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Protein

N-acetylglutamate synthase, mitochondrial

Gene

NAGS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in the regulation of ureagenesis by producing the essential cofactor N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (CPSI) activity.

Catalytic activityi

Acetyl-CoA + L-glutamate = CoA + N-acetyl-L-glutamate.

Enzyme regulationi

Increased by L-arginine.2 Publications

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei401 – 4011Substrate
Binding sitei444 – 4441Substrate

GO - Molecular functioni

  1. acetyl-CoA:L-glutamate N-acetyltransferase activity Source: BHF-UCL

GO - Biological processi

  1. arginine biosynthetic process Source: UniProtKB-UniPathway
  2. cellular nitrogen compound metabolic process Source: Reactome
  3. glutamate metabolic process Source: BHF-UCL
  4. small molecule metabolic process Source: Reactome
  5. urea cycle Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Urea cycle

Enzyme and pathway databases

BRENDAi2.3.1.1. 2681.
ReactomeiREACT_847. Urea cycle.
UniPathwayiUPA00068; UER00106.

Names & Taxonomyi

Protein namesi
Recommended name:
N-acetylglutamate synthase, mitochondrial (EC:2.3.1.1)
Alternative name(s):
Amino-acid acetyltransferase
Cleaved into the following 3 chains:
Gene namesi
Name:NAGS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:17996. NAGS.

Subcellular locationi

GO - Cellular componenti

  1. mitochondrial matrix Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

N-acetylglutamate synthase deficiency2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionRare 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.

See also OMIM:237310
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti200 – 2001C → R in NAGSD; markedly decreases activity. 1 Publication
VAR_023505
Natural varianti279 – 2791A → P in NAGSD. 1 Publication
VAR_023506
Natural varianti410 – 4101S → P in NAGSD; markedly decreases activity. 1 Publication
VAR_023507
Natural varianti430 – 4301L → P in NAGSD; markedly decreases activity. 2 Publications
VAR_023508
Natural varianti484 – 4841W → R in NAGSD; markedly decreases activity. 2 Publications
VAR_023509
Natural varianti518 – 5181A → T in NAGSD; markedly decreases activity. 1 Publication
VAR_023510

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi441 – 4411Y → F: 15% reduction in catalytic activity. 1 Publication
Mutagenesisi479 – 4791N → A: 7-fold reduction in catalytic activity. 1 Publication
Mutagenesisi485 – 4851Y → F: 10-fold reduction in catalytic activity. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi237310. phenotype.
Orphaneti927. Hyperammonemia due to N-acetylglutamate synthetase deficiency.
PharmGKBiPA134968729.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 1818MitochondrionSequence AnalysisAdd
BLAST
Chaini19 – 534516N-acetylglutamate synthase long formSequence AnalysisPRO_0000041930Add
BLAST
Chaini51 – 534484N-acetylglutamate synthase short formBy similarityPRO_0000041931Add
BLAST
Chaini92 – 534443N-acetylglutamate synthase conserved domain formBy similarityPRO_0000041932Add
BLAST

Post-translational modificationi

Probably processed by mitochondrial processing peptidase (MPP). The long form has not yet been isolated (By similarity).By similarity

Proteomic databases

PaxDbiQ8N159.
PRIDEiQ8N159.

PTM databases

PhosphoSiteiQ8N159.

Expressioni

Tissue specificityi

Highly expressed in the adult liver, kidney and small intestine. Weakly expressed in the fetal liver, lung, pancreas, placenta, heart and brain tissue.2 Publications

Gene expression databases

BgeeiQ8N159.
CleanExiHS_NAGS.
ExpressionAtlasiQ8N159. baseline and differential.
GenevestigatoriQ8N159.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi127816. 1 interaction.
IntActiQ8N159. 1 interaction.
MINTiMINT-1431825.
STRINGi9606.ENSP00000293404.

