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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

    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

    • beta-amyloid metabolic process Source: UniProtKB
    • 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
    Complete GO annotation...

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Enzyme and pathway databases

    BRENDAi2.3.1.80. 2681.
    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
    ProteomesiUP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:18069. NAT8.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4242CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei43 – 6321Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST
    Topological domaini64 – 227164LumenalSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    • 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
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi149 – 1491R → K: Loss of the cysteine S-conjugate N-acetyltransferase activity. No effect on protein expression. 1 Publication

    Organism-specific databases

    PharmGKBiPA31450.

    Polymorphism and mutation databases

    BioMutaiNAT8.
    DMDMi145566894.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 227227N-acetyltransferase 8PRO_0000284684Add
    BLAST

    Proteomic databases

    MaxQBiQ9UHE5.
    PaxDbiQ9UHE5.
    PRIDEiQ9UHE5.

    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

    BgeeiQ9UHE5.
    CleanExiHS_GLA.
    HS_NAT8.
    GenevestigatoriQ9UHE5.

    Organism-specific databases

    HPAiCAB045990.

    Interactioni

    Subunit structurei

    Interacts with PROM1. Interacts with BACE1.2 Publications

    Protein-protein interaction databases

    IntActiQ9UHE5. 1 interaction.
    STRINGi9606.ENSP00000272425.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UHE5.
    SMRiQ9UHE5. Positions 86-195.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini61 – 220160N-acetyltransferasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the camello family.1 Publication
    Contains 1 N-acetyltransferase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG236460.
    GeneTreeiENSGT00390000009559.
    HOGENOMiHOG000261685.
    HOVERGENiHBG060476.
    InParanoidiQ9UHE5.
    OMAiHIRKYRE.
    OrthoDBiEOG73Z2W2.
    PhylomeDBiQ9UHE5.
    TreeFamiTF324687.

    Family and domain databases

    Gene3Di3.40.630.30. 2 hits.
    InterProiIPR016181. Acyl_CoA_acyltransferase.
    IPR000182. GNAT_dom.
    [Graphical view]
    PfamiPF00583. Acetyltransf_1. 1 hit.
    [Graphical view]
    SUPFAMiSSF55729. SSF55729. 1 hit.
    PROSITEiPS51186. GNAT. 1 hit.
    [Graphical view]

    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti202 – 2021C → R in CAG28538 (Ref. 4) Curated
    Sequence conflicti212 – 2121T → K in BAA34386 (Ref. 3) Curated
    Sequence conflicti227 – 2271L → Q in AAH12626 (PubMed:15489334).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti104 – 1041E → K No effect on the cysteine S-conjugate N-acetyltransferase activity. 1 Publication
    Corresponds to variant rs13424561 [ dbSNP | Ensembl ].
    VAR_053886
    Natural varianti143 – 1431F → S No effect on the cysteine S-conjugate N-acetyltransferase activity. 4 Publications
    Corresponds to variant rs13538 [ dbSNP | Ensembl ].
    VAR_031805

    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.1. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    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.

    3D structure databases

    ProteinModelPortaliQ9UHE5.
    SMRiQ9UHE5. Positions 86-195.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ9UHE5. 1 interaction.
    STRINGi9606.ENSP00000272425.

    Polymorphism and mutation databases

    BioMutaiNAT8.
    DMDMi145566894.

    Proteomic databases

    MaxQBiQ9UHE5.
    PaxDbiQ9UHE5.
    PRIDEiQ9UHE5.

    Protocols and materials databases

    DNASUi9027.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000272425; ENSP00000272425; ENSG00000144035.
    GeneIDi9027.
    KEGGihsa:9027.
    UCSCiuc002sji.1. human.

