NAT8_HUMAN
ID NAT8_HUMAN Reviewed; 227 AA.
AC Q9UHE5; O75839; Q6LEU4; Q96QI8; Q9UQ17;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=N-acetyltransferase 8;
DE EC=2.3.1.-;
DE AltName: Full=Acetyltransferase 2;
DE Short=ATase2;
DE AltName: Full=Camello-like protein 1;
DE AltName: Full=Cysteinyl-conjugate N-acetyltransferase;
DE Short=CCNAT;
DE EC=2.3.1.80;
GN Name=NAT8 {ECO:0000312|HGNC:HGNC:18069};
GN Synonyms=CML1 {ECO:0000312|EMBL:AAF22303.1},
GN GLA {ECO:0000312|EMBL:BAA34386.1}, TSC501 {ECO:0000312|EMBL:BAA33679.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAA33679.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Kidney {ECO:0000269|PubMed:9852678};
RX PubMed=9852678; DOI=10.1007/s100380050084;
RA Ozaki K., Fujiwara T., Nakamura Y., Takahashi E.;
RT "Isolation and mapping of a novel human kidney- and liver-specific gene
RT homologous to the bacterial acetyltransferases.";
RL J. Hum. Genet. 43:255-258(1998).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF22303.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-143.
RX PubMed=11397015; DOI=10.1006/dbio.2001.0261;
RA Popsueva A.E., Luchinskaya N.N., Ludwig A.V., Zinovjeva O.Y.,
RA Poteryaev D.A., Feigelman M.M., Ponomarev M.B., Berekelya L.,
RA Belyavsky A.V.;
RT "Overexpression of camello, a member of a novel protein family, reduces
RT blastomere adhesion and inhibits gastrulation in Xenopus laevis.";
RL Dev. Biol. 234:483-496(2001).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAA34386.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-143.
RA Yamamoto H., Takahashi M., Yoshimoto M., Hara H., Kitamura K., Nakagawa J.;
RT "GLA, a kidney specific membrane protein highly expressed in renal tubular
RT cells; possible involvement in the chronic renal failure.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305, ECO:0000312|EMBL:BAA34386.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-143.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000312|EMBL:AAH12626.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH12626.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, INTERACTION WITH BACE1, SUBCELLULAR LOCATION, AND INDUCTION BY
RP CERAMIDES.
RX PubMed=19011241; DOI=10.1074/jbc.m804901200;
RA Ko M.H., Puglielli L.;
RT "Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based
RT lysine acetyltransferases post-translationally regulate BACE1 levels.";
RL J. Biol. Chem. 284:2482-2492(2009).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, PATHWAY, CHARACTERIZATION OF VARIANTS LYS-104 AND SER-143, AND
RP MUTAGENESIS OF ARG-149.
RX PubMed=20392701; DOI=10.1074/jbc.m110.110924;
RA Veiga-da-Cunha M., Tyteca D., Stroobant V., Courtoy P.J., Opperdoes F.R.,
RA Van Schaftingen E.;
RT "Molecular identification of NAT8 as the enzyme that acetylates cysteine S-
RT conjugates to mercapturic acids.";
RL J. Biol. Chem. 285:18888-18898(2010).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=22267734; DOI=10.1074/jbc.m111.310136;
RA Ding Y., Ko M.H., Pehar M., Kotch F., Peters N.R., Luo Y., Salamat S.M.,
RA Puglielli L.;
RT "Biochemical inhibition of the acetyltransferases ATase1 and ATase2 reduces
RT beta-secretase (BACE1) levels and Abeta generation.";
RL J. Biol. Chem. 287:8424-8433(2012).
RN [9]
RP FUNCTION, INTERACTION WITH PROM1, AND SUBCELLULAR LOCATION.
RX PubMed=24556617; DOI=10.1016/j.jmb.2014.02.012;
RA Mak A.B., Pehar M., Nixon A.M., Williams R.A., Uetrecht A.C., Puglielli L.,
RA Moffat J.;
RT "Post-translational regulation of CD133 by ATase1/ATase2-mediated lysine
RT acetylation.";
RL J. Mol. Biol. 426:2175-2182(2014).
CC -!- FUNCTION: Acetylates the free alpha-amino group of cysteine S-
CC conjugates to form mercapturic acids (PubMed:20392701). This is the
CC final step in a major route for detoxification of a wide variety of
CC reactive electrophiles which starts with their incorporation into
CC glutathione S-conjugates. The glutathione S-conjugates are then further
CC processed into cysteine S-conjugates and finally mercapturic acids
CC which are water soluble and can be readily excreted in urine or bile.
CC Alternatively, may have a lysine N-acetyltransferase activity
CC catalyzing peptidyl-lysine N6-acetylation of various proteins. Thereby,
CC may regulate apoptosis through the acetylation and the regulation of
CC the expression of PROM1 (PubMed:24556617). May also regulate amyloid
CC beta-peptide secretion through acetylation of BACE1 and the regulation
CC of its expression in neurons (PubMed:19011241).
