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

Summary

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: mouse all
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Genomic context

Location:: 17q21.31

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (44004622..44009068)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (44857133..44861579)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (42081990..42086436)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:481465

RH75045 (e-PCR)
- UniSTS:91606

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables L-glutamate N-acetyltransferase activity	EXP Inferred from Experiment more info	PubMed
enables L-glutamate N-acetyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-glutamate N-acetyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables L-glutamate N-acetyltransferase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in L-arginine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in L-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	HTP more info	PubMed
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

EC 2.3.1.1

XP_011522740.1

EC 2.3.1.1

XP_011522741.1

EC 2.3.1.1

XP_054171243.1

EC 2.3.1.1

XP_054171244.1

EC 2.3.1.1

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

NG_008106.1 RefSeqGene

Range

4959..9405

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

44004622..44009068

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

NC_060941.1 Alternate T2T-CHM13v2.0

Range

44857133..44861579

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054315268.1 → XP_054171243.1 N-acetylglutamate synthase, mitochondrial isoform X1
XM_054315269.1 → XP_054171244.1 N-acetylglutamate synthase, mitochondrial isoform X2

UniProtKB/TrEMBL

Q2NKP2