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NAGS N-acetylglutamate synthase [ Homo sapiens (human) ]

Gene ID: 162417, updated on 3-Apr-2024

Summary

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Official Symbol
NAGSprovided by HGNC
Official Full Name
N-acetylglutamate synthaseprovided by HGNC
Primary source
HGNC:HGNC:17996
See related
Ensembl:ENSG00000161653 MIM:608300; AllianceGenome:HGNC:17996
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AGAS; ARGA
Summary
The N-acetylglutamate synthase gene encodes a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG) from glutamate and acetyl coenzyme-A. NAG is a cofactor of carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle in mammals. This gene may regulate ureagenesis by altering NAG availability and, thereby, CPSI activity. Deficiencies in N-acetylglutamate synthase have been associated with hyperammonemia. [provided by RefSeq, Jul 2008]
Expression
Biased expression in duodenum (RPKM 7.8), small intestine (RPKM 6.4) and 8 other tissues See more
Orthologs
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Genomic context

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Location:
17q21.31
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (44004622..44009068)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (44857133..44861579)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (42081990..42086436)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene pancreatic polypeptide Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:42030343-42030846 Neighboring gene peptide YY Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:42082913-42083668 Neighboring gene Sharpr-MPRA regulatory region 11566 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr17:42091474-42092673 Neighboring gene Sharpr-MPRA regulatory region 15580 Neighboring gene transmembrane protein 101 Neighboring gene uncharacterized LOC124904152 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:42102423-42102924

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene. Häberle J, et al. Hum Mutat, 2021 Dec. PMID 34510628, Free PMC Article
  2. N-Acetylglutamate Synthase Deficiency Due to a Recurrent Sequence Variant in the N-acetylglutamate Synthase Enhancer Region. Williams M, et al. Sci Rep, 2018 Oct 18. PMID 30337552, Free PMC Article
  3. Understanding N-Acetyl-L-Glutamate Synthase Deficiency: Mutational Spectrum, Impact of Clinical Mutations on Enzyme Functionality, and Structural Considerations. Sancho-Vaello E, et al. Hum Mutat, 2016 Jul. PMID 27037498
  4. Inhibition of N-acetylglutamate synthase by various monocarboxylic and dicarboxylic short-chain coenzyme A esters and the production of alternative glutamate esters. Dercksen M, et al. Biochim Biophys Acta, 2014 Dec. PMID 23643712
  5. Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency. Gessler P, et al. Eur J Pediatr, 2010 Feb. PMID 19533169

See all (35) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NAGS, CPS1, and SLC25A13 (Citrin) at the Crossroads of Arginine and Pyrimidines Metabolism in Tumor Cells.
    Title: NAGS, CPS1, and SLC25A13 (Citrin) at the Crossroads of Arginine and Pyrimidines Metabolism in Tumor Cells.
  2. Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene.
    Title: Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene.
  3. Variation in the N-acetylglutamate Synthase Enhancer Region is associated with N-Acetylglutamate Synthase Deficiency.
    Title: N-Acetylglutamate Synthase Deficiency Due to a Recurrent Sequence Variant in the N-acetylglutamate Synthase Enhancer Region.
  4. The specificity of the assay was validated by demonstrating a complete deficiency of NAGS in liver homogenates from Nags -/- mice. CONCLUSION: The novel NAGS enzyme assay reported herein can be used for the diagnosis of inherited NAGS deficiency and may also be of value in the study of secondary hyperammonemia present in various inborn errors of metabolism as well as drug treatment.
    Title: A novel UPLC-MS/MS based method to determine the activity of N-acetylglutamate synthase in liver tissue.
  5. Results identified 36 NAGS mutations in NAGSD patients; 61% of which are missense mutations. Phenotypes associated with these mutations in the GNAT domain are more severe than phenotypes of that of amino acid kinase domain. Enzyme activity and stability assays with 12 mutations, together with in silico structural analysis, support the pathogenic role of most NAGSD-associated mutations found.
    Title: Understanding N-Acetyl-L-Glutamate Synthase Deficiency: Mutational Spectrum, Impact of Clinical Mutations on Enzyme Functionality, and Structural Considerations.
  6. Data indicate the formation of alternative N-acylglutamates by N-acetylglutamate synthase (NAGS).
    Title: Inhibition of N-acetylglutamate synthase by various monocarboxylic and dicarboxylic short-chain coenzyme A esters and the production of alternative glutamate esters.
  7. Sp1, CREB, HNF-1, and NF-Y, known to be responsive to hormones and diet, regulate NAGS transcription
    Title: Transcriptional regulation of N-acetylglutamate synthase.
  8. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
    Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
  10. NAGS deficiency in humans leads to hyperammonemia and can be primary, due to mutations in the NAGS gene or secondary due to other mitochondrial aberrations that interfere with the normal function of the same enzyme.
    Title: N-acetylglutamate synthase: structure, function and defects.
Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Hyperammonemia, type III
MedGen: C0268543 OMIM: 237310 GeneReviews: Urea Cycle Disorders Overview
Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC133025

