N6MT1_MOUSE
ID N6MT1_MOUSE Reviewed; 214 AA.
AC Q6SKR2; D3Z6J0; E9PXT7; Q4KMV5; Q6PRU9;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Methyltransferase N6AMT1 {ECO:0000305};
DE AltName: Full=HemK methyltransferase family member 2 {ECO:0000303|PubMed:19116772};
DE AltName: Full=Lysine N-methyltransferase 9 {ECO:0000250|UniProtKB:Q9Y5N5};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q9Y5N5};
DE AltName: Full=Methylarsonite methyltransferase N6AMT1 {ECO:0000250|UniProtKB:Q9Y5N5};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q9Y5N5};
DE AltName: Full=Protein N(5)-glutamine methyltransferase {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:20606008, ECO:0000269|PubMed:26797129};
GN Name=N6amt1 {ECO:0000312|MGI:MGI:1915018};
GN Synonyms=Hemk2 {ECO:0000303|PubMed:19116772, ECO:0000312|MGI:MGI:1915018},
GN Kmt9 {ECO:0000250|UniProtKB:Q9Y5N5}, Pred28 {ECO:0000303|PubMed:16684535};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RC STRAIN=C57BL/6J;
RX PubMed=16684535; DOI=10.1016/j.febslet.2006.04.074;
RA Ratel D., Ravanat J.L., Charles M.P., Platet N., Breuillaud L., Lunardi J.,
RA Berger F., Wion D.;
RT "Undetectable levels of N6-methyl adenine in mouse DNA: Cloning and
RT analysis of PRED28, a gene coding for a putative mammalian DNA adenine
RT methyltransferase.";
RL FEBS Lett. 580:3179-3184(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=19116772; DOI=10.1007/s11033-008-9437-7;
RA Nie D.S., Liu Y.B., Lu G.X.;
RT "Cloning and primarily function study of two novel putative N5-glutamine
RT methyltransferase (Hemk) splice variants from mouse stem cells.";
RL Mol. Biol. Rep. 36:2221-2228(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=20606008; DOI=10.1128/mcb.00218-10;
RA Liu P., Nie S., Li B., Yang Z.Q., Xu Z.M., Fei J., Lin C., Zeng R.,
RA Xu G.L.;
RT "Deficiency in a glutamine-specific methyltransferase for release factor
RT causes mouse embryonic lethality.";
RL Mol. Cell. Biol. 30:4245-4253(2010).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TRMT112.
RX PubMed=26797129; DOI=10.1074/jbc.m115.711952;
RA Kusevic D., Kudithipudi S., Jeltsch A.;
RT "Substrate specificity of the HEMK2 protein glutamine methyltransferase and
RT identification of novel substrates.";
RL J. Biol. Chem. 291:6124-6133(2016).
CC -!- FUNCTION: Methyltransferase that can methylate proteins and, to a lower
CC extent, arsenic (PubMed:20606008, PubMed:26797129). Catalytic subunit
CC of a heterodimer with TRMT112, which monomethylates 'Lys-12' of histone
CC H4 (H4K12me1), a modification present at the promoters of numerous
CC genes encoding cell cycle regulators (By similarity). Catalytic subunit
CC of a heterodimer with TRMT112, which catalyzes N5-methylation of Glu
CC residue of proteins with a Gly-Gln-Xaa-Xaa-Xaa-Arg motif
CC (PubMed:26797129). Methylates ETF1 on 'Gln-185'; ETF1 needs to be
CC complexed to ERF3 in its GTP-bound form to be efficiently methylated
CC (PubMed:20606008, PubMed:26797129). May also play a role in the
CC modulation of arsenic-induced toxicity by mediating the conversion of
CC monomethylarsonous acid (3+) into the less toxic dimethylarsonic acid
CC (By similarity). It however only plays a limited role in arsenic
CC metabolism compared with AS3MT (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y5N5, ECO:0000269|PubMed:20606008,
CC ECO:0000269|PubMed:26797129}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) + N(6)-
CC methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC Evidence={ECO:0000250|UniProtKB:Q9Y5N5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10025;
CC Evidence={ECO:0000250|UniProtKB:Q9Y5N5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutaminyl-[protein] + S-adenosyl-L-methionine = H(+) +
