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Protein

N-acetyltransferase 8

Gene

NAT8

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

Functioni

Acetylates the free alpha-amino group of cysteine S-conjugates to form mercapturic acids (PubMed:20392701). This is the final step in a major route for detoxification of a wide variety of reactive electrophiles which starts with their incorporation into glutathione S-conjugates. The glutathione S-conjugates are then further processed into cysteine S-conjugates and finally mercapturic acids which are water soluble and can be readily excreted in urine or bile. Alternatively, may have a lysine N-acetyltransferase activity catalyzing peptidyl-lysine N6-acetylation of various proteins. Thereby, may regulate apoptosis through the acetylation and the regulation of the expression of PROM1 (PubMed:24556617). May also regulate amyloid beta-peptide secretion through acetylation of BACE1 and the regulation of its expression in neurons (PubMed:19011241).3 Publications

Catalytic activityi

Acetyl-CoA + an L-cysteine-S-conjugate = CoA + an N-acetyl L-cysteine-S-conjugate.1 Publication

Kineticsi

A Vmax of 4.4 nmol/min/mg enzyme toward S-benzyl-L-cysteine was estimated using crude cell extracts. A Vmax of 3.1 nmol/min/mg enzyme toward acetyl-CoA was estimated using crude cell extracts.
  1. KM=64 µM for S-benzyl-L-cysteine (at 37 degrees Celsius)1 Publication
  2. KM=23 µM for acetyl-CoA (at 37 degrees Celsius)1 Publication

    Pathwayi: glutathione metabolism

    This protein is involved in the pathway glutathione metabolism, which is part of Sulfur metabolism.1 Publication
    View all proteins of this organism that are known to be involved in the pathway glutathione metabolism and in Sulfur metabolism.

    GO - Molecular functioni

    • cysteine-S-conjugate N-acetyltransferase activity Source: UniProtKB
    • lysine N-acetyltransferase activity, acting on acetyl phosphate as donor Source: UniProtKB

    GO - Biological processi

    • amyloid-beta metabolic process Source: UniProtKB
    • cellular protein metabolic process Source: Reactome
    • glutathione metabolic process Source: UniProtKB
    • negative regulation of apoptotic process Source: UniProtKB
    • peptidyl-lysine N6-acetylation Source: UniProtKB
    • positive regulation of gene expression Source: UniProtKB
    • response to drug Source: ProtInc

    Keywordsi

    Molecular functionAcyltransferase, Transferase

    Enzyme and pathway databases

    BRENDAi2.3.1.80. 2681.
    ReactomeiR-HSA-977225. Amyloid fiber formation.
    UniPathwayiUPA00204.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    N-acetyltransferase 8 (EC:2.3.1.-)
    Alternative name(s):
    Acetyltransferase 2
    Short name:
    ATase2
    Camello-like protein 1
    Cysteinyl-conjugate N-acetyltransferase (EC:2.3.1.80)
    Short name:
    CCNAT
    Gene namesi
    Name:NAT8Imported
    Synonyms:CML1Imported, GLAImported, TSC501Imported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:18069. NAT8.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 42CytoplasmicSequence analysisAdd BLAST42
    Transmembranei43 – 63Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
    Topological domaini64 – 227LumenalSequence analysisAdd BLAST164

    GO - Cellular componenti

    • endoplasmic reticulum Source: HPA
    • endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB
    • endoplasmic reticulum-Golgi intermediate compartment membrane Source: UniProtKB
    • endoplasmic reticulum membrane Source: UniProtKB
    • extracellular exosome Source: UniProtKB
    • integral component of membrane Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi149R → K: Loss of the cysteine S-conjugate N-acetyltransferase activity. No effect on protein expression. 1 Publication1

    Organism-specific databases

    DisGeNETi9027.
    OpenTargetsiENSG00000144035.
    PharmGKBiPA31450.

    Polymorphism and mutation databases

    BioMutaiNAT8.
    DMDMi145566894.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002846841 – 227N-acetyltransferase 8Add BLAST227

    Proteomic databases

    MaxQBiQ9UHE5.
    PaxDbiQ9UHE5.
    PeptideAtlasiQ9UHE5.
    PRIDEiQ9UHE5.

    PTM databases

    PhosphoSitePlusiQ9UHE5.