Structurei

Secondary structure

1
534
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi377 – 3815Combined sources
Helixi383 – 3853Combined sources
Helixi388 – 39912Combined sources
Helixi407 – 4115Combined sources
Helixi412 – 4143Combined sources
Beta strandi415 – 4217Combined sources
Beta strandi426 – 43510Combined sources
Beta strandi439 – 4479Combined sources
Helixi451 – 46717Combined sources
Beta strandi471 – 4766Combined sources
Helixi482 – 4876Combined sources
Beta strandi489 – 4946Combined sources
Beta strandi496 – 5038Combined sources
Helixi510 – 52011Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4K30X-ray2.10A/B/X/Y377-534[»]
ProteinModelPortaliQ8N159.
SMRiQ8N159. Positions 115-527.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini375 – 526152N-acetyltransferasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni19 – 376358Amino-acid kinase domain (AAK)Add
BLAST
Regioni474 – 4796Substrate binding

Domaini

The Amino-acid kinase domain (AAK) mediates binding of the allosteric activator L-arginine.

Sequence similaritiesi

Belongs to the acetyltransferase family.Curated
Contains 1 N-acetyltransferase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0548.
GeneTreeiENSGT00390000005602.
HOGENOMiHOG000007983.
HOVERGENiHBG080036.
InParanoidiQ8N159.
KOiK11067.
OMAiMRLIVDV.
OrthoDBiEOG77WWDH.
PhylomeDBiQ8N159.
TreeFamiTF332628.

Family and domain databases

Gene3Di3.40.1160.10. 1 hit.
InterProiIPR016181. Acyl_CoA_acyltransferase.
IPR001048. Asp/Glu/Uridylate_kinase.
IPR006855. DUF619.
IPR011243. GlcNAc_Synth_met.
IPR000182. GNAT_dom.
[Graphical view]
PfamiPF04768. DUF619. 1 hit.
[Graphical view]
PIRSFiPIRSF036442. NAGS_animal. 1 hit.
SUPFAMiSSF53633. SSF53633. 1 hit.
SSF55729. SSF55729. 1 hit.
PROSITEiPS51731. GNAT_NAGS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8N159-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MATALMAVVL RAAAVAPRLR GRGGTGGARR LSCGARRRAA RGTSPGRRLS
60 70 80 90 100
TAWSQPQPPP EEYAGADDVS QSPVAEEPSW VPSPRPPVPH ESPEPPSGRS
110 120 130 140 150
LVQRDIQAFL NQCGASPGEA RHWLTQFQTC HHSADKPFAV IEVDEEVLKC
160 170 180 190 200
QQGVSSLAFA LAFLQRMDMK PLVVLGLPAP TAPSGCLSFW EAKAQLAKSC
210 220 230 240 250
KVLVDALRHN AAAAVPFFGG GSVLRAAEPA PHASYGGIVS VETDLLQWCL
260 270 280 290 300
ESGSIPILCP IGETAARRSV LLDSLEVTAS LAKALRPTKI IFLNNTGGLR
310 320 330 340 350
DSSHKVLSNV NLPADLDLVC NAEWVSTKER QQMRLIVDVL SRLPHHSSAV
360 370 380 390 400
ITAASTLLTE LFSNKGSGTL FKNAERMLRV RSLDKLDQGR LVDLVNASFG
410 420 430 440 450
KKLRDDYLAS LRPRLHSIYV SEGYNAAAIL TMEPVLGGTP YLDKFVVSSS
460 470 480 490 500
RQGQGSGQML WECLRRDLQT LFWRSRVTNP INPWYFKHSD GSFSNKQWIF
510 520 530
FWFGLADIRD SYELVNHAKG LPDSFHKPAS DPGS
Length:534
Mass (Da):58,156
Last modified:October 1, 2002 - v1
Checksum:i1328039080EB936C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti94 – 941E → M in AAN76451. (PubMed:12459178)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti200 – 2001C → R in NAGSD; markedly decreases activity. 1 Publication
VAR_023505
Natural varianti279 – 2791A → P in NAGSD. 1 Publication
VAR_023506
Natural varianti410 – 4101S → P in NAGSD; markedly decreases activity. 1 Publication
VAR_023507
Natural varianti430 – 4301L → P in NAGSD; markedly decreases activity. 2 Publications
VAR_023508
Natural varianti484 – 4841W → R in NAGSD; markedly decreases activity. 2 Publications
VAR_023509
Natural varianti518 – 5181A → T in NAGSD; markedly decreases activity. 1 Publication
VAR_023510

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY116537 Genomic DNA. Translation: AAM75385.1.
AY116538 mRNA. Translation: AAM75386.1.
AK314432 mRNA. Translation: BAG37046.1.
AY158070 mRNA. Translation: AAN76451.1.
CCDSiCCDS11473.1.
RefSeqiNP_694551.1. NM_153006.2.
UniGeneiHs.8876.

