Full text data of NAA10
NAA10
(ARD1, ARD1A, TE2)
[Confidence: low (only semi-automatic identification from reviews)]
N-alpha-acetyltransferase 10; 2.3.1.-; 2.3.1.88 (N-terminal acetyltransferase complex ARD1 subunit homolog A; NatA catalytic subunit)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
N-alpha-acetyltransferase 10; 2.3.1.-; 2.3.1.88 (N-terminal acetyltransferase complex ARD1 subunit homolog A; NatA catalytic subunit)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P41227
ID NAA10_HUMAN Reviewed; 235 AA.
AC P41227; A6NM98;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=N-alpha-acetyltransferase 10;
DE EC=2.3.1.-;
DE EC=2.3.1.88;
DE AltName: Full=N-terminal acetyltransferase complex ARD1 subunit homolog A;
DE AltName: Full=NatA catalytic subunit;
GN Name=NAA10; Synonyms=ARD1, ARD1A, TE2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7981673; DOI=10.1093/hmg/3.7.1061;
RA Tribioli C., Mancini M., Plassart E., Bione S., Rivella S., Sala C.,
RA Torri G., Toniolo D.;
RT "Isolation of new genes in distal Xq28: transcriptional map and
RT identification of a human homologue of the ARD1 N-acetyl transferase
RT of Saccharomyces cerevisiae.";
RL Hum. Mol. Genet. 3:1061-1068(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS
RP SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP NAA15 AND RIBOSOMAL PROTEINS.
RC TISSUE=Thyroid carcinoma;
RX PubMed=15496142; DOI=10.1042/BJ20041071;
RA Arnesen T., Anderson D., Baldersheim C., Lanotte M., Varhaug J.E.,
RA Lillehaug J.R.;
RT "Identification and characterization of the human ARD1-NATH protein
RT acetyltransferase complex.";
RL Biochem. J. 386:433-443(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH HIF1A, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12464182; DOI=10.1016/S0092-8674(02)01085-1;
RA Jeong J.-W., Bae M.-K., Ahn M.-Y., Kim S.-H., Sohn T.-K., Bae M.-H.,
RA Yoo M.-A., Song E.-J., Lee K.-J., Kim K.-W.;
RT "Regulation and destabilization of HIF-1alpha by ARD1-mediated
RT acetylation.";
RL Cell 111:709-720(2002).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP INTERACTION WITH NAA50.
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
RT conserved component of the NatA protein N-alpha-acetyltransferase
RT complex.";
RL Gene 371:291-295(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186 AND SER-205, AND
RP MASS SPECTROMETRY.
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
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:
RT nomenclature, subunits and substrates.";
RL BMC Proc. 3:S2-S2(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH MYLK.
RX PubMed=19826488; DOI=10.1371/journal.pone.0007451;
RA Shin D.H., Chun Y.-S., Lee K.-H., Shin H.-W., Park J.-W.;
RT "Arrest defective-1 controls tumor cell behavior by acetylating myosin
RT light chain kinase.";
RL PLoS ONE 4:E7451-E7451(2009).
RN [13]
RP SUBUNIT.
RX PubMed=20154145; DOI=10.1128/MCB.01199-09;
RA Arnesen T., Starheim K.K., Van Damme P., Evjenth R., Dinh H.,
RA Betts M.J., Ryningen A., Vandekerckhove J., Gevaert K., Anderson D.;
RT "The chaperone-like protein HYPK acts together with NatA in
RT cotranslational N-terminal acetylation and prevention of Huntingtin
RT aggregation.";
RL Mol. Cell. Biol. 30:1898-1909(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182; SER-205; SER-213
RP AND SER-216, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182 AND SER-205, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP VARIANT NATD PRO-37, AND CHARACTERIZATION OF VARIANT NATD PRO-37.
RX PubMed=21700266; DOI=10.1016/j.ajhg.2011.05.017;
RA Rope A.F., Wang K., Evjenth R., Xing J., Johnston J.J., Swensen J.J.,
RA Johnson W.E., Moore B., Huff C.D., Bird L.M., Carey J.C., Opitz J.M.,
RA Stevens C.A., Jiang T., Schank C., Fain H.D., Robison R., Dalley B.,
RA Chin S., South S.T., Pysher T.J., Jorde L.B., Hakonarson H.,
RA Lillehaug J.R., Biesecker L.G., Yandell M., Arnesen T., Lyon G.J.;
RT "Using VAAST to identify an X-linked disorder resulting in lethality
RT in male infants due to N-terminal acetyltransferase deficiency.";
RL Am. J. Hum. Genet. 89:28-43(2011).
CC -!- FUNCTION: In complex with NAA15, displays alpha (N-terminal)
CC acetyltransferase activity. Without NAA15, displays epsilon
CC (internal) acetyltransferase activity towards HIF1A, thereby
CC promoting its degradation. Represses MYLK kinase activity by
CC acetylation, and thus represses tumor cell migration.
CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + peptide = N(alpha)-acetylpeptide
CC + CoA.
CC -!- SUBUNIT: Interacts with HIF1A (via its ODD domain); the
CC interaction increases HIF1A protein stability during normoxia, and
CC down-regulates it when induced by hypoxia. Interacts with NAA15,
CC NAA50 and with the ribosome. Binds to MYLK. Associates with HYPK
CC when in complex with NAA15.
CC -!- INTERACTION:
CC Q15052:ARHGEF6; NbExp=3; IntAct=EBI-747693, EBI-1642523;
CC Q14155:ARHGEF7; NbExp=3; IntAct=EBI-747693, EBI-717515;
CC O55043:Arhgef7 (xeno); NbExp=3; IntAct=EBI-747693, EBI-3649585;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=According to
CC PubMed:12464182 it is cytoplasmic. According to PubMed:15496142,
CC it is nuclear and cytoplasmic. Also present in the free cytosolic
CC and cytoskeleton-bound polysomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P41227-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P41227-2; Sequence=VSP_046205, VSP_046206;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Cleaved by caspases during apoptosis.
CC -!- DISEASE: N-terminal acetyltransferase deficiency (NATD)
CC [MIM:300855]: An enzymatic deficiency resulting in postnatal
CC growth failure with severe delays and dysmorphic features. It is
CC clinically characterized by wrinkled forehead, prominent eyes,
CC widely opened anterior and posterior fontanels, downsloping
CC palpebral fissures, thickened lids, large ears, flared nares,
CC hypoplastic alae, short columella, protruding upper lip, and
CC microretrognathia. There are also delayed closing of fontanels and
CC broad great toes. Skin is characterized by redundancy or laxity
CC with minimal subcutaneous fat, cutaneous capillary malformations,
CC and very fine hair and eyebrows. Death results from cardiogenic
CC shock following arrhythmia. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. ARD1
CC subfamily.
CC -!- SIMILARITY: Contains 1 N-acetyltransferase domain.
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DR EMBL; X77588; CAA54691.1; -; mRNA.
DR EMBL; U52112; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471172; EAW72774.1; -; Genomic_DNA.
DR EMBL; BC000308; AAH00308.1; -; mRNA.
DR EMBL; BC019312; AAH19312.1; -; mRNA.
DR PIR; I38333; I38333.
DR RefSeq; NP_001243048.1; NM_001256119.1.
DR RefSeq; NP_003482.1; NM_003491.3.
DR UniGene; Hs.433291; -.
DR ProteinModelPortal; P41227; -.
DR SMR; P41227; 3-149.
DR IntAct; P41227; 15.
DR MINT; MINT-1499850; -.
DR STRING; 9606.ENSP00000417763; -.
DR PhosphoSite; P41227; -.
DR DMDM; 728880; -.
DR PaxDb; P41227; -.
DR PRIDE; P41227; -.
DR DNASU; 8260; -.
DR Ensembl; ENST00000370009; ENSP00000359026; ENSG00000102030.
DR Ensembl; ENST00000464845; ENSP00000417763; ENSG00000102030.
DR Ensembl; ENST00000596061; ENSP00000469041; ENSG00000268281.
DR Ensembl; ENST00000596770; ENSP00000469576; ENSG00000268281.
DR GeneID; 8260; -.