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables acetyl-CoA:L-glutamate N-acetyltransferase activity EXP
Inferred from Experiment
more info
 PubMed 
enables acetyl-CoA:L-glutamate N-acetyltransferase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables acetyl-CoA:L-glutamate N-acetyltransferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables acetyl-CoA:L-glutamate N-acetyltransferase activity TAS
Traceable Author Statement
more info
 PubMed 
enables methione N-acyltransferase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in arginine biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in arginine biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in glutamate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glutamate metabolic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in urea cycle TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
is_active_in mitochondrial matrix IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
N-acetylglutamate synthase, mitochondrial
Names
amino-acid acetyltransferase
NP_694551.1
XP_011522740.1
XP_011522741.1
XP_054171243.1
XP_054171244.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008106.1 RefSeqGene

    Range
    4959..9405
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_153006.3 → NP_694551.1  N-acetylglutamate synthase, mitochondrial

    See identical proteins and their annotated locations for NP_694551.1

    Status: REVIEWED

    Source sequence(s)
    AC023855, AI241153, AY116538, BF589712
    Consensus CDS
    CCDS11473.1
    UniProtKB/Swiss-Prot
    B2RAZ9, Q8IWR4, Q8N159
    UniProtKB/TrEMBL
    K7EK11
    Related
    ENSP00000293404.2, ENST00000293404.8
    Conserved Domains (2) summary
    cd04236
    Location:102 → 371
    AAK_NAGS-Urea; N-acetylglutamate (NAG) kinase-like domain of the NAG Synthase (NAGS) of the urea cycle found in animals. Ureogenic NAGS is a mitochondrial enzyme catalyzing the formation of NAG from acetylcoenzyme A and L-glutamate; NAG is an essential allosteric ...
    pfam04768
    Location:357 → 520
    NAT; N-acetyltransferase, of N-acetylglutamate synthase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    44004622..44009068
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011524438.2 → XP_011522740.1  N-acetylglutamate synthase, mitochondrial isoform X1

    UniProtKB/TrEMBL
    K7EK11
    Conserved Domains (4) summary
    PRK04531
    Location:115 → 464
    PRK04531; acetylglutamate kinase; Provisional
    cd04236
    Location:102 → 371
    AAK_NAGS-Urea; AAK_NAGS-Urea: N-acetylglutamate (NAG) kinase-like domain of the NAG Synthase (NAGS) of the urea cycle found in animals. Ureogenic NAGS is a mitochondrial enzyme catalyzing the formation of NAG from acetylcoenzyme A and L-glutamate; NAG is an essential ...
    pfam16642
    Location:32 → 93
    KCNQ2_u3; Unstructured region on Potassium channel subunit alpha KvLQT2
    cl14605
    Location:357 → 459
    DUF619-like; DUF619 domain of various N-acetylglutamate Kinases and N-acetylglutamate Synthases

  2. XM_011524439.2 → XP_011522741.1  N-acetylglutamate synthase, mitochondrial isoform X2

    See identical proteins and their annotated locations for XP_011522741.1

    UniProtKB/TrEMBL
    Q2NKP2
    Conserved Domains (2) summary
    cl00452
    Location:1 → 205
    AAK; Amino Acid Kinases (AAK) superfamily, catalytic domain; present in such enzymes like N-acetylglutamate kinase (NAGK), carbamate kinase (CK), aspartokinase (AK), glutamate-5-kinase (G5K) and UMP kinase (UMPK). The AAK superfamily includes kinases that ...
    cl28353
    Location:84 → 359
    PRK05279; N-acetylglutamate synthase; Validated

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    44857133..44861579
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054315268.1 → XP_054171243.1  N-acetylglutamate synthase, mitochondrial isoform X1

  2. XM_054315269.1 → XP_054171244.1  N-acetylglutamate synthase, mitochondrial isoform X2

    UniProtKB/TrEMBL
    Q2NKP2
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8N159.1 GenPept UniProtKB/Swiss-Prot:Q8N159

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