N6MT1_HUMAN
ID N6MT1_HUMAN Reviewed; 214 AA.
AC Q9Y5N5; B2RA97; Q96F73;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2017, sequence version 4.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Methyltransferase N6AMT1 {ECO:0000305};
DE AltName: Full=HemK methyltransferase family member 2 {ECO:0000303|PubMed:18539146};
DE Short=M.HsaHemK2P;
DE AltName: Full=Lysine N-methyltransferase 9 {ECO:0000303|PubMed:31061526};
DE EC=2.1.1.- {ECO:0000269|PubMed:31061526, ECO:0000305|PubMed:31632689};
DE AltName: Full=Methylarsonite methyltransferase N6AMT1;
DE EC=2.1.1.- {ECO:0000269|PubMed:21193388, ECO:0000269|PubMed:25997655};
DE AltName: Full=Protein N(5)-glutamine methyltransferase {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:18539146, ECO:0000269|PubMed:31061526, ECO:0000269|PubMed:31636962, ECO:0000305|PubMed:31632689};
GN Name=N6AMT1 {ECO:0000303|PubMed:30017583, ECO:0000312|HGNC:HGNC:16021};
GN Synonyms=C21orf127 {ECO:0000312|HGNC:HGNC:16021},
GN HEMK2 {ECO:0000303|PubMed:18539146}, KMT9 {ECO:0000303|PubMed:31061526},
GN PRED28 {ECO:0000250|UniProtKB:Q6SKR2};
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] (ISOFORM 1).
RA Reboul J., Misseri Y., Bonnerot C., Mogensen E., Lutfalla G.;
RT "Identification of a novel putative eukaryotic DNA-methyltransferase.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LYS-146 AND
RP LYS-166.
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
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, CATALYTIC ACTIVITY, AND INTERACTION WITH TRMT112.
RX PubMed=18539146; DOI=10.1016/j.febslet.2008.05.045;
RA Figaro S., Scrima N., Buckingham R.H., Heurgue-Hamard V.;
RT "HemK2 protein, encoded on human chromosome 21, methylates translation
RT termination factor eRF1.";
RL FEBS Lett. 582:2352-2356(2008).
RN [7]
RP FUNCTION.
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21193388; DOI=10.1289/ehp.1002733;
RA Ren X., Aleshin M., Jo W.J., Dills R., Kalman D.A., Vulpe C.D., Smith M.T.,
RA Zhang L.;
RT "Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in
RT arsenic biomethylation and its role in arsenic-induced toxicity.";
RL Environ. Health Perspect. 119:771-777(2011).
RN [10]
RP SUBUNIT.
RX PubMed=25851604; DOI=10.1091/mbc.e15-02-0073;
RA Zorbas C., Nicolas E., Wacheul L., Huvelle E., Heurgue-Hamard V.,
RA Lafontaine D.L.;
RT "The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but
RT not rRNA modification are required for ribosome biogenesis.";
RL Mol. Biol. Cell 26:2080-2095(2015).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25997655; DOI=10.1093/toxsci/kfv101;
RA Zhang H., Ge Y., He P., Chen X., Carina A., Qiu Y., Aga D.S., Ren X.;
RT "Interactive effects of N6AMT1 and As3MT in arsenic biomethylation.";
RL Toxicol. Sci. 146:354-362(2015).
RN [12]
RP CAUTION.
RX PubMed=30392959; DOI=10.1016/j.cell.2018.10.006;
RA Xie Q., Wu T.P., Gimple R.C., Li Z., Prager B.C., Wu Q., Yu Y., Wang P.,
RA Wang Y., Gorkin D.U., Zhang C., Dowiak A.V., Lin K., Zeng C., Sui Y.,
RA Kim L.J.Y., Miller T.E., Jiang L., Lee C.H., Huang Z., Fang X., Zhai K.,
RA Mack S.C., Sander M., Bao S., Kerstetter-Fogle A.E., Sloan A.E., Xiao A.Z.,
RA Rich J.N.;
RT "N6-methyladenine DNA modification in glioblastoma.";
RL Cell 175:1228-1243(2018).