DR KEGG; hsa:8260; -.
DR UCSC; uc004fjn.2; human.
DR CTD; 8260; -.
DR GeneCards; GC0XM153194; -.
DR HGNC; HGNC:18704; NAA10.
DR HPA; CAB006269; -.
DR MIM; 300013; gene.
DR MIM; 300855; phenotype.
DR neXtProt; NX_P41227; -.
DR Orphanet; 276432; Premature ageing appearance-developmental delay-cardiac arrhythmia syndrome.
DR PharmGKB; PA38648; -.
DR eggNOG; COG0456; -.
DR HOGENOM; HOG000078523; -.
DR HOVERGEN; HBG050561; -.
DR InParanoid; P41227; -.
DR KO; K00670; -.
DR ChiTaRS; NAA10; human.
DR GeneWiki; ARD1A; -.
DR GenomeRNAi; 8260; -.
DR NextBio; 31019; -.
DR PRO; PR:P41227; -.
DR ArrayExpress; P41227; -.
DR Bgee; P41227; -.
DR CleanEx; HS_ARD1A; -.
DR Genevestigator; P41227; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008080; F:N-acetyltransferase activity; TAS:ProtInc.
DR GO; GO:0004596; F:peptide alpha-N-acetyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006323; P:DNA packaging; TAS:ProtInc.
DR GO; GO:0006475; P:internal protein amino acid acetylation; TAS:ProtInc.
DR GO; GO:0006474; P:N-terminal protein amino acid acetylation; IDA:UniProtKB.
DR Gene3D; 3.40.630.30; -; 1.
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 Acetylation; Acyltransferase; Alternative splicing; Complete proteome;
KW Cytoplasm; Disease mutation; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1 235 N-alpha-acetyltransferase 10.
FT /FTId=PRO_0000074532.
FT DOMAIN 1 152 N-acetyltransferase.
FT REGION 1 58 Interaction with NAA15.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 182 182 Phosphoserine.
FT MOD_RES 186 186 Phosphoserine.
FT MOD_RES 205 205 Phosphoserine.
FT MOD_RES 213 213 Phosphoserine.
FT MOD_RES 216 216 Phosphoserine.
FT VAR_SEQ 114 128 Missing (in isoform 2).
FT /FTId=VSP_046205.
FT VAR_SEQ 129 129 Q -> R (in isoform 2).
FT /FTId=VSP_046206.
FT VARIANT 37 37 S -> P (in NATD; in vitro assays of
FT protein function demonstrates 60 to 80%
FT reduction in NAT activity of the mutant
FT protein toward the in vivo substrate
FT RPP30 protein; the activity toward the
FT substrate HMGA1 protein is reduced by
FT only 20%).
FT /FTId=VAR_066652.
SQ SEQUENCE 235 AA; 26459 MW; 6393A907F5C2DDC4 CRC64;
MNIRNARPED LMNMQHCNLL CLPENYQMKY YFYHGLSWPQ LSYIAEDENG KIVGYVLAKM
EEDPDDVPHG HITSLAVKRS HRRLGLAQKL MDQASRAMIE NFNAKYVSLH VRKSNRAALH
LYSNTLNFQI SEVEPKYYAD GEDAYAMKRD LTQMADELRR HLELKEKGRH VVLGAIENKV
ESKGNSPPSS GEACREEKGL AAEDSGGDSK DLSEVSETTE STDVKDSSEA SDSAS
//
ID NAA10_HUMAN Reviewed; 235 AA.
AC P41227; A6NM98;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=N-alpha-acetyltransferase 10;
DE EC=2.3.1.-;
DE EC=2.3.1.88;
DE AltName: Full=N-terminal acetyltransferase complex ARD1 subunit homolog A;
DE AltName: Full=NatA catalytic subunit;
GN Name=NAA10; Synonyms=ARD1, ARD1A, TE2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7981673; DOI=10.1093/hmg/3.7.1061;
RA Tribioli C., Mancini M., Plassart E., Bione S., Rivella S., Sala C.,
RA Torri G., Toniolo D.;
RT "Isolation of new genes in distal Xq28: transcriptional map and
RT identification of a human homologue of the ARD1 N-acetyl transferase
RT of Saccharomyces cerevisiae.";
RL Hum. Mol. Genet. 3:1061-1068(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS
RP SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP NAA15 AND RIBOSOMAL PROTEINS.
RC TISSUE=Thyroid carcinoma;
RX PubMed=15496142; DOI=10.1042/BJ20041071;
RA Arnesen T., Anderson D., Baldersheim C., Lanotte M., Varhaug J.E.,
RA Lillehaug J.R.;
RT "Identification and characterization of the human ARD1-NATH protein
RT acetyltransferase complex.";
RL Biochem. J. 386:433-443(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH HIF1A, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12464182; DOI=10.1016/S0092-8674(02)01085-1;
RA Jeong J.-W., Bae M.-K., Ahn M.-Y., Kim S.-H., Sohn T.-K., Bae M.-H.,
RA Yoo M.-A., Song E.-J., Lee K.-J., Kim K.-W.;
RT "Regulation and destabilization of HIF-1alpha by ARD1-mediated
RT acetylation.";
RL Cell 111:709-720(2002).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP INTERACTION WITH NAA50.
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
RT conserved component of the NatA protein N-alpha-acetyltransferase
RT complex.";
RL Gene 371:291-295(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186 AND SER-205, AND
RP MASS SPECTROMETRY.
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
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:
RT nomenclature, subunits and substrates.";
RL BMC Proc. 3:S2-S2(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH MYLK.
RX PubMed=19826488; DOI=10.1371/journal.pone.0007451;
RA Shin D.H., Chun Y.-S., Lee K.-H., Shin H.-W., Park J.-W.;
RT "Arrest defective-1 controls tumor cell behavior by acetylating myosin
RT light chain kinase.";
RL PLoS ONE 4:E7451-E7451(2009).
RN [13]
RP SUBUNIT.
RX PubMed=20154145; DOI=10.1128/MCB.01199-09;
RA Arnesen T., Starheim K.K., Van Damme P., Evjenth R., Dinh H.,
RA Betts M.J., Ryningen A., Vandekerckhove J., Gevaert K., Anderson D.;
RT "The chaperone-like protein HYPK acts together with NatA in
RT cotranslational N-terminal acetylation and prevention of Huntingtin
RT aggregation.";
RL Mol. Cell. Biol. 30:1898-1909(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182; SER-205; SER-213
RP AND SER-216, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182 AND SER-205, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP VARIANT NATD PRO-37, AND CHARACTERIZATION OF VARIANT NATD PRO-37.
RX PubMed=21700266; DOI=10.1016/j.ajhg.2011.05.017;
RA Rope A.F., Wang K., Evjenth R., Xing J., Johnston J.J., Swensen J.J.,
RA Johnson W.E., Moore B., Huff C.D., Bird L.M., Carey J.C., Opitz J.M.,
RA Stevens C.A., Jiang T., Schank C., Fain H.D., Robison R., Dalley B.,
RA Chin S., South S.T., Pysher T.J., Jorde L.B., Hakonarson H.,
RA Lillehaug J.R., Biesecker L.G., Yandell M., Arnesen T., Lyon G.J.;
RT "Using VAAST to identify an X-linked disorder resulting in lethality
RT in male infants due to N-terminal acetyltransferase deficiency.";
RL Am. J. Hum. Genet. 89:28-43(2011).
CC -!- FUNCTION: In complex with NAA15, displays alpha (N-terminal)
CC acetyltransferase activity. Without NAA15, displays epsilon
CC (internal) acetyltransferase activity towards HIF1A, thereby
CC promoting its degradation. Represses MYLK kinase activity by
CC acetylation, and thus represses tumor cell migration.
CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + peptide = N(alpha)-acetylpeptide
CC + CoA.
CC -!- SUBUNIT: Interacts with HIF1A (via its ODD domain); the
CC interaction increases HIF1A protein stability during normoxia, and
CC down-regulates it when induced by hypoxia. Interacts with NAA15,
CC NAA50 and with the ribosome. Binds to MYLK. Associates with HYPK
CC when in complex with NAA15.
