LOCUS       NM_176815               3856 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens dihydrofolate reductase 2 (DHFR2), transcript variant
            2, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_176815
VERSION     NM_176815.5
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 3856)
  AUTHORS   Bookey,N., Drago,P., Leung,K.Y., Hughes,L., MacCooey,A., Ozaki,M.,
            Henry,M., De Castro,S.C.P., Doykov,I., Heywood,W.E., Mills,K.,
            Murphy,M.M., Cavalle-Busquets,P., Campbell,S., Burtenshaw,D.,
            Meleady,P., Cahill,P.A., Greene,N.D.E. and Parle-McDermott,A.
  TITLE     The Differential Translation Capabilities of the Human DHFR2 Gene
            Indicates a Developmental and Tissue-Specific Endogenous Protein of
            Low Abundance
  JOURNAL   Mol Cell Proteomics 23 (3), 100718 (2024)
   PUBMED   38224738
  REMARK    GeneRIF: The Differential Translation Capabilities of the Human
            DHFR2 Gene Indicates a Developmental and Tissue-Specific Endogenous
            Protein of Low Abundance.
REFERENCE   2  (bases 1 to 3856)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   3  (bases 1 to 3856)
  AUTHORS   Pangilinan,F., Finlay,E.K., Molloy,A.M., Abaan,H.O., Shane,B.,
            Mills,J.L., Brody,L.C. and Parle-McDermott,A.
  TITLE     A dihydrofolate reductase 2 (DHFR2) variant is associated with risk
            of neural tube defects in an Irish cohort but not in a United
            Kingdom cohort
  JOURNAL   Am J Med Genet A 185 (4), 1307-1311 (2021)
   PUBMED   33544972
  REMARK    GeneRIF: A dihydrofolate reductase 2 (DHFR2) variant is associated
            with risk of neural tube defects in an Irish cohort but not in a
            United Kingdom cohort.
REFERENCE   4  (bases 1 to 3856)
  AUTHORS   Hughes,L., Carton,R., Minguzzi,S., McEntee,G., Deinum,E.E.,
            O'Connell,M.J. and Parle-McDermott,A.
  TITLE     An active second dihydrofolate reductase enzyme is not a feature of
            rat and mouse, but they do have activity in their mitochondria
  JOURNAL   FEBS Lett 589 (15), 1855-1862 (2015)
   PUBMED   25980602
REFERENCE   5  (bases 1 to 3856)
  AUTHORS   Gao,J., Cui,W., Du,Y. and Ji,M.
  TITLE     Insight into the molecular mechanism about lowered dihydrofolate
            binding affinity to dihydrofolate reductase-like 1 (DHFRL1)
  JOURNAL   J Mol Model 19 (12), 5187-5198 (2013)
   PUBMED   24122410
  REMARK    GeneRIF: We hope this work will be useful to understand the general
            characteristics of DHFRL1.
REFERENCE   6  (bases 1 to 3856)
  AUTHORS   Anderson,D.D., Quintero,C.M. and Stover,P.J.
  TITLE     Identification of a de novo thymidylate biosynthesis pathway in
            mammalian mitochondria
  JOURNAL   Proc Natl Acad Sci U S A 108 (37), 15163-15168 (2011)
   PUBMED   21876188
REFERENCE   7  (bases 1 to 3856)
  AUTHORS   McEntee,G., Minguzzi,S., O'Brien,K., Ben Larbi,N., Loscher,C.,
            O'Fagain,C. and Parle-McDermott,A.
  TITLE     The former annotated human pseudogene dihydrofolate reductase-like
            1 (DHFRL1) is expressed and functional
  JOURNAL   Proc Natl Acad Sci U S A 108 (37), 15157-15162 (2011)
   PUBMED   21876184
  REMARK    GeneRIF: The DHFRP4, or dihydrofolate reductase-like 1 (DHFRL1),
            gene is expressed and shares some commonalities with DHFR.
REFERENCE   8  (bases 1 to 3856)
  AUTHORS   Semmler,A., Simon,M., Moskau,S. and Linnebank,M.
  TITLE     Polymorphisms of methionine metabolism and susceptibility to
            meningioma formation: laboratory investigation
  JOURNAL   J Neurosurg 108 (5), 999-1004 (2008)
   PUBMED   18447718
  REMARK    GeneRIF: The results of this study suggest that genetic variants of
            methionine metabolism are associated with meningioma formation
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC130896.3 and AW104373.1.
            
            On Jun 2, 2019 this sequence version replaced NM_176815.4.
            
            Transcript Variant: This variant (2) differs in its 5' UTR,
            compared to variant 1. Variants 1 and 2 encode the same protein.
