HNMT_HUMAN
ID HNMT_HUMAN Reviewed; 292 AA.
AC P50135; B2R9J3; Q546Z6; Q7Z7I2; Q8IU56; Q8WW98; Q9BRW6;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Histamine N-methyltransferase;
DE Short=HMT;
DE EC=2.1.1.8 {ECO:0000269|PubMed:26206890};
GN Name=HNMT;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=7943261; DOI=10.1152/ajplung.1994.267.3.l342;
RA Yamauchi K., Sekizawa K., Suzuki H., Nakazawa H., Ohkawara Y., Katayose D.,
RA Ohtsu H., Tamura G., Shibahara S., Takemura M.;
RT "Structure and function of human histamine N-methyltransferase: critical
RT enzyme in histamine metabolism in airway.";
RL Am. J. Physiol. 267:L342-L349(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=8145732;
RA Girard B., Otterness D.M., Wood T.C., Honchel R., Wieben E.D.,
RA Weinshilboum R.M.;
RT "Human histamine N-methyltransferase pharmacogenetics: cloning and
RT expression of kidney cDNA.";
RL Mol. Pharmacol. 45:461-468(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8605025; DOI=10.1006/bbrc.1996.0271;
RA Aksoy S., Raftogianis R., Weinshilboum R.M.;
RT "Human histamine N-methyltransferase gene: structural characterization and
RT chromosomal location.";
RL Biochem. Biophys. Res. Commun. 219:548-554(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Barnes W.G., Grinde E., Crawford D.R., Herrick-Davis K., Hough L.B.;
RT "Further characterization of the histamine N-methyltransferase gene: a new
RT mRNA species and several 3'-UTR Variants from human brain.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Brain;
RX PubMed=14667820; DOI=10.1016/s0888-7543(03)00236-2;
RA Barnes W.G., Grinde E., Crawford D.R., Herrick-Davis K., Hough L.B.;
RT "Characterization of a new mRNA species from the human histamine N-
RT methyltransferase gene.";
RL Genomics 83:168-171(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Liver, and Prostate;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-221.
RA Thomae B., Wieben E., Eckloff B., Weinshilboum R.M.;
RT "Homo sapiens histamine N-methyltransferase (HNMT) gene, consensus of
RT Coriell PDR 90.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [11]
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., Buerckstuemmer T.,
RA 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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATES AND
RP INHIBITOR.
RX PubMed=11566133; DOI=10.1016/s0969-2126(01)00643-8;
RA Horton J.R., Sawada K., Nishibori M., Zhang X., Cheng X.;
RT "Two polymorphic forms of human histamine methyltransferase: structural,
RT thermal, and kinetic comparisons.";
RL Structure 9:837-849(2001).
RN [14]
RP VARIANT ILE-105, AND POLYMORPHISM.
RX PubMed=9547362; DOI=10.1124/mol.53.4.708;
RA Preuss C.V., Wood T.C., Szumlanski C.L., Raftogianis R.B., Otterness D.M.,
RA Girard B., Scott M.C., Weinshilboum R.M.;
RT "Human histamine N-methyltransferase pharmacogenetics: common genetic
RT polymorphisms that alter activity.";
RL Mol. Pharmacol. 53:708-717(1998).
RN [15]
RP VARIANT ILE-105, AND POLYMORPHISM.
RX PubMed=10803682; DOI=10.1097/00008571-200004000-00007;
RA Yan L., Galinsky R.E., Bernstein J.A., Liggett S.B., Weinshilboum R.M.;
RT "Histamine N-methyltransferase pharmacogenetics: association of a common
RT functional polymorphism with asthma.";
RL Pharmacogenetics 10:261-266(2000).
RN [16]
RP INVOLVEMENT IN MRT51, VARIANTS MRT51 ASP-60 AND PRO-208, CHARACTERIZATION
RP OF VARIANTS MRT51 ASP-60 AND PRO-208, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX PubMed=26206890; DOI=10.1093/hmg/ddv286;
RA Heidari A., Tongsook C., Najafipour R., Musante L., Vasli N., Garshasbi M.,
RA Hu H., Mittal K., McNaughton A.J., Sritharan K., Hudson M., Stehr H.,
RA Talebi S., Moradi M., Darvish H., Arshad Rafiq M., Mozhdehipanah H.,
RA Rashidinejad A., Samiei S., Ghadami M., Windpassinger C.,
RA Gillessen-Kaesbach G., Tzschach A., Ahmed I., Mikhailov A.,
RA Stavropoulos D.J., Carter M.T., Keshavarz S., Ayub M., Najmabadi H.,
RA Liu X., Ropers H.H., Macheroux P., Vincent J.B.;
RT "Mutations in the histamine N-methyltransferase gene, HNMT, are associated
RT with nonsyndromic autosomal recessive intellectual disability.";
RL Hum. Mol. Genet. 24:5697-5710(2015).
CC -!- FUNCTION: Inactivates histamine by N-methylation. Plays an important
CC role in degrading histamine and in regulating the airway response to
CC histamine. {ECO:0000269|PubMed:26206890}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=histamine + S-adenosyl-L-methionine = H(+) + N(tau)-
CC methylhistamine + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:19301,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:58432,
CC ChEBI:CHEBI:58600, ChEBI:CHEBI:59789; EC=2.1.1.8;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00929,
CC ECO:0000269|PubMed:26206890};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.47 uM for histamine (at pH 8.0 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:26206890};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11566133}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26206890}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P50135-1; Sequence=Displayed;
CC Name=2; Synonyms=HNMT-S;
CC IsoId=P50135-2; Sequence=VSP_042027;
CC Name=3;
CC IsoId=P50135-3; Sequence=VSP_043482, VSP_043483;
CC -!- POLYMORPHISM: Variant Ile-105 has a reduced activity and seems to be
CC linked with a predisposition to asthma. {ECO:0000269|PubMed:10803682,
CC ECO:0000269|PubMed:9547362}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 51
CC (MRT51) [MIM:616739]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:26206890}. Note=The disease is caused by variants
CC affecting distinct genetic loci, including the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Has no histamine-methylating activity.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. HNMT family. {ECO:0000255|PROSITE-ProRule:PRU00929}.
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DR EMBL; D16224; BAA03752.1; -; mRNA.
DR EMBL; U08092; AAA17423.1; -; mRNA.
DR EMBL; U44111; AAB18137.1; -; Genomic_DNA.
DR EMBL; U44106; AAB18137.1; JOINED; Genomic_DNA.
DR EMBL; U44107; AAB18137.1; JOINED; Genomic_DNA.
DR EMBL; U44108; AAB18137.1; JOINED; Genomic_DNA.
DR EMBL; U44109; AAB18137.1; JOINED; Genomic_DNA.
DR EMBL; U44110; AAB18137.1; JOINED; Genomic_DNA.
DR EMBL; AF523358; AAN33016.1; -; mRNA.
DR EMBL; AF523359; AAN33017.1; -; mRNA.
DR EMBL; AF523360; AAN33018.1; -; mRNA.
DR EMBL; AF523356; AAN33014.1; -; mRNA.
DR EMBL; AF523357; AAN33015.1; -; mRNA.
DR EMBL; AK313804; BAG36540.1; -; mRNA.
DR EMBL; AC093674; AAY24212.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11612.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11613.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11614.1; -; Genomic_DNA.
DR EMBL; BC005907; AAH05907.1; -; mRNA.
DR EMBL; BC020677; AAH20677.1; -; mRNA.
DR EMBL; AH012839; AAP42155.1; -; Genomic_DNA.
DR CCDS; CCDS2181.1; -. [P50135-1]
DR CCDS; CCDS33296.1; -. [P50135-2]
DR CCDS; CCDS33297.1; -. [P50135-3]
DR PIR; G01409; G01409.
DR RefSeq; NP_001019245.1; NM_001024074.2. [P50135-3]
DR RefSeq; NP_001019246.1; NM_001024075.1. [P50135-2]
DR RefSeq; NP_008826.1; NM_006895.2. [P50135-1]
DR PDB; 1JQD; X-ray; 2.28 A; A/B=1-292.
DR PDB; 1JQE; X-ray; 1.91 A; A/B=1-292.
DR PDB; 2AOT; X-ray; 1.90 A; A/B=1-292.
DR PDB; 2AOU; X-ray; 2.30 A; A/B=1-292.
DR PDB; 2AOV; X-ray; 2.48 A; A/B=1-292.
DR PDB; 2AOW; X-ray; 2.97 A; A/B=1-292.
DR PDB; 2AOX; X-ray; 3.12 A; A/B=1-292.
DR PDBsum; 1JQD; -.
DR PDBsum; 1JQE; -.
DR PDBsum; 2AOT; -.
DR PDBsum; 2AOU; -.
DR PDBsum; 2AOV; -.
DR PDBsum; 2AOW; -.
DR PDBsum; 2AOX; -.
DR AlphaFoldDB; P50135; -.
DR SMR; P50135; -.
DR BioGRID; 109418; 8.
DR IntAct; P50135; 5.
DR STRING; 9606.ENSP00000280097; -.
DR BindingDB; P50135; -.
DR ChEMBL; CHEMBL2190; -.
DR DrugBank; DB00613; Amodiaquine.
DR DrugBank; DB13875; Harmaline.
DR DrugBank; DB05381; Histamine.
DR DrugBank; DB04655; Metoprine.
DR DrugBank; DB01103; Quinacrine.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR DrugBank; DB07106; SKF-91488.
DR DrugCentral; P50135; -.
DR iPTMnet; P50135; -.
DR PhosphoSitePlus; P50135; -.
DR BioMuta; HNMT; -.
DR DMDM; 1708272; -.
DR EPD; P50135; -.
DR jPOST; P50135; -.
DR MassIVE; P50135; -.
DR MaxQB; P50135; -.
DR PaxDb; P50135; -.
DR PeptideAtlas; P50135; -.
DR PRIDE; P50135; -.
DR ProteomicsDB; 56195; -. [P50135-1]
DR ProteomicsDB; 56196; -. [P50135-2]
DR ProteomicsDB; 56197; -. [P50135-3]
DR Antibodypedia; 33593; 313 antibodies from 32 providers.
DR DNASU; 3176; -.
DR Ensembl; ENST00000280096.5; ENSP00000280096.5; ENSG00000150540.14. [P50135-3]
DR Ensembl; ENST00000280097.5; ENSP00000280097.3; ENSG00000150540.14. [P50135-1]
DR Ensembl; ENST00000329366.8; ENSP00000333259.4; ENSG00000150540.14. [P50135-2]
DR Ensembl; ENST00000410115.5; ENSP00000386940.1; ENSG00000150540.14. [P50135-1]
DR Ensembl; ENST00000475675.5; ENSP00000419415.1; ENSG00000150540.14. [P50135-3]
DR GeneID; 3176; -.
DR KEGG; hsa:3176; -.
DR MANE-Select; ENST00000280097.5; ENSP00000280097.3; NM_006895.3; NP_008826.1.
DR UCSC; uc002tvd.4; human. [P50135-1]
DR CTD; 3176; -.
DR DisGeNET; 3176; -.
DR GeneCards; HNMT; -.
DR HGNC; HGNC:5028; HNMT.
DR HPA; ENSG00000150540; Tissue enhanced (liver).
DR MalaCards; HNMT; -.
DR MIM; 605238; gene.
DR MIM; 616739; phenotype.
DR neXtProt; NX_P50135; -.
DR OpenTargets; ENSG00000150540; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA190; -.
DR VEuPathDB; HostDB:ENSG00000150540; -.
DR eggNOG; ENOG502QQJ1; Eukaryota.
DR GeneTree; ENSGT00390000002862; -.
DR HOGENOM; CLU_058117_1_0_1; -.
DR InParanoid; P50135; -.
DR OMA; FSDHSRY; -.
DR OrthoDB; 870728at2759; -.
DR PhylomeDB; P50135; -.
DR TreeFam; TF331080; -.
DR BioCyc; MetaCyc:HS07674-MON; -.
DR BRENDA; 2.1.1.8; 2681.
DR PathwayCommons; P50135; -.
DR Reactome; R-HSA-2408508; Metabolism of ingested SeMet, Sec, MeSec into H2Se.
DR Reactome; R-HSA-70921; Histidine catabolism.
DR SABIO-RK; P50135; -.
DR SignaLink; P50135; -.
DR BioGRID-ORCS; 3176; 16 hits in 1084 CRISPR screens.
DR ChiTaRS; HNMT; human.
DR EvolutionaryTrace; P50135; -.
DR GenomeRNAi; 3176; -.
DR Pharos; P50135; Tchem.
DR PRO; PR:P50135; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P50135; protein.
DR Bgee; ENSG00000150540; Expressed in gall bladder and 203 other tissues.
DR Genevisible; P50135; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:ARUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0046539; F:histamine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0001695; P:histamine catabolic process; IDA:UniProtKB.
DR GO; GO:0001692; P:histamine metabolic process; IMP:ARUK-UCL.
DR GO; GO:0006548; P:histidine catabolic process; TAS:Reactome.
DR GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; TAS:ProtInc.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016673; HHMT-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PIRSF; PIRSF016616; HHMT; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51597; SAM_HNMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant;
KW Intellectual disability; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..292
FT /note="Histamine N-methyltransferase"
FT /id="PRO_0000084021"
FT BINDING 28
FT /ligand="substrate"
FT BINDING 60
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 89
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 94
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 120
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 283
FT /ligand="substrate"
FT VAR_SEQ 47..51
FT /note="IGDTK -> YQNCC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043482"
FT VAR_SEQ 52..292
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043483"
FT VAR_SEQ 64..292
FT /note="GEIDLQILSKVQAQYPGVCINNEVVEPSAEQIAKYKELVAKTSNLENVKFAW
FT HKETSSEYQSRMLEKKELQKWDFIHMIQMLYYVKDIPATLKFFHSLLGTNAKMLIIVVS
FT GSSGWDKLWKKYGSRFPQDDLCQYITSDDLTQMLDNLGLKYECYDLLSTMDISDCFIDG
FT NENGDLLWDFLTETCNFNATAPPDLRAELGKDLQEPEFSAKKEGKVLFNNTLSFIVIEA
FT -> DCLIRGSSRVLKRNSCFILCSTRQKDKPGMRIHDERSSELPFGAARLESKSAFPSF
FT LVSFILF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14667820"
FT /id="VSP_042027"
FT VARIANT 60
FT /note="G -> D (in MRT51; no effect on protein abundance; no
FT effect on protein localization to the cytoplasm; decreased
FT thermal stability; decreased ligand affinity for S-
FT adenosyl-L-methionine; loss of histamine N-
FT methyltransferase activity; dbSNP:rs758252808)"
FT /evidence="ECO:0000269|PubMed:26206890"
FT /id="VAR_076312"
FT VARIANT 105
FT /note="T -> I (in dbSNP:rs11558538)"
FT /evidence="ECO:0000269|PubMed:10803682,
FT ECO:0000269|PubMed:9547362"
FT /id="VAR_010252"
FT VARIANT 208
FT /note="L -> P (in MRT51; loss of protein solubility;
FT increased aggregation in the cytoplasm; dbSNP:rs745756308)"
FT /evidence="ECO:0000269|PubMed:26206890"
FT /id="VAR_076313"
FT CONFLICT 199
FT /note="I -> V (in Ref. 1; BAA03752)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="N -> D (in Ref. 9; AAH20677)"
FT /evidence="ECO:0000305"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 12..23
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:2AOT"
FT TURN 47..50
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 52..60
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 65..77
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 82..88
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 92..103
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 120..128
FT /evidence="ECO:0007829|PDB:2AOT"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 151..160
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 162..173
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:2AOW"
FT HELIX 178..186
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 201..211
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 215..220
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 235..245
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 250..253
FT /evidence="ECO:0007829|PDB:2AOT"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:2AOT"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 272..275
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:2AOT"
FT STRAND 285..291
FT /evidence="ECO:0007829|PDB:2AOT"
SQ SEQUENCE 292 AA; 33295 MW; 9CCADD1EE0CCB653 CRC64;
MASSMRSLFS DHGKYVESFR RFLNHSTEHQ CMQEFMDKKL PGIIGRIGDT KSEIKILSIG
GGAGEIDLQI LSKVQAQYPG VCINNEVVEP SAEQIAKYKE LVAKTSNLEN VKFAWHKETS
SEYQSRMLEK KELQKWDFIH MIQMLYYVKD IPATLKFFHS LLGTNAKMLI IVVSGSSGWD
KLWKKYGSRF PQDDLCQYIT SDDLTQMLDN LGLKYECYDL LSTMDISDCF IDGNENGDLL
WDFLTETCNF NATAPPDLRA ELGKDLQEPE FSAKKEGKVL FNNTLSFIVI EA
