ID HEMK2_HUMAN Reviewed; 214 AA. AC Q9Y5N5; Q96F73; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 13-APR-2016, entry version 129. 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), AND VARIANTS ASP-34; ARG-146 RP AND ARG-166. 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 GENOMIC DNA], AND VARIANT ASP-34. 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ASP-34; RP ARG-146 AND ARG-166. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS RP ASP-34; ARG-146 AND ARG-166. 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 [5] 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 [6] 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 [7] 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). 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. 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; AF227510; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL163248; CAB90428.1; -; 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. DR RefSeq; NP_877426.4; NM_182749.4. DR UniGene; Hs.163846; -. DR ProteinModelPortal; Q9Y5N5; -. DR SMR; Q9Y5N5; 21-214. DR BioGrid; 118872; 6. DR IntAct; Q9Y5N5; 5. DR MINT; MINT-3087317; -. DR STRING; 9606.ENSP00000303584; -. DR BioMuta; N6AMT1; -. DR DMDM; 313104228; -. DR EPD; Q9Y5N5; -. DR MaxQB; Q9Y5N5; -. DR PaxDb; Q9Y5N5; -. DR PRIDE; Q9Y5N5; -. DR DNASU; 29104; -. DR Ensembl; ENST00000351429; ENSP00000286764; ENSG00000156239. DR GeneID; 29104; -. DR KEGG; hsa:29104; -. DR UCSC; uc002ymp.3; human. [Q9Y5N5-1] DR CTD; 29104; -. 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 PharmGKB; PA162396656; -. DR eggNOG; KOG3191; Eukaryota. DR eggNOG; COG2890; LUCA. DR HOGENOM; HOG000219949; -. DR HOVERGEN; HBG052569; -. DR InParanoid; Q9Y5N5; -. DR KO; K19589; -. DR OrthoDB; EOG738066; -. DR PhylomeDB; Q9Y5N5; -. DR TreeFam; TF314919; -. DR BRENDA; 2.1.1.72; 2681. DR GenomeRNAi; 29104; -. DR NextBio; 52151; -. DR PRO; PR:Q9Y5N5; -. DR Proteomes; UP000005640; Chromosome 21. DR Bgee; Q9Y5N5; -. DR CleanEx; HS_N6AMT1; -. DR ExpressionAtlas; Q9Y5N5; baseline and differential. DR Genevisible; Q9Y5N5; HS. DR GO; GO:0043234; C:protein 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:0030307; P:positive regulation of cell growth; IDA:MGI. DR GO; GO:0006479; P:protein methylation; IDA:GOC. 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. 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 N -> D (in dbSNP:rs1997607). FT {ECO:0000269|PubMed:10830953, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.1, ECO:0000269|Ref.3}. FT /FTId=VAR_060445. FT VARIANT 146 146 K -> R (in dbSNP:rs2205447). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.1, ECO:0000269|Ref.3}. FT /FTId=VAR_060446. FT VARIANT 166 166 K -> R (in dbSNP:rs2205446). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.1, ECO:0000269|Ref.3}. FT /FTId=VAR_060447. SQ SEQUENCE 214 AA; 22900 MW; 401B9A533C19F7C6 CRC64; MAGENFATPF HGHVGRGAFS DVYEPAEDTF LLLNALEAAA AELAGVEICL EVGSGSGVVS AFLASMIGPQ ALYMCTDINP EAAACTLETA RCNKVHIQPV ITDLVKGLLP RLTEKVDLLV FNPPYVVTPP QEVGSHGIEA AWAGGKNGRE VMDRFFPLVP DLLSPKGLFY LVTIKENNPE EILKIMKTKG LQGTTALSRQ AGQETLSVLK FTKS //