LOCUS       NM_001361               4669 bp    mRNA    linear   PRI 17-JUN-2024
DEFINITION  Homo sapiens dihydroorotate dehydrogenase (quinone) (DHODH), mRNA;
            nuclear gene for mitochondrial product.
ACCESSION   NM_001361
VERSION     NM_001361.5
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 4669)
  AUTHORS   Ishikawa,C. and Mori,N.
  TITLE     Pivotal role of dihydroorotate dehydrogenase as a therapeutic
            target in adult T-cell leukemia
  JOURNAL   Eur J Haematol 113 (1), 99-109 (2024)
   PUBMED   38558052
  REMARK    GeneRIF: Pivotal role of dihydroorotate dehydrogenase as a
            therapeutic target in adult T-cell leukemia.
REFERENCE   2  (bases 1 to 4669)
  AUTHORS   Wang,S., Li,Y., Lin,Y., Li,J., Guo,L., Wang,H., Lin,X., Liu,Z.,
            Zhang,B., Liao,Z. and Zhang,Z.
  TITLE     Bioinformatics analysis and experimental verification of the
            cancer-promoting effect of DHODH in clear cell renal cell carcinoma
  JOURNAL   Sci Rep 14 (1), 11985 (2024)
   PUBMED   38796629
  REMARK    GeneRIF: Bioinformatics analysis and experimental verification of
            the cancer-promoting effect of DHODH in clear cell renal cell
            carcinoma.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 4669)
  AUTHORS   Yao,L., Yang,N., Zhou,W., Akhtar,M.H., Zhou,W., Liu,C., Song,S.,
            Li,Y., Han,W. and Yu,C.
  TITLE     Exploiting Cancer Vulnerabilities by Blocking of the DHODH and GPX4
            Pathways: A Multifunctional Bodipy/PROTAC Nanoplatform for the
            Efficient Synergistic Ferroptosis Therapy
  JOURNAL   Adv Healthc Mater 12 (26), e2300871 (2023)
   PUBMED   37204046
  REMARK    GeneRIF: Exploiting Cancer Vulnerabilities by Blocking of the DHODH
            and GPX4 Pathways: A Multifunctional Bodipy/PROTAC Nanoplatform for
            the Efficient Synergistic Ferroptosis Therapy.
REFERENCE   4  (bases 1 to 4669)
  AUTHORS   Watanabe,M., Kosaka,H., Sugawara,M., Maemoto,M., Ono,Y., Uemori,T.,
            Shizu,R. and Yoshinari,K.
  TITLE     Screening for DAX1/EWS-FLI1 functional inhibitors identified
            dihydroorotate dehydrogenase as a therapeutic target for Ewing's
            sarcoma
  JOURNAL   Cancer Med 12 (8), 9802-9814 (2023)
   PUBMED   36825574
  REMARK    GeneRIF: Screening for DAX1/EWS-FLI1 functional inhibitors
            identified dihydroorotate dehydrogenase as a therapeutic target for
            Ewing's sarcoma.
REFERENCE   5  (bases 1 to 4669)
  AUTHORS   Olsen,T.K., Dyberg,C., Embaie,B.T., Alchahin,A., Milosevic,J.,
            Ding,J., Otte,J., Tummler,C., Hed Myrberg,I., Westerhout,E.M.,
            Koster,J., Versteeg,R., Ding,H.F., Kogner,P., Johnsen,J.I.,
            Sykes,D.B. and Baryawno,N.
  TITLE     DHODH is an independent prognostic marker and potent therapeutic
            target in neuroblastoma
  JOURNAL   JCI Insight 7 (17), e153836 (2022)
   PUBMED   35943801
  REMARK    GeneRIF: DHODH is an independent prognostic marker and potent
            therapeutic target in neuroblastoma.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4669)
  AUTHORS   Bader,B., Knecht,W., Fries,M. and Loffler,M.
  TITLE     Expression, purification, and characterization of histidine-tagged
            rat and human flavoenzyme dihydroorotate dehydrogenase
  JOURNAL   Protein Expr Purif 13 (3), 414-422 (1998)
   PUBMED   9693067
REFERENCE   7  (bases 1 to 4669)
  AUTHORS   Knecht,W., Bergjohann,U., Gonski,S., Kirschbaum,B. and Loffler,M.