CC N(5)-methyl-L-glutaminyl-[protein] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:57452, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14895,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30011, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61891;
CC Evidence={ECO:0000269|PubMed:20606008, ECO:0000269|PubMed:26797129};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=methylarsonous acid + S-adenosyl-L-methionine =
CC dimethylarsinate + 2 H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:11684, ChEBI:CHEBI:15378, ChEBI:CHEBI:16223,
CC ChEBI:CHEBI:17826, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789;
CC Evidence={ECO:0000250|UniProtKB:Q9Y5N5};
CC -!- SUBUNIT: Heterodimer; heterodimerization with TRMT112 is required for
CC S-adenosyl-L-methionine-binding. {ECO:0000269|PubMed:26797129}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16684535,
CC ECO:0000269|PubMed:19116772}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha {ECO:0000303|PubMed:16684535}, mHemk1
CC {ECO:0000303|PubMed:19116772};
CC IsoId=Q6SKR2-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta {ECO:0000303|PubMed:16684535}, mHemk2
CC {ECO:0000303|PubMed:19116772};
CC IsoId=Q6SKR2-2; Sequence=VSP_059901, VSP_059902;
CC Name=3;
CC IsoId=Q6SKR2-3; Sequence=VSP_059900, VSP_059903;
CC -!- TISSUE SPECIFICITY: Highly expressed in undifferentiated embryonic stem
CC cells (at protein level) (PubMed:19116772). Also expressed in testis
CC and brain, weakly expressed in differentiated embryonic stem cells and
CC kidney (PubMed:19116772). Not expressed in muscle, heart, placenta,
CC pancreas, lung and stomach (PubMed:19116772).
CC {ECO:0000269|PubMed:19116772}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q9Y5N5}.
CC -!- DISRUPTION PHENOTYPE: Early embryonic lethality (PubMed:20606008). The
CC postimplantation development of mutant embryos is impaired, resulting
CC in degeneration around embryonic day 6.5 (PubMed:20606008).
CC {ECO:0000269|PubMed:20606008}.
CC -!- SIMILARITY: Belongs to the eukaryotic/archaeal PrmC-related family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AC140319; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EDK98331.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY583759; AAS94315.1; -; mRNA.
DR EMBL; AY536887; AAS45233.1; -; mRNA.
DR EMBL; AY456393; AAR19227.1; -; mRNA.
DR EMBL; AK145617; BAE26543.1; -; mRNA.
DR EMBL; AC140319; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466521; EDK98330.1; -; Genomic_DNA.
DR EMBL; CH466521; EDK98331.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH466521; EDK98332.1; -; Genomic_DNA.
DR EMBL; BC098330; AAH98330.1; -; mRNA.
DR EMBL; BC116393; AAI16394.1; -; mRNA.
DR EMBL; BC116394; AAI16395.1; -; mRNA.
DR CCDS; CCDS28289.1; -. [Q6SKR2-1]
DR CCDS; CCDS49889.1; -. [Q6SKR2-2]
DR RefSeq; NP_001152803.1; NM_001159331.1. [Q6SKR2-2]
DR RefSeq; NP_080642.1; NM_026366.2. [Q6SKR2-1]
DR AlphaFoldDB; Q6SKR2; -.
DR SMR; Q6SKR2; -.
DR STRING; 10090.ENSMUSP00000061835; -.
DR EPD; Q6SKR2; -.
DR MaxQB; Q6SKR2; -.
DR PaxDb; Q6SKR2; -.
DR PeptideAtlas; Q6SKR2; -.
DR PRIDE; Q6SKR2; -.
DR ProteomicsDB; 308470; -.
DR ProteomicsDB; 308569; -. [Q6SKR2-1]
DR ProteomicsDB; 333143; -.
DR ProteomicsDB; 357615; -.
DR Antibodypedia; 22362; 193 antibodies from 25 providers.
DR DNASU; 67768; -.
DR Ensembl; ENSMUST00000054442; ENSMUSP00000061835; ENSMUSG00000044442. [Q6SKR2-1]
DR Ensembl; ENSMUST00000118310; ENSMUSP00000113229; ENSMUSG00000044442. [Q6SKR2-2]
DR Ensembl; ENSMUST00000120284; ENSMUSP00000112510; ENSMUSG00000044442. [Q6SKR2-3]
DR GeneID; 67768; -.
