ID NAA80_HUMAN Reviewed; 286 AA. AC Q93015; Q93014; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 2. DT 24-JAN-2024, entry version 169. DE RecName: Full=N-alpha-acetyltransferase 80; DE Short=HsNAAA80 {ECO:0000303|PubMed:29581307}; DE EC=2.3.1.- {ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29581307, ECO:0000269|PubMed:30028079}; DE AltName: Full=N-acetyltransferase 6 {ECO:0000303|PubMed:30028079}; DE AltName: Full=Protein fusion-2 {ECO:0000303|PubMed:10644992}; DE Short=Protein fus-2 {ECO:0000303|PubMed:10644992}; GN Name=NAA80 {ECO:0000303|PubMed:29581253, ECO:0000312|HGNC:HGNC:30252}; GN Synonyms=FUS2 {ECO:0000303|PubMed:10644992}, NAT6 GN {ECO:0000303|PubMed:30028079}; 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). RA Fong K., Zabarovsky E., Kashuba V., Kuzmin I., Latif F., Mele G., RA Sekido Y., Bader S., Duh F.-M., Wei M.-H., Lerman M.I., Minna J.D.; RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Pancreas; 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 [4] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=10644992; DOI=10.1038/sj.onc.1203234; RA Zegerman P., Bannister A.J., Kouzarides T.; RT "The putative tumour suppressor Fus-2 is an N-acetyltransferase."; RL Oncogene 19:161-163(2000). RN [5] RP DISCUSSION OF SEQUENCE, TISSUE SPECIFICITY, AND VARIANTS SER-145 AND RP SER-207. RX PubMed=11085536; RG The international lung cancer chromosome 3p21.3 tumor suppressor gene consortium; RA Lerman M.I., Minna J.D.; RT "The 630-kb lung cancer homozygous deletion region on human chromosome RT 3p21.3: identification and evaluation of the resident candidate tumor RT suppressor genes."; RL Cancer Res. 60:6116-6133(2000). RN [6] RP FUNCTION. RX PubMed=30028079; DOI=10.1111/febs.14605; RA Wiame E., Tahay G., Tyteca D., Vertommen D., Stroobant V., Bommer G.T., RA Van Schaftingen E.; RT "NAT6 acetylates the N-terminus of different forms of actin."; RL FEBS J. 285:3299-3316(2018). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP TRP-83; ARG-148; GLY-151 AND TYR-183. RX PubMed=29581253; DOI=10.1073/pnas.1718336115; RA Drazic A., Aksnes H., Marie M., Boczkowska M., Varland S., Timmerman E., RA Foyn H., Glomnes N., Rebowski G., Impens F., Gevaert K., Dominguez R., RA Arnesen T.; RT "NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton RT assembly and cell motility."; RL Proc. Natl. Acad. Sci. U.S.A. 115:4399-4404(2018). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=29581307; DOI=10.1073/pnas.1719251115; RA Goris M., Magin R.S., Foyn H., Myklebust L.M., Varland S., Ree R., RA Drazic A., Bhambra P., Stoeve S.I., Baumann M., Haug B.E., Marmorstein R., RA Arnesen T.; RT "Structural determinants and cellular environment define processed actin as RT the sole substrate of the N-terminal acetyltransferase NAA80."; RL Proc. Natl. Acad. Sci. U.S.A. 115:4405-4410(2018). CC -!