CC {ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:20392701,
CC ECO:0000269|PubMed:24556617}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + an S-substituted L-cysteine = an N-acetyl-L-
CC cysteine-S-conjugate + CoA + H(+); Xref=Rhea:RHEA:19213,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:58717, ChEBI:CHEBI:58718; EC=2.3.1.80;
CC Evidence={ECO:0000269|PubMed:20392701};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=64 uM for S-benzyl-L-cysteine (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20392701};
CC KM=23 uM for acetyl-CoA (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20392701};
CC Note=A Vmax of 4.4 nmol/min/mg enzyme toward S-benzyl-L-cysteine was
CC estimated using crude cell extracts. A Vmax of 3.1 nmol/min/mg enzyme
CC toward acetyl-CoA was estimated using crude cell extracts.;
CC -!- PATHWAY: Sulfur metabolism; glutathione metabolism.
CC {ECO:0000269|PubMed:20392701}.
CC -!- SUBUNIT: Interacts with PROM1. Interacts with BACE1.
CC {ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:24556617}.
CC -!- INTERACTION:
CC Q9UHE5; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-2863634, EBI-11343438;
CC Q9UHE5; O15342: ATP6V0E1; NbExp=3; IntAct=EBI-2863634, EBI-12935759;
CC Q9UHE5; Q13323: BIK; NbExp=3; IntAct=EBI-2863634, EBI-700794;
CC Q9UHE5; P11912: CD79A; NbExp=3; IntAct=EBI-2863634, EBI-7797864;
CC Q9UHE5; Q9HA82: CERS4; NbExp=3; IntAct=EBI-2863634, EBI-2622997;
CC Q9UHE5; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-2863634, EBI-6942903;
CC Q9UHE5; Q15125: EBP; NbExp=3; IntAct=EBI-2863634, EBI-3915253;
CC Q9UHE5; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-2863634, EBI-18304435;
CC Q9UHE5; O15552: FFAR2; NbExp=3; IntAct=EBI-2863634, EBI-2833872;
CC Q9UHE5; Q6ZVE7: GOLT1A; NbExp=3; IntAct=EBI-2863634, EBI-17231387;
CC Q9UHE5; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-2863634, EBI-13345167;
CC Q9UHE5; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-2863634, EBI-18053395;
CC Q9UHE5; Q9HDC5: JPH1; NbExp=3; IntAct=EBI-2863634, EBI-465137;
CC Q9UHE5; O95214: LEPROTL1; NbExp=3; IntAct=EBI-2863634, EBI-750776;
CC Q9UHE5; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-2863634, EBI-373355;
CC Q9UHE5; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-2863634, EBI-3923617;
CC Q9UHE5; Q9BRK0: REEP2; NbExp=3; IntAct=EBI-2863634, EBI-11337973;
CC Q9UHE5; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-2863634, EBI-3920694;
CC Q9UHE5; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-2863634, EBI-18159983;
CC Q9UHE5; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-2863634, EBI-12947623;
CC Q9UHE5; Q96AN5: TMEM143; NbExp=3; IntAct=EBI-2863634, EBI-13342951;
CC Q9UHE5; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-2863634, EBI-8638294;
CC Q9UHE5; Q9Y320: TMX2; NbExp=3; IntAct=EBI-2863634, EBI-6447886;
CC Q9UHE5; Q12999: TSPAN31; NbExp=3; IntAct=EBI-2863634, EBI-17678331;
CC Q9UHE5; Q9BSR8: YIPF4; NbExp=3; IntAct=EBI-2863634, EBI-751253;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate
CC compartment membrane; Single-pass type II membrane protein. Endoplasmic
CC reticulum membrane; Single-pass type II membrane protein.
CC -!- TISSUE SPECIFICITY: Preferentially expressed in liver and kidney. Also
CC detected in brain (at protein level). {ECO:0000269|PubMed:22267734,
CC ECO:0000269|PubMed:9852678}.
CC -!- INDUCTION: Up-regulated by ceramides. {ECO:0000269|PubMed:19011241}.
CC -!- SIMILARITY: Belongs to the camello family.
CC {ECO:0000269|PubMed:11397015}.
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DR EMBL; AB013094; BAA33679.1; -; mRNA.
DR EMBL; AF187813; AAF22303.1; -; mRNA.
DR EMBL; AB019551; BAA34386.1; -; mRNA.
DR EMBL; CR407610; CAG28538.1; -; mRNA.
DR EMBL; BC012626; AAH12626.1; -; mRNA.
DR CCDS; CCDS1926.1; -.
DR PIR; T44342; T44342.
DR RefSeq; NP_003951.3; NM_003960.3.
DR AlphaFoldDB; Q9UHE5; -.
DR SMR; Q9UHE5; -.
DR BioGRID; 114494; 28.