CC -!- INTERACTION:
CC Q15052:ARHGEF6; NbExp=3; IntAct=EBI-747693, EBI-1642523;
CC Q14155:ARHGEF7; NbExp=3; IntAct=EBI-747693, EBI-717515;
CC O55043:Arhgef7 (xeno); NbExp=3; IntAct=EBI-747693, EBI-3649585;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=According to
CC PubMed:12464182 it is cytoplasmic. According to PubMed:15496142,
CC it is nuclear and cytoplasmic. Also present in the free cytosolic
CC and cytoskeleton-bound polysomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P41227-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P41227-2; Sequence=VSP_046205, VSP_046206;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Cleaved by caspases during apoptosis.
CC -!- DISEASE: N-terminal acetyltransferase deficiency (NATD)
CC [MIM:300855]: An enzymatic deficiency resulting in postnatal
CC growth failure with severe delays and dysmorphic features. It is
CC clinically characterized by wrinkled forehead, prominent eyes,
CC widely opened anterior and posterior fontanels, downsloping
CC palpebral fissures, thickened lids, large ears, flared nares,
CC hypoplastic alae, short columella, protruding upper lip, and
CC microretrognathia. There are also delayed closing of fontanels and
CC broad great toes. Skin is characterized by redundancy or laxity
CC with minimal subcutaneous fat, cutaneous capillary malformations,
CC and very fine hair and eyebrows. Death results from cardiogenic
CC shock following arrhythmia. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. ARD1
CC subfamily.
CC -!- SIMILARITY: Contains 1 N-acetyltransferase domain.
CC -----------------------------------------------------------------------
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DR EMBL; X77588; CAA54691.1; -; mRNA.
DR EMBL; U52112; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471172; EAW72774.1; -; Genomic_DNA.
DR EMBL; BC000308; AAH00308.1; -; mRNA.
DR EMBL; BC019312; AAH19312.1; -; mRNA.
DR PIR; I38333; I38333.
DR RefSeq; NP_001243048.1; NM_001256119.1.
DR RefSeq; NP_003482.1; NM_003491.3.
DR UniGene; Hs.433291; -.
DR ProteinModelPortal; P41227; -.
DR SMR; P41227; 3-149.
DR IntAct; P41227; 15.
DR MINT; MINT-1499850; -.
DR STRING; 9606.ENSP00000417763; -.
DR PhosphoSite; P41227; -.
DR DMDM; 728880; -.
DR PaxDb; P41227; -.
DR PRIDE; P41227; -.
DR DNASU; 8260; -.
DR Ensembl; ENST00000370009; ENSP00000359026; ENSG00000102030.
DR Ensembl; ENST00000464845; ENSP00000417763; ENSG00000102030.
DR Ensembl; ENST00000596061; ENSP00000469041; ENSG00000268281.
DR Ensembl; ENST00000596770; ENSP00000469576; ENSG00000268281.
DR GeneID; 8260; -.
DR KEGG; hsa:8260; -.
DR UCSC; uc004fjn.2; human.
DR CTD; 8260; -.
DR GeneCards; GC0XM153194; -.
DR HGNC; HGNC:18704; NAA10.
DR HPA; CAB006269; -.
DR MIM; 300013; gene.
DR MIM; 300855; phenotype.
DR neXtProt; NX_P41227; -.
DR Orphanet; 276432; Premature ageing appearance-developmental delay-cardiac arrhythmia syndrome.
DR PharmGKB; PA38648; -.
DR eggNOG; COG0456; -.
DR HOGENOM; HOG000078523; -.
DR HOVERGEN; HBG050561; -.
DR InParanoid; P41227; -.
DR KO; K00670; -.
DR ChiTaRS; NAA10; human.
DR GeneWiki; ARD1A; -.
DR GenomeRNAi; 8260; -.
DR NextBio; 31019; -.
DR PRO; PR:P41227; -.
DR ArrayExpress; P41227; -.
DR Bgee; P41227; -.
DR CleanEx; HS_ARD1A; -.
DR Genevestigator; P41227; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008080; F:N-acetyltransferase activity; TAS:ProtInc.
DR GO; GO:0004596; F:peptide alpha-N-acetyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006323; P:DNA packaging; TAS:ProtInc.
DR GO; GO:0006475; P:internal protein amino acid acetylation; TAS:ProtInc.
DR GO; GO:0006474; P:N-terminal protein amino acid acetylation; IDA:UniProtKB.
DR Gene3D; 3.40.630.30; -; 1.
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 Acetylation; Acyltransferase; Alternative splicing; Complete proteome;
KW Cytoplasm; Disease mutation; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1 235 N-alpha-acetyltransferase 10.
FT /FTId=PRO_0000074532.
FT DOMAIN 1 152 N-acetyltransferase.
FT REGION 1 58 Interaction with NAA15.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 182 182 Phosphoserine.
FT MOD_RES 186 186 Phosphoserine.
FT MOD_RES 205 205 Phosphoserine.
FT MOD_RES 213 213 Phosphoserine.
FT MOD_RES 216 216 Phosphoserine.
FT VAR_SEQ 114 128 Missing (in isoform 2).
FT /FTId=VSP_046205.
FT VAR_SEQ 129 129 Q -> R (in isoform 2).
FT /FTId=VSP_046206.
FT VARIANT 37 37 S -> P (in NATD; in vitro assays of
FT protein function demonstrates 60 to 80%
FT reduction in NAT activity of the mutant
FT protein toward the in vivo substrate
FT RPP30 protein; the activity toward the
FT substrate HMGA1 protein is reduced by
FT only 20%).
FT /FTId=VAR_066652.
SQ SEQUENCE 235 AA; 26459 MW; 6393A907F5C2DDC4 CRC64;
MNIRNARPED LMNMQHCNLL CLPENYQMKY YFYHGLSWPQ LSYIAEDENG KIVGYVLAKM
EEDPDDVPHG HITSLAVKRS HRRLGLAQKL MDQASRAMIE NFNAKYVSLH VRKSNRAALH
LYSNTLNFQI SEVEPKYYAD GEDAYAMKRD LTQMADELRR HLELKEKGRH VVLGAIENKV
ESKGNSPPSS GEACREEKGL AAEDSGGDSK DLSEVSETTE STDVKDSSEA SDSAS
//
MIM
300013
*RECORD*
*FIELD* NO
300013
*FIELD* TI
*300013 N-ALPHA-ACETYLTRANSFERASE 10, NatA CATALYTIC SUBUNIT; NAA10
;;ARD1 N-ACETYLTRANSFERASE, S. CEREVISIAE, HOMOLOG OF, A; ARD1A;;
read moreARREST-DEFECTIVE PROTEIN 1; ARD1;;
TE2
*FIELD* TX
DESCRIPTION
N-alpha-acetylation is a common protein modification that occurs during
protein synthesis and involves the transfer of an acetyl group from
acetyl-coenzyme A to the protein alpha-amino group. ARD1A, together with
NATH (NARG1, NAA15; 608000), is part of a major
N-alpha-acetyltransferase complex responsible for alpha-acetylation of
proteins and peptides (Sanchez-Puig and Fersht, 2006).
CLONING
Tribioli et al. (1994) described the physical and transcriptional
organization of a region of 140 kb in Xq28, 5-prime to the L1CAM gene
(308840). They established a transcriptional map of the region by
isolating and mapping CpG islands to the physical map, determining
partial nucleotide sequences, and studying the pattern of expression and
orientation of the transcripts. They succeeded in positioning 4
previously identified genes: L1CAM, AVPR2 (300538), HFC1 (300019), and
RENBP (312420). All genes in the region are rather small, ranging in
size from 2 to 30 kb, and very close to one another. With the exception
of the AVPR2 gene, they serve a housekeeping function, having a CpG
island at their 5-prime end and the same orientation of transcription.
This kind of organization is consistent with the one previously
described for the more distal portion of Xq28, between the color vision
pigment genes and the G6PD gene and indicates that genes with a
housekeeping and tissue-specific pattern of expression are interspersed
in the genome but are probably found in different 'transcriptional
domains' (characterized by different orientation). Three new genes were
identified and positioned. One of these, termed TE2, demonstrated 40%
identity with the ARD1 protein of Saccharomyces cerevisiae (Whiteway and
Szostak, 1985), a protein required for the expression of an N-terminal
protein acetyltransferase activity.