- FUNCTION: N-alpha-acetyltransferase that specifically mediates the CC acetylation of the acidic amino terminus of processed forms of CC beta- and gamma-actin (ACTB and ACTG, respectively) (PubMed:30028079, CC PubMed:29581253). N-terminal acetylation of processed beta- and gamma- CC actin regulates actin filament depolymerization and elongation CC (PubMed:29581253). In vivo, preferentially displays N-terminal CC acetyltransferase activity towards acid N-terminal sequences starting CC with Asp-Asp-Asp and Glu-Glu-Glu (PubMed:30028079, PubMed:29581253). In CC vitro, shows high activity towards Met-Asp-Glu-Leu and Met-Asp-Asp-Asp CC (PubMed:10644992, PubMed:29581307). May act as a tumor suppressor CC (PubMed:10644992). {ECO:0000269|PubMed:10644992, CC ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29581307, CC ECO:0000269|PubMed:30028079}. CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + N-terminal L-aspartyl-L-aspartyl-L-aspartyl- CC [protein] = CoA + H(+) + N-terminal N-acetyl-L-aspartyl-L-aspartyl-L- CC aspartyl-[protein]; Xref=Rhea:RHEA:57328, Rhea:RHEA-COMP:14863, CC Rhea:RHEA-COMP:14864, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57288, ChEBI:CHEBI:141602, ChEBI:CHEBI:141604; CC Evidence={ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29581307}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + N-terminal L-glutamyl-L-glutamyl-L-glutamyl- CC [protein] = CoA + H(+) + N-terminal N-acetyl-L-glutamyl-L-glutamyl-L- CC glutamyl-[protein]; Xref=Rhea:RHEA:57324, Rhea:RHEA-COMP:14865, CC Rhea:RHEA-COMP:14866, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57288, ChEBI:CHEBI:141603, ChEBI:CHEBI:141606; CC Evidence={ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29581307}; CC -!- INTERACTION: CC Q93015-2; Q8IYS1: PM20D2; NbExp=3; IntAct=EBI-12126220, EBI-11339910; CC Q93015-2; Q96CD2: PPCDC; NbExp=3; IntAct=EBI-12126220, EBI-724333; CC Q93015-2; O75716: STK16; NbExp=5; IntAct=EBI-12126220, EBI-749295; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10644992, CC ECO:0000269|PubMed:30028079}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q93015-1; Sequence=Displayed; CC Name=2; CC IsoId=Q93015-2; Sequence=VSP_037187; CC -!- TISSUE SPECIFICITY: Strongly expressed in heart and skeletal muscle, CC followed by brain and pancreas, with weak expression in kidney, liver, CC and lung and no expression in placenta. {ECO:0000269|PubMed:11085536}. CC -!- SIMILARITY: Belongs to the acetyltransferase family. {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; AF040706; AAC70913.1; -; mRNA. DR EMBL; AF040705; AAC70912.1; -; mRNA. DR EMBL; U73167; AAC02732.1; -; Genomic_DNA. DR EMBL; BC004483; AAH04483.2; -; mRNA. DR CCDS; CCDS43095.1; -. [Q93015-2] DR CCDS; CCDS56258.1; -. [Q93015-1] DR RefSeq; NP_001186945.1; NM_001200016.1. [Q93015-1] DR RefSeq; NP_001186947.1; NM_001200018.1. [Q93015-1] DR RefSeq; NP_036323.2; NM_012191.3. [Q93015-2] DR PDB; 6NAS; X-ray; 2.90 A; N=56-286. DR PDB; 6NBE; X-ray; 2.00 A; N=56-286. DR PDB; 6NBW; X-ray; 2.50 A; N=56-286. DR PDBsum; 6NAS; -. DR PDBsum; 6NBE; -. DR PDBsum; 6NBW; -. DR AlphaFoldDB; Q93015; -. DR SMR; Q93015; -. DR BioGRID; 117293; 14. DR IntAct; Q93015; 5. DR STRING; 9606.ENSP00000346927; -. DR iPTMnet; Q93015; -. DR