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O95050 (INMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Indolethylamine N-methyltransferase

Short name=Indolamine N-methyltransferase
EC=2.1.1.49
EC=2.1.1.96
Alternative name(s):
Aromatic alkylamine N-methyltransferase
Short name=Amine N-methyltransferase
Short name=Arylamine N-methyltransferase
Thioether S-methyltransferase
Short name=TEMT
Gene names
Name:INMT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length263 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Catalytic activity

S-adenosyl-L-methionine + an amine = S-adenosyl-L-homocysteine + a methylated amine. Ref.1

S-adenosyl-L-methionine + dimethyl sulfide = S-adenosyl-L-homocysteine + trimethylsulfonium. Ref.1

Subunit structure

Monomer By similarity.

Subcellular location

Cytoplasm By similarity.

Tissue specificity

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. Ref.1

Sequence similarities

Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.

Biophysicochemical properties

Kinetic parameters:

KM=2.9 mM for tryptamine Ref.1

Ontologies

Keywords
   Biological processDetoxification
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandS-adenosyl-L-methionine
   Molecular functionMethyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processamine metabolic process

Inferred from direct assay Ref.1. Source: UniProtKB

methylation

Inferred from direct assay Ref.1. Source: UniProtKB

response to toxic substance

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionamine N-methyltransferase activity

Inferred from direct assay Ref.1. Source: UniProtKB

thioether S-methyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95050-1)

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.
Isoform 2 (identifier: O95050-2)

The sequence of this isoform differs from the canonical sequence as follows:
     52-52: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 263263Indolethylamine N-methyltransferase
PRO_0000159712

Regions

Region85 – 873S-adenosyl-L-methionine binding
Region142 – 1432S-adenosyl-L-methionine binding

Sites

Binding site201S-adenosyl-L-methionine
Binding site251S-adenosyl-L-methionine
Binding site631S-adenosyl-L-methionine; via carbonyl oxygen
Binding site691S-adenosyl-L-methionine
Binding site901S-adenosyl-L-methionine
Binding site1631S-adenosyl-L-methionine; via carbonyl oxygen

Amino acid modifications

Modified residue131N6-succinyllysine By similarity
Modified residue961N6-succinyllysine By similarity

Natural variations

Alternative sequence521Missing in isoform 2.
VSP_045922
Natural variant281D → N. Ref.4
Corresponds to variant rs4723010 [ dbSNP | Ensembl ].
VAR_036991
Natural variant2051M → V. Ref.1
Corresponds to variant rs2302339 [ dbSNP | Ensembl ].
VAR_011616
Natural variant2141V → M.
Corresponds to variant rs56800285 [ dbSNP | Ensembl ].
VAR_061373
Natural variant2191E → G. Ref.1 Ref.2 Ref.4
Corresponds to variant rs2302340 [ dbSNP | Ensembl ].
VAR_011617
Natural variant2461N → S.
Corresponds to variant rs6970210 [ dbSNP | Ensembl ].
VAR_036992
Natural variant2541F → C. Ref.2
Corresponds to variant rs4720015 [ dbSNP | Ensembl ].
VAR_036993
Natural variant2581R → H.
Corresponds to variant rs6970605 [ dbSNP | Ensembl ].
VAR_036994

Experimental info

Sequence conflict751C → F in AK313832. Ref.2

Secondary structure

.............................................. 263
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 13, 2007. Version 3.
Checksum: 12B3AC66597E70A3

FASTA26328,891
        10         20         30         40         50         60 
MKGGFTGGDE YQKHFLPRDY LATYYSFDGS PSPEAEMLKF NLECLHKTFG PGGLQGDTLI 

        70         80         90        100        110        120 
DIGSGPTIYQ VLAACDSFQD ITLSDFTDRN REELEKWLKK EPGAYDWTPA VKFACELEGN 

       130        140        150        160        170        180 
SGRWEEKEEK LRAAVKRVLK CDVHLGNPLA PAVLPLADCV LTLLAMECAC CSLDAYRAAL 

       190        200        210        220        230        240 
CNLASLLKPG GHLVTTVTLR LPSYMVGKRE FSCVALEKEE VEQAVLDAGF DIEQLLHSPQ 

       250        260 
SYSVTNAANN GVCFIVARKK PGP 

« Hide

Isoform 2 [UniParc].