  TITLE     Functional expression of a fragment of human dihydroorotate
            dehydrogenase by means of the baculovirus expression vector system,
            and kinetic investigation of the purified recombinant enzyme
  JOURNAL   Eur J Biochem 240 (1), 292-301 (1996)
   PUBMED   8925840
REFERENCE   8  (bases 1 to 4669)
  AUTHORS   Copeland,R.A., Davis,J.P., Dowling,R.L., Lombardo,D., Murphy,K.B.
            and Patterson,T.A.
  TITLE     Recombinant human dihydroorotate dehydrogenase: expression,
            purification, and characterization of a catalytically functional
            truncated enzyme
  JOURNAL   Arch Biochem Biophys 323 (1), 79-86 (1995)
   PUBMED   7487077
REFERENCE   9  (bases 1 to 4669)
  AUTHORS   Barnes,T., Parry,P., Hart,I., Jones,C., Minet,M. and Patterson,D.
  TITLE     Regional mapping of the gene encoding dihydroorotate dehydrogenase,
            an enzyme involved in UMP synthesis, electron transport, and
            superoxide generation, to human chromosome region 16q22
  JOURNAL   Somat Cell Mol Genet 19 (4), 405-411 (1993)
   PUBMED   8211381
REFERENCE   10 (bases 1 to 4669)
  AUTHORS   Minet,M., Dufour,M.E. and Lacroute,F.
  TITLE     Cloning and sequencing of a human cDNA coding for dihydroorotate
            dehydrogenase by complementation of the corresponding yeast mutant
  JOURNAL   Gene 121 (2), 393-396 (1992)
   PUBMED   1446837
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AU130529.1, BC065245.1,
            BE789211.1, AU152444.1, AI499306.1 and AC009087.4.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_001361.4.
            
            Summary: The protein encoded by this gene catalyzes the fourth
            enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate
            to orotate, in de novo pyrimidine biosynthesis. This protein is a
            mitochondrial protein located on the outer surface of the inner
            mitochondrial membrane. [provided by RefSeq, Jul 2008].
            
            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 :: SRR1803616.136604.1,
                                           SRR1803617.224526.1 [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                 :: ENST00000219240.9/
                                                  ENSP00000219240.4
            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                AU130529.1         1-20
            21-1782             BC065245.1         1-1762
            1783-2029           BE789211.1         272-518
            2030-2426           AU152444.1         1-397               c
            2427-2427           AI499306.1         12-12               c
            2428-4669           AC009087.4         89719-91960         c
FEATURES             Location/Qualifiers
     source          1..4669
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q22.2"
     gene            1..4669
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /note="dihydroorotate dehydrogenase (quinone)"
                     /db_xref="GeneID:1723"
                     /db_xref="HGNC:HGNC:2867"
                     /db_xref="MIM:126064"
     exon            1..42
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     CDS             22..1209
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /EC_number="1.3.5.2"
                     /note="human complement of yeast URA1; dihydroorotate
                     oxidase"
                     /codon_start=1
                     /product="dihydroorotate dehydrogenase (quinone),
                     mitochondrial"
                     /protein_id="NP_001352.2"
                     /db_xref="CCDS:CCDS42192.1"
                     /db_xref="GeneID:1723"
                     /db_xref="HGNC:HGNC:2867"
                     /db_xref="MIM:126064"
                     /translation="MAWRHLKKRAQDAVIILGGGGLLFASYLMATGDERFYAEHLMPT