PhosphoSitePlus; Q93015; -. DR BioMuta; NAT6; -. DR DMDM; 25008833; -. DR EPD; Q93015; -. DR jPOST; Q93015; -. DR MassIVE; Q93015; -. DR MaxQB; Q93015; -. DR PaxDb; 9606-ENSP00000346927; -. DR PeptideAtlas; Q93015; -. DR ProteomicsDB; 75670; -. [Q93015-1] DR ProteomicsDB; 75671; -. [Q93015-2] DR Pumba; Q93015; -. DR Antibodypedia; 34876; 209 antibodies from 22 providers. DR DNASU; 24142; -. DR Ensembl; ENST00000354862.4; ENSP00000346927.4; ENSG00000243477.6. [Q93015-2] DR Ensembl; ENST00000417393.1; ENSP00000391893.1; ENSG00000243477.6. [Q93015-1] DR Ensembl; ENST00000443094.3; ENSP00000410610.2; ENSG00000243477.6. [Q93015-1] DR Ensembl; ENST00000443842.1; ENSP00000400559.1; ENSG00000243477.6. [Q93015-1] DR GeneID; 24142; -. DR KEGG; hsa:24142; -. DR MANE-Select; ENST00000443094.3; ENSP00000410610.2; NM_001200016.2; NP_001186945.1. DR UCSC; uc003czi.4; human. [Q93015-1] DR AGR; HGNC:30252; -. DR CTD; 24142; -. DR DisGeNET; 24142; -. DR GeneCards; NAA80; -. DR HGNC; HGNC:30252; NAA80. DR HPA; ENSG00000243477; Tissue enhanced (testis). DR MIM; 607073; gene. DR neXtProt; NX_Q93015; -. DR OpenTargets; ENSG00000243477; -. DR PharmGKB; PA134979782; -. DR VEuPathDB; HostDB:ENSG00000243477; -. DR eggNOG; KOG3397; Eukaryota. DR GeneTree; ENSGT00390000000980; -. DR HOGENOM; CLU_077855_0_0_1; -. DR InParanoid; Q93015; -. DR OMA; IYWMHKD; -. DR OrthoDB; 5402419at2759; -. DR PhylomeDB; Q93015; -. DR TreeFam; TF106312; -. DR BioCyc; MetaCyc:MONOMER66-43060; -. DR BRENDA; 2.3.1.B44; 2681. DR PathwayCommons; Q93015; -. DR SABIO-RK; Q93015; -. DR SignaLink; Q93015; -. DR BioGRID-ORCS; 24142; 13 hits in 1149 CRISPR screens. DR GenomeRNAi; 24142; -. DR Pharos; Q93015; Tbio. DR PRO; PR:Q93015; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q93015; Protein. DR Bgee; ENSG00000243477; Expressed in left testis and 103 other cell types or tissues. DR ExpressionAtlas; Q93015; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:1905502; F:acetyl-CoA binding; IDA:UniProtKB. DR GO; GO:0008080; F:N-acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0004596; F:peptide alpha-N-acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0030047; P:actin modification; IDA:UniProtKB. DR GO; GO:0017190; P:N-terminal peptidyl-aspartic acid acetylation; IDA:UniProtKB. DR GO; GO:0018002; P:N-terminal peptidyl-glutamic acid acetylation; IDA:UniProtKB. DR GO; GO:0006473; P:protein acetylation; IDA:UniProtKB. DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; IMP:UniProtKB. 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 InterPro; IPR039840; NAA80. DR PANTHER; PTHR13538; N-ACETYLTRANSFERASE 6; 1. DR PANTHER; PTHR13538:SF4; N-ALPHA-ACETYLTRANSFERASE 80; 1. DR Pfam; PF00583; Acetyltransf_1; 1. DR SUPFAM; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1. DR PROSITE; PS51186; GNAT; 1. DR Genevisible; Q93015; HS. PE 1: Evidence at protein level; KW 3D-structure; Acyltransferase; Alternative splicing; Cytoplasm; KW Reference proteome; Transferase; Tumor suppressor. FT CHAIN 1..286 FT /note="N-alpha-acetyltransferase 