ID NAT8B_HUMAN Reviewed; 227 AA. AC Q9UHF3; Q0VAD9; Q6NT18; DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 28-JAN-2026, entry version 130. DE RecName: Full=N-acetyltransferase 8B; DE EC=2.3.1.- {ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:22267734, ECO:0000269|PubMed:24556617, ECO:0000269|PubMed:31945187}; DE AltName: Full=Acetyltransferase 1; DE Short=ATase1 {ECO:0000303|PubMed:19011241, ECO:0000303|PubMed:24556617}; DE AltName: Full=Camello-like protein 2; DE AltName: Full=Protein-lysine N6-acetyltransferase 8B {ECO:0000305}; GN Name=NAT8B {ECO:0000312|HGNC:HGNC:30235}; GN Synonyms=CML2 {ECO:0000303|PubMed:16395595, ECO:0000312|EMBL:AAF22299.1}; 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] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Colon tumor {ECO:0000312|EMBL:AAF22299.1}; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS 16-SER--LEU-227 RP DEL AND 168-GLN--LEU-227 DEL. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [3] RP POLYMORPHISM. RX PubMed=16395595; DOI=10.1007/s00439-005-0125-6; RA Hahn Y., Lee B.; RT "Human-specific nonsense mutations identified by genome sequence RT comparisons."; RL Hum. Genet. 119:169-178(2006). RN [4] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INDUCTION BY CERAMIDES, RP AND TOPOLOGY. 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 [5] RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION. 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 [6] RP FUNCTION, CATALYTIC ACTIVITY, 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). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, ACETYLATION AT LYS-99, RP AND MUTAGENESIS OF LYS-99; ARG-149; SER-183 AND SER-190. RX PubMed=31945187; DOI=10.1111/jnc.14958; RA Rigby M.J., Ding Y., Farrugia M.A., Feig M., Cortese G.P., Mitchell H., RA Burger C., Puglielli L.; RT "The endoplasmic reticulum acetyltransferases ATase1/NAT8B and ATase2/NAT8 RT are differentially regulated to adjust engagement of the secretory RT pathway."; RL J. Neurochem. 154:404-423(2020). CC -!- FUNCTION: Endoplasmic reticulum (ER)-membrane-bound lysine N- CC acetyltransferase catalyzing the N6-acetylation of lysine residues in CC the lumen of the ER in various proteins, including PROM1 and BACE1, CC using acetyl-CoA as acetyl donor (PubMed:19011241, PubMed:22267734, CC PubMed:24556617, PubMed:31945187). Thereby, may regulate apoptosis CC through the acetylation and the regulation of the expression of PROM1 CC (PubMed:24556617). Acetylates and stabilizes BACE1 immature protein, CC leading to increased steady-state levels in neurons. By acting on BACE1 CC expression, may regulate amyloid beta-peptide formation CC (PubMed:19011241, PubMed:22267734). N(6)-lysine acetylation in ER CC maintains protein homeostasis and regulates reticulophagy (By CC similarity). {ECO:0000250|UniProtKB:E0CYC6, CC ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:22267734, CC ECO:0000269|PubMed:24556617, ECO:0000269|PubMed:31945187}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] CC + CoA + H(+); Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA- CC COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; CC Evidence={ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:22267734, CC ECO:0000269|PubMed:24556617, ECO:0000269|PubMed:31945187}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45949; CC Evidence={ECO:0000305|PubMed:19011241}; CC -!- ACTIVITY REGULATION: Allosterically regulated by acetylation at residue CC Lys-99. {ECO:0000269|PubMed:31945187}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate CC compartment membrane {ECO:0000269|PubMed:19011241, CC ECO:0000269|PubMed:24556617}; Single-pass type II membrane protein CC {ECO:0000305|PubMed:19011241}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:19011241}; Single-pass type II membrane protein CC {ECO:0000305|PubMed:19011241}. Note=Enriched in the endoplasmic CC reticulum-Golgi intermediate compartment (ERGIC). CC {ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:24556617}. CC -!- INDUCTION: Up-regulated by ceramides (PubMed:19011241). Up-regulated in CC the brain of Alzheimer's disease patients (PubMed:22267734). CC {ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:22267734}. CC -!- PTM: Acetylation on Lys-99 modulates enzymatic activity. CC {ECO:0000269|PubMed:31945187}. CC -!- POLYMORPHISM: The sequence shown in this entry differs from the CC translation of the reference genome assembly (GRCh38/hg38) due to two CC nonsense variants creating stop codons at positions 16 and 168 in the CC reference genome. Both nonsense variants would abolish catalytic CC activity. The sequence shown in this entry is that of the double CC variant p.[Ter16Ser;Ter168Gln]. The variant p.Ter16Ser may be extremely CC rare and is not reported in the Genome Aggregation Database (gnomAD CC v3.1.2). The variant p.Ter168Gln is common in the human population with CC a frequency of 75%. Although the existence of the double variant CC p.