INMT_HUMAN
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 03-AUG-2022, entry version 171.
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 AlphaFoldDB; O95050; -.
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; 150 antibodies from 21 providers.
DR DNASU; 11185; -.
DR Ensembl; ENST00000013222.5; ENSP00000013222.5; ENSG00000241644.2. [O95050-1]
DR Ensembl; ENST00000409539.1; ENSP00000386961.1; ENSG00000241644.2. [O95050-2]
DR GeneID; 11185; -.
DR KEGG; hsa:11185; -.
DR MANE-Select; ENST00000013222.5; ENSP00000013222.5; NM_006774.5; NP_006765.4.
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 VEuPathDB; HostDB:ENSG00000241644; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00390000011708; -.
DR HOGENOM; CLU_082526_2_0_1; -.
DR InParanoid; O95050; -.
DR OMA; CESFQDI; -.
DR OrthoDB; 1054662at2759; -.
DR PhylomeDB; O95050; -.
DR TreeFam; TF313114; -.
DR BioCyc; MetaCyc:HS00305-MON; -.
DR PathwayCommons; O95050; -.
DR Reactome; R-HSA-2408552; Methylation of MeSeH for excretion.
DR SABIO-RK; O95050; -.
DR SignaLink; O95050; -.
DR BioGRID-ORCS; 11185; 9 hits in 1075 CRISPR screens.
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 124 other tissues.
DR Genevisible; O95050; HS.
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 Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR025820; NNMT/PNMT/TEMT_CS.
DR InterPro; IPR000940; NNMT_TEMT_trans.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
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; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..263
FT /note="Indolethylamine N-methyltransferase"
FT /id="PRO_0000159712"
FT BINDING 20
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 25
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 63
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 69
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 85..87
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 90
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 142..143
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 163
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
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:0007829|PDB:2A14"
FT HELIX 17..24
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 33..49
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 56..63
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 78..86
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 88..99
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 108..117
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 124..134
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2A14"
FT TURN 148..151
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 166..169
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 173..184
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 187..200
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:2A14"
FT HELIX 218..227
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 230..238
FT /evidence="ECO:0007829|PDB:2A14"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:2A14"
FT STRAND 252..259
FT /evidence="ECO:0007829|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
