LOCUS       NM_006895               3132 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens histamine N-methyltransferase (HNMT), transcript
            variant 1, mRNA.
ACCESSION   NM_006895
VERSION     NM_006895.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3132)
  AUTHORS   Lu,Y., Dong,C.Z., Bao,D., Zhong,C., Liu,K., Chen,L., Wang,W. and
            Yang,B.
  TITLE     The Thr105Ile Variant (rs11558538) of the Histamine
            N-methyltransferase Gene may be associated with Reduced Risk of
            Parkinson Disease: A Meta-analysis
  JOURNAL   Genet Test Mol Biomarkers 26 (11), 543-549 (2022)
   PUBMED   36378841
  REMARK    GeneRIF: The Thr105Ile Variant (rs11558538) of the Histamine
            N-methyltransferase Gene may be associated with Reduced Risk of
            Parkinson Disease: A Meta-analysis.
REFERENCE   2  (bases 1 to 3132)
  AUTHORS   Kuo,K.T., Lin,C.H., Wang,C.H., Pikatan,N.W., Yadav,V.K., Fong,I.H.,
            Yeh,C.T., Lee,W.H. and Huang,W.C.
  TITLE     HNMT Upregulation Induces Cancer Stem Cell Formation and Confers
            Protection against Oxidative Stress through Interaction with HER2
            in Non-Small-Cell Lung Cancer
  JOURNAL   Int J Mol Sci 23 (3), 1663 (2022)
   PUBMED   35163585
  REMARK    GeneRIF: HNMT Upregulation Induces Cancer Stem Cell Formation and
            Confers Protection against Oxidative Stress through Interaction
            with HER2 in Non-Small-Cell Lung Cancer.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3132)
  AUTHORS   Flores-Clemente,C., Nicolas-Vazquez,M.I., Mera Jimenez,E. and
            Hernandez-Rodriguez,M.
  TITLE     Inhibition of Astrocytic Histamine N-Methyltransferase as a
            Possible Target for the Treatment of Alzheimer's Disease
  JOURNAL   Biomolecules 11 (10), 1408 (2021)
   PUBMED   34680041
  REMARK    GeneRIF: Inhibition of Astrocytic Histamine N-Methyltransferase as
            a Possible Target for the Treatment of Alzheimer's Disease.
            Review article
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3132)
  AUTHORS   Chen,Y., Cao,B., Ou,R., Wei,Q., Chen,X., Zhao,B., Wu,Y., Song,W.
            and Shang,H.F.
  TITLE     Determining the Effect of the HNMT, STK39, and NMD3 Polymorphisms
            on the Incidence of Parkinson's Disease, Amyotrophic Lateral
            Sclerosis, and Multiple System Atrophy in Chinese Populations
  JOURNAL   J Mol Neurosci 64 (4), 574-580 (2018)
   PUBMED   29564728
  REMARK    GeneRIF: NHMT polymorphisms are not associated with Parkinson's
            disease, ALS and multiple system atrophy in Chinese population.
REFERENCE   5  (bases 1 to 3132)
  AUTHORS   Jia,H.Z., Liu,S.L., Zou,Y.F., Chen,X.F., Yu,L., Wan,J., Zhang,H.Y.,
            Chen,Q., Xiong,Y., Yu,B. and Zhang,W.
  TITLE     MicroRNA-223 is involved in the pathogenesis of atopic dermatitis
            by affecting histamine-N-methyltransferase
  JOURNAL   Cell Mol Biol (Noisy-le-grand) 64 (3), 103-107 (2018)
   PUBMED   29506638
  REMARK    GeneRIF: miR-223 participates in the pathogenesis of atopic
            dermatitis through upregulating HNMT indirectly to degrade the
            excessive histamine.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3132)
  AUTHORS   Yan,L., Galinsky,R.E., Bernstein,J.A., Liggett,S.B. and
            Weinshilboum,R.M.
  TITLE     Histamine N-methyltransferase pharmacogenetics: association of a
            common functional polymorphism with asthma
  JOURNAL   Pharmacogenetics 10 (3), 261-266 (2000)
   PUBMED   10803682
REFERENCE   7  (bases 1 to 3132)
  AUTHORS   Preuss,C.V., Wood,T.C., Szumlanski,C.L., Raftogianis,R.B.,
            Otterness,D.M., Girard,B., Scott,M.C. and Weinshilboum,R.M.
  TITLE     Human histamine N-methyltransferase pharmacogenetics: common
            genetic polymorphisms that alter activity
  JOURNAL   Mol Pharmacol 53 (4), 708-717 (1998)
   PUBMED   9547362
REFERENCE   8  (bases 1 to 3132)
  AUTHORS   Aksoy,S., Raftogianis,R. and Weinshilboum,R.
  TITLE     Human histamine N-methyltransferase gene: structural
            characterization and chromosomal location
  JOURNAL   Biochem Biophys Res Commun 219 (2), 548-554 (1996)
   PUBMED   8605025
REFERENCE   9  (bases 1 to 3132)
  AUTHORS   Yamauchi,K., Sekizawa,K., Suzuki,H., Nakazawa,H., Ohkawara,Y.,
            Katayose,D., Ohtsu,H., Tamura,G., Shibahara,S., Takemura,M. et al.
