LOCUS       NM_002396               9031 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens malic enzyme 2 (ME2), transcript variant 1, mRNA;
            nuclear gene for mitochondrial product.
ACCESSION   NM_002396
VERSION     NM_002396.5
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 9031)
  AUTHORS   Teng,P., Cui,K., Yao,S., Fei,B., Ling,F., Li,C. and Huang,Z.
  TITLE     SIRT5-mediated ME2 desuccinylation promotes cancer growth by
            enhancing mitochondrial respiration
  JOURNAL   Cell Death Differ 31 (1), 65-77 (2024)
   PUBMED   38007551
  REMARK    GeneRIF: SIRT5-mediated ME2 desuccinylation promotes cancer growth
            by enhancing mitochondrial respiration.
REFERENCE   2  (bases 1 to 9031)
  AUTHORS   Zhao,M., Yao,P., Mao,Y., Wu,J., Wang,W., Geng,C., Cheng,J., Du,W.
            and Jiang,P.
  TITLE     Malic enzyme 2 maintains protein stability of mutant p53 through
            2-hydroxyglutarate
  JOURNAL   Nat Metab 4 (2), 225-238 (2022)
   PUBMED   35228743
  REMARK    GeneRIF: Malic enzyme 2 maintains protein stability of mutant p53
            through 2-hydroxyglutarate.
REFERENCE   3  (bases 1 to 9031)
  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   4  (bases 1 to 9031)
  AUTHORS   Wu,C.C., Li,H., Xiao,Y., Deng,W.W. and Sun,Z.J.
  TITLE     Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic
            carcinoma and mucoepidermoid carcinoma
  JOURNAL   Oral Dis 26 (8), 1687-1695 (2020)
   PUBMED   32564485
  REMARK    GeneRIF: Expression levels of SIX1, ME2, and AP2M1 in adenoid
            cystic carcinoma and mucoepidermoid carcinoma.
REFERENCE   5  (bases 1 to 9031)
  AUTHORS   Wang,M., Greenberg,D.A. and Stewart,W.C.L.
  TITLE     Replication, reanalysis, and gene expression: ME2 and genetic
            generalized epilepsy
  JOURNAL   Epilepsia 60 (3), 539-546 (2019)
   PUBMED   30719716
  REMARK    GeneRIF: influences susceptibility to adolescent-onset genetic
            generalized epilepsy
REFERENCE   6  (bases 1 to 9031)
  AUTHORS   Bukato,G., Kochan,Z. and Swierczynski,J.
  TITLE     Different regulatory properties of the cytosolic and mitochondrial
            forms of malic enzyme isolated from human brain
  JOURNAL   Int J Biochem Cell Biol 27 (10), 1003-1008 (1995)
   PUBMED   7496989
REFERENCE   7  (bases 1 to 9031)
  AUTHORS   Loeber,G., Infante,A.A., Maurer-Fogy,I., Krystek,E. and
            Dworkin,M.B.
  TITLE     Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning,
            primary structure, and expression in Escherichia coli
  JOURNAL   J Biol Chem 266 (5), 3016-3021 (1991)
   PUBMED   1993674
REFERENCE   8  (bases 1 to 9031)
  AUTHORS   Taroni,F., Gellera,C. and Di Donato,S.
  TITLE     Evidence for two distinct mitochondrial malic enzymes in human
            skeletal muscle: purification and properties of the
            NAD(P)+-dependent enzyme
  JOURNAL   Biochim Biophys Acta 916 (3), 446-454 (1987)
   PUBMED   3689803
REFERENCE   9  (bases 1 to 9031)
  AUTHORS   Siebert,G., Ritter,H. and Kompf,J.
  TITLE     Mitochondrial malic enzyme (E.C.1.1.1.40) in human leukocytes:
            formal genetics and population genetics
  JOURNAL   Hum Genet 51 (3), 319-322 (1979)
   PUBMED   511162
REFERENCE   10 (bases 1 to 9031)
  AUTHORS   Saha,N., Jeremiah,S.J. and Povey,S.
  TITLE     Further data on mitochondrial malic enzyme in man
  JOURNAL   Hum Hered 28 (6), 421-425 (1978)
   PUBMED   680703
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI559761.1, M55905.1,
            AK313391.1, AC087687.5 and CD370709.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_002396.4.
            
            Summary: This gene encodes a mitochondrial NAD-dependent malic
            enzyme, a homotetrameric protein, that catalyzes the oxidative
            decarboxylation of malate to pyruvate. It had previously been
            weakly linked to a syndrome known as Friedreich ataxia that has
            since been shown to be the result of mutation in a completely
            different gene. Certain single-nucleotide polymorphism haplotypes
            of this gene have been shown to increase the risk for idiopathic
            generalized epilepsy. Alternatively spliced transcript variants
            encoding different isoforms found for this gene. [provided by
            RefSeq, Dec 2009].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and 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 :: SRR1803611.6818.1,
                                           SRR1660807.255124.1 [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                 :: ENST00000321341.11/
                                                  ENSP00000321070.5
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-168               BI559761.1         23-190
            169-1369            M55905.1           55-1255
            1370-1958           AK313391.1         1322-1910
            1959-3986           AC087687.5         69336-71363
            3987-4569           CD370709.1         14-596              c
            4570-9031           AC087687.5         71947-76408
FEATURES             Location/Qualifiers
     source          1..9031
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="18"
                     /map="18q21.2"
     gene            1..9031
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /note="malic enzyme 2"
                     /db_xref="GeneID:4200"
                     /db_xref="HGNC:HGNC:6984"
                     /db_xref="MIM:154270"
     exon            1..191
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            192..311
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     CDS             204..1958
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /EC_number="1.1.1.38"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; pyruvic-malic carboxylase; NAD-ME; malic enzyme
                     2, NAD(+)-dependent, mitochondrial; malate dehydrogenase
                     (oxaloacetate-decarboxylating)"
                     /codon_start=1
                     /product="NAD-dependent malic enzyme, mitochondrial
                     isoform 1 precursor"
                     /protein_id="NP_002387.1"
                     /db_xref="CCDS:CCDS11948.1"
                     /db_xref="GeneID:4200"
                     /db_xref="HGNC:HGNC:6984"
                     /db_xref="MIM:154270"
                     /translation="MLSRLRVVSTTCTLACRHLHIKEKGKPLMLNPRTNKGMAFTLQE
                     RQMLGLQGLLPPKIETQDIQALRFHRNLKKMTSPLEKYIYIMGIQERNEKLFYRILQD
                     DIESLMPIVYTPTVGLACSQYGHIFRRPKGLFISISDRGHVRSIVDNWPENHVKAVVV
                     TDGERILGLGDLGVYGMGIPVGKLCLYTACAGIRPDRCLPVCIDVGTDNIALLKDPFY
                     MGLYQKRDRTQQYDDLIDEFMKAITDRYGRNTLIQFEDFGNHNAFRFLRKYREKYCTF
                     NDDIQGTAAVALAGLLAAQKVISKPISEHKILFLGAGEAALGIANLIVMSMVENGLSE
                     QEAQKKIWMFDKYGLLVKGRKAKIDSYQEPFTHSAPESIPDTFEDAVNILKPSTIIGV
                     AGAGRLFTPDVIRAMASINERPVIFALSNPTAQAECTAEEAYTLTEGRCLFASGSPFG
                     PVKLTDGRVFTPGQGNNVYIFPGVALAVILCNTRHISDSVFLEAAKALTSQLTDEELA
                     QGRLYPPLANIQEVSINIAIKVTEYLYANKMAFRYPEPEDKAKYVKERTWRSEYDSLL
                     PDVYEWPESASSPPVITE"
     exon            312..445
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            446..595
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            596..671
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            672..833
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            834..937
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            938..1047
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1048..1145
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1146..1259
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1260..1374
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1375..1517
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1518..1620
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1621..1691
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1692..1790
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1791..9031
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2645..2650
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /note="hexamer: AATAAA"
     polyA_site      2664
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /note="major polyA site"
     regulatory      4548..4553
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /note="hexamer: AATAAT"
     polyA_site      4569
                     /gene="ME2"
                     /gene_synonym="ODS1"
     regulatory      9008..9013
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ME2"
                     /gene_synonym="ODS1"
                     /note="hexamer: AGTAAA"
     polyA_site      9031
                     /gene="ME2"
                     /gene_synonym="ODS1"
ORIGIN      
        1 ctctcggccg ctcttcgggc cgcctctgcg tgtggggccg cccgcgccag tgtgagcctg
       61 agctgacggc ggctccggga ggctcgcaga aggggagggc cgggcggcgc gggagctgag
      121 catcgccagg gcgggcggca gggcgcggcc tctccgccgg gtgtaccacc tgtcgcggcg
      181 cgagacctct ggtgaaagaa aagatgttgt cccggttaag agtagtttcc accacttgta
      241 ctttggcatg tcgacatttg cacataaaag aaaaaggcaa gccacttatg ctgaacccaa
      301 gaacaaacaa gggaatggca tttactttac aagaacgaca aatgcttggt cttcaaggac
      361 ttctacctcc caaaatagag acacaagata ttcaagcctt acgatttcat agaaacttga
      421 agaaaatgac tagccctttg gaaaaatata tctacataat gggaatacaa gaaagaaatg
      481 agaaattgtt ttatagaata ctgcaagatg acattgagag tttaatgcca attgtatata
      541 caccgacggt tggtcttgcc tgctcccagt atggacacat ctttagaaga cctaagggat
      601 tatttatttc gatctcagac agaggtcatg ttagatcaat tgtggataac tggccagaaa
      661 atcatgttaa ggctgttgta gtgactgatg gagagagaat tctgggtctt ggagatctgg
      721 gtgtctatgg aatgggaatt ccagtaggaa aactttgttt gtatacagct tgtgcaggaa
      781 tacggcctga tagatgcctg ccagtgtgta ttgatgtggg aactgataat atcgcactct
      841 taaaagaccc attttacatg ggcttgtacc agaaacgaga tcgcacacaa cagtatgatg
      901 acctgattga tgagtttatg aaagctatta ctgacagata tggccggaac acactcattc
      961 agttcgaaga ctttggaaat cataatgcat tcaggttctt gagaaagtac cgagaaaaat
     1021 attgtacttt caatgatgat attcaaggga cagctgcagt agctctagca ggtcttcttg
     1081 cagcacaaaa agttattagt aaaccaatct ccgaacacaa aatcttattc cttggagcag
     1141 gagaggctgc tcttggaatt gcaaatctta tagttatgtc tatggtagaa aatggcctgt
     1201 cagaacaaga ggcacaaaag aaaatctgga tgtttgacaa gtatggttta ttagttaagg
     1261 gacggaaagc aaaaatagat agttatcagg aaccatttac tcactcagcc ccagagagca
     1321 tacctgatac ttttgaagat gcagtgaata tactgaagcc ttcaactata attggagttg
     1381 caggtgctgg ccgtcttttc actcctgatg taatcagagc catggcctct atcaatgaaa
     1441 ggcctgtaat atttgcatta agtaatccta cagcacaggc agagtgcacg gctgaagaag
     1501 catatacact tacagagggc aggtgtttgt ttgccagtgg cagtccattt gggccagtga
     1561 aacttacaga tgggcgagtc tttacaccag gtcaaggaaa caatgtttat atttttccag
     1621 gtgtggcttt agctgttatt ctctgtaaca cccggcatat tagtgacagt gttttcctag
     1681 aagctgcaaa ggccctgaca agccaattga cagatgaaga gctagcccaa gggagacttt
     1741 acccaccgct tgctaatatt caggaagttt ctattaacat tgctattaaa gttacagaat
     1801 acctatatgc taataaaatg gctttccgat acccagaacc tgaagacaag gccaaatatg
     1861 ttaaagaaag aacatggcgg agtgaatatg attccctgct gccagatgtg tatgaatggc
     1921 cagaatctgc atcaagccct cctgtgataa cagaatagaa gcactcccct gataaatact
     1981 ttctgtgctc cagggaaccc cttttttcag acaagaagag ataatgtctt cagttttatg
     2041 gtgttttctg tgttttgttc tccctgacca ctttggttga tgtatttttt ccatgcgtct
     2101 ccacatctgt tggggtagac gtgttgattg attgcattgc ccaccagcac cctacagtca
     2161 gatagttgtg atgctttaat tctaacatac agcccgtacc acatccagga gatgtaaaaa
     2221 gtgtgtttgt gaatgtcttc acttgtactc taattcagac ttgccaaagt atttgctatt
     2281 tactattatg ggtaatactc ttctctggcc tagttcttac agagctacta aaatagaaat
     2341 ttacttttat ggatagaagt acagaatttt gagaagaaac taaattttca ccaaatttta
     2401 aggaaaaatt gtcattatct aaaaatgttc ttatatatct gcttcatctt accttcatac
     2461 tctgaaattc cctatagcag acagagctag ggaaatatta aaaatttacc ctatttattt
     2521 tctggaacta aatcaagcct taactataac attatgagag taatgggaac tactgctggc
     2581 tttaagtaaa taaaagtcat tgttttcaac agtgtataaa aatcatagtg taaccttttt
     2641 atttaataaa tatcttacat ttaattgctt cagttatgct atcttattgc ccaactagaa
     2701 atttagattt gcttatgaaa aacacatatt tttgttactt ctagatgatt ctaggaggga
     2761 gtataagata cctaatcata tgggaacatc acgtgacttt ttaaatctaa attagtcatg
     2821 cttcacatca aaatgagtca tatttaactg gagaaactat gcccttattc cagaactgat
     2881 gctctttatt gcttgagata attttggaat gttactatga tactgtttct ttgaatatca
     2941 ttagtagtga caactctttc tccattgaag gcagacttaa tttttttaaa ccaccaacat
     3001 taatttagag ctaaatgggg atgaataagg ttggtgttca tctgggaaat gcctttttta
     3061 atcccagtaa aatgggtaat aatggctatc cagaacagtt ttcttgtgtg gcttgcatat
     3121 tgaagaattc taaaggaaaa tatatctgcc taccatgctt gctcttaggg aagaaaactt
     3181 aaatgctcat tctaggatag taacaacaac agataattca tcgataatat gagcatgcac
     3241 agtatttgat attgctctgt aggaaaaaag agacttcatt tttttcatct tctgcctatg
     3301 aatacaaatt gattcttttt tttttttttt ttttttgaga cagagtctca ctctgttacc
     3361 aggctggagt gcagtggtgt gatctcagct cactgcaacc tctgcctccc aggttcaagc
     3421 agttctcctg cctcagcctc ccaagtagct gggactacag gtacacgcca ccacgcccag
     3481 ctaatttttg tatttttagt agagacggga tttcaccatg ttggccagga gggtctcgat
     3541 ttcctgacct cgcgatccgc ccacctcagc cttccaaagt gctgggatta caggcgtgag
     3601 ccaccgcacc cagccaattt tttttttttt tttttttgag acagagtctc gcttttgtcg
     3661 cccagtctgg agtgtagtgg catgatctct gcaacctctg cctcctcggt tcaggcgatt
     3721 cttctgcctt agcctcccaa gtagctggga ttacaggcac cggccaccac acccagctaa
