LOCUS       NM_006636               4403 bp    mRNA    linear   PRI 17-JUN-2024
DEFINITION  Homo sapiens methylenetetrahydrofolate dehydrogenase (NADP+
            dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_006636
VERSION     NM_006636.4
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 4403)
  AUTHORS   Mo,H.Y., Wang,R.B., Ma,M.Y., Zhang,Y., Li,X.Y., Wen,W.R., Han,Y.
            and Tian,T.
  TITLE     MTHFD2-mediated redox homeostasis promotes gastric cancer
            progression under hypoxic conditions
  JOURNAL   Redox Rep 29 (1), 2345455 (2024)
   PUBMED   38723197
  REMARK    GeneRIF: MTHFD2-mediated redox homeostasis promotes gastric cancer
            progression under hypoxic conditions.
REFERENCE   2  (bases 1 to 4403)
  AUTHORS   Silva,R.V.N., Berzotti,L.A., Laia,M.G., Araujo,L.S., Silva,C.A.,
            Ribeiro,K.B., Brandao,M., Michelleti,A.M.R., Machado,J.R. and
            Lira,R.C.P.
  TITLE     Implications of MTHFD2 expression in renal cell carcinoma
            aggressiveness
  JOURNAL   PLoS One 19 (2), e0299353 (2024)
   PUBMED   38422037
  REMARK    GeneRIF: Implications of MTHFD2 expression in renal cell carcinoma
            aggressiveness.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 4403)
  AUTHORS   Wang,J., Yu,Z., Jiang,Y., Le,T., Wu,Y., Li,Z., Zhang,G., Wu,F. and
            Ma,H.
  TITLE     Downregulation of MTHFD2 Inhibits Proliferation and Enhances
            Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway
  JOURNAL   Front Biosci (Landmark Ed) 29 (1), 35 (2024)
   PUBMED   38287824
  REMARK    GeneRIF: Downregulation of MTHFD2 Inhibits Proliferation and
            Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT
            Pathway.
REFERENCE   4  (bases 1 to 4403)
  AUTHORS   Wu,S., Cai,W., Li,Y., Tan,W., Yuan,Y., Zhou,Z., Shi,J., Liu,X. and
            Gao,H.
  TITLE     SNHG3/hsa-miR-455-5p Axis-mediated High Expression of MTHFD2
            Correlates with Tumor Immune Infiltration and Endometrial Carcinoma
            Progression
  JOURNAL   Int J Med Sci 20 (8), 1097-1113 (2023)
   PUBMED   37484807
  REMARK    GeneRIF: SNHG3/hsa-miR-455-5p Axis-mediated High Expression of
            MTHFD2 Correlates with Tumor Immune Infiltration and Endometrial
            Carcinoma Progression.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4403)
  AUTHORS   Deng,X., Liu,X., Hu,B., Liu,J., Fu,B. and Zhang,W.
  TITLE     Upregulation of MTHFD2 is associated with PD-L1 activation in
            bladder cancer via the PI3K/AKT pathway
  JOURNAL   Int J Mol Med 51 (2) (2023)
   PUBMED   36601741
  REMARK    GeneRIF: Upregulation of MTHFD2 is associated with PDL1 activation
            in bladder cancer via the PI3K/AKT pathway.
REFERENCE   6  (bases 1 to 4403)
  AUTHORS   Di Pietro,E., Wang,X.L. and MacKenzie,R.E.
  TITLE     The expression of mitochondrial methylenetetrahydrofolate
            dehydrogenase-cyclohydrolase supports a role in rapid cell growth
  JOURNAL   Biochim Biophys Acta 1674 (1), 78-84 (2004)
   PUBMED   15342116
REFERENCE   7  (bases 1 to 4403)
  AUTHORS   Pawelek,P.D. and MacKenzie,R.E.
  TITLE     Methenyltetrahydrofolate cyclohydrolase is rate limiting for the
            enzymatic conversion of 10-formyltetrahydrofolate to
            5,10-methylenetetrahydrofolate in bifunctional
            dehydrogenase-cyclohydrolase enzymes
  JOURNAL   Biochemistry 37 (4), 1109-1115 (1998)
   PUBMED   9454603
REFERENCE   8  (bases 1 to 4403)
  AUTHORS   Kokame,K., Kato,H. and Miyata,T.
  TITLE     Homocysteine-respondent genes in vascular endothelial cells
            identified by differential display analysis. GRP78/BiP and novel
            genes
  JOURNAL   J Biol Chem 271 (47), 29659-29665 (1996)
   PUBMED   8939898
REFERENCE   9  (bases 1 to 4403)
  AUTHORS   Yang,X.M. and MacKenzie,R.E.