DR KEGG; mmu:67768; -.
DR UCSC; uc007zuc.1; mouse.
DR UCSC; uc007zud.1; mouse. [Q6SKR2-1]
DR UCSC; uc007zue.1; mouse.
DR CTD; 29104; -.
DR MGI; MGI:1915018; N6amt1.
DR VEuPathDB; HostDB:ENSMUSG00000044442; -.
DR eggNOG; KOG3191; Eukaryota.
DR GeneTree; ENSGT00390000013073; -.
DR HOGENOM; CLU_153981_0_0_1; -.
DR InParanoid; Q6SKR2; -.
DR OMA; EWDDWME; -.
DR OrthoDB; 1450330at2759; -.
DR PhylomeDB; Q6SKR2; -.
DR TreeFam; TF314919; -.
DR BRENDA; 2.1.1.297; 3474.
DR Reactome; R-MMU-156581; Methylation.
DR Reactome; R-MMU-72764; Eukaryotic Translation Termination.
DR BioGRID-ORCS; 67768; 31 hits in 74 CRISPR screens.
DR ChiTaRS; N6amt1; mouse.
DR PRO; PR:Q6SKR2; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q6SKR2; protein.
DR Bgee; ENSMUSG00000044442; Expressed in interventricular septum and 218 other tissues.
DR ExpressionAtlas; Q6SKR2; baseline and differential.
DR GO; GO:0035657; C:eRF1 methyltransferase complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0030792; F:methylarsonite methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0008276; F:protein methyltransferase activity; ISO:MGI.
DR GO; GO:0036009; F:protein-glutamine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISS:UniProtKB.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IBA:GO_Central.
DR GO; GO:0009007; F:site-specific DNA-methyltransferase (adenine-specific) activity; ISS:UniProtKB.
DR GO; GO:0018872; P:arsonoacetate metabolic process; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0032775; P:DNA methylation on adenine; ISS:UniProtKB.
DR GO; GO:0034968; P:histone lysine methylation; ISS:UniProtKB.
DR GO; GO:0032259; P:methylation; ISS:UniProtKB.
DR GO; GO:0018364; P:peptidyl-glutamine methylation; IDA:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR GO; GO:0009404; P:toxin metabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR002052; DNA_methylase_N6_adenine_CS.
DR InterPro; IPR004557; PrmC-related.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR007848; Small_mtfrase_dom.
DR Pfam; PF05175; MTS; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR00537; hemK_rel_arch; 1.
DR PROSITE; PS00092; N6_MTASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Methyltransferase; Nucleus;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Ubl conjugation.
FT CHAIN 1..214
FT /note="Methyltransferase N6AMT1"
FT /id="PRO_0000445556"
FT BINDING 53..57
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0ACC1, ECO:0000255|HAMAP-
FT Rule:MF_02126"
FT BINDING 77
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0ACC1"
FT BINDING 122..125
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0ACC1"
FT BINDING 122
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0ACC1"
FT VAR_SEQ 133..150
FT /note="VGSRGIEAAWAGGRNGRE -> VRLTTELSLCSQLFHETK (in isoform
FT 3)"
FT /id="VSP_059900"
FT VAR_SEQ 133..138
FT /note="VGSRGI -> RKSLKQ (in isoform 2)"
FT /id="VSP_059901"
FT VAR_SEQ 139..214
FT /note="Missing (in isoform 2)"
FT /id="VSP_059902"
FT VAR_SEQ 151..214
FT /note="Missing (in isoform 3)"
FT /id="VSP_059903"
FT CONFLICT 75
FT /note="C -> Y (in Ref. 6; AAH98330)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 214 AA; 22984 MW; B8A545E9DABB5F6C CRC64;
MAAPSVPTPL YGHVGRGAFR DVYEPAEDTF LLLDALEAAA AELAGVEICL EVGAGSGVVS
AFLASMIGPR ALYMCTDINP EAAACTLETA RCNRVHVQPV ITDLVHGLLP RLKGKVDLLV
FNPPYVVTPP EEVGSRGIEA AWAGGRNGRE VMDRFFPLAP ELLSPRGLFY LVTVKENNPE
EIFKTMKTRG LQGTTALCRQ AGQEALSVLR FSKS