                     LQGLLDPESAHRLAVRFTSLGLLPRARFQDSDMLEVRVLGHKFRNPVGIAAGFDKHGE
                     AVDGLYKMGFGFVEIGSVTPKPQEGNPRPRVFRLPEDQAVINRYGFNSHGLSVVEHRL
                     RARQQKQAKLTEDGLPLGVNLGKNKTSVDAAEDYAEGVRVLGPLADYLVVNVSSPNTA
                     GLRSLQGKAELRRLLTKVLQERDGLRRVHRPAVLVKIAPDLTSQDKEDIASVVKELGI
                     DGLIVTNTTVSRPAGLQGALRSETGGLSGKPLRDLSTQTIREMYALTQGRVPIIGVGG
                     VSSGQDALEKIRAGASLVQLYTALTFWGPPVVGKVKRELEALLKEQGFGGVTDAIGAD
                     HRR"
     exon            43..255
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     exon            256..455
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     exon            456..538
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     exon            539..726
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     exon            727..840
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     exon            841..994
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     exon            995..1154
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     exon            1155..4669
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1494..1499
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /note="hexamer: AATAAA"
     polyA_site      1515
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /note="major polyA site"
     regulatory      2036..2041
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /note="hexamer: GATAAA"
     polyA_site      2066
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
     regulatory      4651..4656
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
                     /note="hexamer: AATATA"
     polyA_site      4669
                     /gene="DHODH"
                     /gene_synonym="DHOdehase; POADS; URA1"
ORIGIN      
        1 gggcttaatg acggaaggag catggcgtgg agacacctga aaaagcgggc ccaggatgct
       61 gtgatcatcc tggggggagg aggacttctc ttcgcctcct acctgatggc cacgggagat
      121 gagcgtttct atgctgaaca cctgatgccg actctgcagg ggctgctgga cccggagtca
      181 gcccacagac tggctgttcg cttcacctcc ctggggctcc ttccacgggc cagatttcaa
      241 gactctgaca tgctggaagt gagagttctg ggccataaat tccgaaatcc agtaggaatt
      301 gctgcaggat ttgacaagca tggggaagcc gtggacggac tttataagat gggctttggt
      361 tttgttgaga taggaagtgt gactccaaaa cctcaggaag gaaaccctag acccagagtc
      421 ttccgcctcc ctgaggacca agctgtcatt aacaggtatg gatttaacag tcacgggctt
      481 tcagtggtgg aacacaggtt acgggccaga cagcagaagc aggccaagct cacagaagat
      541 ggactgcctc tgggggtcaa cttggggaag aacaagacct cagtggacgc cgcggaggac
      601 tacgcagaag gggtgcgcgt actgggcccc ctggccgact acctggtggt gaatgtgtcc
      661 agccccaaca ctgccgggct gcggagcctt cagggaaagg ccgagctgcg ccgcctgctg
      721 accaaggtgc tgcaggagag ggatggcttg cggagagtgc acaggccggc agtcctggtg
      781 aagatcgctc ctgacctcac cagccaggat aaggaggaca ttgccagtgt ggtcaaagag
      841 ttgggcatcg atgggctgat tgttacgaac accaccgtga gtcgccctgc gggcctccag
      901 ggtgccctgc gctctgaaac aggagggctg agtgggaagc ccctccggga tttatcaact
      961 caaaccattc gggagatgta tgcactcacc caaggccgag ttcccataat tggggttggt
     1021 ggtgtgagca gcgggcagga cgcgctggag aagatccggg caggggcctc cctggtgcag
     1081 ctgtacacgg ccctcacctt ctgggggcca cccgttgtgg gcaaagtcaa gcgggaactg
     1141 gaggcccttc tgaaagagca gggctttggc ggagtcacag atgccattgg agcagatcat
     1201 cggaggtgag gacagcgtct gacgggaagc ctgatctgga accttcccaa ggactcaggc
     1261 aagcctttgt ggctggatca tgagaggagg gactccatct tgagccatgt cccccagcca
     1321 tggcatggct gcactgtaaa cgccaatcgg ggggtcacca ggatcaaccg caggctttct
     1381 tcagtccctt ggtcagacca taaactgcat ttttgattct ttgtggattc aaaccctagg
     1441 atccatcagt cttgcaagga cattgaatat taggaggaaa aagtcatgga aaaaataaag
     1501 ccatttagaa cctgggtttc aacgctagcc ctttctggtt tgccataggc cctgccaaga
     1561 tactgcaggt ccatccaggc ctctgctatc tgcatctgca gtgggcttcc caggaacttg