RN [13]
RP MUTAGENESIS OF 122-ASN--TYR-125.
RX PubMed=30017583; DOI=10.1016/j.molcel.2018.06.015;
RA Xiao C.L., Zhu S., He M., Chen D., Zhang Q., Chen Y., Yu G., Liu J.,
RA Xie S.Q., Luo F., Liang Z., Wang D.P., Bo X.C., Gu X.F., Wang K., Yan G.R.;
RT "N6-methyladenine DNA modification in the human genome.";
RL Mol. Cell 71:306-318(2018).
RN [14]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), INTERACTION WITH TRMT112, AND
RP UBIQUITINATION.
RX PubMed=31466382; DOI=10.3390/biom9090422;
RA Leetsi L., Ounap K., Abroi A., Kurg R.;
RT "The Common Partner of Several Methyltransferases TRMT112 Regulates the
RT Expression of N6AMT1 Isoforms in Mammalian Cells.";
RL Biomolecules 9:0-0(2019).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TRMT112.
RX PubMed=31632689; DOI=10.1038/s41421-019-0119-5;
RA Woodcock C.B., Yu D., Zhang X., Cheng X.;
RT "Human HemK2/KMT9/N6AMT1 is an active protein methyltransferase, but does
RT not act on DNA in vitro, in the presence of Trm112.";
RL Cell Discov. 5:50-50(2019).
RN [16]
RP FUNCTION, AND CAUTION.
RX PubMed=32203414; DOI=10.1038/s41589-020-0504-2;
RA Musheev M.U., Baumgaertner A., Krebs L., Niehrs C.;
RT "The origin of genomic N6-methyl-deoxyadenosine in mammalian cells.";
RL Nat. Chem. Biol. 16:630-634(2020).
RN [17]
RP INTERACTION WITH TRMT112.
RX PubMed=34948388; DOI=10.3390/ijms222413593;
RA Brumele B., Mutso M., Telanne L., Ounap K., Spunde K., Abroi A., Kurg R.;
RT "Human TRMT112-Methyltransferase Network Consists of Seven Partners
RT Interacting with a Common Co-Factor.";
RL Int. J. Mol. Sci. 22:13593-13593(2021).
RN [18] {ECO:0007744|PDB:6KMR, ECO:0007744|PDB:6KMS}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE AND TRMT112, FUNCTION, CATALYTIC ACTIVITY,
RP INTERACTION WITH TRMT112, AND MUTAGENESIS OF GLU-24; GLU-27; ASP-28;
RP GLU-51; LEU-72; ASP-77; ILE-78; ALA-83; ASP-103; LEU-108; ASN-122; GLU-132;
RP GLU-139; ARG-154; GLU-176 AND GLU-204.
RX PubMed=31636962; DOI=10.1038/s41421-019-0121-y;
RA Li W., Shi Y., Zhang T., Ye J., Ding J.;
RT "Structural insight into human N6amt1-Trm112 complex functioning as a
RT protein methyltransferase.";
RL Cell Discov. 5:51-51(2019).
RN [19] {ECO:0007744|PDB:6H1D, ECO:0007744|PDB:6H1E}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 8-214 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE AND TRMT112, FUNCTION, CATALYTIC ACTIVITY,
RP INTERACTION WITH TRMT112, AND MUTAGENESIS OF ASP-103; ASN-122 AND TYR-125.
RX PubMed=31061526; DOI=10.1038/s41594-019-0219-9;
RA Metzger E., Wang S., Urban S., Willmann D., Schmidt A., Offermann A.,
RA Allen A., Sum M., Obier N., Cottard F., Ulferts S., Preca B.T., Hermann B.,
RA Maurer J., Greschik H., Hornung V., Einsle O., Perner S., Imhof A.,
RA Jung M., Schule R.;
RT "KMT9 monomethylates histone H4 lysine 12 and controls proliferation of
RT prostate cancer cells.";
RL Nat. Struct. Mol. Biol. 26:361-371(2019).