  TITLE     Structure and function of human histamine N-methyltransferase:
            critical enzyme in histamine metabolism in airway
  JOURNAL   Am J Physiol 267 (3 Pt 1), L342-L349 (1994)
   PUBMED   7943261
REFERENCE   10 (bases 1 to 3132)
  AUTHORS   Girard,B., Otterness,D.M., Wood,T.C., Honchel,R., Wieben,E.D. and
            Weinshilboum,R.M.
  TITLE     Human histamine N-methyltransferase pharmacogenetics: cloning and
            expression of kidney cDNA
  JOURNAL   Mol Pharmacol 45 (3), 461-468 (1994)
   PUBMED   8145732
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF523358.1, AF523360.1,
            AC093674.2 and AA935821.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_006895.2.
            
            Summary: In mammals, histamine is metabolized by two major
            pathways: N(tau)-methylation via histamine N-methyltransferase and
            oxidative deamination via diamine oxidase. This gene encodes the
            first enzyme which is found in the cytosol and uses
            S-adenosyl-L-methionine as the methyl donor. In the mammalian
            brain, the neurotransmitter activity of histamine is controlled by
            N(tau)-methylation as diamine oxidase is not found in the central
            nervous system. A common genetic polymorphism affects the activity
            levels of this gene product in red blood cells. Multiple
            alternatively spliced transcript variants that encode different
            proteins have been found for this gene. [provided by RefSeq, Jul
            2008].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and it encodes the longest protein (isoform 1).
            
            Sequence Note: The RefSeq transcript and protein were derived from
            transcript and genomic sequence to make the sequence consistent
            with the reference genome assembly. The genomic coordinates used
            for the transcript record were based on alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803611.114944.1,
                                           SRR1660805.150107.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000280097.5/ ENSP00000280097.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-943               AF523358.1         163-1105
            944-1425            AF523360.1         1106-1587
            1426-2906           AC093674.2         72161-73641
            2907-3132           AA935821.1         7-232               c
FEATURES             Location/Qualifiers
     source          1..3132
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q22.1"
     gene            1..3132
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /note="histamine N-methyltransferase"
                     /db_xref="GeneID:3176"
                     /db_xref="HGNC:HGNC:5028"
                     /db_xref="MIM:605238"
     exon            1..156
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /inference="alignment:Splign:2.1.0"
     CDS             20..898
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /EC_number="2.1.1.8"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /codon_start=1
                     /product="histamine N-methyltransferase isoform 1"
                     /protein_id="NP_008826.1"
                     /db_xref="CCDS:CCDS2181.1"
                     /db_xref="GeneID:3176"
                     /db_xref="HGNC:HGNC:5028"
                     /db_xref="MIM:605238"
                     /translation="MASSMRSLFSDHGKYVESFRRFLNHSTEHQCMQEFMDKKLPGII
                     GRIGDTKSEIKILSIGGGAGEIDLQILSKVQAQYPGVCINNEVVEPSAEQIAKYKELV
                     AKTSNLENVKFAWHKETSSEYQSRMLEKKELQKWDFIHMIQMLYYVKDIPATLKFFHS
                     LLGTNAKMLIIVVSGSSGWDKLWKKYGSRFPQDDLCQYITSDDLTQMLDNLGLKYECY
                     DLLSTMDISDCFIDGNENGDLLWDFLTETCNFNATAPPDLRAELGKDLQEPEFSAKKE
                     GKVLFNNTLSFIVIEA"
     exon            157..209
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /inference="alignment:Splign:2.1.0"
     exon            210..317
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /inference="alignment:Splign:2.1.0"
     exon            318..448
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /inference="alignment:Splign:2.1.0"
     exon            449..542
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /inference="alignment:Splign:2.1.0"
     exon            543..3132
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1403..1408
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /note="hexamer: ATTAAA"
     polyA_site      1426