  TITLE     NAD-dependent methylenetetrahydrofolate
            dehydrogenase-methenyltetrahydrofolate cyclohydrolase is the
            mammalian homolog of the mitochondrial enzyme encoded by the yeast
            MIS1 gene
  JOURNAL   Biochemistry 32 (41), 11118-11123 (1993)
   PUBMED   8218174
REFERENCE   10 (bases 1 to 4403)
  AUTHORS   Peri,K.G., Belanger,C. and Mackenzie,R.E.
  TITLE     Nucleotide sequence of the human NAD-dependent methylene
            tetrahydrofolate dehydrogenase-cyclohydrolase
  JOURNAL   Nucleic Acids Res 17 (21), 8853 (1989)
   PUBMED   2587219
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BX475613.1, BC017054.1,
            CB124593.1 and AC073263.5.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_006636.3.
            
            Summary: This gene encodes a nuclear-encoded mitochondrial
            bifunctional enzyme with methylenetetrahydrofolate dehydrogenase
            and methenyltetrahydrofolate cyclohydrolase activities. The enzyme
            functions as a homodimer and is unique in its absolute requirement
            for magnesium and inorganic phosphate. Formation of the
            enzyme-magnesium complex allows binding of NAD. Alternative
            splicing results in two different transcripts, one protein-coding
            and the other not protein-coding. This gene has a pseudogene on
            chromosome 7. [provided by RefSeq, Mar 2009].
            
            Transcript Variant: This variant (1) represents the shorter
            transcript and is the protein-coding transcript.
            
            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 :: AK130664.1, SRR1803612.261966.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000394053.7/
                                                  ENSP00000377617.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-20                BX475613.1         54-73
            21-2123             BC017054.1         1-2103
            2124-2136           CB124593.1         532-544
            2137-4403           AC073263.5         143782-146048
FEATURES             Location/Qualifiers
     source          1..4403
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p13.1"
     gene            1..4403
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /note="methylenetetrahydrofolate dehydrogenase (NADP+
                     dependent) 2, methenyltetrahydrofolate cyclohydrolase"
                     /db_xref="GeneID:10797"
                     /db_xref="HGNC:HGNC:7434"
                     /db_xref="MIM:604887"
     exon            1..128
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /inference="alignment:Splign:2.1.0"
     CDS             28..1080
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /EC_number="3.5.4.9"
                     /EC_number="1.5.1.15"
                     /note="isoform A precursor is encoded by transcript
                     variant 1; NAD-dependent methylene tetrahydrofolate
                     dehydrogenase cyclohydrolase; bifunctional
                     methylenetetrahydrofolate dehydrogenase/cyclohydrolase,
                     mitochondrial"
                     /codon_start=1
                     /product="bifunctional methylenetetrahydrofolate
                     dehydrogenase/cyclohydrolase, mitochondrial isoform A
                     precursor"
                     /protein_id="NP_006627.2"
                     /db_xref="CCDS:CCDS1935.2"
                     /db_xref="GeneID:10797"
                     /db_xref="HGNC:HGNC:7434"
                     /db_xref="MIM:604887"
                     /translation="MAATSLMSALAARLLQPAHSCSLRLRPFHLAAVRNEAVVISGRK
                     LAQQIKQEVRQEVEEWVASGNKRPHLSVILVGENPASHSYVLNKTRAAAVVGINSETI
                     MKPASISEEELLNLINKLNNDDNVDGLLVQLPLPEHIDERRICNAVSPDKDVDGFHVI