    Organism-specific databases

    CTDi9027.
    GeneCardsiGC02M073779.
    HGNCiHGNC:18069. NAT8.
    HPAiCAB045990.
    MIMi606716. gene.
    neXtProtiNX_Q9UHE5.
    PharmGKBiPA31450.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiNOG236460.
    GeneTreeiENSGT00390000009559.
    HOGENOMiHOG000261685.
    HOVERGENiHBG060476.
    InParanoidiQ9UHE5.
    OMAiHIRKYRE.
    OrthoDBiEOG73Z2W2.
    PhylomeDBiQ9UHE5.
    TreeFamiTF324687.

    Enzyme and pathway databases

    UniPathwayiUPA00204.
    BRENDAi2.3.1.80. 2681.

    Miscellaneous databases

    GeneWikiiNAT8.
    GenomeRNAii9027.
    NextBioi33825.
    PROiQ9UHE5.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9UHE5.
    CleanExiHS_GLA.
    HS_NAT8.
    GenevestigatoriQ9UHE5.

    Family and domain databases

    Gene3Di3.40.630.30. 2 hits.
    InterProiIPR016181. Acyl_CoA_acyltransferase.
    IPR000182. GNAT_dom.
    [Graphical view]
    PfamiPF00583. Acetyltransf_1. 1 hit.
    [Graphical view]
    SUPFAMiSSF55729. SSF55729. 1 hit.
    PROSITEiPS51186. GNAT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Isolation and mapping of a novel human kidney- and liver-specific gene homologous to the bacterial acetyltransferases."
      Ozaki K., Fujiwara T., Nakamura Y., Takahashi E.
      J. Hum. Genet. 43:255-258(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Tissue: Kidney1 Publication.
    2. "Overexpression of camello, a member of a novel protein family, reduces blastomere adhesion and inhibits gastrulation in Xenopus laevis."
      Popsueva A.E., Luchinskaya N.N., Ludwig A.V., Zinovjeva O.Y., Poteryaev D.A., Feigelman M.M., Ponomarev M.B., Berekelya L., Belyavsky A.V.
      Dev. Biol. 234:483-496(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-143.
    3. "GLA, a kidney specific membrane protein highly expressed in renal tubular cells; possible involvement in the chronic renal failure."
      Yamamoto H., Takahashi M., Yoshimoto M., Hara H., Kitamura K., Nakagawa J.
      Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-143.
    4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-143.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: KidneyImported.
    6. "Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels."
      Ko M.H., Puglielli L.
      J. Biol. Chem. 284:2482-2492(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH BACE1, SUBCELLULAR LOCATION, INDUCTION BY CERAMIDES.
    7. "Molecular identification of NAT8 as the enzyme that acetylates cysteine S-conjugates to mercapturic acids."
      Veiga-da-Cunha M., Tyteca D., Stroobant V., Courtoy P.J., Opperdoes F.R., Van Schaftingen E.
      J. Biol. Chem. 285:18888-18898(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, PATHWAY, CHARACTERIZATION OF VARIANTS LYS-104 AND SER-143, MUTAGENESIS OF ARG-149.
    8. "Biochemical inhibition of the acetyltransferases ATase1 and ATase2 reduces beta-secretase (BACE1) levels and Abeta generation."
      Ding Y., Ko M.H., Pehar M., Kotch F., Peters N.R., Luo Y., Salamat S.M., Puglielli L.
      J. Biol. Chem. 287:8424-8433(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    9. "Post-translational regulation of CD133 by ATase1/ATase2-mediated lysine acetylation."
      Mak A.B., Pehar M., Nixon A.M., Williams R.A., Uetrecht A.C., Puglielli L., Moffat J.
      J. Mol. Biol. 426:2175-2182(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PROM1, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiNAT8_HUMAN
    AccessioniPrimary (citable) accession number: Q9UHE5
    Secondary accession number(s): O75839
    , Q6LEU4, Q96QI8, Q9UQ17
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 17, 2007
    Last sequence update: April 17, 2007
    Last modified: May 27, 2015
    This is version 92 of the entry and version 2 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

    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

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.