            
            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.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803616.25445.1,
                                           SRR1803611.279509.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000314636.3/ ENSP00000319170.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-171               AC130896.3         43303-43473
            172-3836            AC130896.3         44613-48277
            3837-3856           AW104373.1         8-27                c
FEATURES             Location/Qualifiers
     source          1..3856
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q11.2"
     gene            1..3856
                     /gene="DHFR2"
                     /gene_synonym="DHFRL1; DHFRP4"
                     /note="dihydrofolate reductase 2"
                     /db_xref="GeneID:200895"
                     /db_xref="HGNC:HGNC:27309"
                     /db_xref="MIM:616588"
     exon            1..171
                     /gene="DHFR2"
                     /gene_synonym="DHFRL1; DHFRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            172..3856
                     /gene="DHFR2"
                     /gene_synonym="DHFRL1; DHFRP4"
                     /inference="alignment:Splign:2.1.0"
     CDS             267..830
                     /gene="DHFR2"
                     /gene_synonym="DHFRL1; DHFRP4"
                     /EC_number="1.5.1.3"
                     /note="dihydrofolate reductase pseudogene 4; dihydrofolate
                     reductase-like protein 1; dihydrofolate reductase,
                     mitochondrial; dihydrofolate reductase like 1"
                     /codon_start=1
                     /product="dihydrofolate reductase 2, mitochondrial"
                     /protein_id="NP_789785.1"
                     /db_xref="CCDS:CCDS2926.1"
                     /db_xref="GeneID:200895"
                     /db_xref="HGNC:HGNC:27309"
                     /db_xref="MIM:616588"
                     /translation="MFLLLNCIVAVSQNMGIGKNGDLPRPPLRNEFRYFQRMTTTSSV
                     EGKQNLVIMGRKTWFSIPEKNRPLKDRINLVLSRELKEPPQGAHFLARSLDDALKLTE
                     RPELANKVDMIWIVGGSSVYKEAMNHLGHLKLFVTRIMQDFESDTFFSEIDLEKYKLL
                     PEYPGVLSDVQEGKHIKYKFEVCEKDD"
     regulatory      3835..3840
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DHFR2"
                     /gene_synonym="DHFRL1; DHFRP4"
                     /note="hexamer: AATAAA"
     polyA_site      3856
                     /gene="DHFR2"
                     /gene_synonym="DHFRL1; DHFRP4"
                     /note="major polyA site"
ORIGIN      
        1 agttacttcc ggtagctggt aaaggctgat acttcccagg acgcggaggt aacgggccag
       61 ggccaaagcg actttcgcta cttggattgg tcggcgtagc tttgggcggc cggaccttag
      121 aaagtcacac atctgcgcgc ctgtgcggcc cctgcttctg cggatgctga ggcacgtaaa
      181 aaaatttgaa gaagggaatt tcgcggcatt cttggcctgg cttcctggcg tagccagcaa
      241 gttcggaggt gttaaccgct gctgtcatgt ttcttttgct aaactgcatc gtcgctgtgt
      301 cccaaaacat gggcatcggc aagaacgggg acctgcccag gccgccgctc aggaatgaat
      361 tcaggtattt ccagagaatg accacaactt cttcagtaga gggtaaacag aatctggtga
      421 ttatgggtag gaagacctgg ttctccattc ctgagaagaa tcgaccttta aaggatagaa
      481 ttaatttagt tctcagcaga gaactcaagg aacctccaca aggagctcat tttcttgcca
      541 gaagtttgga tgatgcctta aaacttactg aacgaccaga attagcaaat aaagtagaca
      601 tgatttggat agttggtggc agttctgttt ataaggaagc catgaatcac ctaggccatc
      661 ttaaactatt tgtgacaagg atcatgcagg actttgaaag tgacacgttt ttttcagaaa
      721 ttgacttgga gaaatataaa cttctgcctg aatacccagg tgttctctct gatgtccagg
      781 aggggaaaca catcaagtac aaatttgaag tatgtgagaa ggatgattaa tatgaaggtg
      841 ttttctggtt taagttgttc cccctccctc tgagaaaagt atgcattttt acattagaaa
