LOCUS       NM_017614               2603 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens betaine--homocysteine S-methyltransferase 2 (BHMT2),
            transcript variant 1, mRNA.
ACCESSION   NM_017614
VERSION     NM_017614.5
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 2603)
  AUTHORS   Luo,M., Wang,T., Huang,P., Zhang,S., Song,X., Sun,M., Liu,Y.,
            Wei,J., Shu,J., Zhong,T., Chen,Q., Zhu,P. and Qin,J.
  TITLE     Association of Maternal Betaine-Homocysteine Methyltransferase
            (BHMT) and BHMT2 Genes Polymorphisms with Congenital Heart Disease
            in Offspring
  JOURNAL   Reprod Sci 30 (1), 309-325 (2023)
   PUBMED   35835902
  REMARK    GeneRIF: Association of Maternal Betaine-Homocysteine
            Methyltransferase (BHMT) and BHMT2 Genes Polymorphisms with
            Congenital Heart Disease in Offspring.
REFERENCE   2  (bases 1 to 2603)
  AUTHORS   Wang,P., Wu,T., Schwender,H., Wang,H., Shi,B., Wang,Z.Q., Yuan,Y.,
            Liu,D.J., Wang,M.Y., Li,J., Zhou,Z.B., Zhu,H.P. and Beaty,T.H.
  TITLE     Evidence of interaction between genes in the folate/homocysteine
            metabolic pathway in controlling risk of non-syndromic oral cleft
  JOURNAL   Oral Dis 24 (5), 820-828 (2018)
   PUBMED   29356306
  REMARK    GeneRIF: Our study suggested markers in BHMT/BHMT2 and DMGDH might
            affect the risk of NSCL/P through pairwise interaction.
REFERENCE   3  (bases 1 to 2603)
  AUTHORS   Li,M., Li,J., Wei,C., Lu,Q., Tang,X., Erickson,S.W., MacLeod,S.L.
            and Hobbs,C.A.
  TITLE     A Three-Way Interaction among Maternal and Fetal Variants
            Contributing to Congenital Heart Defects
  JOURNAL   Ann Hum Genet 80 (1), 20-31 (2016)
   PUBMED   26612412
  REMARK    GeneRIF: A three-way interaction among maternal and fetal variants
            in BHMT2, GSTP1 and GPX3 contribute to congenital heart defects
REFERENCE   4  (bases 1 to 2603)
  AUTHORS   Ganu,R.S., Ishida,Y., Koutmos,M., Kolokotronis,S.O., Roca,A.L.,
            Garrow,T.A. and Schook,L.B.
  TITLE     Evolutionary Analyses and Natural Selection of Betaine-Homocysteine
            S-Methyltransferase (BHMT) and BHMT2 Genes
  JOURNAL   PLoS One 10 (7), e0134084 (2015)
   PUBMED   26213999
  REMARK    GeneRIF: The faster evolutionary rate of BHMT2 overall suggests
            that selective constraints were reduced relative to BHMT.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2603)
  AUTHORS   Tang,X., Cleves,M.A., Nick,T.G., Li,M., MacLeod,S.L.,
            Erickson,S.W., Li,J., Shaw,G.M., Mosley,B.S. and Hobbs,C.A.
  CONSRTM   National Birth Defects Prevention Study
  TITLE     Obstructive heart defects associated with candidate genes, maternal
            obesity, and folic acid supplementation
  JOURNAL   Am J Med Genet A 167 (6), 1231-1242 (2015)
   PUBMED   25846410
  REMARK    GeneRIF: Multiple SNPs in BHMT and BHMT2 were identified to be
            associated with the occurrence of infant obstructive heart defects
            and interaction effects with maternal use of folic acid
            supplements.
REFERENCE   6  (bases 1 to 2603)
  AUTHORS   Giusti,B., Sestini,I., Saracini,C., Sticchi,E., Bolli,P., Magi,A.,
            Gori,A.M., Marcucci,R., Gensini,G.F. and Abbate,R.
