P41227 (NAA10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N-alpha-acetyltransferase 10
EC=2.3.1.-
EC=2.3.1.88

Alternative name(s):
N-terminal acetyltransferase complex ARD1 subunit homolog A
NatA catalytic subunit

Gene names

Name:	NAA10
Synonyms:	ARD1, ARD1A, TE2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	235 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In complex with NAA15, displays alpha (N-terminal) acetyltransferase activity. Without NAA15, displays epsilon (internal) acetyltransferase activity towards HIF1A, thereby promoting its degradation. Represses MYLK kinase activity by acetylation, and thus represses tumor cell migration. Ref.2 Ref.4 Ref.11
Catalytic activity	Acetyl-CoA + peptide = N(alpha)-acetylpeptide + CoA.
Subunit structure	Interacts with HIF1A (via its ODD domain); the interaction increases HIF1A protein stability during normoxia, and downregulates it when induced by hypoxia. Interacts with NAA15, NAA50 and with the ribosome. Binds to MYLK. Ref.2 Ref.4 Ref.6 Ref.11
Subcellular location	Cytoplasm. Nucleus. Note: According to Ref.4 it is cytoplasmic. According to Ref.2, it is nuclear and cytoplasmic. Also present in the free cytosolic and cytoskeleton-bound polysomes. Ref.2 Ref.4
Tissue specificity	Ubiquitous. Ref.4
Post-translational modification	Cleaved by caspases during apoptosis.
Involvement in disease	Defects in NAA10 are the cause of N-terminal acetyltransferase deficiency (NATD) [MIM:300855]. NATD is an enzymatic deficiency resulting in postnatal growth failure with severe delays and dysmorphic features. It is clinically 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 are also delayed closing of fontanels and broad great toes. Skin is characterized by redundancy or laxity with minimal subcutaneous fat, cutaneous capillary malformations, and very fine hair and eyebrows. Death results from cardiogenic shock following arrhythmia. Ref.13
Sequence similarities	Belongs to the acetyltransferase family. ARD1 subfamily. Contains 1 N-acetyltransferase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Disease	Disease mutation
Molecular function	Acyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA packaging Traceable author statement. Source: ProtInc N-terminal protein amino acid acetylation Inferred from direct assay Ref.2. Source: UniProtKB internal protein amino acid acetylation Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB nucleus Inferred from direct assay Ref.2. Source: UniProtKB
Molecular function	peptide alpha-N-acetyltransferase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARHGEF6	Q15052	3	EBI-747693,EBI-1642523
ARHGEF7	Q14155	3	EBI-747693,EBI-717515
Arhgef7	O55043	3	EBI-747693,EBI-3649585	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 235	235	N-alpha-acetyltransferase 10		PRO_0000074532
Regions
	Domain	1 – 152	152	N-acetyltransferase
	Region	1 – 58	58	Interaction with NAA15
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.9
	Modified residue	182	1	Phosphoserine Ref.5 Ref.9
	Modified residue	186	1	Phosphoserine Ref.7 Ref.8 Ref.9
	Modified residue	189	1	Phosphoserine Ref.9
	Modified residue	205	1	Phosphoserine Ref.8
	Modified residue	228	1	Phosphoserine Ref.9
	Modified residue	231	1	Phosphoserine Ref.9
Natural variations
	Natural variant	37	1	S → P in NATD; in vitro assays of protein function demonstrates 60 to 80% reduction in NAT activity of the mutant protein toward the in vivo substrate RPP30 protein; the activity toward the substrate HMGA1 protein is reduced by only 20%. Ref.13		VAR_066652