CC -!- FUNCTION: Methyltransferase that can methylate proteins and, to a lower
CC extent, arsenic (PubMed:18539146, PubMed:21193388, PubMed:30017583,
CC PubMed:31636962, PubMed:31061526). Catalytic subunit of a heterodimer
CC with TRMT112, which monomethylates 'Lys-12' of histone H4 (H4K12me1), a
CC modification present at the promoters of numerous genes encoding cell
CC cycle regulators (PubMed:31061526). Catalytic subunit of a heterodimer
CC with TRMT112, which catalyzes N5-methylation of Glu residue of proteins
CC with a Gly-Gln-Xaa-Xaa-Xaa-Arg motif (PubMed:18539146, PubMed:31632689,
CC PubMed:31636962). Methylates ETF1 on 'Gln-185'; ETF1 needs to be
CC complexed to ERF3 in its GTP-bound form to be efficiently methylated
CC (PubMed:18539146, PubMed:20606008, PubMed:31636962, PubMed:31061526).
CC May also play a role in the modulation of arsenic-induced toxicity by
CC mediating the conversion of monomethylarsonous acid (3+) into the less
CC toxic dimethylarsonic acid (PubMed:21193388, PubMed:25997655). It
CC however only plays a limited role in arsenic metabolism compared with
CC AS3MT (PubMed:25997655). {ECO:0000269|PubMed:18539146,
CC ECO:0000269|PubMed:20606008, ECO:0000269|PubMed:21193388,
CC ECO:0000269|PubMed:25997655, ECO:0000269|PubMed:30017583,
CC ECO:0000269|PubMed:31061526, ECO:0000269|PubMed:31632689,
CC ECO:0000269|PubMed:31636962}.
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:0000269|PubMed:31061526, ECO:0000305|PubMed:31632689};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10025;
CC Evidence={ECO:0000269|PubMed:31061526, ECO:0000305|PubMed:31632689};
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:18539146, ECO:0000269|PubMed:31061526,
CC ECO:0000269|PubMed:31636962, ECO:0000305|PubMed:31632689};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57453;
CC Evidence={ECO:0000269|PubMed:18539146, ECO:0000269|PubMed:31061526,
CC ECO:0000269|PubMed:31636962, ECO:0000305|PubMed:31632689};
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:0000269|PubMed:21193388, ECO:0000269|PubMed:25997655};
CC -!- SUBUNIT: Heterodimer; heterodimerization with TRMT112 is required for
CC S-adenosyl-L-methionine-binding. {ECO:0000269|PubMed:18539146,
CC ECO:0000269|PubMed:25851604, ECO:0000269|PubMed:31061526,
CC ECO:0000269|PubMed:31466382, ECO:0000269|PubMed:31632689,
CC ECO:0000269|PubMed:31636962, ECO:0000269|PubMed:34948388}.
CC -!- SUBUNIT: [Isoform 2]: Does not interact with TRMT112.
CC {ECO:0000269|PubMed:31466382}.
CC -!- INTERACTION:
CC Q9Y5N5; Q9UI30: TRMT112; NbExp=2; IntAct=EBI-7966667, EBI-373326;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6SKR2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000303|PubMed:31466382}; Synonyms=Alpha
CC {ECO:0000303|PubMed:18539146}, N6AMT1iso1
CC {ECO:0000303|PubMed:31466382};
CC IsoId=Q9Y5N5-1; Sequence=Displayed;
CC Name=2 {ECO:0000303|PubMed:31466382}; Synonyms=Beta
CC {ECO:0000303|PubMed:18539146}, N6AMT1iso2
CC {ECO:0000303|PubMed:31466382};
CC IsoId=Q9Y5N5-2; Sequence=VSP_040294;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in
CC parathyroid and pituitary glands, followed by adrenal gland and kidney,
CC and lowest expression in leukocytes and mammary gland.
CC {ECO:0000269|PubMed:21193388}.
CC -!- PTM: [Isoform 1]: Ubiquitinated, leading to its degradation by the
CC proteasome. {ECO:0000269|PubMed:31466382}.
CC -!- PTM: [Isoform 2]: Ubiquitinated, leading to its degradation by the
CC proteasome. {ECO:0000269|PubMed:31466382}.