Using Northern blot analysis, Sugiura et al. (2003) showed mouse Ard1
was ubiquitously expressed. By database analysis and PCR, Kim et al.
(2006) identified 3 splice variants of mouse Ard1 and 2 splice variants
of human ARD1. The mouse variants encoded proteins of 235-, 225-, and
198-amino acids. Ard1(235) and Ard1(225) have well-conserved
N-acetyltransferase domains, but Ard1(198) has only a partial domain.
The human ARD1 variants encoded proteins of 131- and 235-amino acids.
The C-terminal region of mouse Ard1(225) differs from that of both mouse
and human ARD1(235), likely due to alternative splicing of exon 8.
Western blot analysis of human cell lines showed a major intense band of
about 32 kD, which corresponded to ARD1(235). In contrast, mouse
fibroblasts strongly expressed a 30-kD protein, corresponding to
Ard1(225).
Asaumi et al. (2005) cloned ARD1 and identified it as a potential APP
(104760)-binding protein in a yeast 2-hybrid assay. The 235-amino acid
protein contains an N-acetyltransferase domain, a highly conserved
acetyl-coenzyme A binding motif, and a C-terminal APP-binding domain.
GENE FUNCTION
N-terminal protein acetylation is one of the most common protein
modifications that appear to play a role in many biologic processes. The
most extensively studied acetylated proteins are the 4 histones, which
in all eukaryotic cells organize the nucleosome particles and are
subject to an enzyme-catalyzed cycle of acetylation and deacetylation
which plays a role in chromatin structure, transcriptional activation,
and cell cycle transit. Lack of acetylation of histone H4 distinguishes
the inactive from the active mammalian X chromosome (Jeppesen and
Turner, 1993).
Using the yeast 2-hybrid system to identify proteins that interact with
the ODD domain of HIF1A (603348), Jeong et al. (2002) identified mouse
Ard1. They established the function of Ard1 as a protein
acetyltransferase in mammalian cells by direct binding to HIF1A to
regulate its stability. Jeong et al. (2002) also showed that
Ard1-mediated acetylation enhances interaction of HIF1A with VHL
(608537) and HIF1A ubiquitination, suggesting that the acetylation of
HIF1A by ARD1 is critical to proteasomal degradation. They concluded
that the role of ARD1 in the acetylation of HIF1A provides a key
regulatory mechanism underlying HIF1A stability. By assaying ARD1
variants expressed in HeLa cells, Kim et al. (2006) determined that
mouse Ard1(225), but not mouse or human ARD1(235) strongly decreased
VEGF (192240) mRNA expression under hypoxic conditions. As described by
Jeong et al. (2002), Ard1(225) mediated epsilon-acetylation of a HIF1A
lysine residue; however, mouse and human ARD1(235) had weaker effects.
Kim et al. (2006) concluded that the different ARD1 isoforms may have
different effects on HIF1A stability and acetylation.
Using in vitro translated mouse proteins, Sugiura et al. (2003) showed
that Ard1 and Narg1, which they called Nat1, assembled to form a
functional acetyltransferase. Narg1 alone showed no activity.
Immunoprecipitation and Western blot analysis demonstrated that Narg1
and Ard1 coassembled in mammalian cells. By cotransfection of rat kidney
fibroblasts, they showed that Narg1 and Ard1 localized to the cytoplasm
in both overlapping and separate compartments. In situ hybridization
demonstrated that during mouse brain development, Narg1 and Ard1 were
highly expressed in areas of cell division and migration, and their
expression appeared to be downregulated as neurons differentiated. Narg1
and Ard1 were expressed in proliferating mouse embryonic carcinoma
cells. Treatment of these cells with retinoic acid initiated neuronal
differentiation and downregulation of Narg1 and Ard1 as a neuronal
marker gene was induced. Sugiura et al. (2003) concluded that NARG1 and
ARD1 play a role in the generation and differentiation of neurons.
Asaumi et al. (2005) confirmed interaction of APP with ARD1 in mammalian
cells by coimmunoprecipitation studies. Using human ACTH as a substrate,
they showed that the ARD1/NATH (NARG1; 608000) complex has strong
N-terminal transferase activity. Immunoprecipitation and Western
blotting experiments showed that ARD1 and NATH formed a complex in
HEK293 cells. Because APP-binding proteins can modulate APP metabolism,
they tested the ability of ARD1 to modulate beta-amyloid-40 secretion
and found that coexpression of both ARD1 and NATH was required to
suppress beta-amyloid-40 generation from APP. APP endocytosis assay in
HEK293 cells showed that ARD1 and NATH suppressed endocytosis of APP.
Using reciprocal immunoprecipitation, followed by mass spectroscopic
analysis, Arnesen et al. (2005) showed that endogenous ARD1 and NATH
formed stable complexes in several human cell lines and that the complex
showed N-terminal acetylation activity. Mutation analysis and
examination of proteolytic fragments indicated that interaction was
mediated through an N-terminal domain of ARD1 and the C-terminal end of
NATH. Immunoprecipitation analysis showed ARD1 and NATH associated with
several ribosomal proteins. ARD1 and NATH were also detected in isolated
polysomes; however, they were predominantly nonpolysomal. Endogenous
ARD1 was present in both the nuclei and cytoplasm in several human cell
lines, whereas NATH was predominantly in the cytoplasm, despite the
presence of a well-defined nuclear localization signal within the NATH
coiled-coil region. Both ARD1 and NATH were cleaved in a
caspase-dependent manner during apoptosis in stressed HeLa cells, which
resulted in reduced acetylation activity.
Using size-exclusion chromatography, circular dichroism, and
fluorescence spectroscopy, Sanchez-Puig and Fersht (2006) found that
ARD1 consists of a compact globular region comprising two-thirds of the
protein and a flexible unstructured C terminus. In addition, ARD1 could
assume a misfolded conformation and form amyloid protofilaments under
physiologic conditions of pH and temperature. The process was
accelerated by thermal denaturation and high protein concentration.
Limited proteolysis of ARD1 protofilaments revealed a
proteolysis-resistant core within the acetyltransferase domain.
MOLECULAR GENETICS
- Ogden Syndrome
Rope et al. (2011) identified a missense mutation in the NAA10 gene
(ser37 to pro; 300013.0001) in 2 families segregating a lethal X-linked
recessive disorder of infancy, designated Ogden syndrome (OGDNS;
300855), characterized by an aged appearance due to lack of subcutaneous
fat and loose skin, and craniofacial anomalies including prominent eyes,
large ears, downslanting palpebral fissures, flared nares, hypoplastic
alae, short columella, protruding upper lip, and microretrognathia. The
boys had initial hypotonia progressing to hypertonia, global
developmental delay, usually unilateral cryptorchidism, and cardiac
arrhythmias leading to death in the first or second year of life.
- Lenz Microphthalmia Syndrome
By exome sequencing in 3 affected brothers with Lenz microphthalmia
syndrome (MCOPS1; 309800), Esmailpour et al. (2014) identified a splice
site mutation in the NAA10 gene (300013.0002) that was confirmed by
Sanger sequencing in the 3 sibs and their obligate heterozygote mother,
as well as in a maternal aunt and her daughter, but was not found in 4
unaffected family members. There was evidence for reduced expressivity
in heterozygotes.
*FIELD* AV
.0001
OGDEN SYNDROME
NAA10, SER37PRO
Rope et al. (2011) identified 2 unrelated families segregating a lethal
X-linked disorder, Ogden syndrome (OGDNS; 300855). The 2 families had
independent occurrences of a T-to-C transition at nucleotide 109 of the
NAA10 gene, resulting in a serine-to-proline substitution at codon 37
(S37P). The NAA10 gene encodes the catalytic subunit of the N-terminal
acetyltransferase. Substitution of proline for serine at position 37 is
likely to affect structure, and in vitro assays of protein function
demonstrated 60 to 80% reduction in NAT activity of the mutant protein
toward the in vivo substrate RNase P protein p30 (606115). In contrast,
the activity toward the substrate high mobility group protein A1
(600701) was reduced by only 20%.
