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Q8N159

- NAGS_HUMAN

UniProt

Q8N159 - NAGS_HUMAN

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Protein

N-acetylglutamate synthase, mitochondrial

Gene
NAGS
Organism
Homo sapiens (Human)
Status
Reviewed - 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.1 Publication

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 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.2 Publications
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.
Mutagenesisi479 – 4791N → A: 7-fold reduction in catalytic activity.
Mutagenesisi485 – 4851Y → F: 10-fold reduction in catalytic activity.

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 – 1818Mitochondrion Reviewed predictionAdd
BLAST
Chaini19 – 534516N-acetylglutamate synthase long form Reviewed predictionPRO_0000041930Add
BLAST
Chaini51 – 534484N-acetylglutamate synthase short form By similarityPRO_0000041931Add
BLAST
Chaini92 – 534443N-acetylglutamate synthase conserved domain form By similarityPRO_0000041932Add
BLAST

Post-translational modificationi

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

ArrayExpressiQ8N159.
BgeeiQ8N159.
CleanExiHS_NAGS.
GenevestigatoriQ8N159.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

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 strandi378 – 3825
Helixi383 – 3853
Helixi388 – 39912
Helixi407 – 4115
Helixi412 – 4143
Beta strandi415 – 4206
Beta strandi424 – 43512
Beta strandi438 – 44710
Helixi451 – 46717
Beta strandi471 – 4766
Helixi482 – 4876
Beta strandi489 – 4946
Beta strandi496 – 5038
Helixi508 – 5103
Helixi511 – 5199

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini378 – 528151N-acetyltransferaseAdd
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.

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0548.
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.
PROSITEiPS51186. GNAT. 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

MATALMAVVL RAAAVAPRLR GRGGTGGARR LSCGARRRAA RGTSPGRRLS    50
TAWSQPQPPP EEYAGADDVS QSPVAEEPSW VPSPRPPVPH ESPEPPSGRS 100
LVQRDIQAFL NQCGASPGEA RHWLTQFQTC HHSADKPFAV IEVDEEVLKC 150
QQGVSSLAFA LAFLQRMDMK PLVVLGLPAP TAPSGCLSFW EAKAQLAKSC 200
KVLVDALRHN AAAAVPFFGG GSVLRAAEPA PHASYGGIVS VETDLLQWCL 250
ESGSIPILCP IGETAARRSV LLDSLEVTAS LAKALRPTKI IFLNNTGGLR 300
DSSHKVLSNV NLPADLDLVC NAEWVSTKER QQMRLIVDVL SRLPHHSSAV 350
ITAASTLLTE LFSNKGSGTL FKNAERMLRV RSLDKLDQGR LVDLVNASFG 400
KKLRDDYLAS LRPRLHSIYV SEGYNAAAIL TMEPVLGGTP YLDKFVVSSS 450
RQGQGSGQML WECLRRDLQT LFWRSRVTNP INPWYFKHSD GSFSNKQWIF 500
FWFGLADIRD SYELVNHAKG LPDSFHKPAS DPGS 534
Length:534
Mass (Da):58,156
Last modified:October 1, 2002 - v1
Checksum:i1328039080EB936C
GO

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti94 – 941E → M in AAN76451. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AY116537 Genomic DNA. Translation: AAM75385.1 .
AY116538 mRNA. Translation: AAM75386.1 .
AK314432 mRNA. Translation: BAG37046.1 .
AY158070 mRNA. Translation: AAN76451.1 .
CCDSi CCDS11473.1.
RefSeqi NP_694551.1. NM_153006.2.
UniGenei Hs.8876.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4K30 X-ray 2.10 A/B/X/Y 377-534 [» ]
ProteinModelPortali Q8N159.
SMRi Q8N159. Positions 115-527.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q8N159. 1 interaction.
MINTi MINT-1431825.
STRINGi 9606.ENSP00000293404.

Chemistry

DrugBanki DB00142. L-Glutamic Acid.

PTM databases

PhosphoSitei Q8N159.

Polymorphism databases

DMDMi 74714699.

Proteomic databases

PaxDbi Q8N159.
PRIDEi Q8N159.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000293404 ; ENSP00000293404 ; ENSG00000161653 .
GeneIDi 162417.
KEGGi hsa:162417.
UCSCi uc002ies.3. human.

Organism-specific databases

CTDi 162417.
GeneCardsi GC17P042082.
HGNCi HGNC:17996. NAGS.
MIMi 237310. phenotype.
608300. gene.
neXtProti NX_Q8N159.
Orphaneti 927. Hyperammonemia due to N-acetylglutamate synthetase deficiency.
PharmGKBi PA134968729.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0548.
HOGENOMi HOG000007983.
HOVERGENi HBG080036.
InParanoidi Q8N159.
KOi K11067.
OMAi MRLIVDV.
OrthoDBi EOG77WWDH.
PhylomeDBi Q8N159.
TreeFami TF332628.

Enzyme and pathway databases

UniPathwayi UPA00068 ; UER00106 .
BRENDAi 2.3.1.1. 2681.
Reactomei REACT_847. Urea cycle.

Miscellaneous databases

ChiTaRSi NAGS. human.
GenomeRNAii 162417.
NextBioi 88165.
PROi Q8N159.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8N159.
Bgeei Q8N159.
CleanExi HS_NAGS.
Genevestigatori Q8N159.

Family and domain databases

Gene3Di 3.40.1160.10. 1 hit.
InterProi IPR016181. Acyl_CoA_acyltransferase.
IPR001048. Asp/Glu/Uridylate_kinase.
IPR006855. DUF619.
IPR011243. GlcNAc_Synth_met.
IPR000182. GNAT_dom.
[Graphical view ]
Pfami PF04768. DUF619. 1 hit.
[Graphical view ]
PIRSFi PIRSF036442. NAGS_animal. 1 hit.
SUPFAMi SSF53633. SSF53633. 1 hit.
SSF55729. SSF55729. 1 hit.
PROSITEi PS51186. GNAT. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 103 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

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