CC -!- SIMILARITY: Belongs to the eukaryotic/archaeal PrmC-related family.
CC {ECO:0000305}.
CC -!- CAUTION: Was reported to have N(6)-adenine-specific DNA
CC methyltransferase by mediating methylation of DNA on the 6th position
CC of adenine (N(6)-methyladenosine) (PubMed:30017583). The existence of
CC N(6)-methyladenosine on DNA is unclear in mammals (PubMed:32203414).
CC According to a report, the majority of N(6)-methyladenosine in DNA
CC originates from RNA catabolism via a nucleotide salvage pathway and is
CC misincorporated by DNA polymerases, arguing against a role as
CC epigenetic DNA mark in mammalian cells (PubMed:32203414). Moreover,
CC subsequent studies could not confirm the role of N6AMT1 as a N(6)-
CC adenine-specific DNA methyltransferase (PubMed:30392959,
CC PubMed:31632689, PubMed:31636962). {ECO:0000269|PubMed:30017583,
CC ECO:0000269|PubMed:30392959, ECO:0000269|PubMed:31632689,
CC ECO:0000269|PubMed:31636962, ECO:0000269|PubMed:32203414}.
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DR EMBL; AF139682; AAD38520.1; -; mRNA.
DR EMBL; AK314100; BAG36794.1; -; mRNA.
DR EMBL; AF227510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL163248; CAB90428.1; -; Genomic_DNA.
DR EMBL; AMYH02037685; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF570251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF457188; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KC877845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471079; EAX09939.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09940.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09941.1; -; Genomic_DNA.
DR EMBL; BC011554; AAH11554.1; -; mRNA.
DR CCDS; CCDS33525.1; -. [Q9Y5N5-2]
DR CCDS; CCDS33526.1; -. [Q9Y5N5-1]
DR RefSeq; NP_037372.4; NM_013240.5. [Q9Y5N5-1]
DR RefSeq; NP_877426.4; NM_182749.4. [Q9Y5N5-2]
DR PDB; 6H1D; X-ray; 1.94 A; A=8-214.
DR PDB; 6H1E; X-ray; 1.90 A; A=8-214.
DR PDB; 6K0X; X-ray; 2.20 A; A=2-214.
DR PDB; 6KHS; X-ray; 1.90 A; A=1-214.
DR PDB; 6KMR; X-ray; 2.00 A; B=1-214.
DR PDB; 6KMS; X-ray; 3.20 A; C/D=1-214.
DR PDB; 6PED; X-ray; 2.30 A; A=1-214.
DR PDBsum; 6H1D; -.
DR PDBsum; 6H1E; -.
DR PDBsum; 6K0X; -.
DR PDBsum; 6KHS; -.
DR PDBsum; 6KMR; -.
DR PDBsum; 6KMS; -.
DR PDBsum; 6PED; -.
DR AlphaFoldDB; Q9Y5N5; -.
DR SMR; Q9Y5N5; -.
DR BioGRID; 118872; 7.
DR IntAct; Q9Y5N5; 5.
DR MINT; Q9Y5N5; -.
DR STRING; 9606.ENSP00000303584; -.
DR BioMuta; N6AMT1; -.
DR DMDM; 313104228; -.
DR EPD; Q9Y5N5; -.
DR jPOST; Q9Y5N5; -.
DR MassIVE; Q9Y5N5; -.
DR MaxQB; Q9Y5N5; -.
DR PaxDb; Q9Y5N5; -.
DR PeptideAtlas; Q9Y5N5; -.
DR PRIDE; Q9Y5N5; -.
DR ProteomicsDB; 86454; -. [Q9Y5N5-1]
DR ProteomicsDB; 86455; -. [Q9Y5N5-2]
DR Antibodypedia; 22362; 193 antibodies from 25 providers.
DR DNASU; 29104; -.
DR Ensembl; ENST00000303775.10; ENSP00000303584.5; ENSG00000156239.12. [Q9Y5N5-1]
DR Ensembl; ENST00000351429.7; ENSP00000286764.4; ENSG00000156239.12. [Q9Y5N5-2]
DR Ensembl; ENST00000460212.1; ENSP00000436490.1; ENSG00000156239.12. [Q9Y5N5-1]
DR GeneID; 29104; -.