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /note="major polyA site"
     regulatory      3002..3007
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /note="hexamer: AGTAAA"
     polyA_site      3024
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
     regulatory      3096..3101
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /note="hexamer: AATAAA"
     polyA_site      3132
                     /gene="HNMT"
                     /gene_synonym="HMT; HNMT-S1; HNMT-S2; MRT51"
                     /note="major polyA site"
ORIGIN      
        1 ctttctcaga aaaccaaata tggcatcttc catgaggagc ttgttttctg accacgggaa
       61 atatgttgaa tctttccgga ggtttctcaa ccattccacg gaacaccagt gcatgcagga
      121 attcatggac aagaagctgc caggcataat aggaaggatt ggagacacaa aatcagaaat
      181 taagattcta agcataggcg gaggtgcagg tgaaattgat cttcaaattc tctccaaagt
      241 tcaggctcaa tacccaggag tttgtatcaa caatgaagtt gttgagccaa gtgctgaaca
      301 aattgccaaa tacaaagagc ttgtagccaa gacatcgaac ctcgagaacg taaagtttgc
      361 ttggcataag gagacatcat ctgaatacca aagtagaatg ttggagaaaa aggagcttca
      421 aaagtgggac tttattcata tgattcaaat gctgtattat gtaaaagaca tcccagctac
      481 cctgaaattc ttccatagtc tcttaggtac caatgctaag atgctcatta ttgttgtgtc
      541 aggaagcagt ggctgggaca agctgtggaa aaagtacgga tcacgctttc cccaggatga
      601 cctctgccag tatatcacat cagatgacct cactcagatg ctggacaacc tagggcttaa
      661 gtatgagtgc tatgaccttt tgtccaccat ggatatatct gactgcttta ttgatggtaa
      721 tgaaaatgga gacctgcttt gggatttttt gactgaaacc tgcaacttta atgccacagc
      781 accacctgat ctcagagcag agcttgggaa agatctacaa gagcctgaat ttagtgctaa
      841 gaaagagggg aaggttcttt ttaataatac tctgagtttc atagtgattg aggcataact
      901 atcaatcaca aaagtatatt caaaaattat attttgaaca actcgaatca ctcatttatt
      961 tccatattaa aatcacaaac tcatccatta atgtagataa agcactgttt ggatatgaga
     1021 tgtagcaaat tccaatacat tattggactt ccatttggaa tcatatggga tactgctggt
     1081 cttatcctgt ccctcctcca ggtagagaga ccacaagcag gctcaacata acataagcta
     1141 gaaaaattag atgactgaat ttctatggca tattgataat aaaattcatt ccatttgctg
     1201 attgtctgaa attttctaga atactaataa aatacatact atagattctt tattagtgaa
     1261 gtatgcacta atcaatactt tgaacacaaa gcctgtgtta ctgatttggc cgttttgtga
     1321 agaaacattt atctttgtac gttcttctat tgtgctttct atctaatttt tattaatttg
     1381 taagagtaag cacctttaga atattaaaaa ttaattcttt atcacatgtt gtcatttctt
     1441 cccattgtgt tttctcttgt aattttatct gtgaattaat agctttttgt ttgtcttttt
     1501 gatatactga agttttctat tatattcagc cagatttttt tttaagtctc ggcttctgat
     1561 acattttaaa agaccttcta aaaccaaggt tttagaatac taacatttta tcaaaataat
     1621 attatagttt tgcttttttt aaaaaatgaa atctttacta tgtttgaaat ttagataagt
     1681 ataaacagtg agaacaaact gtttcccctc aaaataatag ccagatgtat aaacaaaatt
     1741 tattgaagaa caaagaaaca caaaactaaa cctgttctag cttaaaatgc agcttttacc
     1801 agatttctag gaattgggta aatgcaaggt tctagaaaac cttcaatgca ttttgatact
     1861 ttatagtttc ttatgtcact ctcaagaact cctataagac caagagtcat ctttggactg
     1921 taggatttca ggggggtttt gaaaacaaat ttgatgtttc ttatttttaa taataacgct
     1981 ctgttatttt tgacataaac agtacattta ataattaata aataaatatt ttaagtatgt
     2041 aaataattag tactccctgt cacaaacaaa acaaaagtaa ggttttacta aacagctcat
     2101 gagccctcat tctgccagtg aggaagcctt caaccccgtg tgatactcac tctttcatgc
     2161 aatagggctt ccatgtaatg ttgccgtata atcactttaa aaagttaaac gacccatctc
     2221 aatcacctag tttatcccca gggaatacac tggcatagag agcctattta cactaataaa
     2281 ctaccaagct ttgttgttca taataagtaa aatggacttg cattgctctc ttttttggac
     2341 aacttcatca atgctttttg aattatatgt ttcaacaaat gaaacgacag ttatccaatc
     2401 agattcctga aaatgaacac tgaaccgtta atcatactga tatgtactac tgacaaagga
     2461 aatctgtgag gcacacatga ttgatgggta tggggccatg aagaccttga agagcttcac
     2521 cagaagtatg gaaatcaaga ctttacagag tcttttgtat aaagcacacg tgcaaaaaca
     2581 aacaaaatta gaactaacaa tgctattgaa agatacaaaa gaattgcagt ccatagattg
     2641 gtgtttgtaa atatggcctt tttctcgtcc ttattaaacc cttagtatac aaggataaat
     2701 aaattctcac ctgcttaatt ttagtgcaat tgaaacacat aagccttttt aaagagagaa
     2761 attcccatga aaacctacta gtcagcaatg ggaagttgta taaattcaag ggataaacct
     2821 atccctgttt tcttcctgca ctgtatgata ataccaaaat ttgggacagt cacatactaa
     2881 cttttcagat ttgttcttgt gtttcagaaa aaagtgctca gcatgaattt ggaatgttgt
     2941 tttatgtatt gttgtggatc tctcagtgtt taacatggtg ccttgcatat ggtaaatgct
     3001 aagtaaagcg ggatcaatga attatttcct tctcaaacat ttatcttata ccttgtgtgt
     3061 tcatattatt attataaaca gagctcaaga aacccaataa agttatgtgt tgccagtgta
     3121 aaccttaact ta
//
