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Protein

Indolethylamine N-methyltransferase

Gene

INMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Functions as thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide. Plays an important role in the detoxification of selenium compounds (By similarity). Catalyzes the N-methylation of tryptamine and structurally related compounds.By similarity1 Publication

Catalytic activityi

S-adenosyl-L-methionine + an amine = S-adenosyl-L-homocysteine + a methylated amine.1 Publication
S-adenosyl-L-methionine + dimethyl sulfide = S-adenosyl-L-homocysteine + trimethylsulfonium.1 Publication

Kineticsi

  1. KM=2.9 mM for tryptamine1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei20S-adenosyl-L-methionine1
    Binding sitei25S-adenosyl-L-methionine1
    Binding sitei63S-adenosyl-L-methionine; via carbonyl oxygen1
    Binding sitei69S-adenosyl-L-methionine1
    Binding sitei90S-adenosyl-L-methionine1
    Binding sitei163S-adenosyl-L-methionine; via carbonyl oxygen1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionMethyltransferase, Transferase
    Biological processDetoxification
    LigandS-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciMetaCyc:HS00305-MONOMER
    ReactomeiR-HSA-2408552 Methylation of MeSeH for excretion
    SABIO-RKiO95050

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Indolethylamine N-methyltransferase (EC:2.1.1.49, EC:2.1.1.96)
    Short name:
    Indolamine N-methyltransferase
    Alternative name(s):
    Aromatic alkylamine N-methyltransferase
    Short name:
    Amine N-methyltransferase
    Short name:
    Arylamine N-methyltransferase
    Thioether S-methyltransferase
    Short name:
    TEMT
    Gene namesi
    Name:INMT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000241644.2
    HGNCiHGNC:6069 INMT
    MIMi604854 gene
    neXtProtiNX_O95050

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi11185
    OpenTargetsiENSG00000241644
    PharmGKBiPA403

    Chemistry databases

    ChEMBLiCHEMBL2131

    Polymorphism and mutation databases

    BioMutaiINMT

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001597121 – 263Indolethylamine N-methyltransferaseAdd BLAST263

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei13N6-succinyllysineBy similarity1
    Modified residuei96N6-succinyllysineBy similarity1

    Proteomic databases

    PaxDbiO95050
    PeptideAtlasiO95050
    PRIDEiO95050
    ProteomicsDBi50633

    PTM databases

    iPTMnetiO95050
    PhosphoSitePlusiO95050

    Expressioni

    Tissue specificityi

    Widely expressed. The highest levels were in thyroid, adrenal gland, adult and fetal lung. Intermediate levels in heart, placenta, skeletal muscle, testis, small intestine, pancreas, stomach, spinal cord, lymph node and trachea. Very low levels in adult and fetal kidney and liver, in adult spleen, thymus, ovary, colon and bone marrow. Not expressed in peripheral blood leukocytes and brain.1 Publication

    Gene expression databases

    BgeeiENSG00000241644 Expressed in 142 organ(s), highest expression level in right lung
    CleanExiHS_INMT
    GenevisibleiO95050 HS

    Organism-specific databases

    HPAiHPA061343

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    KLHL12Q53G595EBI-10191038,EBI-740929

    Protein-protein interaction databases

    BioGridi116355, 1 interactor
    IntActiO95050, 2 interactors

    Chemistry databases

    BindingDBiO95050

    Structurei

    Secondary structure

    1263
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliO95050
    SMRiO95050
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO95050

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni85 – 87S-adenosyl-L-methionine binding3
    Regioni142 – 143S-adenosyl-L-methionine binding2

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG410IFTZ Eukaryota
    ENOG41128ZR LUCA
    GeneTreeiENSGT00390000011708
    HOGENOMiHOG000013229
    HOVERGENiHBG000797
    InParanoidiO95050
    KOiK00562
    OMAiAMECACC
    OrthoDBiEOG091G0EF7
    PhylomeDBiO95050
    TreeFamiTF313114

