LOCUS       NM_182977               6421 bp    mRNA    linear   PRI 07-FEB-2025
DEFINITION  Homo sapiens nicotinamide nucleotide transhydrogenase (NNT),
            transcript variant 2, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_182977
VERSION     NM_182977.3
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 6421)
  AUTHORS   Francisco,A., Goler,A.M.Y., Navarro,C.D.C., Onder,A., Yildiz,M.,
            Kendir Demirkol,Y., Karademir Yilmaz,B., Seven Menevse,T., Guran,T.
            and Castilho,R.F.
  TITLE     Lack of NAD(P)+ transhydrogenase activity in patients with primary
            adrenal insufficiency due to NNT variants
  JOURNAL   Eur J Endocrinol 190 (2), 130-138 (2024)
   PUBMED   38261461
  REMARK    GeneRIF: Lack of NAD(P)+ transhydrogenase activity in patients with
            primary adrenal insufficiency due to NNT variants.
            Erratum:[Eur J Endocrinol. 2024 Sep 30;191(4):X3. doi:
            10.1093/ejendo/lvae118.. PMID: 39361449]
REFERENCE   2  (bases 1 to 6421)
  AUTHORS   Grayson,C. and Mailloux,R.J.
  TITLE     Coenzyme Q10 and nicotinamide nucleotide transhydrogenase:
            Sentinels for mitochondrial hydrogen peroxide signaling
  JOURNAL   Free Radic Biol Med 208, 260-271 (2023)
   PUBMED   37573896
  REMARK    GeneRIF: Coenzyme Q10 and nicotinamide nucleotide transhydrogenase:
            Sentinels for mitochondrial hydrogen peroxide signaling.
            Review article
REFERENCE   3  (bases 1 to 6421)
  AUTHORS   Han,Y., Zhang,Y.Y., Pan,Y.Q., Zheng,X.J., Liao,K., Mo,H.Y.,
            Sheng,H., Wu,Q.N., Liu,Z.X., Zeng,Z.L., Yang,W., Yuan,S.Q.,
            Huang,P., Ju,H.Q. and Xu,R.H.
  TITLE     IL-1beta-associated NNT acetylation orchestrates iron-sulfur
            cluster maintenance and cancer immunotherapy resistance
  JOURNAL   Mol Cell 83 (11), 1887-1902 (2023)
   PUBMED   37244254
  REMARK    GeneRIF: IL-1beta-associated NNT acetylation orchestrates
            iron-sulfur cluster maintenance and cancer immunotherapy
            resistance.
REFERENCE   4  (bases 1 to 6421)
  AUTHORS   Bodoni,A.F., Coeli-Lacchini,F.B., Gebenlian,J.L., Sobral,L.M.,
            Garcia,C.B., Silva,W.A., Peronni,K.C., Ramalho,L.N.Z.,
            Ramalho,F.S., Moreira,A.C., de Castro,M., Leopoldino,A.M. and
            Antonini,S.R.R.
  TITLE     Nicotinamide Nucleotide Transhydrogenase Is Essential for Adrenal
            Steroidogenesis: Clinical and In Vitro Lessons
  JOURNAL   J Clin Endocrinol Metab 108 (6), 1464-1474 (2023)
   PUBMED   36478070
  REMARK    GeneRIF: Nicotinamide Nucleotide Transhydrogenase Is Essential for
            Adrenal Steroidogenesis: Clinical and In Vitro Lessons.
REFERENCE   5  (bases 1 to 6421)
  AUTHORS   Krasovec,T., Sikonja,J., Zerjav Tansek,M., Debeljak,M., Ilovar,S.,
            Trebusak Podkrajsek,K., Bertok,S., Tesovnik,T., Kovac,J., Suput
            Omladic,J., Hartmann,M.F., Wudy,S.A., Avbelj Stefanija,M.,
            Battelino,T., Kotnik,P. and Groselj,U.
  TITLE     Long-Term Follow-Up of Three Family Members with a Novel NNT
            Pathogenic Variant Causing Primary Adrenal Insufficiency
  JOURNAL   Genes (Basel) 13 (5), 717 (2022)
   PUBMED   35627102
  REMARK    GeneRIF: Long-Term Follow-Up of Three Family Members with a Novel
            NNT Pathogenic Variant Causing Primary Adrenal Insufficiency.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 6421)
  AUTHORS   White,S.A., Peake,S.J., McSweeney,S., Leonard,G., Cotton,N.P. and
            Jackson,J.B.
