NAT8L_HUMAN
ID NAT8L_HUMAN Reviewed; 302 AA.
AC Q8N9F0;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=N-acetylaspartate synthetase {ECO:0000305};
DE Short=NAA synthetase;
DE EC=2.3.1.17 {ECO:0000269|PubMed:19524112, ECO:0000269|PubMed:19807691, ECO:0000269|PubMed:20385109};
DE AltName: Full=Camello-like protein 3;
DE AltName: Full=N-acetyltransferase 8-like protein;
GN Name=NAT8L {ECO:0000312|HGNC:HGNC:26742}; Synonyms=CML3;
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 [LARGE SCALE GENOMIC DNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 101-291.
RX PubMed=15146197; DOI=10.1038/nbt971;
RA Brandenberger R., Wei H., Zhang S., Lei S., Murage J., Fisk G.J., Li Y.,
RA Xu C., Fang R., Guegler K., Rao M.S., Mandalam R., Lebkowski J.,
RA Stanton L.W.;
RT "Transcriptome characterization elucidates signaling networks that control
RT human ES cell growth and differentiation.";
RL Nat. Biotechnol. 22:707-716(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 112-302.
RC TISSUE=Brain, and PNS;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 117-302.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP IDENTIFICATION.
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=19524112; DOI=10.1016/j.neuint.2009.03.003;
RA Arun P., Moffett J.R., Namboodiri A.M.;
RT "Evidence for mitochondrial and cytoplasmic N-acetylaspartate synthesis in
RT SH-SY5Y neuroblastoma cells.";
RL Neurochem. Int. 55:219-225(2009).
RN [7]
RP TISSUE SPECIFICITY, INVOLVEMENT IN NACED, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19807691; DOI=10.1042/bj20091024;
RA Wiame E., Tyteca D., Pierrot N., Collard F., Amyere M., Noel G.,
RA Desmedt J., Nassogne M.C., Vikkula M., Octave J.N., Vincent M.F.,
RA Courtoy P.J., Boltshauser E., van Schaftingen E.;
RT "Molecular identification of aspartate N-acetyltransferase and its mutation
RT in hypoacetylaspartia.";
RL Biochem. J. 425:127-136(2010).
RN [8]
RP ACTIVITY REGULATION, INDUCTION BY METHAMPHETAMINE, SUBCELLULAR LOCATION,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20385109; DOI=10.1016/j.brainres.2010.04.008;
RA Ariyannur P.S., Moffett J.R., Manickam P., Pattabiraman N., Arun P.,
RA Nitta A., Nabeshima T., Madhavarao C.N., Namboodiri A.M.;
RT "Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic
RT enzyme: implications for specialized acetyl coenzyme A metabolism in the
RT CNS.";
RL Brain Res. 1335:1-13(2010).
CC -!- FUNCTION: Catalyzes the synthesis of N-acetylaspartate acid (NAA) from
CC L-aspartate and acetyl-CoA (PubMed:19524112, PubMed:19807691,
CC PubMed:20385109). Promotes dopamine uptake by regulating TNF-alpha
CC expression (By similarity). Attenuates methamphetamine-induced
CC inhibition of dopamine uptake (PubMed:20385109).
CC {ECO:0000250|UniProtKB:Q3UGX3, ECO:0000269|PubMed:19524112,
CC ECO:0000269|PubMed:19807691, ECO:0000269|PubMed:20385109}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-aspartate = CoA + H(+) + N-acetyl-L-aspartate;
CC Xref=Rhea:RHEA:14165, ChEBI:CHEBI:15378, ChEBI:CHEBI:16953,
CC ChEBI:CHEBI:29991, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.1.17;
CC Evidence={ECO:0000269|PubMed:19524112, ECO:0000269|PubMed:19807691,
CC ECO:0000269|PubMed:20385109};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14166;
CC Evidence={ECO:0000305|PubMed:19524112};
CC -!- ACTIVITY REGULATION: Aminooxyacetic acid (AOAA) blocks its activity in
CC both cytoplasm and mitochondria. {ECO:0000269|PubMed:20385109}.
CC -!- INTERACTION:
CC Q8N9F0; P40855: PEX19; NbExp=3; IntAct=EBI-14384265, EBI-594747;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19524112}.
CC Microsome membrane {ECO:0000250|UniProtKB:D3ZVU9}; Single-pass membrane
CC protein {ECO:0000255}. Mitochondrion membrane
CC {ECO:0000269|PubMed:19524112}; Single-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q3UGX3}; Single-pass membrane protein
CC {ECO:0000255}. Note=Its enzymatic activity contribution is
CC quantitatively larger in mitochondrial compartment than in
CC extramitochondrial compartment. {ECO:0000269|PubMed:19524112}.
CC -!- TISSUE SPECIFICITY: Expressed in brain. {ECO:0000269|PubMed:19807691}.
CC -!- INDUCTION: By methamphetamine in brain, via dopamine receptor
CC activation (at protein level). {ECO:0000269|PubMed:20385109}.