[Ter16Ser;Ter168Gln] has not been proven in normal tissues, several CC lines of evidence support its existence in certain tumors or cell CC lines. It has been cloned from a colon tumor and has also been detected CC at the mRNA level in H4 neuroglioma cell line, as well as in the CC neuroblastoma cell line SH-SY5Y (PubMed:11397015, PubMed:19011241). In CC H4 and SH-SY5Y cells, its mRNA level can be up-regulated by ceramides. CC In H4 cells, the silencing of NAT8B double variant often leads to cell CC death, suggesting a function in these cells (PubMed:19011241). CC Functional assays show that NAT8B possesses robust N-acetyltransferase CC activity in a similar, but not identical way to its paralog NAT8 CC (PubMed:19011241, PubMed:24556617). {ECO:0000269|PubMed:11397015, CC ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:24556617}. CC -!- SIMILARITY: Belongs to the NAT8 family. {ECO:0000305}. CC -!- CAUTION: The sequence shown in this entry differs from the translation CC of the reference genome assembly (GRCh38/hg38) due to two nonsense CC variants creating stop codons at positions 16 and 168 in the reference CC genome. {ECO:0000305}. 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; AF185571; AAF22299.1; -; mRNA. DR EMBL; AC092653; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR AlphaFoldDB; Q9UHF3; -. DR SMR; Q9UHF3; -. DR BioGRID; 119557; 21. DR FunCoup; Q9UHF3; 43. DR IntAct; Q9UHF3; 20. DR iPTMnet; Q9UHF3; -. DR PhosphoSitePlus; Q9UHF3; -. DR BioMuta; NAT8B; -. DR MassIVE; Q9UHF3; -. DR PeptideAtlas; Q9UHF3; -. DR ProteomicsDB; 84340; -. DR DNASU; 51471; -. DR AGR; HGNC:30235; -. DR ClinPGx; PA162396978; -. DR DisGeNET; 51471; -. DR GeneCards; NAT8B; -. DR HGNC; HGNC:30235; NAT8B. DR MIM; 608190; gene. DR InParanoid; Q9UHF3; -. DR OrthoDB; 41532at2759; -. DR PAN-GO; Q9UHF3; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9UHF3; -. DR BRENDA; 2.3.1.32; 2681. DR PathwayCommons; Q9UHF3; -. DR Reactome; R-HSA-977225; Amyloid fiber formation. DR SignaLink; Q9UHF3; -. DR BioGRID-ORCS; 51471; 9 hits in 243 CRISPR screens. DR GenomeRNAi; 51471; -. DR Pharos; Q9UHF3; Tbio. DR PRO; PR:Q9UHF3; -. DR Proteomes; UP000005640; Unplaced. DR RNAct; Q9UHF3; protein. 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; NAS:UniProtKB. DR GO; GO:0004468; F:L-lysine N-acetyltransferase activity, acting on acetyl phosphate as donor; TAS:Reactome. DR GO; GO:0008080; F:N-acetyltransferase activity; IBA:GO_Central. DR GO; GO:0061733; F:protein-lysine-acetyltransferase activity; IDA:UniProtKB. DR GO; GO:1990000; P:amyloid fibril formation; TAS:Reactome. DR GO; GO:0050435; P:amyloid-beta metabolic process; IMP:UniProtKB. DR GO; GO:0001702; P:gastrulation with mouth forming second; NAS: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:0016241; P:regulation of macroautophagy; ISS:UniProtKB. DR GO; GO:0140500; P:regulation of reticulophagy; ISS:UniProtKB. DR CDD; cd04301; NAT_SF; 1. DR FunFam; 3.40.630.30:FF:000118; N-acetyltransferase family 8 member 3; 1. DR Gene3D; 3.40.630.30; -; 1. DR InterPro; IPR016181; Acyl_CoA_acyltransferase. DR InterPro; IPR000182; GNAT_dom. DR InterPro; IPR050769; NAT_camello-type. 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. PE 1: Evidence at protein level; KW Acetylation; Acyltransferase; Endoplasmic reticulum; Membrane; KW Proteomics identification; Reference proteome; Signal-anchor; Transferase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..227 FT /note="N-acetyltransferase 8B" FT /id="PRO_0000284685" FT TOPO_DOM 1..42 FT /note="Cytoplasmic" FT /evidence="ECO:0000255, ECO:0000269|PubMed:19011241" FT TRANSMEM 43..63 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000305|PubMed:19011241" FT TOPO_DOM 64..227 FT /note="Lumenal" FT /evidence="ECO:0000255, ECO:0000269|PubMed:19011241" FT DOMAIN 61..214 FT /note="N-acetyltransferase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532" FT MOD_RES 99 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31945187" FT VARIANT 16..227 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:15815621, FT ECO:0000269|PubMed:16395595" FT /id="VAR_088065" FT VARIANT 168..227 FT /note="Missing (in dbSNP:rs4852974)" FT /evidence="ECO:0000269|PubMed:15815621, FT ECO:0000269|PubMed:16395595" FT /id="VAR_088066" FT MUTAGEN 99 FT /note="K->E,R: Diminishes protein-lysine N6- FT acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:31945187" FT MUTAGEN 149 FT /note="R->A: Exhibits reduced protein-lysine N6- FT acetyltransferase activity; when associated with A-183 and FT A-190." FT /evidence="ECO:0000269|PubMed:31945187" FT MUTAGEN 183 FT /note="S->A: Exhibits reduced protein-lysine N6- FT acetyltransferase activity; when associated with A-149 and FT A-190." FT /evidence="ECO:0000269|PubMed:31945187" FT MUTAGEN 190 FT /note="S->A: Exhibits reduced protein-lysine N6- FT acetyltransferase activity; when associated with A-149 and FT A-183." FT /evidence="ECO:0000269|PubMed:31945187" SQ SEQUENCE 227 AA; 25366 MW; E45FBA89E1E03CB0 CRC64; MAPYHIRKYQ ESDRKSVVGL LSGGMAEHAP ATFRRLLKLP RTLILLLGGA LALLLVSGSW ILALVFSLSL LPALWFLAKK PWTRYVDIAL RTDMSDITKS YLSECGSCFW VAESEEKVVG TVGALPVDDP TLREKRLQLF HLSVDNEHRG QGIAKALVRT VLQFARDQGY SEVVLDTSNI QLSAMGLYQS LGFKKTGQSF FHVWARLVDL HTVHFIYHLP SAQAGRL //