ID   INMT_HUMAN              Reviewed;         263 AA.
AC   O95050; B8ZZ69; Q3KP49; Q9P1Y2; Q9UBY4; Q9UHQ0;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 3.
DT   22-APR-2020, entry version 161.
DE   RecName: Full=Indolethylamine N-methyltransferase;
DE            Short=Indolamine N-methyltransferase;
DE            EC=2.1.1.49;
DE            EC=2.1.1.96;
DE   AltName: Full=Aromatic alkylamine N-methyltransferase;
DE            Short=Amine N-methyltransferase;
DE            Short=Arylamine N-methyltransferase;
DE   AltName: Full=Thioether S-methyltransferase;
DE            Short=TEMT;
GN   Name=INMT;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS VAL-205 AND
RP   GLY-219, CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RC   TISSUE=Placenta, and Skeletal muscle;
RX   PubMed=10552930; DOI=10.1006/geno.1999.5960;
RA   Thompson M.A., Moon E., Kim U.-J., Xu J., Siciliano M.J.,
RA   Weinshilboum R.M.;
RT   "Human indolethylamine N-methyltransferase: cDNA cloning and expression,
RT   gene cloning, and chromosomal localization.";
RL   Genomics 61:285-297(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS GLY-219
RP   AND CYS-254.
RC   TISSUE=Lung;
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].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ASN-28 AND
RP   GLY-219.
RC   TISSUE=Lung, and Spleen;
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   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-12.
RX   PubMed=15014171; DOI=10.1093/molbev/msh100;
RA   Kitano T., Liu Y.-H., Ueda S., Saitou N.;
RT   "Human-specific amino acid changes found in 103 protein-coding genes.";
RL   Mol. Biol. Evol. 21:936-944(2004).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH
RP   S-ADENOSYL-L-HOMOCYSTEINE.
RG   Structural genomics consortium (SGC);
RT   "The crystal structure of human indolethylamine N-methyltransferase in
RT   complex with SAH.";
RL   Submitted (JUN-2005) to the PDB data bank.
CC   -!- FUNCTION: Functions as thioether S-methyltransferase and is active with
CC       a variety of thioethers and the corresponding selenium and tellurium
CC       compounds, including 3-methylthiopropionaldehyde, dimethyl selenide,
CC       dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol,
CC       methyl-n-propyl sulfide and diethyl sulfide. Plays an important role in
CC       the detoxification of selenium compounds (By similarity). Catalyzes the
CC       N-methylation of tryptamine and structurally related compounds.
CC       {ECO:0000250, ECO:0000269|PubMed:10552930}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a tertiary amine + S-adenosyl-L-methionine = a methylated
CC         tertiary amine + H(+) + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:53928, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:137982, ChEBI:CHEBI:137983;
CC         EC=2.1.1.49; Evidence={ECO:0000269|PubMed:10552930};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a secondary amine + S-adenosyl-L-methionine = a methylated
CC         secondary amine + H(+) + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:53924, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:137419, ChEBI:CHEBI:137984;
CC         EC=2.1.1.49; Evidence={ECO:0000269|PubMed:10552930};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a primary amine + S-adenosyl-L-methionine = a methylated
CC         primary amine + H(+) + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:23136, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:65296, ChEBI:CHEBI:131823;
CC         EC=2.1.1.49; Evidence={ECO:0000269|PubMed:10552930};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dimethyl sulfide + S-adenosyl-L-methionine = S-adenosyl-L-
CC         homocysteine + trimethylsulfonium; Xref=Rhea:RHEA:19613,
CC         ChEBI:CHEBI:17434, ChEBI:CHEBI:17437, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789; EC=2.1.1.96;
CC         Evidence={ECO:0000269|PubMed:10552930};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=2.9 mM for tryptamine {ECO:0000269|PubMed:10552930};
CC   -!- SUBUNIT: Monomer. {ECO:0000250}.
CC   -!- INTERACTION:
CC       O95050; Q53G59: KLHL12; NbExp=6; IntAct=EBI-10191038, EBI-740929;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O95050-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O95050-2; Sequence=VSP_045922;
CC   -!- TISSUE SPECIFICITY: Widely expressed. The highest levels were in
CC       thyroid, adrenal gland, adult and fetal lung. Intermediate levels in
CC       heart, placenta, skeletal muscle, testis, small intestine, pancreas,
CC       stomach, spinal cord, lymph node and trachea. Very low levels in adult
CC       and fetal kidney and liver, in adult spleen, thymus, ovary, colon and
CC       bone marrow. Not expressed in peripheral blood leukocytes and brain.