  TITLE     The high-resolution structure of the NADP(H)-binding component
            (dIII) of proton-translocating transhydrogenase from human heart
            mitochondria
  JOURNAL   Structure 8 (1), 1-12 (2000)
   PUBMED   10673423
REFERENCE   7  (bases 1 to 6421)
  AUTHORS   Arkblad,E.L., Helou,K., Levan,G. and Rydstrom,J.
  TITLE     Mapping of the rat and mouse nicotinamide nucleotide
            transhydrogenase gene
  JOURNAL   Mamm Genome 8 (9), 703 (1997)
   PUBMED   9271681
REFERENCE   8  (bases 1 to 6421)
  AUTHORS   Zieger,B. and Ware,J.
  TITLE     Cloning and deduced amino acid sequence of human nicotinamide
            nucleotide transhydrogenase
  JOURNAL   DNA Seq 7 (6), 369-373 (1997)
   PUBMED   9524818
REFERENCE   9  (bases 1 to 6421)
  AUTHORS   Forsmark-Andree,P., Persson,B., Radi,R., Dallner,G. and Ernster,L.
  TITLE     Oxidative modification of nicotinamide nucleotide transhydrogenase
            in submitochondrial particles: effect of endogenous ubiquinol
  JOURNAL   Arch Biochem Biophys 336 (1), 113-120 (1996)
   PUBMED   8951041
REFERENCE   10 (bases 1 to 6421)
  AUTHORS   Arkblad,E.L., Betsholtz,C. and Rydstrom,J.
  TITLE     The cDNA sequence of proton-pumping nicotinamide nucleotide
            transhydrogenase from man and mouse
  JOURNAL   Biochim Biophys Acta 1273 (3), 203-205 (1996)
   PUBMED   8616157
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BU429380.1, BC110543.1,
            AC010435.6 and AW771969.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_182977.2.
            
            Summary: This gene encodes an integral protein of the inner
            mitochondrial membrane. The enzyme couples hydride transfer between
            NAD(H) and NADP(+) to proton translocation across the inner
            mitochondrial membrane. Under most physiological conditions, the
            enzyme uses energy from the mitochondrial proton gradient to
            produce high concentrations of NADPH. The resulting NADPH is used
            for biosynthesis and in free radical detoxification. [provided by
            RefSeq, Sep 2016].
            
            Transcript Variant: This variant (2) differs in the 5' UTR compared
            to variant 1. Variants 1 and 2 encode the same 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 :: SRR1660803.149280.1,
                                           SRR1660809.145310.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: PMID: 12592411; reported by
                                                  MitoCarta
            MANE Ensembl match                 :: ENST00000344920.9/
                                                  ENSP00000343873.4
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-97                BU429380.1         61-157
            98-3917             BC110543.1         1-3820
            3918-4361           AC010435.6         134380-134823
            4362-4591           AW771969.1         12-241              c
            4592-6421           AC010435.6         135054-136883
FEATURES             Location/Qualifiers
     source          1..6421
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5p12"
     gene            1..6421
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /note="nicotinamide nucleotide transhydrogenase"
                     /db_xref="GeneID:23530"
                     /db_xref="HGNC:HGNC:7863"
                     /db_xref="MIM:607878"
     exon            1..115
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            116..319
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     CDS             169..3429
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /EC_number="7.1.1.1"
                     /note="isoform 1 is encoded by transcript variant 2;
                     pyridine nucleotide transhydrogenase; NAD(P)
                     transhydrogenase, mitochondrial"
                     /codon_start=1
                     /product="NAD(P) transhydrogenase, mitochondrial isoform
                     1"
                     /protein_id="NP_892022.2"
                     /db_xref="CCDS:CCDS3949.1"
                     /db_xref="GeneID:23530"
                     /db_xref="HGNC:HGNC:7863"
                     /db_xref="MIM:607878"
                     /translation="MANLLKTVVTGCSCPLLSNLGSCKGLRVKKDFLRTFYTHQELWC
                     KAPVKPGIPYKQLTVGVPKEIFQNEKRVALSPAGVQNLVKQGFNVVVESGAGEASKFS
                     DDHYRVAGAQIQGAKEVLASDLVVKVRAPMVNPTLGVHEADLLKTSGTLISFIYPAQN
