105108, ECO:0000269|PubMed:23128673"
FT   BINDING         154..163
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03130,
FT                   ECO:0000269|PubMed:23105108, ECO:0000269|PubMed:23128673"
FT   SITE            53
FT                   /note="Crucial for catalytic activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03130,
FT                   ECO:0000269|PubMed:23128673"
FT   VAR_SEQ         189..297
FT                   /note="AVQLRKVPPRKPEGEIKPYSLMEREVVREEQRVLPWPFVRPGGPPHSPPLLP
FT                   SSPQSRSLSVGSSPSRAPLRPAAATVLQQGQTPSSPLNDSCRAKRTSSLNRSRLSFH
FT                   -> GTPPSPLTDQGMYGFFGPTEKSSPKKARGRDQTLFANGKRSGSGGAEGSPLAICSP
FT                   RGSPPLSPSTSVISSIPFSQCGILPQPGPASPRRGHGPPAGSDPLIPAQRQLQGKTHQF
FT                   SK (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_040229"
FT   MUTAGEN         45
FT                   /note="L->A: Reduces activity to 30%."
FT                   /evidence="ECO:0000269|PubMed:23105108"
FT   MUTAGEN         53
FT                   /note="Q->A: Reduces activity to 1.5%."
FT                   /evidence="ECO:0000269|PubMed:23128673"
FT   MUTAGEN         117
FT                   /note="D->A: Reduces activity to 3%. Causes the formation
FT                   of a constitutive dimer in solution."
FT                   /evidence="ECO:0000269|PubMed:23105108"
FT   MUTAGEN         126
FT                   /note="R->E: Reduces activity to 19%."
FT                   /evidence="ECO:0000269|PubMed:23105108"
FT   MUTAGEN         131
FT                   /note="S->L: No effect."
FT                   /evidence="ECO:0000269|PubMed:23105108"
FT   MUTAGEN         151
FT                   /note="D->A: Reduces activity to 1%."
FT                   /evidence="ECO:0000269|PubMed:23105108"
FT   MUTAGEN         154
FT                   /note="S->A: Reduces activity to 8%."
FT                   /evidence="ECO:0000269|PubMed:23105108"
FT   STRAND          1..4
FT                   /evidence="ECO:0007829|PDB:4H6U"
FT   HELIX           7..10
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   STRAND          13..20
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   HELIX           21..28
FT                   /evidence="ECO:0007829|PDB:4H6U"
FT   HELIX           35..52
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   HELIX           62..67
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   STRAND          71..77
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   HELIX           80..83
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   STRAND          86..95
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   STRAND          98..101
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   STRAND          107..110
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   STRAND          113..120
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   HELIX           122..124
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   HELIX           129..141
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   HELIX           145..147
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   STRAND          148..152
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   HELIX           155..165
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   STRAND          174..179
FT                   /evidence="ECO:0007829|PDB:4HKF"
FT   HELIX           181..183
FT                   /evidence="ECO:0007829|PDB:4HKF"
SQ   SEQUENCE   297 AA;  33202 MW;  3F08861B19D635EB CRC64;
     MDFPYDLNAL FPERISVLDS NLSAGRKAHG RPDPLPQVTT VIDELGKASS KAQQLPAPIT
     SAAKLQANRH HLYLLKDGEQ NGGRGVIVGF LKVGYKKLFL LDQRGAHLET EPLCVLDFYV
     TETLQRHGYG SELFDFMLKH KQVEPAQMAY DRPSPKFLSF LEKRYDLRNS VPQVNNFVVF
     AGFFQSRSAV QLRKVPPRKP EGEIKPYSLM EREVVREEQR VLPWPFVRPG GPPHSPPLLP
     SSPQSRSLSV GSSPSRAPLR PAAATVLQQG QTPSSPLNDS CRAKRTSSLN RSRLSFH
//