DR KEGG; hsa:29104; -.
DR MANE-Select; ENST00000303775.10; ENSP00000303584.5; NM_013240.6; NP_037372.4.
DR UCSC; uc002ymo.3; human.
DR UCSC; uc002ymp.3; human. [Q9Y5N5-1]
DR CTD; 29104; -.
DR DisGeNET; 29104; -.
DR GeneCards; N6AMT1; -.
DR HGNC; HGNC:16021; N6AMT1.
DR HPA; ENSG00000156239; Low tissue specificity.
DR MIM; 614553; gene.
DR neXtProt; NX_Q9Y5N5; -.
DR OpenTargets; ENSG00000156239; -.
DR PharmGKB; PA162396656; -.
DR VEuPathDB; HostDB:ENSG00000156239; -.
DR eggNOG; KOG3191; Eukaryota.
DR GeneTree; ENSGT00390000013073; -.
DR InParanoid; Q9Y5N5; -.
DR OMA; EWDDWME; -.
DR OrthoDB; 1450330at2759; -.
DR PhylomeDB; Q9Y5N5; -.
DR TreeFam; TF314919; -.
DR BioCyc; MetaCyc:ENSG00000156239-MON; -.
DR BRENDA; 2.1.1.137; 2681.
DR BRENDA; 2.1.1.72; 2681.
DR PathwayCommons; Q9Y5N5; -.
DR Reactome; R-HSA-156581; Methylation.
DR Reactome; R-HSA-72764; Eukaryotic Translation Termination.
DR SignaLink; Q9Y5N5; -.
DR BioGRID-ORCS; 29104; 346 hits in 1093 CRISPR screens.
DR ChiTaRS; N6AMT1; human.
DR GenomeRNAi; 29104; -.
DR Pharos; Q9Y5N5; Tbio.
DR PRO; PR:Q9Y5N5; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q9Y5N5; protein.
DR Bgee; ENSG00000156239; Expressed in ventricular zone and 122 other tissues.
DR Genevisible; Q9Y5N5; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035657; C:eRF1 methyltransferase complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0030792; F:methylarsonite methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0008276; F:protein methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0036009; F:protein-glutamine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; IDA: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; IDA:UniProtKB.
DR GO; GO:0018872; P:arsonoacetate metabolic process; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0032775; P:DNA methylation on adenine; IDA:UniProtKB.
DR GO; GO:0034968; P:histone lysine methylation; IDA:UniProtKB.
DR GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR GO; GO:0018364; P:peptidyl-glutamine methylation; IDA:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:MGI.
DR GO; GO:0009404; P:toxin metabolic process; IDA: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 3D-structure; Alternative splicing; Chromatin regulator; Methyltransferase;
KW Nucleus; Reference proteome; S-adenosyl-L-methionine; Transferase;
KW Ubl conjugation.