.0002
MICROPHTHALMIA, SYNDROMIC 1 (1 family)
NAA10, IVS7DS, T-A, +2
In 3 affected brothers with Lenz microphthalmia syndrome (MCOPS1;
309800), originally studied by Forrester et al. (2001), Esmailpour et
al. (2014) identified a c.471+2T-A transition in intron 7 of the NAA10
gene, predicted to severely alter exon 7 splicing. The mutation was also
detected in their obligate heterozygote mother, as well as in a maternal
aunt and her daughter, but was not found in 4 unaffected family members.
Heterozygous individuals displayed cutaneous syndactyly and short
terminal phalanges, features that were not seen in family members who
did not carry the mutation. Analysis of patient cDNA revealed the
presence of aberrant transcripts. Patient fibroblasts lacked expression
of full-length NAA10, and staining suggested that mutant NAA10
aggregated in the cytoplasm; in addition, the fibroblasts displayed cell
proliferation defects. Expression studies showed significant
dysregulation of microphthalmia-associated genes and their downstream
pathways, including STRA6 (610745). Retinol uptake assay showed a
significant decrease in retinol uptake by patient fibroblasts compared
to controls.
*FIELD* RF
1. Arnesen, T.; Anderson, D.; Baldersheim, C.; Lanotte, M.; Varhaug,
J. E.; Lillehaug, J. R.: Identification and characterization of the
human ARD1-NATH protein acetyltransferase complex. Biochem. J. 386:
433-443, 2005.
2. Asaumi, M.; Iijima, K.; Sumioka, A.; Iijima-Ando, K.; Kirino, Y.;
Nakaya, T.; Suzuki, T.: Interaction of N-terminal acetyltransferase
with the cytoplasmic domain of beta-amyloid precursor protein and
its effect on A-beta secretion. J. Biochem. 137: 147-155, 2005.
3. Esmailpour, T.; Riazifar, H.; Liu, L.; Donkervoort, S.; Huang,
V. H.; Madaan, S.; Shoucri, B. M.; Busch, A.; Wu, J.; Towbin, A.;
Chadwick, R. B.; Sequeira, A.; Vawter, M. P.; Sun, G.; Johnston, J.
J.; Biesecker, L. G.; Kawaguchi, R.; Sun, H.; Kimonis, V.; Huang,
T.: A splice donor mutation in NAA10 results in the dysregulation
of the retinoic acid signalling pathway and causes Lenz microphthalmia
syndrome. J. Med. Genet. 15Jan, 2014. Note: Advance Electronic Publication.
4. Forrester, S.; Kovach, M. J.; Reynolds, N. M.; Urban, R.; Kimonis,
V.: Manifestations in four males with and an obligate carrier of
the Lenz microphthalmia syndrome. Am. J. Med. Genet. 98: 92-100,
2001.
5. Jeong, J.-W.; Bae, M.-K.; Ahn, M.-Y.; Kim, S.-H.; Sohn, T.-K.;
Bae, M.-H.; Yoo, M.-A.; Song, E. J.; Lee, K.-J.; Kim, K.-W.: Regulation
and destabilization of HIF-1-alpha by ARD1-mediated acetylation. Cell 111:
709-720, 2002.
6. Jeppesen, P.; Turner, B. M.: The inactive X chromosome in female
mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic
marker for gene expression. Cell 74: 281-289, 1993.
7. Kim, S.-H.; Park, J. A.; Kim, J. H.; Lee, J.-W.; Seo, J. H.; Jung,
B.-K.; Chun, K.-H.; Jeong, J.-W.; Bae, M.-K.; Kim, K.-W.: Characterization
of ARD1 variants in mammalian cells. Biochem. Biophys. Res. Commun. 340:
422-427, 2006.
8. Rope, A. F.; Wang, K.; Evjenth, R.; Xing, J.; Johnston, J. J.;
Swensen, J. J.; Johnson, W. E.; Moore, B.; Huff, C. D.; Bird, L. M.;
Carey, J. C.; Opitz, J. M.; and 16 others: Using VAAST to identify
an X-linked disorder resulting in lethality in male infants due to
N-terminal acetyltransferase deficiency. Am. J. Hum. Genet. 89:
28-43, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 345 only, 2011.
9. Sanchez-Puig, N.; Fersht, A. R.: Characterization of the native
and fibrillar conformation of the human N-alpha-acetyltransferase
ARD1. Protein Sci. 15: 1968-1976, 2006.
10. Sugiura, N.; Adams, S. M.; Corriveau, R. A.: An evolutionarily
conserved N-terminal acetyltransferase complex associated with neuronal
development. J. Biol. Chem. 278: 40113-40120, 2003.
11. Tribioli, C.; Mancini, M.; Plassart, E.; Bione, S.; Rivella, S.;
Sala, C.; Torri, G.; Toniolo, D.: Isolation of new genes in distal
Xq28: transcriptional map and identification of a human homologue
of the ARD1 N-acetyltransferase of Saccharomyces cerevisiae. Hum.
Molec. Genet. 3: 1061-1067, 1994.
12. Whiteway, M.; Szostak, J. W.: The ARD1 gene of yeast functions
in the switch between the mitotic cell cycle and alternative developmental
pathways. Cell 43: 483-492, 1985.
*FIELD* CN
Marla J. F. O'Neill - updated: 01/29/2014
Ada Hamosh - updated: 8/19/2011
Patricia A. Hartz - updated: 3/6/2007
Stefanie A. Nelson - updated: 2/22/2007
Stylianos E. Antonarakis - updated: 1/17/2003
*FIELD* CD
Victor A. McKusick: 2/4/1996
*FIELD* ED
carol: 01/29/2014
mcolton: 1/28/2014
carol: 12/20/2011
carol: 9/13/2011
alopez: 9/12/2011
alopez: 8/24/2011
terry: 8/19/2011
carol: 7/6/2011
alopez: 6/17/2010
wwang: 3/6/2007
wwang: 2/22/2007
ckniffin: 8/3/2005
ckniffin: 3/23/2004
mgross: 1/17/2003
joanna: 8/31/1998
joanna: 2/4/1996
*RECORD*
*FIELD* NO
300013
*FIELD* TI
*300013 N-ALPHA-ACETYLTRANSFERASE 10, NatA CATALYTIC SUBUNIT; NAA10
;;ARD1 N-ACETYLTRANSFERASE, S. CEREVISIAE, HOMOLOG OF, A; ARD1A;;
read moreARREST-DEFECTIVE PROTEIN 1; ARD1;;
TE2
*FIELD* TX
DESCRIPTION
N-alpha-acetylation is a common protein modification that occurs during
protein synthesis and involves the transfer of an acetyl group from
acetyl-coenzyme A to the protein alpha-amino group. ARD1A, together with
NATH (NARG1, NAA15; 608000), is part of a major
N-alpha-acetyltransferase complex responsible for alpha-acetylation of
proteins and peptides (Sanchez-Puig and Fersht, 2006).
CLONING
Tribioli et al. (1994) described the physical and transcriptional
organization of a region of 140 kb in Xq28, 5-prime to the L1CAM gene
(308840). They established a transcriptional map of the region by
isolating and mapping CpG islands to the physical map, determining
partial nucleotide sequences, and studying the pattern of expression and
orientation of the transcripts. They succeeded in positioning 4
previously identified genes: L1CAM, AVPR2 (300538), HFC1 (300019), and
RENBP (312420). All genes in the region are rather small, ranging in
size from 2 to 30 kb, and very close to one another. With the exception
of the AVPR2 gene, they serve a housekeeping function, having a CpG
island at their 5-prime end and the same orientation of transcription.
This kind of organization is consistent with the one previously
described for the more distal portion of Xq28, between the color vision
pigment genes and the G6PD gene and indicates that genes with a
housekeeping and tissue-specific pattern of expression are interspersed
in the genome but are probably found in different 'transcriptional
domains' (characterized by different orientation). Three new genes were
identified and positioned. One of these, termed TE2, demonstrated 40%
identity with the ARD1 protein of Saccharomyces cerevisiae (Whiteway and
Szostak, 1985), a protein required for the expression of an N-terminal
protein acetyltransferase activity.