    Family and domain databases

    InterProiView protein in InterPro
    IPR025820 NNMT/PNMT/TEMT_CS
    IPR000940 NNMT_TEMT_trans
    IPR029063 SAM-dependent_MTases
    PANTHERiPTHR10867 PTHR10867, 1 hit
    PfamiView protein in Pfam
    PF01234 NNMT_PNMT_TEMT, 1 hit
    PIRSFiPIRSF000384 PNMTase, 1 hit
    SUPFAMiSSF53335 SSF53335, 1 hit
    PROSITEiView protein in PROSITE
    PS01100 NNMT_PNMT_TEMT, 1 hit
    PS51681 SAM_MT_NNMT_PNMT_TEMT, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
    Isoform 1 (identifier: O95050-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MKGGFTGGDE YQKHFLPRDY LATYYSFDGS PSPEAEMLKF NLECLHKTFG
    60 70 80 90 100
    PGGLQGDTLI DIGSGPTIYQ VLAACDSFQD ITLSDFTDRN REELEKWLKK
    110 120 130 140 150
    EPGAYDWTPA VKFACELEGN SGRWEEKEEK LRAAVKRVLK CDVHLGNPLA
    160 170 180 190 200
    PAVLPLADCV LTLLAMECAC CSLDAYRAAL CNLASLLKPG GHLVTTVTLR
    210 220 230 240 250
    LPSYMVGKRE FSCVALEKEE VEQAVLDAGF DIEQLLHSPQ SYSVTNAANN
    260
    GVCFIVARKK PGP
    Length:263
    Mass (Da):28,891
    Last modified:November 13, 2007 - v3
    Checksum:i12B3AC66597E70A3
    GO
    Isoform 2 (identifier: O95050-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         52-52: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:262
    Mass (Da):28,834
    Checksum:i0DEF8C52DEFE814B
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti75C → F in AK313832 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_03699128D → N1 PublicationCorresponds to variant dbSNP:rs4723010Ensembl.1
    Natural variantiVAR_011616205M → V1 PublicationCorresponds to variant dbSNP:rs2302339Ensembl.1
    Natural variantiVAR_061373214V → M. Corresponds to variant dbSNP:rs56800285Ensembl.1
    Natural variantiVAR_011617219E → G3 PublicationsCorresponds to variant dbSNP:rs2302340Ensembl.1
    Natural variantiVAR_036992246N → S. Corresponds to variant dbSNP:rs6970210Ensembl.1
    Natural variantiVAR_036993254F → C1 PublicationCorresponds to variant dbSNP:rs4720015Ensembl.1
    Natural variantiVAR_036994258R → H. Corresponds to variant dbSNP:rs6970605Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_04592252Missing in isoform 2. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF128846 mRNA Translation: AAF18304.1
    AF128847 mRNA Translation: AAF18305.1
    AF128848 Genomic DNA Translation: AAF18306.1
    AK313832 mRNA No translation available.
    AC004976 Genomic DNA No translation available.
    AC006022 Genomic DNA Translation: AAD04723.1
    BC033813 mRNA Translation: AAH33813.1
    BC106902 mRNA Translation: AAI06903.1
    BC106903 mRNA Translation: AAI06904.1
    AB041362 Genomic DNA Translation: BAA94451.1
    CCDSiCCDS5430.1 [O95050-1]
    CCDS56479.1 [O95050-2]
    RefSeqiNP_001186148.1, NM_001199219.1 [O95050-2]
    NP_006765.4, NM_006774.4 [O95050-1]
    UniGeneiHs.632629