FT CHAIN 1..214
FT /note="Methyltransferase N6AMT1"
FT /id="PRO_0000088049"
FT REGION 103..104
FT /note="S-adenosyl-L-methionine"
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0000269|PubMed:31636962, ECO:0007744|PDB:6H1D,
FT ECO:0007744|PDB:6H1E, ECO:0007744|PDB:6KMR,
FT ECO:0007744|PDB:6KMS"
FT BINDING 24
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0007744|PDB:6H1E"
FT BINDING 29
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0000269|PubMed:31636962, ECO:0007744|PDB:6H1D,
FT ECO:0007744|PDB:6H1E, ECO:0007744|PDB:6KMR,
FT ECO:0007744|PDB:6KMS"
FT BINDING 51..53
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0000269|PubMed:31636962, ECO:0007744|PDB:6H1D,
FT ECO:0007744|PDB:6H1E, ECO:0007744|PDB:6KMR,
FT ECO:0007744|PDB:6KMS"
FT BINDING 77
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0000269|PubMed:31636962, ECO:0007744|PDB:6H1D,
FT ECO:0007744|PDB:6H1E, ECO:0007744|PDB:6KMR,
FT ECO:0007744|PDB:6KMS"
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:0000269|PubMed:31061526,
FT ECO:0000269|PubMed:31636962, ECO:0000305|PubMed:30017583,
FT ECO:0007744|PDB:6H1D, ECO:0007744|PDB:6H1E,
FT ECO:0007744|PDB:6KMR, ECO:0007744|PDB:6KMS"
FT BINDING 122
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0007744|PDB:6H1E"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0007744|PDB:6H1E"
FT VAR_SEQ 105..132
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040294"
FT VARIANT 34
FT /note="D -> N (in dbSNP:rs1997607)"
FT /id="VAR_060445"
FT VARIANT 146
FT /note="R -> K (in dbSNP:rs2205447)"
FT /evidence="ECO:0000269|PubMed:10830953"
FT /id="VAR_060446"
FT VARIANT 166
FT /note="R -> K (in dbSNP:rs2205446)"
FT /evidence="ECO:0000269|PubMed:10830953"
FT /id="VAR_060447"
FT MUTAGEN 24
FT /note="E->K: Reduced protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 27
FT /note="E->K: Abolished protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 28
FT /note="D->N: Abolished protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 51
FT /note="E->A: Abolished protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 72
FT /note="L->D: Strongly reduced protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 77
FT /note="D->A: Abolished protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 78
FT /note="I->A: Abolished protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 83
FT /note="A->D: Strongly reduced protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 103
FT /note="D->A: Abolished protein N(5)-glutamine
FT methyltransferase activity. Abolished histone-lysine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0000269|PubMed:31636962"
FT MUTAGEN 108
FT /note="L->D: Strongly reduced protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 122..125
FT /note="NPPY->AAAA: Abolished DNA methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30017583"
FT MUTAGEN 122
FT /note="N->A: Abolished protein N(5)-glutamine
FT methyltransferase activity. Abolished histone-lysine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31061526,
FT ECO:0000269|PubMed:31636962"
FT MUTAGEN 125
FT /note="Y->A: Abolished protein N(5)-glutamine
FT methyltransferase activity without affecting histone-lysine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31061526"
FT MUTAGEN 132
FT /note="E->K: Abolished protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 139
FT /note="E->K: Reduced protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 154
FT /note="R->A: Slightly reduced protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 176
FT /note="E->K: Abolished protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT MUTAGEN 204
FT /note="E->K: Abolished protein N(5)-glutamine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:31636962"
FT TURN 12..15
FT /evidence="ECO:0007829|PDB:6H1E"
FT HELIX 17..19
FT /evidence="ECO:0007829|PDB:6H1E"
FT HELIX 27..38
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:6KHS"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 58..67
FT /evidence="ECO:0007829|PDB:6KHS"
FT STRAND 71..79
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 80..93
FT /evidence="ECO:0007829|PDB:6KHS"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:6KHS"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:6KHS"
FT TURN 109..115
FT /evidence="ECO:0007829|PDB:6KHS"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 138..141
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 150..155
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 159..162
FT /evidence="ECO:0007829|PDB:6KHS"
FT STRAND 163..174
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:6KHS"
FT HELIX 179..188
FT /evidence="ECO:0007829|PDB:6KHS"
FT STRAND 192..201
FT /evidence="ECO:0007829|PDB:6KHS"
FT STRAND 204..212
FT /evidence="ECO:0007829|PDB:6KHS"
SQ SEQUENCE 214 AA; 22957 MW; 65512C91DC85ADDB CRC64;
MAGENFATPF HGHVGRGAFS DVYEPAEDTF LLLDALEAAA AELAGVEICL EVGSGSGVVS
AFLASMIGPQ ALYMCTDINP EAAACTLETA RCNKVHIQPV ITDLVKGLLP RLTEKVDLLV
FNPPYVVTPP QEVGSHGIEA AWAGGRNGRE VMDRFFPLVP DLLSPRGLFY LVTIKENNPE
EILKIMKTKG LQGTTALSRQ AGQETLSVLK FTKS