Using Northern blot analysis, Sugiura et al. (2003) showed mouse Ard1
was ubiquitously expressed. By database analysis and PCR, Kim et al.
(2006) identified 3 splice variants of mouse Ard1 and 2 splice variants
of human ARD1. The mouse variants encoded proteins of 235-, 225-, and
198-amino acids. Ard1(235) and Ard1(225) have well-conserved
N-acetyltransferase domains, but Ard1(198) has only a partial domain.
The human ARD1 variants encoded proteins of 131- and 235-amino acids.
The C-terminal region of mouse Ard1(225) differs from that of both mouse
and human ARD1(235), likely due to alternative splicing of exon 8.
Western blot analysis of human cell lines showed a major intense band of
about 32 kD, which corresponded to ARD1(235). In contrast, mouse
fibroblasts strongly expressed a 30-kD protein, corresponding to
Ard1(225).
Asaumi et al. (2005) cloned ARD1 and identified it as a potential APP
(104760)-binding protein in a yeast 2-hybrid assay. The 235-amino acid
protein contains an N-acetyltransferase domain, a highly conserved
acetyl-coenzyme A binding motif, and a C-terminal APP-binding domain.
GENE FUNCTION
N-terminal protein acetylation is one of the most common protein
modifications that appear to play a role in many biologic processes. The
most extensively studied acetylated proteins are the 4 histones, which
in all eukaryotic cells organize the nucleosome particles and are
subject to an enzyme-catalyzed cycle of acetylation and deacetylation
which plays a role in chromatin structure, transcriptional activation,
and cell cycle transit. Lack of acetylation of histone H4 distinguishes
the inactive from the active mammalian X chromosome (Jeppesen and
Turner, 1993).
Using the yeast 2-hybrid system to identify proteins that interact with
the ODD domain of HIF1A (603348), Jeong et al. (2002) identified mouse
Ard1. They established the function of Ard1 as a protein
acetyltransferase in mammalian cells by direct binding to HIF1A to
regulate its stability. Jeong et al. (2002) also showed that
Ard1-mediated acetylation enhances interaction of HIF1A with VHL
(608537) and HIF1A ubiquitination, suggesting that the acetylation of
HIF1A by ARD1 is critical to proteasomal degradation. They concluded
that the role of ARD1 in the acetylation of HIF1A provides a key
regulatory mechanism underlying HIF1A stability. By assaying ARD1
variants expressed in HeLa cells, Kim et al. (2006) determined that
mouse Ard1(225), but not mouse or human ARD1(235) strongly decreased
VEGF (192240) mRNA expression under hypoxic conditions. As described by
Jeong et al. (2002), Ard1(225) mediated epsilon-acetylation of a HIF1A
lysine residue; however, mouse and human ARD1(235) had weaker effects.
Kim et al. (2006) concluded that the different ARD1 isoforms may have
different effects on HIF1A stability and acetylation.
Using in vitro translated mouse proteins, Sugiura et al. (2003) showed
that Ard1 and Narg1, which they called Nat1, assembled to form a
functional acetyltransferase. Narg1 alone showed no activity.
Immunoprecipitation and Western blot analysis demonstrated that Narg1
and Ard1 coassembled in mammalian cells. By cotransfection of rat kidney
fibroblasts, they showed that Narg1 and Ard1 localized to the cytoplasm
in both overlapping and separate compartments. In situ hybridization
demonstrated that during mouse brain development, Narg1 and Ard1 were
highly expressed in areas of cell division and migration, and their
expression appeared to be downregulated as neurons differentiated. Narg1
and Ard1 were expressed in proliferating mouse embryonic carcinoma
cells. Treatment of these cells with retinoic acid initiated neuronal
differentiation and downregulation of Narg1 and Ard1 as a neuronal
marker gene was induced. Sugiura et al. (2003) concluded that NARG1 and
ARD1 play a role in the generation and differentiation of neurons.
Asaumi et al. (2005) confirmed interaction of APP with ARD1 in mammalian
cells by coimmunoprecipitation studies. Using human ACTH as a substrate,
they showed that the ARD1/NATH (NARG1; 608000) complex has strong
N-terminal transferase activity. Immunoprecipitation and Western
blotting experiments showed that ARD1 and NATH formed a complex in
HEK293 cells. Because APP-binding proteins can modulate APP metabolism,
they tested the ability of ARD1 to modulate beta-amyloid-40 secretion
and found that coexpression of both ARD1 and NATH was required to
suppress beta-amyloid-40 generation from APP. APP endocytosis assay in
HEK293 cells showed that ARD1 and NATH suppressed endocytosis of APP.
Using reciprocal immunoprecipitation, followed by mass spectroscopic
analysis, Arnesen et al. (2005) showed that endogenous ARD1 and NATH
formed stable complexes in several human cell lines and that the complex
showed N-terminal acetylation activity. Mutation analysis and
examination of proteolytic fragments indicated that interaction was
mediated through an N-terminal domain of ARD1 and the C-terminal end of
NATH. Immunoprecipitation analysis showed ARD1 and NATH associated with
several ribosomal proteins. ARD1 and NATH were also detected in isolated
polysomes; however, they were predominantly nonpolysomal. Endogenous
ARD1 was present in both the nuclei and cytoplasm in several human cell
lines, whereas NATH was predominantly in the cytoplasm, despite the
presence of a well-defined nuclear localization signal within the NATH
coiled-coil region. Both ARD1 and NATH were cleaved in a
caspase-dependent manner during apoptosis in stressed HeLa cells, which
resulted in reduced acetylation activity.
Using size-exclusion chromatography, circular dichroism, and
fluorescence spectroscopy, Sanchez-Puig and Fersht (2006) found that
ARD1 consists of a compact globular region comprising two-thirds of the
protein and a flexible unstructured C terminus. In addition, ARD1 could
assume a misfolded conformation and form amyloid protofilaments under
physiologic conditions of pH and temperature. The process was
accelerated by thermal denaturation and high protein concentration.
Limited proteolysis of ARD1 protofilaments revealed a
proteolysis-resistant core within the acetyltransferase domain.
MOLECULAR GENETICS
- Ogden Syndrome
Rope et al. (2011) identified a missense mutation in the NAA10 gene
(ser37 to pro; 300013.0001) in 2 families segregating a lethal X-linked
recessive disorder of infancy, designated Ogden syndrome (OGDNS;
300855), characterized by an aged appearance due to lack of subcutaneous
fat and loose skin, and craniofacial anomalies including prominent eyes,
large ears, downslanting palpebral fissures, flared nares, hypoplastic
alae, short columella, protruding upper lip, and microretrognathia. The
boys had initial hypotonia progressing to hypertonia, global
developmental delay, usually unilateral cryptorchidism, and cardiac
arrhythmias leading to death in the first or second year of life.
- Lenz Microphthalmia Syndrome
By exome sequencing in 3 affected brothers with Lenz microphthalmia
syndrome (MCOPS1; 309800), Esmailpour et al. (2014) identified a splice
site mutation in the NAA10 gene (300013.0002) that was confirmed by
Sanger sequencing in the 3 sibs and their obligate heterozygote mother,
as well as in a maternal aunt and her daughter, but was not found in 4
unaffected family members. There was evidence for reduced expressivity
in heterozygotes.
*FIELD* AV
.0001
OGDEN SYNDROME
NAA10, SER37PRO
Rope et al. (2011) identified 2 unrelated families segregating a lethal
X-linked disorder, Ogden syndrome (OGDNS; 300855). The 2 families had
independent occurrences of a T-to-C transition at nucleotide 109 of the
NAA10 gene, resulting in a serine-to-proline substitution at codon 37
(S37P). The NAA10 gene encodes the catalytic subunit of the N-terminal
acetyltransferase. Substitution of proline for serine at position 37 is
likely to affect structure, and in vitro assays of protein function
demonstrated 60 to 80% reduction in NAT activity of the mutant protein
toward the in vivo substrate RNase P protein p30 (606115). In contrast,
the activity toward the substrate high mobility group protein A1
(600701) was reduced by only 20%.