     3781 tttttgtatt tttagtagag atggggtttc accatgttgg ccaggctggt ctcaaaatcc
     3841 tgacttcagg tgatccaccc actttggcct cccaaagtgc tgggattaca ggcgtgagcc
     3901 accacacctg gtccaattca tcataattct gaatataatt taataatttt aaaatggtcg
     3961 caatggcatt gccatttgga gtatgggaaa atgcagttgg ttaattcatt gaacagatta
     4021 gtaaagtcag aagtcttttt cataacatac ggtcacaatt cctttctttt aattaaagac
     4081 aaaaggttta tgggttttgg tttgtttgtt ttagatatgg ggttttgcta tgtcaccctt
     4141 gctggagggc ggtggctgtt cacaggcgtg ggtcatagag cactgcagcc tggaactcct
     4201 gggttcaagc tctcctcctg cctcagcctc ctgagcagct tggactaaag gtgtgcacca
     4261 ccgcacctgg ctgagaggct tctgtttttc atgttccctt tatcaaaaca aaatcacgcc
     4321 taaacatact ctctgtgtga aatcttgatt ttagttcaac ctaagaaata taataaatat
     4381 aaacctgttt cttgcttagt gtttattgaa ggcaggaacg tatgctgaat taaagtaatt
     4441 ttactacgaa gtttgcttat taagtatgcc tggtacagtc ttcatggaag ttattaagta
     4501 ttttaaggaa aaaaataggc taaatggcat atagcctgct taaataaaat aattctattt
     4561 ttttaaaaag ctcccaattg tcattgttat ttaccagtca atctttcaac aagtatcaat
     4621 tattggatgt aaattaaagt aaaattgctt aatatttaag ctaagaatac aggaaggact
     4681 atgagcattg aggaaatcgg gggaggccag aatggcatca agctggaaaa gaaattaaaa
     4741 cattaccttc gatgagactt tacctagcaa gaaggtaatt attttgaata acagcaatag
     4801 agaatctttt attttgaatt gagaagaaat tctgatgatt agagtgtcag taagtagtag
     4861 gaaaaggtaa gaatacatgt gtttctaatc tcccaccacc acctgttgta tggaacaaat
     4921 tggattacta gcaagggtaa ggtttattga caatgagaag ttttagtcca agattttagt
     4981 taaaatattt taaaattttt tgattcataa ccaagaagtt gcctcagatc actgtgaagc
     5041 tttaaaatgc aggtgccttt gctcctcctc cctccaggcc cccgggggca gagccctggc
     5101 tggtgtctct tcaggaggac ccctgacaca ccgattctgc cctcacaatc actgccttaa
     5161 agcaggcagc agaatctttt ggagaactaa caagattctg atgctgatgc atagggcctg
     5221 gggtggggcc tcagattctg cttttttttt tttttttttt ttttttttta aacagggtct
     5281 ctttcttttt cctttctcac tcaggctgca gtgagtggcg tgatcttggc tcactgcaac
     5341 ctccacttcc tgggctcaaa cgatcctccc gcctcagcct cctgagtagc tgggactata
     5401 ggcgcaagtc tatgcaacca cccagctaat ttttgtattt ttagaagagt gggggttttg
     5461 ccacgttgcc tgggctggtc tcgaactcct gacctcaagt gatccaacca cctcagcctc
     5521 ccaaagtgct ggaattacag gcatgagcca ctgcacccag ccaagaatgt ccacttctga
     5581 caagctccca ggtgatgcct atgctgctgg tacagtgaac aacatgctga gaggcattgc
     5641 tccaggatac tgcatgtagt gagcagttct ttagcgttta tgtgtcatat acttcaagtt
     5701 acatgaaaaa gatcaactga aattatgttc ttacacagaa tagttttcat ctagttttat
     5761 tatgttttta caggctgttt acaagaacaa aaatagagaa tttttgaaca tatttttctg
     5821 aaaacataaa aactagagta ctctttaatt ctaaattata gatttgtagc atacttagta
     5881 aacttagtaa ccaattttca tttgtaaaag attagctatc aaatggacat ttatttctct
     5941 tagttttctt atgacatgac ttgccttata tcctttgtcc tttttctgta acttgtcagc
     6001 ctctggagaa ataggatttt acatttttgc aaatgagttg ccaatgaatt aagatcaaaa
     6061 cgtcattatt aaggagtatg aagcattatt tactggctct cagataacag aaaacccaaa
     6121 agggatggtg gcggagtgaa gaaagccttg ccttgggaaa aatacttcaa atgctcccat
     6181 agtttttttt cctcaagccc agtcagtatc cttcaaggat aactttttca tacctttttt
     6241 ttggtttgtt tgtttctgct agctttatga cagaggttat aatattcttt tctcctctct
     6301 tctttgacgt gttacgttgt cttttttttt ttttttttaa cttcttcata ctcttaaaaa
     6361 gctccagaat ggccaggcgc agtggctcac gcctataatc ccagcacttt gggaggccaa