  TITLE     High-throughput multiplex single-nucleotide polymorphism (SNP)
            analysis in genes involved in methionine metabolism
  JOURNAL   Biochem Genet 46 (7-8), 406-423 (2008)
   PUBMED   18427977
  REMARK    GeneRIF: Observational study of genetic testing. (HuGE Navigator)
REFERENCE   7  (bases 1 to 2603)
  AUTHORS   Szegedi,S.S., Castro,C.C., Koutmos,M. and Garrow,T.A.
  TITLE     Betaine-homocysteine S-methyltransferase-2 is an
            S-methylmethionine-homocysteine methyltransferase
  JOURNAL   J Biol Chem 283 (14), 8939-8945 (2008)
   PUBMED   18230605
  REMARK    GeneRIF: Betaine-homocysteine S-methyltransferase-2 is an
            S-methylmethionine-homocysteine methyltransferase.
REFERENCE   8  (bases 1 to 2603)
  AUTHORS   Wang,A.G., Yoon,S.Y., Oh,J.H., Jeon,Y.J., Kim,M., Kim,J.M.,
            Byun,S.S., Yang,J.O., Kim,J.H., Kim,D.G., Yeom,Y.I., Yoo,H.S.,
            Kim,Y.S. and Kim,N.S.
  TITLE     Identification of intrahepatic cholangiocarcinoma related genes by
            comparison with normal liver tissues using expressed sequence tags
  JOURNAL   Biochem Biophys Res Commun 345 (3), 1022-1032 (2006)
   PUBMED   16712791
REFERENCE   9  (bases 1 to 2603)
  AUTHORS   Weisberg,I.S., Park,E., Ballman,K.V., Berger,P., Nunn,M., Suh,D.S.,
            Breksa,A.P. 3rd, Garrow,T.A. and Rozen,R.
  TITLE     Investigations of a common genetic variant in betaine-homocysteine
            methyltransferase (BHMT) in coronary artery disease
  JOURNAL   Atherosclerosis 167 (2), 205-214 (2003)
   PUBMED   12818402
  REMARK    GeneRIF: Hyperhomocysteinemia, a risk factor for coronary diseases,
            can be caused by genetic mutations in BHMT2 metabolism.
REFERENCE   10 (bases 1 to 2603)
  AUTHORS   Chadwick,L.H., McCandless,S.E., Silverman,G.L., Schwartz,S.,
            Westaway,D. and Nadeau,J.H.
  TITLE     Betaine-homocysteine methyltransferase-2: cDNA cloning, gene
            sequence, physical mapping, and expression of the human and mouse
            genes
  JOURNAL   Genomics 70 (1), 66-73 (2000)
   PUBMED   11087663
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CB140104.1, BC020665.1 and
            AC008502.8.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_017614.4.