80" FT /id="PRO_0000074536" FT DOMAIN 60..207 FT /note="N-acetyltransferase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532" FT REGION 33..54 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 212..269 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 235..262 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 85 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q59DX8" FT BINDING 90..93 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q59DX8" FT BINDING 141..143 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000250|UniProtKB:Q59DX8" FT BINDING 149..154 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000250|UniProtKB:Q59DX8" FT BINDING 179 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000250|UniProtKB:Q59DX8" FT VAR_SEQ 1 FT /note="M -> MQELTLSPGPAKLTPTLDPTHRM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_037187" FT VARIANT 145 FT /note="R -> S (in non-small cell lung cancer cell lines)" FT /evidence="ECO:0000269|PubMed:11085536" FT /id="VAR_014224" FT VARIANT 207 FT /note="T -> S (in non-small cell lung cancer cell lines; FT dbSNP:rs200439690)" FT /evidence="ECO:0000269|PubMed:11085536" FT /id="VAR_014225" FT MUTAGEN 83 FT /note="W->F: In NAA80mut; abolished acetyltransferase FT activity; when associated with Q-148, D-151 and F-183." FT /evidence="ECO:0000269|PubMed:29581253" FT MUTAGEN 148 FT /note="R->Q: In NAA80mut; abolished acetyltransferase FT activity; when associated with F-83, D-151 and F-183." FT /evidence="ECO:0000269|PubMed:29581253" FT MUTAGEN 151 FT /note="G->D: In NAA80mut; abolished acetyltransferase FT activity; when associated with F-83, Q-148 and F-183." FT /evidence="ECO:0000269|PubMed:29581253" FT MUTAGEN 183 FT /note="Y->F: In NAA80mut; abolished acetyltransferase FT activity; when associated with F-83, Q-148 and D-151." FT /evidence="ECO:0000269|PubMed:29581253" FT STRAND 61..64 FT /evidence="ECO:0007829|PDB:6NBE" FT HELIX 65..67 FT /evidence="ECO:0007829|PDB:6NBE" FT HELIX 69..71 FT /evidence="ECO:0007829|PDB:6NBE" FT HELIX 72..82 FT /evidence="ECO:0007829|PDB:6NBE" FT HELIX 87..95 FT /evidence="ECO:0007829|PDB:6NBE" FT STRAND 103..110 FT /evidence="ECO:0007829|PDB:6NBE" FT STRAND 112..116 FT /evidence="ECO:0007829|PDB:6NBE" FT STRAND 119..129 FT /evidence="ECO:0007829|PDB:6NBE" FT STRAND 135..143 FT /evidence="ECO:0007829|PDB:6NBE" FT HELIX 145..147 FT /evidence="ECO:0007829|PDB:6NBE" FT HELIX 152..166 FT /evidence="ECO:0007829|PDB:6NBE" FT STRAND 171..177 FT /evidence="ECO:0007829|PDB:6NBE" FT HELIX 180..185 FT /evidence="ECO:0007829|PDB:6NBE" FT HELIX 269..271 FT /evidence="ECO:0007829|PDB:6NBE" FT STRAND 280..285 FT /evidence="ECO:0007829|PDB:6NBE" SQ SEQUENCE 286 AA; 31445 MW; A755E2E3367625DB CRC64; MELILSTSPA ELTLDPACQP KLPLDSTCQP EMTFNPGPTE LTLDPEHQPE ETPAPSLAEL TLEPVHRRPE LLDACADLIN DQWPRSRTSR LHSLGQSSDA FPLCLMLLSP HPTLEAAPVV VGHARLSRVL NQPQSLLVET VVVARALRGR GFGRRLMEGL EVFARARGFR KLHLTTHDQV HFYTHLGYQL GEPVQGLVFT SRRLPATLLN AFPTAPSPRP PRKAPNLTAQ AAPRGPKGPP LPPPPPLPEC LTISPPVPSG PPSKSLLETQ YQNVRGRPIF WMEKDI //