Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q8N159

- NAGS_HUMAN

UniProt

Q8N159 - NAGS_HUMAN

Protein

N-acetylglutamate synthase, mitochondrial

Gene

NAGS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 104 (01 Oct 2014)
      Sequence version 1 (01 Oct 2002)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    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

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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

    ArrayExpressiQ8N159.
    BgeeiQ8N159.
    CleanExiHS_NAGS.
    GenevestigatoriQ8N159.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

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

    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:
    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.

    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

    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: October 1, 2014
    This is version 104 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