CC       {ECO:0000269|PubMed:10552930}.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. NNMT/PNMT/TEMT family. {ECO:0000305}.
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DR   EMBL; AF128846; AAF18304.1; -; mRNA.
DR   EMBL; AF128847; AAF18305.1; -; mRNA.
DR   EMBL; AF128848; AAF18306.1; -; Genomic_DNA.
DR   EMBL; AK313832; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC004976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC006022; AAD04723.1; -; Genomic_DNA.
DR   EMBL; BC033813; AAH33813.1; -; mRNA.
DR   EMBL; BC106902; AAI06903.1; -; mRNA.
DR   EMBL; BC106903; AAI06904.1; -; mRNA.
DR   EMBL; AB041362; BAA94451.1; -; Genomic_DNA.
DR   CCDS; CCDS5430.1; -. [O95050-1]
DR   CCDS; CCDS56479.1; -. [O95050-2]
DR   RefSeq; NP_001186148.1; NM_001199219.1. [O95050-2]
DR   RefSeq; NP_006765.4; NM_006774.4. [O95050-1]
DR   PDB; 2A14; X-ray; 1.70 A; A=1-263.
DR   PDBsum; 2A14; -.
DR   SMR; O95050; -.
DR   BioGrid; 116355; 3.
DR   IntAct; O95050; 2.
DR   STRING; 9606.ENSP00000013222; -.
DR   BindingDB; O95050; -.
DR   ChEMBL; CHEMBL2131; -.
DR   iPTMnet; O95050; -.
DR   PhosphoSitePlus; O95050; -.
DR   BioMuta; INMT; -.
DR   MassIVE; O95050; -.
DR   PaxDb; O95050; -.
DR   PeptideAtlas; O95050; -.
DR   PRIDE; O95050; -.
DR   ProteomicsDB; 50633; -. [O95050-1]
DR   ProteomicsDB; 7318; -.
DR   Antibodypedia; 35018; 140 antibodies.
DR   Ensembl; ENST00000013222; ENSP00000013222; ENSG00000241644. [O95050-1]
DR   Ensembl; ENST00000409539; ENSP00000386961; ENSG00000241644. [O95050-2]
DR   GeneID; 11185; -.
DR   KEGG; hsa:11185; -.
DR   UCSC; uc003tbs.1; human. [O95050-1]
DR   CTD; 11185; -.
DR   DisGeNET; 11185; -.
DR   GeneCards; INMT; -.
DR   HGNC; HGNC:6069; INMT.
DR   HPA; ENSG00000241644; Tissue enhanced (lung).
DR   MIM; 604854; gene.
DR   neXtProt; NX_O95050; -.
DR   OpenTargets; ENSG00000241644; -.
DR   PharmGKB; PA403; -.
DR   eggNOG; ENOG410IFTZ; Eukaryota.
DR   eggNOG; ENOG41128ZR; LUCA.
DR   GeneTree; ENSGT00390000011708; -.
DR   HOGENOM; CLU_082526_2_0_1; -.
DR   InParanoid; O95050; -.
DR   KO; K00562; -.
DR   OMA; YRAALCN; -.
DR   OrthoDB; 1054662at2759; -.
DR   PhylomeDB; O95050; -.
DR   TreeFam; TF313114; -.
DR   BioCyc; MetaCyc:HS00305-MONOMER; -.
DR   Reactome; R-HSA-2408552; Methylation of MeSeH for excretion.
DR   SABIO-RK; O95050; -.
DR   ChiTaRS; INMT; human.
DR   EvolutionaryTrace; O95050; -.
DR   GenomeRNAi; 11185; -.
DR   Pharos; O95050; Tchem.
DR   PRO; PR:O95050; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; O95050; protein.
DR   Bgee; ENSG00000241644; Expressed in right lung and 141 other tissues.
DR   Genevisible; O95050; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0030748; F:amine N-methyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0008170; F:N-methyltransferase activity; IBA:GO_Central.