DR IntAct; Q9UHE5; 27.
DR STRING; 9606.ENSP00000272425; -.
DR iPTMnet; Q9UHE5; -.
DR PhosphoSitePlus; Q9UHE5; -.
DR BioMuta; NAT8; -.
DR DMDM; 145566894; -.
DR MassIVE; Q9UHE5; -.
DR MaxQB; Q9UHE5; -.
DR PaxDb; Q9UHE5; -.
DR PeptideAtlas; Q9UHE5; -.
DR PRIDE; Q9UHE5; -.
DR ProteomicsDB; 84334; -.
DR Antibodypedia; 47469; 245 antibodies from 24 providers.
DR DNASU; 9027; -.
DR Ensembl; ENST00000272425.4; ENSP00000272425.3; ENSG00000144035.4.
DR GeneID; 9027; -.
DR KEGG; hsa:9027; -.
DR MANE-Select; ENST00000272425.4; ENSP00000272425.3; NM_003960.4; NP_003951.3.
DR UCSC; uc002sji.2; human.
DR CTD; 9027; -.
DR DisGeNET; 9027; -.
DR GeneCards; NAT8; -.
DR HGNC; HGNC:18069; NAT8.
DR HPA; ENSG00000144035; Tissue enriched (kidney).
DR MIM; 606716; gene.
DR neXtProt; NX_Q9UHE5; -.
DR OpenTargets; ENSG00000144035; -.
DR PharmGKB; PA31450; -.
DR VEuPathDB; HostDB:ENSG00000144035; -.
DR eggNOG; KOG3139; Eukaryota.
DR GeneTree; ENSGT00950000182932; -.
DR HOGENOM; CLU_013985_10_1_1; -.
DR InParanoid; Q9UHE5; -.
DR OMA; DQGYSQV; -.
DR OrthoDB; 1341682at2759; -.
DR PhylomeDB; Q9UHE5; -.
DR TreeFam; TF324687; -.
DR BioCyc; MetaCyc:ENSG00000144035-MON; -.
DR BRENDA; 2.3.1.80; 2681.
DR PathwayCommons; Q9UHE5; -.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; Q9UHE5; -.
DR UniPathway; UPA00204; -.
DR BioGRID-ORCS; 9027; 15 hits in 1037 CRISPR screens.
DR GeneWiki; NAT8; -.
DR GenomeRNAi; 9027; -.
DR Pharos; Q9UHE5; Tbio.
DR PRO; PR:Q9UHE5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9UHE5; protein.
DR Bgee; ENSG00000144035; Expressed in adult organism and 109 other tissues.
DR Genevisible; Q9UHE5; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0047198; F:cysteine-S-conjugate N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004468; F:lysine N-acetyltransferase activity, acting on acetyl phosphate as donor; IDA:UniProtKB.
DR GO; GO:0008080; F:N-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:1990000; P:amyloid fibril formation; TAS:Reactome.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IMP:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0018003; P:peptidyl-lysine N6-acetylation; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; TAS:ProtInc.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR Pfam; PF00583; Acetyltransf_1; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Endoplasmic reticulum; Membrane; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..227
FT /note="N-acetyltransferase 8"
FT /id="PRO_0000284684"
FT TOPO_DOM 1..42
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..63
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 64..227
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 61..220
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT VARIANT 104
FT /note="E -> K (no effect on the cysteine S-conjugate N-
FT acetyltransferase activity; dbSNP:rs13424561)"
FT /evidence="ECO:0000269|PubMed:20392701"
FT /id="VAR_053886"
FT VARIANT 143
FT /note="F -> S (no effect on the cysteine S-conjugate N-
FT acetyltransferase activity; dbSNP:rs13538)"
FT /evidence="ECO:0000269|PubMed:11397015,
FT ECO:0000269|PubMed:20392701, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.4"
FT /id="VAR_031805"
FT MUTAGEN 149
FT /note="R->K: Loss of the cysteine S-conjugate N-
FT acetyltransferase activity. No effect on protein
FT expression."
FT /evidence="ECO:0000269|PubMed:20392701"
FT CONFLICT 202
FT /note="C -> R (in Ref. 4; CAG28538)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="T -> K (in Ref. 3; BAA34386)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="L -> Q (in Ref. 5; AAH12626)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 227 AA; 25619 MW; B6CEAC98EFB0D6C8 CRC64;
MAPCHIRKYQ ESDRQWVVGL LSRGMAEHAP ATFRQLLKLP RTLILLLGGP LALLLVSGSW
LLALVFSISL FPALWFLAKK PWTEYVDMTL CTDMSDITKS YLSERGSCFW VAESEEKVVG
MVGALPVDDP TLREKRLQLF HLFVDSEHRR QGIAKALVRT VLQFARDQGY SEVILDTGTI
QLSAMALYQS MGFKKTGQSF FCVWARLVAL HTVHFIYHLP SSKVGSL