Sequences

	Sequence		Length	Mass (Da)
	P41227 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 6393A907F5C2DDC4	FASTA	235	26,459
	10 20 30 40 50 60 MNIRNARPED LMNMQHCNLL CLPENYQMKY YFYHGLSWPQ LSYIAEDENG KIVGYVLAKM 70 80 90 100 110 120 EEDPDDVPHG HITSLAVKRS HRRLGLAQKL MDQASRAMIE NFNAKYVSLH VRKSNRAALH 130 140 150 160 170 180 LYSNTLNFQI SEVEPKYYAD GEDAYAMKRD LTQMADELRR HLELKEKGRH VVLGAIENKV 190 200 210 220 230 ESKGNSPPSS GEACREEKGL AAEDSGGDSK DLSEVSETTE STDVKDSSEA SDSAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae." Tribioli C., Mancini M., Plassart E., Bione S., Rivella S., Sala C., Torri G., Toniolo D. Hum. Mol. Genet. 3:1061-1068(1994) [PubMed: 7981673] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification and characterization of the human ARD1-NATH protein acetyltransferase complex." Arnesen T., Anderson D., Baldersheim C., Lanotte M., Varhaug J.E., Lillehaug J.R. Biochem. J. 386:433-443(2005) [PubMed: 15496142] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NAA15 AND RIBOSOMAL PROTEINS. Tissue: Thyroid carcinoma.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[4]	"Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation." 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. Cell 111:709-720(2002) [PubMed: 12464182] [Abstract] Cited for: INTERACTION WITH HIF1A, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved component of the NatA protein N-alpha-acetyltransferase complex." Arnesen T., Anderson D., Torsvik J., Halseth H.B., Varhaug J.E., Lillehaug J.R. Gene 371:291-295(2006) [PubMed: 16507339] [Abstract] Cited for: INTERACTION WITH NAA50.
[7]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186 AND SER-205, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182; SER-186; SER-189; SER-228 AND SER-231, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"A synopsis of eukaryotic Nalpha-terminal acetyltransferases: nomenclature, subunits and substrates." Polevoda B., Arnesen T., Sherman F. BMC Proc. 3:S2-S2(2009) [PubMed: 19660095] [Abstract] Cited for: NOMENCLATURE.
[11]	"Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase." Shin D.H., Chun Y.-S., Lee K.-H., Shin H.-W., Park J.-W. PLoS ONE 4:E7451-E7451(2009) [PubMed: 19826488] [Abstract] Cited for: FUNCTION, INTERACTION WITH MYLK.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency." 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., Stevens C.A., Jiang T., Schank C., Fain H.D., Robison R., Dalley B. , Chin S., South S.T., Pysher T.J., Jorde L.B., Hakonarson H., Lillehaug J.R., Biesecker L.G., Yandell M., Arnesen T., Lyon G.J. Am. J. Hum. Genet. 89:28-43(2011) [PubMed: 21700266] [Abstract] Cited for: VARIANT NATD PRO-37, CHARACTERIZATION OF VARIANT NATD PRO-37.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X77588 mRNA. Translation: CAA54691.1. BC000308 mRNA. Translation: AAH00308.1. BC019312 mRNA. Translation: AAH19312.1.
IPI	IPI00013184.
PIR	I38333.
RefSeq	NP_003482.1. NM_003491.2.
UniGene	Hs.433291.
3D structure databases
ProteinModelPortal	P41227.
SMR	P41227. Positions 1-150.
ModBase	Search...
Protein-protein interaction databases
IntAct	P41227. 13 interactions.
MINT	MINT-1499850.
STRING	P41227.
PTM databases
PhosphoSite	P41227.
Polymorphism databases
DMDM	728880.
Proteomic databases
PRIDE	P41227.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000464845; ENSP00000417763; ENSG00000102030.
GeneID	8260.
KEGG	hsa:8260.
NMPDR	fig|9606.3.peg.33620.
UCSC	uc004fjm.1. human.
Organism-specific databases
CTD	8260.
GeneCards	GC0XM153194.
H-InvDB	HIX0017143.
HGNC	HGNC:18704. NAA10.
HPA	CAB006269.
MIM	300013. gene. 300855. phenotype.
neXtProt	NX_P41227.
PharmGKB	PA165757060. PA38648.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00550000074803.
HOGENOM	HBG742014.
HOVERGEN	HBG050561.
InParanoid	P41227.
OrthoDB	EOG4Z0B6F.
PhylomeDB	P41227.
Enzyme and pathway databases
Pathway_Interaction_DB	hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.
Gene expression databases
ArrayExpress	P41227.
Bgee	P41227.
CleanEx	HS_ARD1A.
Genevestigator	P41227.
GermOnline	ENSG00000102030. Homo sapiens.
Family and domain databases
InterPro	IPR000182. AcTrfase_GCN5-related_dom. IPR016181. Acyl_CoA_acyltransferase. [Graphical view]
Gene3D	G3DSA:3.40.630.30. Acyl_CoA_acyltransferase. 1 hit.
KO	K00670.
Pfam	PF00583. Acetyltransf_1. 1 hit. [Graphical view]
SUPFAM	SSF55729. Acyl_CoA_acyltransferase. 1 hit.
PROSITE	PS51186. GNAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	31019.
SOURCE	Search...

Entry information

Entry name

NAA10_HUMAN

Accession

Primary (citable) accession number: P41227

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	January 25, 2012
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.