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Q8N159 (NAGS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
N-acetylglutamate synthase, mitochondrial

EC=2.3.1.1
Alternative name(s):
Amino-acid acetyltransferase
Gene names
Name:NAGS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length534 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 1818Mitochondrion Potential
Chain19 – 534516N-acetylglutamate synthase long form Potential
PRO_0000041930
Chain51 – 534484N-acetylglutamate synthase short form By similarity
PRO_0000041931
Chain92 – 534443N-acetylglutamate synthase conserved domain form By similarity
PRO_0000041932

Regions

Domain378 – 528151N-acetyltransferase

Natural variations

Natural variant2001C → R in NAGSD; markedly decreases activity. Ref.4
VAR_023505
Natural variant2791A → P in NAGSD. Ref.1
VAR_023506
Natural variant4101S → P in NAGSD; markedly decreases activity. Ref.4
VAR_023507
Natural variant4301L → P in NAGSD; markedly decreases activity. Ref.1 Ref.4
VAR_023508
Natural variant4841W → R in NAGSD; markedly decreases activity. Ref.1 Ref.4
VAR_023509
Natural variant5181A → T in NAGSD; markedly decreases activity. Ref.4
VAR_023510

Experimental info

Sequence conflict941E → M in AAN76451. Ref.3

Secondary structure

........................... 534
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8N159 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 1328039080EB936C

FASTA53458,156
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
RefSeqNP_694551.1. NM_153006.2.
UniGeneHs.8876.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4K30X-ray2.10A/B/X/Y377-534[»]
ProteinModelPortalQ8N159.
SMRQ8N159. Positions 115-527.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8N159. 1 interaction.
MINTMINT-1431825.
STRING9606.ENSP00000293404.

Chemistry

DrugBankDB00142. L-Glutamic Acid.

PTM databases

PhosphoSiteQ8N159.

Polymorphism databases

DMDM74714699.

Proteomic databases

PaxDbQ8N159.
PRIDEQ8N159.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293404; ENSP00000293404; ENSG00000161653.
GeneID162417.
KEGGhsa:162417.
UCSCuc002ies.3. human.

Organism-specific databases

CTD162417.
GeneCardsGC17P042082.
HGNCHGNC:17996. NAGS.
MIM237310. phenotype.
608300. gene.
neXtProtNX_Q8N159.
Orphanet927. Hyperammonemia due to N-acetylglutamate synthetase deficiency.
PharmGKBPA134968729.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0548.
HOGENOMHOG000007983.
HOVERGENHBG080036.
InParanoidQ8N159.
KOK11067.
OMAMRLIVDV.
OrthoDBEOG77WWDH.
PhylomeDBQ8N159.
TreeFamTF332628.

Enzyme and pathway databases

BRENDA2.3.1.1. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00068; UER00106.

Gene expression databases

ArrayExpressQ8N159.
BgeeQ8N159.
CleanExHS_NAGS.
GenevestigatorQ8N159.

Family and domain databases

Gene3D3.40.1160.10. 1 hit.
InterProIPR016181. Acyl_CoA_acyltransferase.
IPR001048. Asp/Glu/Uridylate_kinase.
IPR006855. DUF619.
IPR011243. GlcNAc_Synth_met.
IPR000182. GNAT_dom.
[Graphical view]
PfamPF04768. DUF619. 1 hit.
[Graphical view]
PIRSFPIRSF036442. NAGS_animal. 1 hit.
SUPFAMSSF53633. SSF53633. 1 hit.
SSF55729. SSF55729. 1 hit.
PROSITEPS51186. GNAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNAGS. human.
GenomeRNAi162417.
NextBio88165.
PROQ8N159.
SOURCESearch...

Entry information

Entry nameNAGS_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM