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 27-MAR-2024, entry version 199. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 13. DR IntAct; P50135; 6. DR MINT; P50135; -. 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; 9606-ENSP00000280097; -. DR PeptideAtlas; P50135; -. DR ProteomicsDB; 56195; -. [P50135-1] DR ProteomicsDB; 56196; -. [P50135-2] DR ProteomicsDB; 56197; -. [P50135-3] DR Pumba; P50135; -. DR Antibodypedia; 33593; 349 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 AGR; HGNC:5028; -. 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; LPQNDLC; -. DR OrthoDB; 5388438at2759; -. DR PhylomeDB; P50135; -. DR TreeFam; TF331080; -. DR BioCyc; MetaCyc:HS07674-MONOMER; -. 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; 17 hits in 1164 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 205 other cell types or tissues. 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 CDD; cd02440; AdoMet_MTases; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR016673; HHMT-like. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR Pfam; PF13489; Methyltransf_23; 1. DR PIRSF; PIRSF016616; HHMT; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51597; SAM_HNMT; 1. DR Genevisible; P50135; HS. 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 FT S-adenosyl-L-methionine; loss of histamine FT N-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 //