NAA80_HUMAN
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 03-AUG-2022, entry version 161.
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},
GN NAT6 {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; 13.
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; Q93015; -.
DR PeptideAtlas; Q93015; -.
DR PRIDE; Q93015; -.
DR ProteomicsDB; 75670; -. [Q93015-1]
DR ProteomicsDB; 75671; -. [Q93015-2]
DR Antibodypedia; 34876; 193 antibodies from 21 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 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; THDQLHF; -.
DR PhylomeDB; Q93015; -.
DR TreeFam; TF106312; -.
DR BioCyc; MetaCyc:MON66-43060; -.
DR BRENDA; 2.3.1.B44; 2681.
DR PathwayCommons; Q93015; -.
DR SignaLink; Q93015; -.
DR BioGRID-ORCS; 24142; 13 hits in 1075 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 101 other tissues.
DR ExpressionAtlas; Q93015; baseline and differential.
DR Genevisible; Q93015; HS.
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 InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR039840; NAA80.
DR PANTHER; PTHR13538; PTHR13538; 1.
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; 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