            
            Summary: Homocysteine is a sulfur-containing amino acid that plays
            a crucial role in methylation reactions. Transfer of the methyl
            group from betaine to homocysteine creates methionine, which
            donates the methyl group to methylate DNA, proteins, lipids, and
            other intracellular metabolites. The protein encoded by this gene
            is one of two methyl transferases that can catalyze the transfer of
            the methyl group from betaine to homocysteine. Anomalies in
            homocysteine metabolism have been implicated in disorders ranging
            from vascular disease to neural tube birth defects such as spina
            bifida. Alternatively spliced transcript variants encoding
            different isoforms have been found for this gene. [provided by
            RefSeq, May 2010].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript 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 :: SRR1803611.205463.1,
                                           SRR1803612.275269.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000255192.8/ ENSP00000255192.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2                 CB140104.1         44-45
            3-1660              BC020665.1         1-1658
            1661-2603           AC008502.8         77763-78705
FEATURES             Location/Qualifiers
     source          1..2603
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q14.1"
     gene            1..2603
                     /gene="BHMT2"
                     /note="betaine--homocysteine S-methyltransferase 2"
                     /db_xref="GeneID:23743"
                     /db_xref="HGNC:HGNC:1048"
                     /db_xref="MIM:605932"
     exon            1..49
                     /gene="BHMT2"
                     /inference="alignment:Splign:2.1.0"
     CDS             17..1108
                     /gene="BHMT2"
                     /EC_number="2.1.1.10"
                     /note="isoform 1 is encoded by transcript variant 1;
                     betaine-homocysteine methyltransferase 2; SMM-hcy
                     methyltransferase; S-methylmethionine--homocysteine
                     S-methyltransferase BHMT2"
                     /codon_start=1
                     /product="S-methylmethionine--homocysteine
                     S-methyltransferase BHMT2 isoform 1"
                     /protein_id="NP_060084.2"
                     /db_xref="CCDS:CCDS4045.1"
                     /db_xref="GeneID:23743"
                     /db_xref="HGNC:HGNC:1048"
                     /db_xref="MIM:605932"
                     /translation="MAPAGRPGAKKGILERLESGEVVIGDGSFLITLEKRGYVKAGLW
                     TPEAVIEHPDAVRQLHMEFLRAGSNVMQTFTFSASEDNMESKWEDVNAAACDLAREVA
                     GKGDALVAGGICQTSIYKYQKDEARIKKLFRQQLEVFAWKNVDFLIAEYFEHVEEAVW
                     AVEVLKESDRPVAVTMCIGPEGDMHDITPGECAVRLVKAGASIVGVNCRFGPDTSLKT
                     MELMKEGLEWAGLKAHLMVQPLGFHAPDCGKEGFVDLPEYPFGLESRVATRWDIQKYA
                     REAYNLGVRYIGGCCGFEPYHIRAIAEELAPERGFLPPASEKHGSWGSGLDMHTKPWI
                     RARARREYWENLLPASGRPFCPSLSKPDF"
     exon            50..182
                     /gene="BHMT2"
                     /inference="alignment:Splign:2.1.0"
     exon            183..274
                     /gene="BHMT2"
                     /inference="alignment:Splign:2.1.0"
     exon            275..466
                     /gene="BHMT2"
                     /inference="alignment:Splign:2.1.0"
     exon            467..614
                     /gene="BHMT2"
                     /inference="alignment:Splign:2.1.0"
     exon            615..797
                     /gene="BHMT2"
                     /inference="alignment:Splign:2.1.0"
     exon            798..1026
                     /gene="BHMT2"
