LOCUS       NM_000791               3919 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens dihydrofolate reductase (DHFR), transcript variant 1,
            mRNA.
ACCESSION   NM_000791
VERSION     NM_000791.4
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 3919)
  AUTHORS   Saha,S., Jungas,T.T., Ohayon,D., Audouard,C., Ye,T., Fawal,M.A. and
            Davy,A.
  TITLE     Dihydrofolate reductase activity controls neurogenic transitions in
            the developing neocortex
  JOURNAL   Development 150 (20) (2023)
   PUBMED   37665322
  REMARK    GeneRIF: Dihydrofolate reductase activity controls neurogenic
            transitions in the developing neocortex.
REFERENCE   2  (bases 1 to 3919)
  AUTHORS   Li,J., Lin,J., Kohen,A., Singh,P., Francis,K. and Cheatum,C.M.
  TITLE     Evolution of Optimized Hydride Transfer Reaction and Overall Enzyme
            Turnover in Human Dihydrofolate Reductase
  JOURNAL   Biochemistry 60 (50), 3822-3828 (2021)
   PUBMED   34875176
  REMARK    GeneRIF: Evolution of Optimized Hydride Transfer Reaction and
            Overall Enzyme Turnover in Human Dihydrofolate Reductase.
REFERENCE   3  (bases 1 to 3919)
  AUTHORS   Karimi,E., Heshmati,E. and Khalifeh,K.
  TITLE     Evolutionary adaptation of DHFR via expression of enzyme isoforms
            with various binding properties and dynamics behavior: a
            bioinformatics and computational study
  JOURNAL   Biol Chem 403 (7), 643-652 (2021)
   PUBMED   34905670
  REMARK    GeneRIF: Evolutionary adaptation of DHFR via expression of enzyme
            isoforms with various binding properties and dynamics behavior: a
            bioinformatics and computational study.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3919)
  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   5  (bases 1 to 3919)
  AUTHORS   Adesina,A.S., Luk,L.Y.P. and Allemann,R.K.
  TITLE     Cryo-kinetics Reveal Dynamic Effects on the Chemistry of Human
            Dihydrofolate Reductase
  JOURNAL   Chembiochem 22 (14), 2410-2414 (2021)
   PUBMED   33876533
  REMARK    GeneRIF: Cryo-kinetics Reveal Dynamic Effects on the Chemistry of
            Human Dihydrofolate Reductase.
REFERENCE   6  (bases 1 to 3919)
  AUTHORS   Stockman,B.J., Nirmala,N.R., Wagner,G., Delcamp,T.J., DeYarman,M.T.
            and Freisheim,J.H.
  TITLE     Sequence-specific 1H and 15N resonance assignments for human
            dihydrofolate reductase in solution
  JOURNAL   Biochemistry 31 (1), 218-229 (1992)
   PUBMED   1731871
REFERENCE   7  (bases 1 to 3919)
  AUTHORS   Beltzer,J.P. and Spiess,M.
  TITLE     In vitro binding of the asialoglycoprotein receptor to the beta
            adaptin of plasma membrane coated vesicles
  JOURNAL   EMBO J 10 (12), 3735-3742 (1991)
   PUBMED   1935897
REFERENCE   8  (bases 1 to 3919)
  AUTHORS   Davies,J.F. 2nd, Delcamp,T.J., Prendergast,N.J., Ashford,V.A.,
            Freisheim,J.H. and Kraut,J.
  TITLE     Crystal structures of recombinant human dihydrofolate reductase
            complexed with folate and 5-deazafolate
  JOURNAL   Biochemistry 29 (40), 9467-9479 (1990)
   PUBMED   2248959
REFERENCE   9  (bases 1 to 3919)
  AUTHORS   Appleman,J.R., Beard,W.A., Delcamp,T.J., Prendergast,N.J.,
            Freisheim,J.H. and Blakley,R.L.
  TITLE     Unusual transient- and steady-state kinetic behavior is predicted
            by the kinetic scheme operational for recombinant human
            dihydrofolate reductase
  JOURNAL   J Biol Chem 265 (5), 2740-2748 (1990)
   PUBMED   2303423
REFERENCE   10 (bases 1 to 3919)
  AUTHORS   Will,C.L. and Dolnick,B.J.
  TITLE     5-Fluorouracil inhibits dihydrofolate reductase precursor mRNA
            processing and/or nuclear mRNA stability in methotrexate-resistant
            KB cells
  JOURNAL   J Biol Chem 264 (35), 21413-21421 (1989)
   PUBMED   2592384
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC010270.8, CB988944.1,
            AC008434.5, BC003584.1 and AA489055.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000791.3.
            
            Summary: Dihydrofolate reductase converts dihydrofolate into
            tetrahydrofolate, a methyl group shuttle required for the de novo
            synthesis of purines, thymidylic acid, and certain amino acids.
            While the functional dihydrofolate reductase gene has been mapped
            to chromosome 5, multiple intronless processed pseudogenes or
            dihydrofolate reductase-like genes have been identified on separate
            chromosomes. Dihydrofolate reductase deficiency has been linked to
            megaloblastic anemia. Several transcript variants encoding
            different isoforms have been found for this gene. [provided by
            RefSeq, Mar 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            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 :: BC000192.1, SRR1163658.305558.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145544 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            CDS uses downstream in-frame AUG :: upstream AUG and CDS extension
                                                is not conserved
            MANE Ensembl match               :: ENST00000439211.7/
                                                ENSP00000396308.2
            RefSeq Select criteria           :: based on conservation,
                                                expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2                 AC010270.8         88547-88548
            3-290               CB988944.1         30-317
            291-454             AC008434.5         6492-6655
            455-1156            BC003584.1         415-1116
            1157-3482           AC008434.5         32197-34522
            3483-3919           AA489055.1         16-452              c
FEATURES             Location/Qualifiers
     source          1..3919
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q14.1"
     gene            1..3919
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /note="dihydrofolate reductase"
                     /db_xref="GeneID:1719"
                     /db_xref="HGNC:HGNC:2861"
                     /db_xref="MIM:126060"
     exon            1..580
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /inference="alignment:Splign:2.1.0"
     CDS             495..1058
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /EC_number="1.5.1.3"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /codon_start=1
                     /product="dihydrofolate reductase isoform 1"
                     /protein_id="NP_000782.1"
                     /db_xref="CCDS:CCDS47240.1"
                     /db_xref="GeneID:1719"
                     /db_xref="HGNC:HGNC:2861"
                     /db_xref="MIM:126060"
                     /translation="MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSV
                     EGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTE
                     QPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLL
                     PEYPGVLSDVQEEKGIKYKFEVYEKND"
     exon            581..630
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /inference="alignment:Splign:2.1.0"
     exon            631..736
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /inference="alignment:Splign:2.1.0"
     exon            737..863
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /inference="alignment:Splign:2.1.0"
     exon            864..979
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /inference="alignment:Splign:2.1.0"
     exon            980..3919
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /inference="alignment:Splign:2.1.0"
     polyA_site      1527
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /note="major polyA site"
     regulatory      3532..3537
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /note="hexamer: AATGAA"
     polyA_site      3563
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /note="major polyA site"
     regulatory      3893..3898
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /note="hexamer: AATAAA"
     polyA_site      3919
                     /gene="DHFR"
                     /gene_synonym="DHFR1; DHFRP1; DYR"
                     /note="major polyA site"
ORIGIN      
        1 agtcccagac agaacctact atgtgcggcg gcagctgggg cgggaaggcg ggagctgggg
       61 gcgctggggg cgctgcggcc gctgcggccg ctgcagccgc tgcagcgcca gggtccacct
      121 ggtcggctgc acctgtggag gaggaggtgg atttcaggct tcccgtagac tggaagaatc
      181 ggctcaaaac cgcttgcctc gcaggggctg agctggaggc agcgaggccg cccgacgcag
      241 gcttccggcg agacatggca gggcaaggat ggcagcccgg cggcagggcc tggcgaggag
      301 cgcgagcccg cggccgcagt tcccaggcgt ctgcgggcgc gagcacgccg cgaccctgcg
      361 tgcgccgggg cgggggggcg gggcctcgcc tgcacaaatg gggacgaggg gggcggggcg
      421 gccacaattt cgcgccaaac ttgaccgcgc gttctgctgt aacgagcggg ctcggaggtc
      481 ctcccgctgc tgtcatggtt ggttcgctaa actgcatcgt cgctgtgtcc cagaacatgg
      541 gcatcggcaa gaacggggac ctgccctggc caccgctcag gaatgaattc agatatttcc
      601 agagaatgac cacaacctct tcagtagaag gtaaacagaa tctggtgatt atgggtaaga
      661 agacctggtt ctccattcct gagaagaatc gacctttaaa gggtagaatt aatttagttc
      721 tcagcagaga actcaaggaa cctccacaag gagctcattt tctttccaga agtctagatg
      781 atgccttaaa acttactgaa caaccagaat tagcaaataa agtagacatg gtctggatag
      841 ttggtggcag ttctgtttat aaggaagcca tgaatcaccc aggccatctt aaactatttg
      901 tgacaaggat catgcaagac tttgaaagtg acacgttttt tccagaaatt gatttggaga
      961 aatataaact tctgccagaa tacccaggtg ttctctctga tgtccaggag gagaaaggca
     1021 ttaagtacaa atttgaagta tatgagaaga atgattaata tgaaggtgtt ttctagttta
     1081 agttgttccc cctccctctg aaaaaagtat gtatttttac attagaaaag gttttttgtt
     1141 gactttagat ctataattat ttctaagcaa ctagttttta ttccccacta ctcttgtctc
     1201 tatcagatac catttatgag acattcttgc tataactaag tgcttctcca agaccccaac
     1261 tgagtcccca gcacctgcta cagtgagctg ccattccaca cccatcacat gtggcactct
     1321 tgccagtcct tgacattgtc gggcttttca catgttggta atatttatta aagatgaaga
     1381 tccacatacc cttcaactga gcagtttcac tagtggaaat accaaaagct tcctacgtgt
     1441 atatccagag gtttgtagat aaatgttgcc accttgtttg taacagtgaa aaattgaaaa
     1501 caacctggaa gtccagtgat gggaaaatga gtatgtttct gtcttagatt ggggaaccca
     1561 aagcagattg caagactgaa atttcagtga aagcagtgta tttgctaggt cataccagaa
     1621 atcatcaatt gaggtacgga gaaactgaac tgagaaggta agaaaagcaa tttaaagtca
     1681 gcgagcaggt tctcattgat aacaagctcc atactgctga gatacaggga aatggagggg
     1741 ggaaagctgg agtattgatc ccgcccccct ccttggttgt cagctccctg tcctgtgtgt
     1801 gggcggaaca tagtccagct gctctatagc aagtctcagg tgtttgcagt aagaagctgc
     1861 tggcatgcac gggaacagtg aatgccaaac acttaaagca attcgatgtt taagtatgta
     1921 agttcttttt tttttagaca gcgtttcgct cttgttgccc aggctagcat gcaatggtgt
     1981 gacctcggct tactgcaacc tccgccttcc cagattcaag cgattctcct gcctcaggct
     2041 cccaagtagc taggaccagg tgcgcgccac cacgcccggc taatttttgt attttgtatt
     2101 tttagtagag atggggtttc accatgttgg tcaggctagt ctcgaactcg tgaccgcaag
     2161 cgattcaccc acctcagcct cccaaagtgc tgggattacc ggcttgagcc accacacccg
     2221 gcacatcttc attcttttta tgtagtaaaa agtataaggc cacacatggt ttatttgaag
     2281 tattttataa tttaaaaaaa tacagaagca ggaaaaccaa ttataagttc aagtgaggga
     2341 tgatggttgc ttgaaccaaa gggttgcatg tagtaagaaa ttgtgattta agatatattt
     2401 taaagttata agtagcagga tattctgatg gagtttgact ttggttttgg gcccagggag
     2461 tttcagatgc ctttgagaaa tgaatgaagt agagagaaaa taaaagaaaa accagccagg
     2521 cacagtggct cacacctgta atcccagcgc tttgggaggc taaggcaggc agatcacttg
     2581 agaccagctt gggcaacatg gcaaagcccc atctctacaa aaaacacaaa aattagctgg
     2641 gcattgtggc gcacacctgt attcccatct agtcaggaag ctgagatgga agaattaatt
     2701 gagcccacga gttcaaggct gcagtgagtc gtgattgtgc cactgcactc cagccggggt
     2761 gacagaagag accttgtctc gaaaaggaat ctgaaaacaa tggaaccatg ccttcataat
     2821 tctagaaagt tattttcaac tgataaatct atattcaccc aaataatcaa gggtgaaggt
     2881 aaaataatac atttttagac aagcaaagac tcaggggtta cctccatgtg ccctttttag
     2941 ggaagctgtt ggagaaaata ctccagcaaa atgaaggagt acacaaacca gagaatgaca
     3001 tgaatccagc aaataggatc caacacaggc aatattccag ctatggagct agctttaaaa
     3061 aggaacagta aaaatattaa tcggttagct gggtggaatg gcccatgcct gtagtcccag
     3121 ctactcagga ggctcagcag caggacgact tgagcccaag agttccagac cagcctggcc
     3181 accttagtga gatcccttct cttaaaaata ataacttatt gccagatttg gggcatttgg
     3241 aaagaagttc attgaagata aagcaaaagt aaaaaaaaaa aaaaaaaaaa caaggggaaa
     3301 gggttggtta ggcaatcatt ctagggcaga aagaagtaca ggataggaag agcataatac
     3361 actgtttttc tcaacaagga gcagtatgta cacagtcata atgatgtgac tgcttagccc
     3421 ctaaatatgg taactactct gggacaatat gggaggaaaa gtgaagattg tgatggtgta
     3481 agagctaaat cctcatctgt catatccaga aatcactata taatatataa taatgaaatg
     3541 actaagttat gtgaggaaaa aaacagaaga cattgctaaa agagttaaaa gtcattgctc
     3601 tggagaatta ggagggatgg ggcaggggac tgttaggatg cattataaac tgaaaagcct
     3661 ttttaaaatt ttatgtatta atatatgcat tcacttgaaa aactaaaaaa aaacaataat
     3721 ttggaaaaac ccatgaaggt aactaacgga aggaaaaact aagagaatga aaagtatttg
     3781 cctctggaaa gaacaactgg caggactgtt gttttcattg taagactttt ggagccattt
     3841 aattgtactt aaccattttc atctatttct ttaataagaa caattccatc ttaataaaga
     3901 gttacacttg ttaataagt
//
