Q8N159 (NAGS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N-acetylglutamate synthase, mitochondrial
EC=2.3.1.1

Alternative name(s):
Amino-acid acetyltransferase

Cleaved into the following 3 chains:

1. N-acetylglutamate synthase long form
2. N-acetylglutamate synthase short form
3. N-acetylglutamate synthase conserved domain form

Gene names

Name:

NAGS

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	534 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a role in the regulation of ureagenesis by producing variable amounts of N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (CPSI) activity.
Catalytic activity	Acetyl-CoA + L-glutamate = CoA + N-acetyl-L-glutamate.
Enzyme regulation	Increased by L-arginine. Ref.3
Pathway	Amino-acid biosynthesis; L-arginine biosynthesis; N(2)-acetyl-L-ornithine from L-glutamate: step 1/4.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Highly expressed in the adult liver, kidney and small intestine. Weakly expressed in the fetal liver, lung, pancreas, placenta, heart and brain tissue. Ref.1 Ref.3
Post-translational modification	Probably processed by mitochondrial processing peptidase (MPP). The long form has not yet been isolated By similarity.
Involvement in disease	N-acetylglutamate synthase deficiency (NAGSD) [MIM:237310]: Rare autosomal recessively inherited metabolic disorder leading to severe neonatal or late-onset hyperammonemia without increased excretion of orotic acid. Clinical symptoms are somnolence, tachypnea, feeding difficulties, a severe neurologic presentation characterized by uncontrollable movements, developmental delay, visual impairment, failure to thrive and hyperammonemia precipitated by the introduction of high-protein diet or febrile illness. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.4
Sequence similarities	Belongs to the acetyltransferase family. Contains 1 N-acetyltransferase domain.

Ontologies

Keywords
Biological process	Urea cycle
Cellular component	Mitochondrion
Disease	Disease mutation
Domain	Transit peptide
Molecular function	Acyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	arginine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway glutamate metabolic process Traceable author statement PubMed 21757002. Source: BHF-UCL urea cycle Traceable author statement. Source: Reactome
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	acetyl-CoA:L-glutamate N-acetyltransferase activity Traceable author statement PubMed 21757002. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 18	18	Mitochondrion Potential
	Chain	19 – 534	516	N-acetylglutamate synthase long form Potential		PRO_0000041930
	Chain	51 – 534	484	N-acetylglutamate synthase short form By similarity		PRO_0000041931
	Chain	92 – 534	443	N-acetylglutamate synthase conserved domain form By similarity		PRO_0000041932
Regions
	Domain	378 – 528	151	N-acetyltransferase
Natural variations
	Natural variant	200	1	C → R in NAGSD; markedly decreases activity. Ref.4		VAR_023505
	Natural variant	279	1	A → P in NAGSD. Ref.1		VAR_023506
	Natural variant	410	1	S → P in NAGSD; markedly decreases activity. Ref.4		VAR_023507
	Natural variant	430	1	L → P in NAGSD; markedly decreases activity. Ref.1 Ref.4		VAR_023508
	Natural variant	484	1	W → R in NAGSD; markedly decreases activity. Ref.1 Ref.4		VAR_023509
	Natural variant	518	1	A → T in NAGSD; markedly decreases activity. Ref.4		VAR_023510
Experimental info
	Sequence conflict	94	1	E → M in AAN76451. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q8N159 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 1328039080EB936C	FASTA	534	58,156
	10 20 30 40 50 60 MATALMAVVL RAAAVAPRLR GRGGTGGARR LSCGARRRAA RGTSPGRRLS TAWSQPQPPP 70 80 90 100 110 120 EEYAGADDVS QSPVAEEPSW VPSPRPPVPH ESPEPPSGRS LVQRDIQAFL NQCGASPGEA 130 140 150 160 170 180 RHWLTQFQTC HHSADKPFAV IEVDEEVLKC QQGVSSLAFA LAFLQRMDMK PLVVLGLPAP 190 200 210 220 230 240 TAPSGCLSFW EAKAQLAKSC KVLVDALRHN AAAAVPFFGG GSVLRAAEPA PHASYGGIVS 250 260 270 280 290 300 VETDLLQWCL ESGSIPILCP IGETAARRSV LLDSLEVTAS LAKALRPTKI IFLNNTGGLR 310 320 330 340 350 360 DSSHKVLSNV NLPADLDLVC NAEWVSTKER QQMRLIVDVL SRLPHHSSAV ITAASTLLTE 370 380 390 400 410 420 LFSNKGSGTL FKNAERMLRV RSLDKLDQGR LVDLVNASFG KKLRDDYLAS LRPRLHSIYV 430 440 450 460 470 480 SEGYNAAAIL TMEPVLGGTP YLDKFVVSSS RQGQGSGQML WECLRRDLQT LFWRSRVTNP 490 500 510 520 530 INPWYFKHSD GSFSNKQWIF FWFGLADIRD SYELVNHAKG LPDSFHKPAS DPGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutation analysis in patients with N-acetylglutamate synthase deficiency." Haeberle J., Schmidt E., Pauli S., Kreuder J.G., Plecko B., Galler A., Wermuth B., Harms E., Koch H.G. Hum. Mutat. 21:593-597(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, VARIANTS NAGSD PRO-279; PRO-430 AND ARG-484.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Small intestine.
[3]	"Cloning and expression of the human N-acetylglutamate synthase gene." Caldovic L., Morizono H., Gracia Panglao M., Gallegos R., Yu X., Shi D., Malamy M.H., Allewell N.M., Tuchman M. Biochem. Biophys. Res. Commun. 299:581-586(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 94-534, ENZYME REGULATION, TISSUE SPECIFICITY. Tissue: Liver.
[4]	"Identification of novel mutations of the human N-acetylglutamate synthase gene and their functional investigation by expression studies." Schmidt E., Nuoffer J.-M., Haeberle J., Pauli S., Guffon N., Vianey-Saban C., Wermuth B., Koch H.G. Biochim. Biophys. Acta 1740:54-59(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NAGSD ARG-200; PRO-410; PRO-430; ARG-484 AND THR-518, CHARACTERIZATION OF VARIANTS NAGSD ARG-200; PRO-410; PRO-430; ARG-484 AND THR-518.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

