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 24-JAN-2024, entry version 149. 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}, GLA GN {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 29. 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; 9606-ENSP00000272425; -. DR PeptideAtlas; Q9UHE5; -. DR ProteomicsDB; 84334; -. DR Antibodypedia; 47469; 261 antibodies from 24 providers. DR DNASU; 9027; -. DR Ensembl; ENST00000272425.4; ENSP00000272425.3; ENSG00000144035.4. DR Ensembl; ENST00000707634.1; ENSP00000516938.1; ENSG00000291479.1. 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 AGR; HGNC:18069; -. 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; MAPCHIR; -. DR OrthoDB; 74682at2759; -. DR PhylomeDB; Q9UHE5; -. DR TreeFam; TF324687; -. DR BioCyc; MetaCyc:ENSG00000144035-MONOMER; -. 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 1113 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 110 other cell types or tissues. 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:0016020; C: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:0006749; P:glutathione metabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0018003; P:peptidyl-lysine N6-acetylation; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR CDD; cd04301; NAT_SF; 1. DR Gene3D; 3.40.630.30; -; 1. DR InterPro; IPR016181; Acyl_CoA_acyltransferase. DR InterPro; IPR000182; GNAT_dom. DR PANTHER; PTHR13947; GNAT FAMILY N-ACETYLTRANSFERASE; 1. DR PANTHER; PTHR13947:SF48; N-ACETYLTRANSFERASE 8-RELATED; 1. DR Pfam; PF00583; Acetyltransf_1; 1. DR SUPFAM; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1. DR PROSITE; PS51186; GNAT; 1. DR Genevisible; Q9UHE5; HS. 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 FT N-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 FT N-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 FT N-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 //