                     NVGRMCLDQYSMLPATPWGVWEIIKRTGIPTLGKNVVVAGRSKNVGMPIAMLLHTDGA
                     HERPGGDATVTISHRYTPKEQLKKHTILADIVISAAGIPNLITADMIKEGAAVIDVGI
                     NRVHDPVTAKPKLVGDVDFEGVRQKAGYITPVPGGVGPMTVAMLMKNTIIAAKKVLRL
                     EEREVLKSKELGVATN"
     exon            129..313
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /inference="alignment:Splign:2.1.0"
     exon            314..436
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /inference="alignment:Splign:2.1.0"
     exon            437..589
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /inference="alignment:Splign:2.1.0"
     exon            590..697
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /inference="alignment:Splign:2.1.0"
     exon            698..790
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /inference="alignment:Splign:2.1.0"
     exon            791..916
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /inference="alignment:Splign:2.1.0"
     exon            917..4403
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /inference="alignment:Splign:2.1.0"
     polyA_site      1908
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /note="major polyA site"
     regulatory      2073..2078
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /note="hexamer: ATTAAA"
     regulatory      2097..2102
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /note="hexamer: AATAAA"
     polyA_site      2105
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
     polyA_site      2136
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
     regulatory      4163..4168
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /note="hexamer: ATTAAA"
     polyA_site      4186
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
     regulatory      4372..4377
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
                     /note="hexamer: AATAAA"
     polyA_site      4403
                     /gene="MTHFD2"
                     /gene_synonym="NMDMC"
ORIGIN      
        1 ctcccggcgc agtcaccggc gcggtctatg gctgcgactt ctctaatgtc tgctttggct
       61 gcccggctgc tgcagcccgc gcacagctgc tcccttcgcc ttcgcccttt ccacctcgcg
      121 gcagttcgaa atgaagctgt tgtcatttct ggaaggaaac tggcccagca gatcaagcag
      181 gaagtgcggc aggaggtaga agagtgggtg gcctcaggca acaaacggcc acacctgagt
      241 gtgatcctgg ttggcgagaa tcctgcaagt cactcctatg tcctcaacaa aaccagggca
      301 gctgcagttg tgggaatcaa cagtgagaca attatgaaac cagcttcaat ttcagaggaa
      361 gaattgttga atttaatcaa taaactgaat aatgatgata atgtagatgg cctccttgtt
      421 cagttgcctc ttccagagca tattgatgag agaaggatct gcaatgctgt ttctccagac
      481 aaggatgttg atggctttca tgtaattaat gtaggacgaa tgtgtttgga tcagtattcc
      541 atgttaccgg ctactccatg gggtgtgtgg gaaataatca agcgaactgg cattccaacc
      601 ctagggaaga atgtggttgt ggctggaagg tcaaaaaacg ttggaatgcc cattgcaatg
      661 ttactgcaca cagatggggc gcatgaacgt cccggaggtg atgccactgt tacaatatct
      721 catcgatata ctcccaaaga gcagttgaag aaacatacaa ttcttgcaga tattgtaata
      781 tctgctgcag gtattccaaa tctgatcaca gcagatatga tcaaggaagg agcagcagtc
      841 attgatgtgg gaataaatag agttcacgat cctgtaactg ccaaacccaa gttggttgga
      901 gatgtggatt ttgaaggagt cagacaaaaa gctgggtata tcactccagt tcctggaggt
      961 gttggcccca tgacagtggc aatgctaatg aagaatacca ttattgctgc aaaaaaggtg
     1021 ctgaggcttg aagagcgaga agtgctgaag tctaaagagc ttggggtagc cactaattaa
     1081 ctactgtgtc ttctgtgtca caaacagcac tccaggccag ctcaagaagc aaagcaggcc
     1141 aatagaaatg caatattttt aatttattct actgaaatgg tttaaaatga tgccttgtat
     1201 ttattgaaag cttaaatggg tgggtgtttc tgcacatacc tctgcagtac ctcaccaggg
     1261 agcattccag tatcatgcag ggtcctgtga tctagccagg agcagccatt aacctagtga
     1321 ttaatatggg agacattacc atatggagga tggatgcttc actttgtcaa gcacctcagt