.0002
MICROPHTHALMIA, SYNDROMIC 1 (1 family)
NAA10, IVS7DS, T-A, +2
In 3 affected brothers with Lenz microphthalmia syndrome (MCOPS1;
309800), originally studied by Forrester et al. (2001), Esmailpour et
al. (2014) identified a c.471+2T-A transition in intron 7 of the NAA10
gene, predicted to severely alter exon 7 splicing. The mutation was also
detected in their obligate heterozygote mother, as well as in a maternal
aunt and her daughter, but was not found in 4 unaffected family members.
Heterozygous individuals displayed cutaneous syndactyly and short
terminal phalanges, features that were not seen in family members who
did not carry the mutation. Analysis of patient cDNA revealed the
presence of aberrant transcripts. Patient fibroblasts lacked expression
of full-length NAA10, and staining suggested that mutant NAA10
aggregated in the cytoplasm; in addition, the fibroblasts displayed cell
proliferation defects. Expression studies showed significant
dysregulation of microphthalmia-associated genes and their downstream
pathways, including STRA6 (610745). Retinol uptake assay showed a
significant decrease in retinol uptake by patient fibroblasts compared
to controls.
*FIELD* RF
1. Arnesen, T.; Anderson, D.; Baldersheim, C.; Lanotte, M.; Varhaug,
J. E.; Lillehaug, J. R.: Identification and characterization of the
human ARD1-NATH protein acetyltransferase complex. Biochem. J. 386:
433-443, 2005.
2. Asaumi, M.; Iijima, K.; Sumioka, A.; Iijima-Ando, K.; Kirino, Y.;
Nakaya, T.; Suzuki, T.: Interaction of N-terminal acetyltransferase
with the cytoplasmic domain of beta-amyloid precursor protein and
its effect on A-beta secretion. J. Biochem. 137: 147-155, 2005.
3. Esmailpour, T.; Riazifar, H.; Liu, L.; Donkervoort, S.; Huang,
V. H.; Madaan, S.; Shoucri, B. M.; Busch, A.; Wu, J.; Towbin, A.;
Chadwick, R. B.; Sequeira, A.; Vawter, M. P.; Sun, G.; Johnston, J.
J.; Biesecker, L. G.; Kawaguchi, R.; Sun, H.; Kimonis, V.; Huang,
T.: A splice donor mutation in NAA10 results in the dysregulation
of the retinoic acid signalling pathway and causes Lenz microphthalmia
syndrome. J. Med. Genet. 15Jan, 2014. Note: Advance Electronic Publication.
4. Forrester, S.; Kovach, M. J.; Reynolds, N. M.; Urban, R.; Kimonis,
V.: Manifestations in four males with and an obligate carrier of
the Lenz microphthalmia syndrome. Am. J. Med. Genet. 98: 92-100,
2001.
5. Jeong, J.-W.; Bae, M.-K.; Ahn, M.-Y.; Kim, S.-H.; Sohn, T.-K.;
Bae, M.-H.; Yoo, M.-A.; Song, E. J.; Lee, K.-J.; Kim, K.-W.: Regulation
and destabilization of HIF-1-alpha by ARD1-mediated acetylation. Cell 111:
709-720, 2002.
6. Jeppesen, P.; Turner, B. M.: The inactive X chromosome in female
mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic
marker for gene expression. Cell 74: 281-289, 1993.
7. Kim, S.-H.; Park, J. A.; Kim, J. H.; Lee, J.-W.; Seo, J. H.; Jung,
B.-K.; Chun, K.-H.; Jeong, J.-W.; Bae, M.-K.; Kim, K.-W.: Characterization
of ARD1 variants in mammalian cells. Biochem. Biophys. Res. Commun. 340:
422-427, 2006.
8. Rope, A. F.; Wang, K.; Evjenth, R.; Xing, J.; Johnston, J. J.;
Swensen, J. J.; Johnson, W. E.; Moore, B.; Huff, C. D.; Bird, L. M.;
Carey, J. C.; Opitz, J. M.; and 16 others: Using VAAST to identify
an X-linked disorder resulting in lethality in male infants due to
N-terminal acetyltransferase deficiency. Am. J. Hum. Genet. 89:
28-43, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 345 only, 2011.
9. Sanchez-Puig, N.; Fersht, A. R.: Characterization of the native
and fibrillar conformation of the human N-alpha-acetyltransferase
ARD1. Protein Sci. 15: 1968-1976, 2006.
10. Sugiura, N.; Adams, S. M.; Corriveau, R. A.: An evolutionarily
conserved N-terminal acetyltransferase complex associated with neuronal
development. J. Biol. Chem. 278: 40113-40120, 2003.
11. Tribioli, C.; Mancini, M.; Plassart, E.; Bione, S.; Rivella, S.;
Sala, C.; Torri, G.; Toniolo, D.: Isolation of new genes in distal
Xq28: transcriptional map and identification of a human homologue
of the ARD1 N-acetyltransferase of Saccharomyces cerevisiae. Hum.
Molec. Genet. 3: 1061-1067, 1994.
12. Whiteway, M.; Szostak, J. W.: The ARD1 gene of yeast functions
in the switch between the mitotic cell cycle and alternative developmental
pathways. Cell 43: 483-492, 1985.
*FIELD* CN
Marla J. F. O'Neill - updated: 01/29/2014
Ada Hamosh - updated: 8/19/2011
Patricia A. Hartz - updated: 3/6/2007
Stefanie A. Nelson - updated: 2/22/2007
Stylianos E. Antonarakis - updated: 1/17/2003
*FIELD* CD
Victor A. McKusick: 2/4/1996
*FIELD* ED
carol: 01/29/2014
mcolton: 1/28/2014
carol: 12/20/2011
carol: 9/13/2011
alopez: 9/12/2011
alopez: 8/24/2011
terry: 8/19/2011
carol: 7/6/2011
alopez: 6/17/2010
wwang: 3/6/2007
wwang: 2/22/2007
ckniffin: 8/3/2005
ckniffin: 3/23/2004
mgross: 1/17/2003
joanna: 8/31/1998
joanna: 2/4/1996
MIM
300855
*RECORD*
*FIELD* NO
300855
*FIELD* TI
#300855 OGDEN SYNDROME; OGDNS
;;N-TERMINAL ACETYLTRANSFERASE DEFICIENCY; NATD
*FIELD* TX
read moreA number sign (#) is used with this entry because of evidence that Ogden
syndrome (OGDNS) is caused by mutation in the NAA10 gene (300013) on
chromosome Xq28.
CLINICAL FEATURES
Rope et al. (2011) reported 2 families segregating an X-linked recessive
condition characterized by postnatal growth failure with severe delays
and dysmorphic features characterized by wrinkled forehead, prominent
eyes, widely opened anterior and posterior fontanels, downsloping
palpebral fissures, thickened lids, large ears, flared nares,
hypoplastic alae, short columella, protruding upper lip, and
microretrognathia. There were also delayed closing of fontanels and
broad great toes. Skin was characterized by redundancy or laxity with
minimal subcutaneous fat, cutaneous capillary malformations, and very
fine hair and eyebrows. Death resulted from cardiogenic shock following
arrhythmia, which was noted in all affected individuals, all males.
Several of the boys had structural anomalies of their hearts including
ventricular septal defect, atrial septal defect, and pulmonary artery
stenosis. Arrhythmias included torsade de pointes, premature ventricular
contraction (PVC), premature atrial contraction (PAC), supraventricular
tachycardia (SVtach), and ventricular tachycardia (Vtach). Most of the
children had inguinal hernia, and the majority had unilateral
cryptorchidism. All had neonatal hypotonia progressing to hypertonia,
and cerebral atrophy on MRI; several, but not all, had neurogenic
scoliosis. Death occurred prior to 2 years in all cases and prior to 1
year in the majority.
MOLECULAR GENETICS
Rope et al. (2011) used X chromosome exon sequencing to identify a
missense mutation (S37P; 300013.0001) in the NAA10 gene, encoding the
catalytic subunit of the major human N-terminal acetyltransferase. The
ser37-to-pro mutation was not identified in any unaffected family
members or in 401 participants in the ClinSeq project, 180 genomes in
the 1000 Genomes Project, the 10Gen dataset, 184 Danish exomes, or 40
whole genomes from the Complete Genomics Diversity Panel. There was no
evidence of identity by descent between the families, and Rope et al.