    Genome annotation databases

    EnsembliENST00000013222; ENSP00000013222; ENSG00000241644 [O95050-1]
    ENST00000409539; ENSP00000386961; ENSG00000241644 [O95050-2]
    GeneIDi11185
    KEGGihsa:11185
    UCSCiuc003tbs.1 human [O95050-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF128846 mRNA Translation: AAF18304.1
    AF128847 mRNA Translation: AAF18305.1
    AF128848 Genomic DNA Translation: AAF18306.1
    AK313832 mRNA No translation available.
    AC004976 Genomic DNA No translation available.
    AC006022 Genomic DNA Translation: AAD04723.1
    BC033813 mRNA Translation: AAH33813.1
    BC106902 mRNA Translation: AAI06903.1
    BC106903 mRNA Translation: AAI06904.1
    AB041362 Genomic DNA Translation: BAA94451.1
    CCDSiCCDS5430.1 [O95050-1]
    CCDS56479.1 [O95050-2]
    RefSeqiNP_001186148.1, NM_001199219.1 [O95050-2]
    NP_006765.4, NM_006774.4 [O95050-1]
    UniGeneiHs.632629

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2A14X-ray1.70A1-263[»]
    ProteinModelPortaliO95050
    SMRiO95050
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116355, 1 interactor
    IntActiO95050, 2 interactors

    Chemistry databases

    BindingDBiO95050
    ChEMBLiCHEMBL2131

    PTM databases

    iPTMnetiO95050
    PhosphoSitePlusiO95050

    Polymorphism and mutation databases

    BioMutaiINMT

    Proteomic databases

    PaxDbiO95050
    PeptideAtlasiO95050
    PRIDEiO95050
    ProteomicsDBi50633

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000013222; ENSP00000013222; ENSG00000241644 [O95050-1]
    ENST00000409539; ENSP00000386961; ENSG00000241644 [O95050-2]
    GeneIDi11185
    KEGGihsa:11185
    UCSCiuc003tbs.1 human [O95050-1]

    Organism-specific databases

    CTDi11185
    DisGeNETi11185
    EuPathDBiHostDB:ENSG00000241644.2
    GeneCardsiINMT
    HGNCiHGNC:6069 INMT
    HPAiHPA061343
    MIMi604854 gene
    neXtProtiNX_O95050
    OpenTargetsiENSG00000241644
    PharmGKBiPA403
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410IFTZ Eukaryota
    ENOG41128ZR LUCA
    GeneTreeiENSGT00390000011708
    HOGENOMiHOG000013229
    HOVERGENiHBG000797
    InParanoidiO95050
    KOiK00562
    OMAiAMECACC
    OrthoDBiEOG091G0EF7
    PhylomeDBiO95050
    TreeFamiTF313114

    Enzyme and pathway databases

    BioCyciMetaCyc:HS00305-MONOMER
    ReactomeiR-HSA-2408552 Methylation of MeSeH for excretion
    SABIO-RKiO95050

    Miscellaneous databases

    EvolutionaryTraceiO95050
    GenomeRNAii11185
    PROiPR:O95050
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000241644 Expressed in 142 organ(s), highest expression level in right lung
    CleanExiHS_INMT
    GenevisibleiO95050 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR025820 NNMT/PNMT/TEMT_CS
    IPR000940 NNMT_TEMT_trans
    IPR029063 SAM-dependent_MTases
    PANTHERiPTHR10867 PTHR10867, 1 hit
    PfamiView protein in Pfam
    PF01234 NNMT_PNMT_TEMT, 1 hit
    PIRSFiPIRSF000384 PNMTase, 1 hit
    SUPFAMiSSF53335 SSF53335, 1 hit
    PROSITEiView protein in PROSITE
    PS01100 NNMT_PNMT_TEMT, 1 hit
    PS51681 SAM_MT_NNMT_PNMT_TEMT, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiINMT_HUMAN
    AccessioniPrimary (citable) accession number: O95050
    Secondary accession number(s): B8ZZ69
    , Q3KP49, Q9P1Y2, Q9UBY4, Q9UHQ0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 13, 2007
    Last modified: November 7, 2018
    This is version 150 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
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