CC -!- DISEASE: N-acetylaspartate deficiency (NACED) [MIM:614063]: A metabolic
CC disorder resulting in truncal ataxia, marked developmental delay,
CC seizures, and secondary microcephaly. {ECO:0000269|PubMed:19807691}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the camello family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH93906.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH93908.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI03749.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC04426.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL132868; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CN256164; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC093906; AAH93906.1; ALT_INIT; mRNA.
DR EMBL; BC093908; AAH93908.1; ALT_INIT; mRNA.
DR EMBL; BC103748; AAI03749.1; ALT_INIT; mRNA.
DR EMBL; AK094797; BAC04426.1; ALT_INIT; mRNA.
DR CCDS; CCDS3359.2; -.
DR RefSeq; NP_848652.2; NM_178557.3.
DR AlphaFoldDB; Q8N9F0; -.
DR SMR; Q8N9F0; -.
DR BioGRID; 130978; 22.
DR IntAct; Q8N9F0; 3.
DR STRING; 9606.ENSP00000413064; -.
DR GuidetoPHARMACOLOGY; 3144; -.
DR iPTMnet; Q8N9F0; -.
DR PhosphoSitePlus; Q8N9F0; -.
DR BioMuta; NAT8L; -.
DR DMDM; 259016335; -.
DR EPD; Q8N9F0; -.
DR MassIVE; Q8N9F0; -.
DR MaxQB; Q8N9F0; -.
DR PaxDb; Q8N9F0; -.
DR PeptideAtlas; Q8N9F0; -.
DR PRIDE; Q8N9F0; -.
DR ProteomicsDB; 72525; -.
DR Antibodypedia; 50620; 89 antibodies from 22 providers.
DR DNASU; 339983; -.
DR Ensembl; ENST00000423729.3; ENSP00000413064.2; ENSG00000185818.8.
DR GeneID; 339983; -.
DR KEGG; hsa:339983; -.
DR MANE-Select; ENST00000423729.3; ENSP00000413064.2; NM_178557.4; NP_848652.2.
DR UCSC; uc003geq.3; human.
DR CTD; 339983; -.
DR DisGeNET; 339983; -.
DR GeneCards; NAT8L; -.
DR HGNC; HGNC:26742; NAT8L.
DR HPA; ENSG00000185818; Group enriched (adipose tissue, brain).
DR MalaCards; NAT8L; -.
DR MIM; 610647; gene.
DR MIM; 614063; phenotype.
DR neXtProt; NX_Q8N9F0; -.
DR OpenTargets; ENSG00000185818; -.
DR PharmGKB; PA162396985; -.
DR VEuPathDB; HostDB:ENSG00000185818; -.
DR eggNOG; KOG3139; Eukaryota.
DR GeneTree; ENSGT00950000182932; -.
DR HOGENOM; CLU_013985_10_0_1; -.
DR InParanoid; Q8N9F0; -.
DR OMA; HCGPPDM; -.
DR OrthoDB; 1341682at2759; -.
DR PhylomeDB; Q8N9F0; -.
DR TreeFam; TF324687; -.
DR BRENDA; 2.3.1.17; 2681.
DR PathwayCommons; Q8N9F0; -.
DR Reactome; R-HSA-8963693; Aspartate and asparagine metabolism.
DR SignaLink; Q8N9F0; -.
DR SIGNOR; Q8N9F0; -.
DR BioGRID-ORCS; 339983; 8 hits in 1039 CRISPR screens.
DR ChiTaRS; NAT8L; human.
DR GenomeRNAi; 339983; -.
DR Pharos; Q8N9F0; Tbio.
DR PRO; PR:Q8N9F0; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8N9F0; protein.
DR Bgee; ENSG00000185818; Expressed in lateral nuclear group of thalamus and 142 other tissues.
DR Genevisible; Q8N9F0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0017188; F:aspartate N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008080; F:N-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0009066; P:aspartate family amino acid metabolic process; TAS:Reactome.
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; Cytoplasm; Endoplasmic reticulum; Membrane; Microsome;
KW Mitochondrion; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..302
FT /note="N-acetylaspartate synthetase"
FT /id="PRO_0000305229"
FT TRANSMEM 121..141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 143..283
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT REGION 46..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..62
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 302 AA; 32837 MW; 2080E54930F3292B CRC64;
MHCGPPDMVC ETKIVAAEDH EALPGAKKDA LLAAAGAMWP PLPAAPGPAA APPAPPPAPV
AQPHGGAGGA GPPGGRGVCI REFRAAEQEA ARRIFYDGIM ERIPNTAFRG LRQHPRAQLL
YALLAALCFA VSRSLLLTCL VPAALLGLRY YYSRKVIRAY LECALHTDMA DIEQYYMKPP
GSCFWVAVLD GNVVGIVAAR AHEEDNTVEL LRMSVDSRFR GKGIAKALGR KVLEFAVVHN
YSAVVLGTTA VKVAAHKLYE SLGFRHMGAS DHYVLPGMTL SLAERLFFQV RYHRYRLQLR
EE