DR   GO; GO:0102707; F:S-adenosyl-L-methionine:beta-alanine N-methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004790; F:thioether S-methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0009308; P:amine metabolic process; IDA:UniProtKB.
DR   GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR   GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR   InterPro; IPR025820; NNMT/PNMT/TEMT_CS.
DR   InterPro; IPR000940; NNMT_TEMT_trans.
DR   InterPro; IPR029063; SAM-dependent_MTases.
DR   PANTHER; PTHR10867; PTHR10867; 1.
DR   Pfam; PF01234; NNMT_PNMT_TEMT; 1.
DR   PIRSF; PIRSF000384; PNMTase; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   PROSITE; PS01100; NNMT_PNMT_TEMT; 1.
DR   PROSITE; PS51681; SAM_MT_NNMT_PNMT_TEMT; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Detoxification;
KW   Methyltransferase; Polymorphism; Reference proteome;
KW   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..263
FT                   /note="Indolethylamine N-methyltransferase"
FT                   /id="PRO_0000159712"
FT   REGION          85..87
FT                   /note="S-adenosyl-L-methionine binding"
FT   REGION          142..143
FT                   /note="S-adenosyl-L-methionine binding"
FT   BINDING         20
FT                   /note="S-adenosyl-L-methionine"
FT   BINDING         25
FT                   /note="S-adenosyl-L-methionine"
FT   BINDING         63
FT                   /note="S-adenosyl-L-methionine; via carbonyl oxygen"
FT   BINDING         69
FT                   /note="S-adenosyl-L-methionine"
FT   BINDING         90
FT                   /note="S-adenosyl-L-methionine"
FT   BINDING         163
FT                   /note="S-adenosyl-L-methionine; via carbonyl oxygen"
FT   MOD_RES         13
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P40936"
FT   MOD_RES         96
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P40936"
FT   VAR_SEQ         52
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_045922"
FT   VARIANT         28
FT                   /note="D -> N (in dbSNP:rs4723010)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_036991"
FT   VARIANT         205
FT                   /note="M -> V (in dbSNP:rs2302339)"
FT                   /evidence="ECO:0000269|PubMed:10552930"
FT                   /id="VAR_011616"
FT   VARIANT         214
FT                   /note="V -> M (in dbSNP:rs56800285)"
FT                   /id="VAR_061373"
FT   VARIANT         219
FT                   /note="E -> G (in dbSNP:rs2302340)"
FT                   /evidence="ECO:0000269|PubMed:10552930,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT                   /id="VAR_011617"
FT   VARIANT         246
FT                   /note="N -> S (in dbSNP:rs6970210)"
FT                   /id="VAR_036992"
FT   VARIANT         254
FT                   /note="F -> C (in dbSNP:rs4720015)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_036993"
FT   VARIANT         258
FT                   /note="R -> H (in dbSNP:rs6970605)"
FT                   /id="VAR_036994"
FT   CONFLICT        75
FT                   /note="C -> F (in Ref. 2; AK313832)"
FT                   /evidence="ECO:0000305"
FT   HELIX           8..14
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           17..24
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           33..49
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          56..63
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           69..71
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           74..76
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          78..86
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           88..99
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           108..117
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           121..123
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           124..134
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          135..140
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          145..147
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   TURN            148..151
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          157..164
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           166..169
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           173..184
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          187..200
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          203..206
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          209..212
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   HELIX           218..227
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          230..238
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   TURN            244..246
FT                   /evidence="ECO:0000244|PDB:2A14"
FT   STRAND          252..259
FT                   /evidence="ECO:0000244|PDB:2A14"
SQ   SEQUENCE   263 AA;  28891 MW;  12B3AC66597E70A3 CRC64;
     MKGGFTGGDE YQKHFLPRDY LATYYSFDGS PSPEAEMLKF NLECLHKTFG PGGLQGDTLI
     DIGSGPTIYQ VLAACDSFQD ITLSDFTDRN REELEKWLKK EPGAYDWTPA VKFACELEGN
     SGRWEEKEEK LRAAVKRVLK CDVHLGNPLA PAVLPLADCV LTLLAMECAC CSLDAYRAAL
     CNLASLLKPG GHLVTTVTLR LPSYMVGKRE FSCVALEKEE VEQAVLDAGF DIEQLLHSPQ
     SYSVTNAANN GVCFIVARKK PGP
//