Checksum: 0DEF8C52DEFE814B
Show »

FASTA26228,834

References

« Hide 'large scale' references
[1]"Human indolethylamine N-methyltransferase: cDNA cloning and expression, gene cloning, and chromosomal localization."
Thompson M.A., Moon E., Kim U.-J., Xu J., Siciliano M.J., Weinshilboum R.M.
Genomics 61:285-297(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS VAL-205 AND GLY-219, CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
Tissue: Placenta and Skeletal muscle.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS GLY-219 AND CYS-254.
Tissue: Lung.
[3]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ASN-28 AND GLY-219.
Tissue: Lung and Spleen.
[5]"Human-specific amino acid changes found in 103 protein-coding genes."
Kitano T., Liu Y.-H., Ueda S., Saitou N.
Mol. Biol. Evol. 21:936-944(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-12.
[6]"The crystal structure of human indolethylamine N-methyltransferase in complex with SAH."
Structural genomics consortium (SGC)
Submitted (JUN-2005) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS5430.1. [O95050-1]
CCDS56479.1. [O95050-2]
RefSeqNP_001186148.1. NM_001199219.1. [O95050-2]
NP_006765.4. NM_006774.4. [O95050-1]
UniGeneHs.632629.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2A14X-ray1.70A1-263[»]
ProteinModelPortalO95050.
SMRO95050. Positions 5-261.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000013222.

Chemistry

BindingDBO95050.
ChEMBLCHEMBL2131.

PTM databases

PhosphoSiteO95050.

Proteomic databases

PaxDbO95050.
PRIDEO95050.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000013222; ENSP00000013222; ENSG00000241644. [O95050-1]
ENST00000409539; ENSP00000386961; ENSG00000241644. [O95050-2]
GeneID11185.
KEGGhsa:11185.
UCSCuc003tbs.1. human. [O95050-1]

Organism-specific databases

CTD11185.
GeneCardsGC07P030737.
HGNCHGNC:6069. INMT.
HPAHPA055180.
MIM604854. gene.
neXtProtNX_O95050.
PharmGKBPA403.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG71857.
HOGENOMHOG000013229.
HOVERGENHBG000797.
InParanoidO95050.
KOK00562.
OMAAMECACC.
OrthoDBEOG7673B9.
PhylomeDBO95050.
TreeFamTF313114.

Enzyme and pathway databases

BioCycMetaCyc:HS00305-MONOMER.

Gene expression databases

ArrayExpressO95050.
BgeeO95050.
CleanExHS_INMT.
GenevestigatorO95050.

Family and domain databases

Gene3D3.40.50.150. 1 hit.
InterProIPR025817. Amine_MeTrfase.
IPR025820. NNMT/PNMT/TEMT_CS.
IPR000940. NNMT_TEMT_trans.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PANTHERPTHR10867. PTHR10867. 1 hit.
PfamPF01234. NNMT_PNMT_TEMT. 1 hit.
[Graphical view]
PIRSFPIRSF000384. PNMTase. 1 hit.
SUPFAMSSF53335. SSF53335. 1 hit.
PROSITEPS01100. NNMT_PNMT_TEMT. 1 hit.
PS51681. SAM_MT_NNMT_PNMT_TEMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO95050.
GenomeRNAi11185.
NextBio42567.
PROO95050.
SOURCESearch...

Entry information

Entry nameINMT_HUMAN
AccessionPrimary (citable) accession number: O95050
Secondary accession number(s): B8ZZ69 expand/collapse secondary AC list , Q3KP49, Q9P1Y2, Q9UBY4, Q9UHQ0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 13, 2007
Last modified: July 9, 2014
This is version 119 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM