ID   NAGS_HUMAN              Reviewed;         534 AA.
AC   Q8N159; Q8IWR4;
DT   13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   04-DEC-2007, entry version 39.
DE   N-acetylglutamate synthase, mitochondrial precursor (EC 2.3.1.1)
DE   (Amino-acid acetyltransferase) [Contains: N-acetylglutamate synthase
DE   long form; N-acetylglutamate synthase short form; N-acetylglutamate
DE   synthase conserved domain form].
GN   Name=NAGS;
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 [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND
RP   VARIANTS NAGSD PRO-279; PRO-430 AND ARG-484.
RX   MEDLINE=22637991; PubMed=12754705; DOI=10.1002/humu.10216;
RA   Haeberle J., Schmidt E., Pauli S., Kreuder J.G., Plecko B., Galler A.,
RA   Wermuth B., Harms E., Koch H.G.;
RT   "Mutation analysis in patients with N-acetylglutamate synthase
RT   deficiency.";
RL   Hum. Mutat. 21:593-597(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 94-534, ENZYME REGULATION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Liver;
RX   MEDLINE=22347014; PubMed=12459178; DOI=10.1016/S0006-291X(02)02696-7;
RA   Caldovic L., Morizono H., Gracia Panglao M., Gallegos R., Yu X.,
RA   Shi D., Malamy M.H., Allewell N.M., Tuchman M.;
RT   "Cloning and expression of the human N-acetylglutamate synthase
RT   gene.";
RL   Biochem. Biophys. Res. Commun. 299:581-586(2002).
RN   [3]
RP   VARIANTS NAGSD ARG-200; PRO-410; PRO-430; ARG-484 AND THR-518, AND
RP   CHARACTERIZATION OF VARIANTS NAGSD ARG-200; PRO-410; PRO-430; ARG-484
RP   AND THR-518.
RX   PubMed=15878741; DOI=10.1016/j.bbadis.2005.02.006;
RA   Schmidt E., Nuoffer J.-M., Haeberle J., Pauli S., Guffon N.,
RA   Vianey-Saban C., Wermuth B., Koch H.G.;
RT   "Identification of novel mutations of the human N-acetylglutamate
RT   synthase gene and their functional investigation by expression
RT   studies.";
RL   Biochim. Biophys. Acta 1740:54-59(2005).
CC   -!- FUNCTION: Plays a role in the regulation of ureagenesis by
CC       producing variable amounts of N-acetylglutamate (NAG), thus
CC       modulating carbamoylphosphate synthase I (CPSI) activity.
CC   -!- CATALYTIC ACTIVITY: Acetyl-CoA + L-glutamate = CoA + N-acetyl-L-
CC       glutamate.
CC   -!- ENZYME REGULATION: Increased by L-arginine.
CC   -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; N(2)-
CC       acetyl-L-ornithine from L-glutamate: step 1/4.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the adult liver, kidney
CC       and small intestine. Weakly expressed in the fetal liver, lung,
CC       pancreas, placenta, heart and brain tissue.
CC   -!- PTM: Probably processed by mitochondrial processing peptidase
CC       (MPP). The long form has not yet been isolated (By similarity).
CC   -!- DISEASE: Defects in NAGS are the cause of N-acetylglutamate
CC       synthase deficiency (NAGSD) [MIM:237310]. NAGSD is a rare
CC       autosomal recessively inherited metabolic disorder leading to
CC       severe neonatal or late onset hyperammonemia without increased
CC       excretion of orotic acid. Clinical symptoms are somnolence,
CC       tachypnea, feeding difficulties, a severe neurologic presentation
CC       characterized by uncontrollable movements, developmental delay,
CC       visual impairment, failure to thrive and hyperammonemia
CC       precipitated by the introduction of high-protein diet or febrile
CC       illness.
CC   -!- SIMILARITY: Belongs to the acetyltransferase family.
CC   -!- SIMILARITY: Contains 1 N-acetyltransferase domain.
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.genetests.org/query?gene=NAGS";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=N-acetylglutamate synthase
CC       entry;
CC       URL="http://en.wikipedia.org/wiki/N-acetylglutamate_synthase";
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DR   EMBL; AY116537; AAM75385.1; -; Genomic_DNA.
DR   EMBL; AY116538; AAM75386.1; -; mRNA.
DR   EMBL; AY158070; AAN76451.1; -; mRNA.
DR   RefSeq; NP_694551.1; -.
DR   UniGene; Hs.8876; -.
DR   Ensembl; ENSG00000161653; Homo sapiens.
DR   GeneID; 162417; -.
DR   KEGG; hsa:162417; -.
DR   HGNC; HGNC:17996; NAGS.
DR   MIM; 237310; phenotype.
DR   MIM; 608300; gene.
DR   Orphanet; 927; N-acetylglutamate synthetase deficiency.
DR   PharmGKB; PA134968729; -.
DR   Reactome; REACT_13; Metabolism of amino acids.
DR   ArrayExpress; Q8N159; -.
DR   CleanEx; HS_NAGS; -.
DR   GermOnline; ENSG00000161653; Homo sapiens.
DR   GO; GO:0004042; F:amino-acid N-acetyltransferase activity; IEA:EC.
DR   InterPro; IPR001048; Asp/Glu/Uridylate_kinase.
DR   InterPro; IPR006855; DUF619.
DR   InterPro; IPR000182; GCN5acetyl_trans.
DR   InterPro; IPR011243; NAG_synth_animal.
DR   Gene3D; G3DSA:3.40.1160.10; Aa_kinase; 1.
DR   Pfam; PF04768; DUF619; 1.
DR   PIRSF; PIRSF036442; NAGS_animal; 1.
DR   PROSITE; PS51186; GNAT; 1.
PE   1: Evidence at protein level;
KW   Acyltransferase; Disease mutation; Mitochondrion; Transferase;
KW   Transit peptide; Urea cycle.
FT   TRANSIT       1     18       Mitochondrion (Potential).
FT   CHAIN        19    534       N-acetylglutamate synthase long form
FT                                (Potential).
FT                                /FTId=PRO_0000041930.
FT   CHAIN        51    534       N-acetylglutamate synthase short form (By
FT                                similarity).
FT                                /FTId=PRO_0000041931.
FT   CHAIN        92    534       N-acetylglutamate synthase conserved
FT                                domain form (By similarity).
FT                                /FTId=PRO_0000041932.
FT   DOMAIN      378    528       N-acetyltransferase.
FT   VARIANT     200    200       C -> R (in NAGSD; markedly decreases
FT                                activity).
FT                                /FTId=VAR_023505.
FT   VARIANT     279    279       A -> P (in NAGSD).
FT                                /FTId=VAR_023506.
FT   VARIANT     410    410       S -> P (in NAGSD; markedly decreases
FT                                activity).
FT                                /FTId=VAR_023507.
FT   VARIANT     430    430       L -> P (in NAGSD; markedly decreases
FT                                activity).
FT                                /FTId=VAR_023508.
FT   VARIANT     484    484       W -> R (in NAGSD; markedly decreases
FT                                activity).
FT                                /FTId=VAR_023509.
FT   VARIANT     518    518       A -> T (in NAGSD; markedly decreases
FT                                activity).
FT                                /FTId=VAR_023510.
FT   CONFLICT     94     94       E -> M (in Ref. 2).
SQ   SEQUENCE   534 AA;  58156 MW;  1328039080EB936C CRC64;
     MATALMAVVL RAAAVAPRLR GRGGTGGARR LSCGARRRAA RGTSPGRRLS TAWSQPQPPP
     EEYAGADDVS QSPVAEEPSW VPSPRPPVPH ESPEPPSGRS LVQRDIQAFL NQCGASPGEA
     RHWLTQFQTC HHSADKPFAV IEVDEEVLKC QQGVSSLAFA LAFLQRMDMK PLVVLGLPAP
     TAPSGCLSFW EAKAQLAKSC KVLVDALRHN AAAAVPFFGG GSVLRAAEPA PHASYGGIVS
     VETDLLQWCL ESGSIPILCP IGETAARRSV LLDSLEVTAS LAKALRPTKI IFLNNTGGLR
     DSSHKVLSNV NLPADLDLVC NAEWVSTKER QQMRLIVDVL SRLPHHSSAV ITAASTLLTE
     LFSNKGSGTL FKNAERMLRV RSLDKLDQGR LVDLVNASFG KKLRDDYLAS LRPRLHSIYV
     SEGYNAAAIL TMEPVLGGTP YLDKFVVSSS RQGQGSGQML WECLRRDLQT LFWRSRVTNP
     INPWYFKHSD GSFSNKQWIF FWFGLADIRD SYELVNHAKG LPDSFHKPAS DPGS
//