      901 agggactttt gttgacttca gatctatgga taattatttc taagcaacgt gtttttattc
      961 ctcactaatc ttggctatat cagataccat ttatgaaaca ttcttgctat aactgtctct
     1021 ccaagacccc gactgagtcc ccagcacctg ctacagtgag ctgccattcc acacccatca
     1081 catgtggcac tcttgccact ccttgacatt gtcaggcttt tctaatgttg gtagtattta
     1141 ttaaagatga agatgcacat acccttcagc tgagcagttt cactagtagg aaataccaaa
     1201 agcttcgtac atgtatatcc agaggtttgt agacaaatgt tgcagccttt tttgtaacag
     1261 tgaaaaactg aaaacaacct ggaagtccag tgatgggaaa atgaatatat ttctgtctta
     1321 gattggggaa cccaaagcag attccaagac tgaaatttaa gtgaaagcag tttatttgct
     1381 aggtcatacc agaagtcatc aatcgaagta tggagaaatg gaactgagaa ggtaaaaacc
     1441 agttcaaaat cagtgaggag gttctcaatg gtaacgagct ccatactgct gagatacagg
     1501 gaaacggagg ggagaaagct agagtattta acccccactc cttggttgtc agctccctgt
     1561 cctgtgtgtg ggcagaacgt actccaccta ctcaatagca agttccaggt gtttgctgaa
     1621 agaagctgct gtaatgtacg ggaacggtga atgccaaaca cttaaagcaa ttccatgttt
     1681 aagtatgtaa actcttcata cttttttttt tttttctttt taagacagaa tttcactctt
     1741 gttgcccagg cggagtgcaa tggaacaacc ttggctcacg gcaacttcag ccttcccagg
     1801 ttcaagcaat tctcctgcct caggctcctg ggtggctggg actacaggcg cgtgccacca
     1861 cgccaggcta attttgtatt tttggtgggg acattccatg ttggtcaggc tagtctcgaa
     1921 ctcctgacct caggtgatcc tcctgcctcg gccttcaggg gtgctgggat tacaggcatc
     1981 agccactgca cttggcagat cttcattctt ttagtaaaaa gtataaagcc acacatggtt
     2041 tatttgaaat attttataat ttaaaaaagt acagaagcag gaaaaccaat tctaggttca
     2101 agtgagggat gatggtagtt tgaaccaaag gattgcatgt ggtaagaaat tgtgatttaa
     2161 gatatatttt aaagttggaa gtagcaggat attctgatgg agtttgactt tggttttggg
     2221 cccactgagt ttgagatgcc tttgagaaat gaaagaagta gagagagaat taaaaactgg
     2281 ccaggagtgg tggctcacgc ctgtggtccc agcactttgg ggggctgagg tgggtggatc
     2341 acctgagacc agcttgggca acatggtgga gccctgtctc tacagaagat acaaaaattg
     2401 gctgggcatt gtggcacaca cctgtagtct cgtctactca cggggctgag atggaggatt
     2461 caattgagcc catgagttca aggctgcagt gagtcgtgat tttgccactg cactcctgcc
     2521 tgggtgacag aagagaccct gtctcaaaaa agaatctgaa aacaacggaa ccatgccttc
     2581 agaattctat aaagttattt tcaactgata aatctatatt caggcaaaga atcaagggtg
     2641 aaggtaaaat aatacatttt tagacaagca aagactcagg ggttacatgt accctttctt
     2701 gggaagctat cggagaaaat actccagcaa aatgaaggcg tacacaaacc agagaatgac
     2761 gtggatccag caaatagtat ccaacacagg caatattcca gctatggagc tagctttaaa
     2821 aagaaacagt aaaaatacta atagattagc tgggtgggat ggcccatgct tgtagtccca
     2881 gctactcagg aggctaagca aaaggatggc ttgagcccaa gagttcagag cagcctggcc
     2941 accatagtga gatcccttct cttaaaaata ataggttatt gccagatttg gggcatttgg
     3001 aaagaagtgc attgaagata aagcaaaagt aaaaaaaaaa aaaaacaaaa aaaaacaagg
     3061 gggaagggtt ggttaggcaa taattaattc tagggcagga agaagtacag gataggaagt
     3121 aagagcatca tacgctgttt ttctcaacaa tgggcaatat gtacatagtc ataatgatgt
     3181 ggtgactgac tgcttagccc ctaaatctgg taactacttt gggacaatat ggggggaaaa
     3241 gtgaagatag tgatggtgta agagctaaat cctcatctgt catatcaaga aatcactata
     3301 taatgtataa cataatcaag aaatgactaa gtagttatgt gaagaaaaga atggaacatt
     3361 gctagaagag ttagaagtca ttgctccaga gaattaggag ggatggggca ggggactgtt
     3421 aggatgcatt ataaactgaa gaggctttta aagattacat gtattaatat atgtattcac
     3481 ttgaaaaact aaaaaaatag taatttttta aaacccatgg aggtaactac cagaaggaaa
     3541 aactaagaga atgaaaagtg ctttcctctg gaaagaacaa gtcgcaggac tgttttcatt
     3601 gtaagacttt tggagccatt tgattttact taaccatttt catatatttc tttaataaaa
     3661 ataattctat cttaataaaa agttacactc attcattaaa aaaagaattt taagactgta
     3721 ataagaatca tagtttattt ctgttagaga aaggcaatgt gttatacttg gaaagaggtc
     3781 atattaattt tatcacattt ttgggactca gcatctttat attttctgat tttaaataaa
     3841 caactttgct tatgaa
//