     6421 ggcaggcgga tcacgaggtc aggagatcaa gaccatcctg gctgacacgg tgaaaccctg
     6481 tctctactaa aaatacaaaa acttagccag gcgtggtggc gggcgcctgt agtcccaggt
     6541 actcgggagt ctgaggagtg aacccgggag gtggaggttg cagtgagctg agatcgcacc
     6601 gctgcactcc agcctgggcg acagagtgag cctccatctc aaaaaaaaaa aaaaaaaaaa
     6661 aaaaaaaaaa aaaaaaatct ccagggttct gttgaattca ccaaaatggg gtcagctctg
     6721 gtgagcctat gtaatactcg agaacattaa tataaaccca tagctcttta ctgggcttcc
     6781 atttaaaggg aagtcctaag aatgaaatgg caccagcatc ctgtttccat ccaagacaag
     6841 accacacgtg ttcaggtgcc atgtattcat atagctctca actgattggt gatttgcact
     6901 ttgtgcatct aattattaaa atgaaactct ctacaggtga gctgaagtaa catacttcat
     6961 atttaaaaag ttcacagcaa tttgaccata gaaaactttc tcatctgaaa tcagggtaag
     7021 tttttttaat gtaagcagag aaaaaaataa agcagtgttt tatttcaaat ttcagtaagt
     7081 tcaggtgggc ctaattaaga catgactatt attacaaatc ctattcttgc cagaagttac
     7141 ttagatagat tagtgattag attttaaaaa cattattttc ctttcttgaa taaggaaaat
     7201 tgtgcatctc aaagagaaaa gtaaatatgg aaatatgttc atagttcagt tgcataaaat
     7261 agacacatta agtcaagtga tttgaatgct tagtgtcttt tggtaaacag cattttgtca
     7321 acaaactttt catatggcta tagaatcttg ttttttccaa ataaaaactt tgcaattggg
     7381 agttattcct ccattcagca cactttttaa tgttaagact aggggaaact tgtgggtata
     7441 tattcagtgg ttttcaggat tttcttttat gttctagaaa agtaattttt cctttcctag
     7501 ttttaagtat atattcaagc aaatcgttga ttcctataca gccattggat tatcaccaac
     7561 acatttggta tatacagtgg gccgataatg acaaactaaa gtttgtggtt aatacctact
     7621 ctataccaga cactgttcta aggatccgac atatttaatc ctctgtttac cctctgtttc
     7681 tgtgcctgat ttacagacag agacagaggc acagagaggt taaatgactt gtcaaaggtc
     7741 ttatgatgtg tggcagagcc tgggttttta gctcaaaccc ctctcagtga agaaagcctt
     7801 ctgtgtaggc aatttcatct aataccttca tgaattgtta cttcagatga gaattctcac
     7861 ttattctttt tttttttttt ttttcttttc tttgagacag ccttgctctg tctcccaggc
     7921 tggagtgcag tggcgcaatc tcagctcact gcaagctccg cctcccgggt tatgccattc
     7981 tcctgcctca gccttccgag tagctcggac tacaggcgcc cgccacctcg cccagctaat
     8041 tttttgtatt tttagtagag acggggtttc accgtgttag ccaggatggt ctcgatctcc
     8101 tgacctcatg atccacccgc ctcggcctcc caaagtgctg ggattacagg cgtgagccac
     8161 cgcgcccggc ctcacttagt cttttaccag ttcatctgat ttttactttg ttcccattta
     8221 taattcaaat ataatataaa cgtcttattc atttagtctt cagcatttta agtattcgac
     8281 acgaacatta aagatttggt gttgaattta ataaattaca ccaaaaagtc tcagtagcca
     8341 attcactaac atcttttgat ttggtaatct tcacagaatc aacaactgtt aacacttctg
     8401 tgcaaataaa tttcagttgt gcttatatat tataatattc actttaggaa tccacctgtc
     8461 aatttgcaat tcaattataa ggtatatttt aagtgatatc tatgtattgt atacacatat
     8521 tccattgaaa ggtgagaata attagaaagt agtaatataa aaatgtgtat gaaataagaa
     8581 ctttcttaaa agacctagtt tagctaaata tatgacaata taaaatgtct gcccaatgtt
     8641 ttattatact ttgtctaatg acctttaaat ttaactgaaa ttaaaaccgt acttttgcag
     8701 ttgatatttt tgtgttccct ttgttaacat accaagcact aattattgac ttcaaggaag
     8761 ccacgtattg caagtcattg cttagccttt cacatctgag tgttgataag atgacggaat
     8821 gggtagtctt gtagtaattg cttatgggaa tgctagttta agaggaatgc cttgtataga
     8881 acatattata ccagattgac ttgttaaaaa tggttccaag aatcagtcta aaaacttcag
     8941 aattatgtga attatttttt ctctgttgtg atatgttgta atgagatgtg tgttcttata
     9001 ttttcttagt aaaattttct taagcataaa a
//
