ID HEMK2_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 12-SEP-2018, entry version 145. DE RecName: Full=HemK methyltransferase family member 2; DE EC=2.1.1.-; DE AltName: Full=M.HsaHemK2P; DE AltName: Full=N(6)-adenine-specific DNA methyltransferase 1; GN Name=N6AMT1; Synonyms=C21orf127, HEMK2; ORFNames=PRED28; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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- RT 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 RP AND LYS-166. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, 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 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., RA Buerckstuemmer T., 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 [8] 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., RA Smith M.T., Zhang L.; RT "Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) RT in arsenic biomethylation and its role in arsenic-induced toxicity."; RL Environ. Health Perspect. 119:771-777(2011). RN [9] 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 RT but not rRNA modification are required for ribosome biogenesis."; RL Mol. Biol. Cell 26:2080-2095(2015). CC -!- FUNCTION: Heterodimeric methyltransferase that catalyzes N5- CC methylation of ETF1 on 'Gln-185', using S-adenosyl L-methionine as CC methyl donor. ETF1 needs to be complexed to ERF3 in its GTP-bound CC form to be efficiently methylated. May play a role in the CC modulation of arsenic-induced toxicity. May be involved in the CC conversion of monomethylarsonous acid (3+) into the less toxic CC dimethylarsonic acid. {ECO:0000269|PubMed:18539146, CC ECO:0000269|PubMed:21193388}. CC -!- SUBUNIT: Heterodimer with TRMT112 (PubMed:18539146, CC PubMed:25851604). {ECO:0000269|PubMed:18539146, CC ECO:0000269|PubMed:25851604}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y5N5-1; Sequence=Displayed; CC Name=2; 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 CC kidney, and lowest expression in leukocytes and mammary gland. CC {ECO:0000269|PubMed:21193388}. CC -!- SIMILARITY: Belongs to the eukaryotic/archaeal PrmC-related CC family. {ECO:0000305}. CC -!- CAUTION: Was originally (Ref.1) proposed to be a DNA CC methyltransferase, but was then shown to be a protein CC methyltransferase. {ECO:0000305|PubMed:18539146}. 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; 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 UniGene; Hs.163846; -. DR ProteinModelPortal; Q9Y5N5; -. DR SMR; Q9Y5N5; -. DR BioGrid; 118872; 6. DR IntAct; Q9Y5N5; 5. DR MINT; Q9Y5N5; -. DR STRING; 9606.ENSP00000303584; -. DR BioMuta; N6AMT1; -. DR DMDM; 313104228; -. DR EPD; Q9Y5N5; -. DR PaxDb; Q9Y5N5; -. DR PeptideAtlas; Q9Y5N5; -. DR PRIDE; Q9Y5N5; -. DR ProteomicsDB; 86454; -. DR ProteomicsDB; 86455; -. [Q9Y5N5-2] DR DNASU; 29104; -. DR Ensembl; ENST00000303775; ENSP00000303584; ENSG00000156239. [Q9Y5N5-1] DR Ensembl; ENST00000351429; ENSP00000286764; ENSG00000156239. [Q9Y5N5-2] DR Ensembl; ENST00000460212; ENSP00000436490; ENSG00000156239. [Q9Y5N5-1] DR GeneID; 29104; -. DR KEGG; hsa:29104; -. DR UCSC; uc002ymo.3; human. DR UCSC; uc002ymp.3; human. [Q9Y5N5-1] DR CTD; 29104; -. DR DisGeNET; 29104; -. DR EuPathDB; HostDB:ENSG00000156239.11; -. DR GeneCards; N6AMT1; -. DR H-InvDB; HIX0020675; -. DR HGNC; HGNC:16021; N6AMT1. DR HPA; CAB034133; -. DR HPA; CAB034135; -. DR HPA; HPA059242; -. DR MIM; 614553; gene. DR neXtProt; NX_Q9Y5N5; -. DR OpenTargets; ENSG00000156239; -. DR PharmGKB; PA162396656; -. DR eggNOG; KOG3191; Eukaryota. DR eggNOG; COG2890; LUCA. DR GeneTree; ENSGT00390000013073; -. DR HOGENOM; HOG000219949; -. DR HOVERGEN; HBG052569; -. DR InParanoid; Q9Y5N5; -. DR KO; K19589; -. DR OMA; EWDDWME; -. DR OrthoDB; EOG091G0XHW; -. DR PhylomeDB; Q9Y5N5; -. DR TreeFam; TF314919; -. DR BRENDA; 2.1.1.72; 2681. DR Reactome; R-HSA-156581; Methylation. DR Reactome; R-HSA-72764; Eukaryotic Translation Termination. DR GenomeRNAi; 29104; -. DR PRO; PR:Q9Y5N5; -. DR Proteomes; UP000005640; Chromosome 21. DR Bgee; ENSG00000156239; Expressed in 161 organ(s), highest expression level in corpus callosum. DR CleanEx; HS_N6AMT1; -. DR ExpressionAtlas; Q9Y5N5; baseline and differential. DR Genevisible; Q9Y5N5; HS. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro. DR GO; GO:0008276; F:protein methyltransferase activity; IDA:MGI. DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IBA:GO_Central. DR GO; GO:0030307; P:positive regulation of cell growth; IDA:MGI. DR InterPro; IPR002052; DNA_methylase_N6_adenine_CS. DR InterPro; IPR004557; PrmC-related. DR InterPro; IPR029063; SAM-dependent_MTases. 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; Complete proteome; Methyltransferase; KW Polymorphism; Reference proteome; S-adenosyl-L-methionine; KW Transferase. FT CHAIN 1 214 HemK methyltransferase family member 2. FT /FTId=PRO_0000088049. FT REGION 53 57 S-adenosyl-L-methionine binding. FT {ECO:0000250}. FT REGION 122 125 Substrate binding. {ECO:0000250}. FT BINDING 77 77 S-adenosyl-L-methionine. {ECO:0000250}. FT BINDING 122 122 S-adenosyl-L-methionine. {ECO:0000250}. FT VAR_SEQ 105 132 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_040294. FT VARIANT 34 34 D -> N (in dbSNP:rs1997607). FT /FTId=VAR_060445. FT VARIANT 146 146 R -> K (in dbSNP:rs2205447). FT {ECO:0000269|PubMed:10830953}. FT /FTId=VAR_060446. FT VARIANT 166 166 R -> K (in dbSNP:rs2205446). FT {ECO:0000269|PubMed:10830953}. FT /FTId=VAR_060447. 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 //