N-acetylglutamate synthase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY116537 Genomic DNA. Translation: AAM75385.1. AY116538 mRNA. Translation: AAM75386.1. AK314432 mRNA. Translation: BAG37046.1. AY158070 mRNA. Translation: AAN76451.1.
IPI	IPI00166092.
RefSeq	NP_694551.1. NM_153006.2.
UniGene	Hs.8876.
3D structure databases
ProteinModelPortal	Q8N159.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N159. 1 interaction.
MINT	MINT-1431825.
STRING	9606.ENSP00000293404.
PTM databases
PhosphoSite	Q8N159.
Polymorphism databases
DMDM	74714699.
Proteomic databases
PaxDb	Q8N159.
PRIDE	Q8N159.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000293404; ENSP00000293404; ENSG00000161653.
GeneID	162417.
KEGG	hsa:162417.
UCSC	uc002ies.3. human.
Organism-specific databases
CTD	162417.
GeneCards	GC17P042082.
HGNC	HGNC:17996. NAGS.
MIM	237310. phenotype. 608300. gene.
neXtProt	NX_Q8N159.
Orphanet	927. Hyperammonemia due to N-acetylglutamate synthetase deficiency.
PharmGKB	PA134968729.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0548.
HOGENOM	HOG000007983.
HOVERGEN	HBG080036.
InParanoid	Q8N159.
KO	K11067.
OMA	MRLIVDV.
OrthoDB	EOG4KPT9R.
PhylomeDB	Q8N159.
Enzyme and pathway databases
BRENDA	2.3.1.1. 2681.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00068; UER00106.
Gene expression databases
ArrayExpress	Q8N159.
Bgee	Q8N159.
CleanEx	HS_NAGS.
Genevestigator	Q8N159.
GermOnline	ENSG00000161653. Homo sapiens.
Family and domain databases
Gene3D	3.40.1160.10. 1 hit.
InterPro	IPR016181. Acyl_CoA_acyltransferase. IPR001048. Asp/Glu/Uridylate_kinase. IPR006855. DUF619. IPR011243. GlcNAc_Synth_met. IPR000182. GNAT_dom. [Graphical view]
Pfam	PF04768. DUF619. 1 hit. [Graphical view]
PIRSF	PIRSF036442. NAGS_animal. 1 hit.
SUPFAM	SSF53633. Aa_kinase. 1 hit. SSF55729. Acyl_CoA_acyltransferase. 1 hit.
PROSITE	PS51186. GNAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NAGS. human.
DrugBank	DB00142. L-Glutamic Acid.
GenomeRNAi	162417.
NextBio	88165.
SOURCE	Search...

Entry information

Entry name

NAGS_HUMAN

Accession

Primary (citable) accession number: Q8N159
Secondary accession number(s): B2RAZ9, Q8IWR4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 92 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.