    Expressioni

    Tissue specificityi

    Preferentially expressed in liver and kidney. Also detected in brain (at protein level).2 Publications

    Inductioni

    Up-regulated by ceramides.1 Publication

    Gene expression databases

    BgeeiENSG00000144035.
    CleanExiHS_GLA.
    HS_NAT8.
    GenevisibleiQ9UHE5. HS.

    Organism-specific databases

    HPAiCAB045990.
    HPA074519.

    Interactioni

    Subunit structurei

    Interacts with PROM1. Interacts with BACE1.2 Publications

    Protein-protein interaction databases

    BioGridi114494. 1 interactor.
    IntActiQ9UHE5. 1 interactor.
    STRINGi9606.ENSP00000272425.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UHE5.
    SMRiQ9UHE5.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini61 – 220N-acetyltransferasePROSITE-ProRule annotationAdd BLAST160

    Sequence similaritiesi

    Belongs to the camello family.1 Publication

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3139. Eukaryota.
    COG0456. LUCA.
    GeneTreeiENSGT00390000009559.
    HOGENOMiHOG000261685.
    HOVERGENiHBG060476.
    InParanoidiQ9UHE5.
    KOiK20838.
    OMAiYHIRKYR.
    OrthoDBiEOG091G0LL0.
    PhylomeDBiQ9UHE5.
    TreeFamiTF324687.

    Family and domain databases

    InterProiView protein in InterPro
    IPR016181. Acyl_CoA_acyltransferase.
    IPR000182. GNAT_dom.
    PfamiView protein in Pfam
    PF00583. Acetyltransf_1. 1 hit.
    SUPFAMiSSF55729. SSF55729. 1 hit.
    PROSITEiView protein in PROSITE
    PS51186. GNAT. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q9UHE5-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAPCHIRKYQ ESDRQWVVGL LSRGMAEHAP ATFRQLLKLP RTLILLLGGP
    60 70 80 90 100
    LALLLVSGSW LLALVFSISL FPALWFLAKK PWTEYVDMTL CTDMSDITKS
    110 120 130 140 150
    YLSERGSCFW VAESEEKVVG MVGALPVDDP TLREKRLQLF HLFVDSEHRR
    160 170 180 190 200
    QGIAKALVRT VLQFARDQGY SEVILDTGTI QLSAMALYQS MGFKKTGQSF
    210 220
    FCVWARLVAL HTVHFIYHLP SSKVGSL
    Length:227
    Mass (Da):25,619
    Last modified:April 17, 2007 - v2
    Checksum:iB6CEAC98EFB0D6C8
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti202C → R in CAG28538 (Ref. 4) Curated1
    Sequence conflicti212T → K in BAA34386 (Ref. 3) Curated1
    Sequence conflicti227L → Q in AAH12626 (PubMed:15489334).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_053886104E → K No effect on the cysteine S-conjugate N-acetyltransferase activity. 1 PublicationCorresponds to variant dbSNP:rs13424561Ensembl.1
    Natural variantiVAR_031805143F → S No effect on the cysteine S-conjugate N-acetyltransferase activity. 4 PublicationsCorresponds to variant dbSNP:rs13538Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB013094 mRNA. Translation: BAA33679.1.
    AF187813 mRNA. Translation: AAF22303.1.
    AB019551 mRNA. Translation: BAA34386.1.
    CR407610 mRNA. Translation: CAG28538.1.
    BC012626 mRNA. Translation: AAH12626.1.
    CCDSiCCDS1926.1.
    PIRiT44342.
    RefSeqiNP_003951.3. NM_003960.3.
    UniGeneiHs.14637.

    Genome annotation databases

    EnsembliENST00000272425; ENSP00000272425; ENSG00000144035.
    GeneIDi9027.
    KEGGihsa:9027.
    UCSCiuc002sji.2. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiNAT8_HUMAN
    AccessioniPrimary (citable) accession number: Q9UHE5
    Secondary accession number(s): O75839
    , Q6LEU4, Q96QI8, Q9UQ17
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 17, 2007
    Last sequence update: April 17, 2007
    Last modified: August 30, 2017
    This is version 110 of the entry and version 2 of the sequence. See 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: 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. SIMILARITY comments
      Index of protein domains and families