     1621 actgtctttc atttgatctt tatttttgtt tatttaatat tttaaacttt attttaaaaa
     1681 tatttcaaac ataagggcgg ggtgtggtgg ctcatgcctg taatcccagc actttgggag
     1741 gccgaggcgg gcggatcacc tgaggccagg agttggagac cagccaggcc accatggtga
     1801 aaccctgtct ctaccaaaaa tacaaaaaat tagccagata ttgtggcagg cacttttaat
     1861 cccagctact cgggaggctg aggcaggaga attgcttgaa cctgggaggc ggaggttgca
     1921 gtgagccaag attgcaccag tgcactccag cttgggcgac agatcaagac tctgtcacac
     1981 acaaaacaaa caaacaaatt ttcccgtttc tctctgtccc tttctctata acatggataa
     2041 aatattcacg tcttatgtat ttattattgc tgagtcattg gtgccttatt cttcagtgtt
     2101 tcagtctgta tctcctaagc atcctgatgt tagttttttg actataaaat tgacctgcat
     2161 tctttactag caattcaaac ggtacagcac tcttgaagtg taaacattcc tgttcctcct
     2221 caccccactc tgcagacatg cctttctgtc tgtcctccca gacttttccc ctgcataaag
     2281 atgttcattt tgtacataca ctcagacata catgtggctg tattttttgt ataccgattt
     2341 ctggatggaa tgcacactgt tatctgttta gttactttat gttttcatac aaatgacatc
     2401 atcccacaaa tagaattctg ccatttactt tcttcactat tcttatgtgg catggttcat
     2461 gctgggcctc ggtcttttga gtggggtctg tttacccagt cccctgttgg tgatcacatc
     2521 gctaacttcc ggcgttttcc tatcaccatc ggtgcctccg tgaacacctt gtgaatgtgc
     2581 ctgtgccttc gttctggtgt cggtgcagag cagggtccaa ggggcgtgac agctgggctg
     2641 aggggctggc atgtttcaca ttctgataga tagagccaag ttgctcctat caggttttca
     2701 agctgcccat ttcccaccgt ggagacagca acagagggga catccccagc tcctctggct
     2761 ctgcctgttc aaagctaccc tgtgaggcct gaagacagag ctgccctgaa ggcagctcat
     2821 gtccactgaa cactgactgt gggctggatg ctgtgccaag ggcttgacgt ttcctcttta
     2881 aggatgagga aacgggcaga gaagcggctg attgtccagt ccccctgcgt ggaggctgct
     2941 tggctgggct cgagcccagc ggtgtggtca tagagcatgt tgtgctgaat ggctctgcca
     3001 tggaccaagc cttggctgct ctaaaagccg gctcattgcc ttctgcttct ccggattcgt
     3061 tccttactcc aggaagagca gtgcactgaa ggagaaatgg gaatgggcaa aaggaaccac
     3121 atgctggcca gacccctgcg gggtcacttt cctcagcctg ggctccgaca tgccacgtca
     3181 ggtgccagcg cacatactct ggacaccctc ctcattctct ctgggctttg atgctctctg
     3241 tgagtcatct gccctccctt tcccatgcta caggcatcta ccttgctctg tcccacctaa
     3301 tagcttcagg actgaacaat tcaggaaagg gaagggaagg ggtggaggag aagagggaag
     3361 agtcggccct tggaaggttc tccacggaag actgcctttt ttttttttga gatggagtct
     3421 cgctgtgtcg cccagcctgg agtgcagtgg catgatctca gctcactgca aactccgcct
     3481 cctgggttca ggggattctt cagcctcagc ctccagagta gctgggacta caggtgcatg
     3541 ccactgtgcc ctgctaattt ttgtattttt agtagagacg gggtttcacc atattggcca
     3601 ggctggtctc gaactcctga cctcttggtc cacccgcctc agcctcccaa agtgctggga
     3661 ttacaggtgc aagccaccgc gcctggctcg agagactgac attctgtctc agcacagctg
     3721 gaagaggctg cttgagcacc aggataagga gttgtcttgc attcaggggc catgtggtgt
     3781 gcggatacct atttttcttt cttttctttt ttttttctga gacagagtct cgctctgtct
     3841 cccaggctag agtgcagtgg catgatctca gctcactgca acctctgtct cccgggttca
     3901 agcaattctt ctgcctcagc ctcccaagta gctgggatta caggtgccca ctaccacacc
     3961 cagctaattt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt
     4021 ttttgagatg gagtcctgct ctgtcacccc ggctggagtg cagtggtgcg atctcagctc
     4081 actgcaagct ccgcctcccg ggttcacact attctcctgc ctcagcctcc cgagtagctg
     4141 ggactacagg cgcctgccac catgcctggc tagttttttt gtattttaag tagagacagg
     4201 gtttcaccgt gttagccagg atggttcgat ctcctgacct catgatctgg ccgcctcagt
     4261 ctcccaaagt gctgagatta caggcgtgag ccagcgtgcc tggctaattt ttgtattttt
     4321 agtagagacg gggtttcacc atgttggcca ggctggtctc gaacccctga cctcaagcaa
     4381 tccacccacc ttggcctccc aaagagctga gattacaggt gtgagccacc gcacccggcc
     4441 caaggatacc tatttttctt aatgctggaa gccacactca gacaccagag cagctctcaa
     4501 tgctgggaat cctgggagac tgatgatgac cgcgtctccc tctgggacca aggatggtgg
     4561 aagggtgtgc agaattccaa atgttattta catcactcac tcttgtgtgg agtgcataat
     4621 tgtctttgct tgccaatttc atatcagtta aatataagca gtaagctaa
//