                     /inference="alignment:Splign:2.1.0"
     exon            1027..2603
                     /gene="BHMT2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1638..1643
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BHMT2"
                     /note="hexamer: AATAAA"
     polyA_site      1659
                     /gene="BHMT2"
                     /note="major polyA site"
     regulatory      2582..2587
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BHMT2"
                     /note="hexamer: AATAAA"
     polyA_site      2603
                     /gene="BHMT2"
ORIGIN      
        1 acagagccgc ggcaccatgg cacctgctgg acgcccgggg gccaagaagg ggattttgga
       61 gcgcctggag agtggggagg ttgtgattgg agatggcagc tttctcatta ctctggagaa
      121 gagaggctat gtgaaggctg ggctctggac tccagaggca gtgatagaac acccagacgc
      181 agttcgtcaa cttcacatgg aattcttgag agcaggatca aatgtcatgc agacttttac
      241 cttttctgcc agtgaggaca atatggaaag caagtgggaa gatgtaaatg ctgctgcctg
      301 tgacctcgcc agggaagtgg ctggcaaagg tgatgctttg gtagcagggg ggatctgcca
      361 gacatcaata tacaaatacc agaaggatga agctagaatt aaaaaacttt ttcgacaaca
      421 gctagaagtt tttgcctgga aaaatgtgga cttcttgatt gcagagtatt ttgagcacgt
      481 tgaagaagct gtgtgggctg tggaagtctt aaaagaatca gatagacccg tggcagttac
      541 catgtgcata ggcccagagg gagacatgca tgatataacc cccggagaat gtgctgtgag
      601 gctggtgaag gcaggggctt ccatcgttgg cgtgaactgc cgctttgggc ccgacaccag
      661 cttgaagacg atggagctca tgaaggaggg tcttgagtgg gcagggctga aagcgcacct
      721 catggtgcag cctctggggt tccacgcgcc tgactgtggc aaagaggggt ttgtggatct
      781 cccagaatat ccctttggac tggagtccag agttgccacc agatgggata ttcaaaaata
      841 cgccagagag gcctacaacc tgggggtcag gtacattggc gggtgctgtg gatttgagcc
      901 ctaccacatc agggcaattg cagaggagct ggccccagaa aggggctttt tgccaccagc
      961 ttcagaaaaa cacggcagct ggggaagtgg tttggacatg cacaccaaac cctggattag
     1021 agcaagggct cgaagggagt attgggagaa tctgctgcca gcttcaggca gacctttctg
     1081 tccttcgctg tcaaagccag acttctaagg agtagtgaaa gaaaaccctg aaataatcga
     1141 acaggaaaaa gttgccctca agcctgacct ggaaccgttc ctcaccttca tcctcaccat
     1201 gccctgctat ctccagctgc tgagcagctg aggtgctgca gccccttccc ttccagccca
     1261 caagtgtgtg catattgagc tcctgctgtg gttaagcact gcaacagact ctaccagaga
     1321 tgcaaagaga agcgagagag gcaccttgtt ctccaagaac ttactgtcca atcatgctgt
     1381 ggtgcattcc tttgaagatc atgaagaata gccaaacttg tctttgaggg tgaatttgac
     1441 actttaaaat aatcagaagt cactgagacc caaagctagt gaataattca agtgactaag
     1501 ctagatactt gaggatgata gagcaacact aaactaaagc aatgagtctg ctttttttaa
     1561 tgatttatac aatgactcca aaggcaatcc caaagaaaag atgtaaagaa tgttttgagc
     1621 aatggtagca ttattgaaat aaatgtttaa ctatccaaag tgattacttt caaagatgat
     1681 ttttacttaa agatattagg tctggccagg cgaagtgact cacacctgca atcccagcac
     1741 tttgggaggc cgaggcgggc ggatcacctg aggtcagcag ttcaagacca gcctgaccaa
     1801 catggtgaaa ccctgtctct accaaaatac aaaaattagc cgggcatgat ggcgggtgcc
     1861 tgtaatccca gctactcggg aggctgaggc aggagaatcg cttgaaccca ggaggcggag
     1921 cttgcagtga gccgagatca ggccattgca cttcagcctg ggtgacagag tgagactcca
     1981 tctcaaaaaa aaaaaaaaaa gatattaggt cctagaattt ttaaaatgtg tcttcataat
     2041 cataggtagc taggttataa actatttaaa gacaagatca cgtgataagc ttataatctt
     2101 ctcataattc cccttactta gcattgtgtt agacatacta ataggtgcac agtgaaatac
     2161 ttattgttga ttgtttaaaa ataaagtttt agaaaacctt ttcaaaagtc agagtttagg
     2221 ccaggggcac aggctgacac ctataatccc agcactttgg gaggccaggg cgggcagatc
     2281 acttgggtca agagttcaag gccagcctgg ccaacatggc aaaaccccat ctctactaaa
     2341 taaaatacaa aaattatcca ggcatggtgg tgcatgcctg taatcccagc tacttggagg
     2401 ctgaggcatg agaattgctt gaacctggga ggcagaggtt gcagtgagct gagatcgccc
     2461 cactgcaatc cagcctggga gacataattc aaatctattt tggtcttata tcttcttatg
     2521 tttgtgttat ttcatgtgtg ccagtttctc tttttttcac aacaatttat caatttgtgg
     2581 caataaaaat gatttacctt tta
//