(2011) concluded that the mutation arose independently in each family.
Serine-37 and its surrounding residues are conserved among eukaryotes.
Acetylation assays demonstrated significantly impaired biochemical
activity of the mutant NAA10 protein.
*FIELD* RF
1. Rope, A. F.; Wang, K.; Evjenth, R.; Xing, J.; Johnston, J. J.;
Swensen, J. J.; Johnson, W. E.; Moore, B.; Huff, C. D.; Bird, L. M.;
Carey, J. C.; Opitz, J. M.; and 16 others: Using VAAST to identify
an X-linked disorder resulting in lethality in male infants due to
N-terminal acetyltransferase deficiency. Am. J. Hum. Genet. 89:
28-43, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 345 only, 2011.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Other];
Postnatal growth failure
HEAD AND NECK:
[Face];
Wrinkled forehead;
[Ears];
Large ears;
[Eyes];
Prominent eyes;
Downslanting palpebral fissures;
Thick eyelids;
Sparse eyebrows;
[Nose];
Flared nares;
Hypoplastic alae nasai;
Short columella;
[Mouth];
Protruding upper lip;
Microretrognathia
CARDIOVASCULAR:
[Heart];
Ventral septal defect (VSD);
Atrial septal defect (ASD);
Arrhythmias;
Torsade de pointes;
Premature ventricular contraction (PVC);
Premature atrial contraction (PAC);
Supraventricular tachycardia (SVtach);
Ventricular tachycardia (Vtach);
[Vascular];
Pulmonary artery stenosis
GENITOURINARY:
[Internal genitalia, male];
Cryptorchidism;
Inguinal hernia
SKELETAL:
[Skull];
Delayed closure of fontanels;
[Spine];
Scoliosis (in some patients);
[Feet];
Broad great toes
SKIN, NAILS, HAIR:
[Skin];
Cutis laxa;
Redundant skin;
Wrinkled forehead;
Cutaneous capillary malformations;
[Hair];
Fine hair (in some patients);
Sparse eyebrows
MUSCLE, SOFT TISSUE:
Minimal subcutaneous fat
NEUROLOGIC:
[Central nervous system];
Hypotonia progressing to hypertonia;
Cerebral atrophy
MISCELLANEOUS:
Death usually associated with cardiogenic shock preceded by arrhythmia
MOLECULAR BASIS:
Caused by mutation in the NatA catalytic subunit N-alpha-acetyltransferase-10
gene (NAA10, 300013.0001)
*FIELD* CD
Ada Hamosh: 8/24/2011
*FIELD* ED
joanna: 05/25/2012
joanna: 9/12/2011
alopez: 8/24/2011
*FIELD* CD
Ada Hamosh: 8/24/2011
*FIELD* ED
carol: 12/20/2011
carol: 9/13/2011
alopez: 9/12/2011
alopez: 8/24/2011
*RECORD*
*FIELD* NO
300855
*FIELD* TI
#300855 OGDEN SYNDROME; OGDNS
;;N-TERMINAL ACETYLTRANSFERASE DEFICIENCY; NATD
*FIELD* TX
read moreA number sign (#) is used with this entry because of evidence that Ogden
syndrome (OGDNS) is caused by mutation in the NAA10 gene (300013) on
chromosome Xq28.
CLINICAL FEATURES
Rope et al. (2011) reported 2 families segregating an X-linked recessive
condition characterized by postnatal growth failure with severe delays
and dysmorphic features characterized by wrinkled forehead, prominent
eyes, widely opened anterior and posterior fontanels, downsloping
palpebral fissures, thickened lids, large ears, flared nares,
hypoplastic alae, short columella, protruding upper lip, and
microretrognathia. There were also delayed closing of fontanels and
broad great toes. Skin was characterized by redundancy or laxity with
minimal subcutaneous fat, cutaneous capillary malformations, and very
fine hair and eyebrows. Death resulted from cardiogenic shock following
arrhythmia, which was noted in all affected individuals, all males.
Several of the boys had structural anomalies of their hearts including
ventricular septal defect, atrial septal defect, and pulmonary artery
stenosis. Arrhythmias included torsade de pointes, premature ventricular
contraction (PVC), premature atrial contraction (PAC), supraventricular
tachycardia (SVtach), and ventricular tachycardia (Vtach). Most of the
children had inguinal hernia, and the majority had unilateral
cryptorchidism. All had neonatal hypotonia progressing to hypertonia,
and cerebral atrophy on MRI; several, but not all, had neurogenic
scoliosis. Death occurred prior to 2 years in all cases and prior to 1
year in the majority.
MOLECULAR GENETICS
Rope et al. (2011) used X chromosome exon sequencing to identify a
missense mutation (S37P; 300013.0001) in the NAA10 gene, encoding the
catalytic subunit of the major human N-terminal acetyltransferase. The
ser37-to-pro mutation was not identified in any unaffected family
members or in 401 participants in the ClinSeq project, 180 genomes in
the 1000 Genomes Project, the 10Gen dataset, 184 Danish exomes, or 40
whole genomes from the Complete Genomics Diversity Panel. There was no
evidence of identity by descent between the families, and Rope et al.
(2011) concluded that the mutation arose independently in each family.
Serine-37 and its surrounding residues are conserved among eukaryotes.
Acetylation assays demonstrated significantly impaired biochemical
activity of the mutant NAA10 protein.
*FIELD* RF
1. Rope, A. F.; Wang, K.; Evjenth, R.; Xing, J.; Johnston, J. J.;
Swensen, J. J.; Johnson, W. E.; Moore, B.; Huff, C. D.; Bird, L. M.;
Carey, J. C.; Opitz, J. M.; and 16 others: Using VAAST to identify
an X-linked disorder resulting in lethality in male infants due to
N-terminal acetyltransferase deficiency. Am. J. Hum. Genet. 89:
28-43, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 345 only, 2011.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Other];
Postnatal growth failure
HEAD AND NECK:
[Face];
Wrinkled forehead;
[Ears];
Large ears;
[Eyes];
Prominent eyes;
Downslanting palpebral fissures;
Thick eyelids;
Sparse eyebrows;
[Nose];
Flared nares;
Hypoplastic alae nasai;
Short columella;
[Mouth];
Protruding upper lip;
Microretrognathia
CARDIOVASCULAR:
[Heart];
Ventral septal defect (VSD);
Atrial septal defect (ASD);
Arrhythmias;
Torsade de pointes;
Premature ventricular contraction (PVC);
Premature atrial contraction (PAC);
Supraventricular tachycardia (SVtach);
Ventricular tachycardia (Vtach);
[Vascular];
Pulmonary artery stenosis
GENITOURINARY:
[Internal genitalia, male];
Cryptorchidism;
Inguinal hernia
SKELETAL:
[Skull];
Delayed closure of fontanels;
[Spine];
Scoliosis (in some patients);
[Feet];
Broad great toes
SKIN, NAILS, HAIR:
[Skin];
Cutis laxa;
Redundant skin;
Wrinkled forehead;
Cutaneous capillary malformations;
[Hair];
Fine hair (in some patients);
Sparse eyebrows
MUSCLE, SOFT TISSUE:
Minimal subcutaneous fat
NEUROLOGIC:
[Central nervous system];
Hypotonia progressing to hypertonia;
Cerebral atrophy
MISCELLANEOUS:
Death usually associated with cardiogenic shock preceded by arrhythmia
MOLECULAR BASIS:
Caused by mutation in the NatA catalytic subunit N-alpha-acetyltransferase-10
gene (NAA10, 300013.0001)
*FIELD* CD
Ada Hamosh: 8/24/2011
*FIELD* ED
joanna: 05/25/2012
joanna: 9/12/2011
alopez: 8/24/2011
*FIELD* CD
Ada Hamosh: 8/24/2011
*FIELD* ED
carol: 12/20/2011
carol: 9/13/2011
alopez: 9/12/2011
alopez: 8/24/2011