Genome annotation databases

EnsembliENST00000293404; ENSP00000293404; ENSG00000161653.
GeneIDi162417.
KEGGihsa:162417.
UCSCiuc002ies.3. human.

Polymorphism databases

DMDMi74714699.

Cross-referencesi

Web resourcesi

Wikipedia

N-acetylglutamate synthase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY116537 Genomic DNA. Translation: AAM75385.1.
AY116538 mRNA. Translation: AAM75386.1.
AK314432 mRNA. Translation: BAG37046.1.
AY158070 mRNA. Translation: AAN76451.1.
CCDSiCCDS11473.1.
RefSeqiNP_694551.1. NM_153006.2.
UniGeneiHs.8876.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4K30X-ray2.10A/B/X/Y377-534[»]
ProteinModelPortaliQ8N159.
SMRiQ8N159. Positions 115-527.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127816. 1 interaction.
IntActiQ8N159. 1 interaction.
MINTiMINT-1431825.
STRINGi9606.ENSP00000293404.

PTM databases

PhosphoSiteiQ8N159.

Polymorphism databases

DMDMi74714699.

Proteomic databases

PaxDbiQ8N159.
PRIDEiQ8N159.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000293404; ENSP00000293404; ENSG00000161653.
GeneIDi162417.
KEGGihsa:162417.
UCSCiuc002ies.3. human.

Organism-specific databases

CTDi162417.
GeneCardsiGC17P042082.
HGNCiHGNC:17996. NAGS.
MIMi237310. phenotype.
608300. gene.
neXtProtiNX_Q8N159.
Orphaneti927. Hyperammonemia due to N-acetylglutamate synthetase deficiency.
PharmGKBiPA134968729.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0548.
GeneTreeiENSGT00390000005602.
HOGENOMiHOG000007983.
HOVERGENiHBG080036.
InParanoidiQ8N159.
KOiK11067.
OMAiMRLIVDV.
OrthoDBiEOG77WWDH.
PhylomeDBiQ8N159.
TreeFamiTF332628.

Enzyme and pathway databases

UniPathwayiUPA00068; UER00106.
BRENDAi2.3.1.1. 2681.
ReactomeiREACT_847. Urea cycle.

Miscellaneous databases

ChiTaRSiNAGS. human.
GenomeRNAii162417.
NextBioi88165.
PROiQ8N159.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N159.
CleanExiHS_NAGS.
ExpressionAtlasiQ8N159. baseline and differential.
GenevestigatoriQ8N159.

Family and domain databases

Gene3Di3.40.1160.10. 1 hit.
InterProiIPR016181. Acyl_CoA_acyltransferase.
IPR001048. Asp/Glu/Uridylate_kinase.
IPR006855. DUF619.
IPR011243. GlcNAc_Synth_met.
IPR000182. GNAT_dom.
[Graphical view]
PfamiPF04768. DUF619. 1 hit.
[Graphical view]
PIRSFiPIRSF036442. NAGS_animal. 1 hit.
SUPFAMiSSF53633. SSF53633. 1 hit.
SSF55729. SSF55729. 1 hit.
PROSITEiPS51731. GNAT_NAGS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 94-534, ENZYME REGULATION, TISSUE SPECIFICITY.
    Tissue: Liver.
  4. "Crystal structure of the N-acetyltransferase domain of human N-acetyl-L-glutamate synthase in complex with N-acetyl-L-glutamate provides insights into its catalytic and regulatory mechanisms."
    Zhao G., Jin Z., Allewell N.M., Tuchman M., Shi D.
    PLoS ONE 8:E70369-E70369(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 377-534 IN COMPLEX WITH N-ACETYL-GLUTAMATE, ENZYME REGULATION, SUBSTRATE-BINDING SITES, SUBUNIT, MUTAGENESIS OF TYR-441; ASN-479 AND TYR-485.
  5. "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.

Entry informationi

Entry nameiNAGS_HUMAN
AccessioniPrimary (citable) accession number: Q8N159
Secondary accession number(s): B2RAZ9, Q8IWR4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: October 1, 2002
Last modified: February 4, 2015
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.