     1381 tacacattcg ccttttctag gattgcattt cccaagtgct attgcaataa cagttgatac
     1441 tcattttagg taccaaacct tttgagttca actgatcaaa ccaaaggaaa agtgttgcta
     1501 gagaaaatta gggaaaaggt gaaaaagaaa aaatggtagt aattgagcag aaaaaaatta
     1561 atttatatat gtattgattg gcaaccagat ttatctaagt agaactgaat tggctaggaa
     1621 aaaagaaaaa ctgcatgtta atcattttcc taagctgtcc ttttgaggct tagtcagttt
     1681 attgggaaaa tgtttaggat tattccttgc tattagtact cattttatgt atgttaccct
     1741 tcagtaagtt ctccccattt tagttttcta ggactgaaag gattcttttc tacattatac
     1801 atgtgtgttg tcatatttgg cttttgctat atactttaac ttcattgtta aatttttgta
     1861 ttgtatagtt tctttggtgt atcttaaaac ctatttttga aaaacaaact tggcttgata
     1921 atcatttggg cagcttgggt aagtacgcaa cttacttttc caccaaagaa ctgtcagcag
     1981 ctgcctgctt ttctgtgatg tatgtatcct gttgactttt ccagaaattt tttaagagtt
     2041 tgagttacta ttgaatttaa tcagactttc tgattaaagg gttttctttc ttttttaata
     2101 aaacacatct gtctggtatg gtatgaattt ctgaaattct gtcttcctat gactcctagt
     2161 tgtgacctaa ccagtttttt tctcatttaa tcaatgtagc tattcctata ttcagtaaca
     2221 cttacttcta tagccttaaa tagataattt tttttcttct attttttttt ttttttttgt
     2281 agagatgggg tcttgctatg ttgcctgggc tggtattgaa ctcctggcct caagcaatca
     2341 atcctcttgc ctcagcttcc cagagggctg ggattacagg cctgggccac ccacacccaa
     2401 acagaggttt aaagagcttt ggagaaacca gcctcgtcct ccagtctctt tgtttgtttg
     2461 ttttgagact gagtcttgct ctgttgccca ggctggagtg cagtggcatg atctcgggtc
     2521 actgcaacct ctgcctctcg ggttcaaaca attcttgtgc ctcagcctcc tgagtagctg
     2581 ggattacagg tgcatgccac catgcctggc taatttttgt gtttttagta gagatggggt
     2641 ttcatcacat tggccaggct ggtctcaaac tcctgacctc aagtgatcca cctgcctcgg
     2701 cctcccaaaa tgctaggatt acaggcgtga gccactgcac ctggcctgtc ctacagtctt
     2761 atatcacaac aggttgtgcc aagctaggag cttaatctgt aaaatacttg aggcagggat
     2821 aggtttgtct gttttggctt ttggctttca tgcgagcaga agtagctcct gctctaggca
     2881 gcttgaggca gaaagagaag aaacaattga gttgacctac ctccgtcctc gttcttctgc
     2941 cagctggcgt tattcttttg atagttctct ggagtttaaa gaagtttaga tagtttgctg
     3001 gagatgtttt tgtaagtgac gtatagctta tgtctctaat ccatgcctgc ttacctagat
     3061 tattaaatgt ggagcaagat gaccagacag gattaaattt tattgaatta cagttacaag
     3121 tggaaaaaat gactgactta ctgcatggag aagtattatg tcaacctgtt aaaagctatg
     3181 gaaattaaaa tgttcatgta tatacaaaat ataaatgaca tgtaaggtaa aattacagtg
     3241 atcaatttac aacaaagaaa ttaacagtag ttttccagct tgtttgatta atcaagcagg
     3301 tttactcttg aatccatagc atttctacaa tttaatttgg acaaagttct attccagatc
     3361 agccaggttt taaaactgaa atgtgttaag ggtggattgt tagcttcccc aggattggtg
     3421 tggatgataa atactttttt taaaaattaa ttattattgt ttataagaca tggattccag
     3481 ctgtctccct ggctggagtg cagtggcatg attatagctc actgcagcct tgaactcctg
     3541 gacttaaacg atcctcctgc atcagcctct gaaatggctg ggactacagg tgtgtgccag
     3601 catgcctagc taatttttaa acatttgttt agagatgggt ctcactatgt tgcccaggct
     3661 ggtcttgacc tcctgacctc tgctgattcc ccccacctct gcctcccaag tagcgggatt
     3721 acaggtgtga gccactgtgt ctgacaagaa tttatactta agcataggag atggttctgg
     3781 aaattctaag aaattctgct ctcagtaaga gtagaggttt ggagctttac ctcttggcag
     3841 tatcccttgg aagggagctc tgagattaaa tgtaatcaaa cacttattga gagctttcta
     3901 tggaccaggc actacactag acgctgggaa ttacagaggc aattacctgt cctatactca
     3961 aggtgttaat gatctagtgt catttttctt taaaaaagaa agcacctgca tttgtcatct
     4021 tgagcaaata tagtaactct aacctcaagg ttcaagtgat ttactcaagg tttaaatcat
     4081 agttgttttg gagaaagtaa gtgtcagatg cactgtggct gtcagggtca tagtaggcat
     4141 taaatcaaca tggttggtgt tcattaaatg tggattgaag ataaaatgac tgatcttaag
     4201 tttcatgagg aataggtttg cttcattgaa actggttttt atcttcccaa atagttttca
     4261 atcattcctt taaagtacta ggttgattaa tattgcaaag ttgtaatgta aaatgtgacc
     4321 ttacctctgt ctaacctgta ttgttcacat gaatgggagt ttgactttgg gaataaacat
     4381 tgaaaatttg cagggaggac cca
//