                     PELLNKLSQRKTTVLAMDQVPRVTIAQGYDALSSMANIAGYKAVVLAANHFGRFFTGQ
                     ITAAGKVPPAKILIVGGGVAGLASAGAAKSMGAIVRGFDTRAAALEQFKSLGAEPLEV
                     DLKESGEGQGGYAKEMSKEFIEAEMKLFAQQCKEVDILISTALIPGKKAPVLFNKEMI
                     ESMKEGSVVVDLAAEAGGNFETTKPGELYIHKGITHIGYTDLPSRMATQASTLYSNNI
                     TKLLKAISPDKDNFYFDVKDDFDFGTMGHVIRGTVVMKDGKVIFPAPTPKNIPQGAPV
                     KQKTVAELEAEKAATITPFRKTMSTASAYTAGLTGILGLGIAAPNLAFSQMVTTFGLA
                     GIVGYHTVWGVTPALHSPLMSVTNAISGLTAVGGLALMGGHLYPSTTSQGLAALAAFI
                     SSVNIAGGFLVTQRMLDMFKRPTDPPEYNYLYLLPAGTFVGGYLAALYSGYNIEQIMY
                     LGSGLCCVGALAGLSTQGTARLGNALGMIGVAGGLAATLGVLKPGPELLAQMSGAMAL
                     GGTIGLTIAKRIQISDLPQLVAAFHSLVGLAAVLTCIAEYIIEYPHFATDAAANLTKI
                     VAYLGTYIGGVTFSGSLIAYGKLQGLLKSAPLLLPGRHLLNAGLLAASVGGIIPFMVD
                     PSFTTGITCLGSVSALSAVMGVTLTAAIGGADMPVVITVLNSYSGWALCAEGFLLNNN
                     LLTIVGALIGSSGAILSYIMCVAMNRSLANVILGGYGTTSTAGGKPMEISGTHTEINL
                     DNAIDMIREANSIIITPGYGLCAAKAQYPIADLVKMLTEQGKKVRFGIHPVAGRMPGQ
                     LNVLLAEAGVPYDIVLEMDEINHDFPDTDLVLVIGANDTVNSAAQEDPNSIIAGMPVL
                     EVWKSKQVIVMKRSLGVGYAAVDNPIFYKPNTAMLLGDAKKTCDALQAKVRESYQK"
     exon            320..549
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            550..767
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            768..855
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            856..944
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            945..1132
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1133..1266
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1267..1458
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1459..1612
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1613..1774
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1775..1885
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1886..2031
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2032..2227
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2228..2461
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2462..2622
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2623..2802
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2803..2962
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2963..3044
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3045..3163
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3164..3279
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3280..6421
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4233..4238
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /note="hexamer: AATAAA"
     polyA_site      4259
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /note="major polyA site"
     regulatory      4493..4498
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /note="hexamer: AGTAAA"
     polyA_site      4518
                     /gene="NNT"
                     /gene_synonym="GCCD4"
     regulatory      4563..4568
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /note="hexamer: AATATA"
     polyA_site      4585
                     /gene="NNT"
                     /gene_synonym="GCCD4"
     regulatory      6225..6230
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /note="hexamer: AAGAAA"
     polyA_site      6246
                     /gene="NNT"
                     /gene_synonym="GCCD4"
     regulatory      6401..6406
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NNT"
                     /gene_synonym="GCCD4"
                     /note="hexamer: AATACA"
     polyA_site      6421
                     /gene="NNT"
                     /gene_synonym="GCCD4"
ORIGIN      
        1 gctgttcttc cgggttggag gcgcagcgcc gcggggccca agcccgggtc tgccagcgcg
       61 acgtcctctc gcggccctca gggcacagcc caaggctgtc agcctcccgg cccagtgatt
      121 tgccttcaag gaaactgggg agtcagaaaa ttgggaactc atatcaacat ggcaaaccta
      181 ttgaaaacag tggtgactgg ctgctcgtgt cctctactta gcaatttggg gtcctgtaag
      241 ggtctacgtg tgaagaagga ttttttacga acattttata ctcaccaaga actgtggtgt
      301 aaagcgcctg taaaaccagg aattccatat aagcaactga ctgttggagt ccccaaagag
      361 atattccaaa atgagaagcg agtggcattg tctcctgctg gtgttcagaa cttggtcaag
      421 cagggtttta atgttgtcgt ggaatcgggt gcgggcgaag cttccaagtt ctcagatgat
      481 cactatagag tggcaggtgc ccaaatccaa ggggcaaagg aagtgctggc ttctgatttg
      541 gtggtcaaag tgcgagcccc tatggttaat ccaacattag gtgttcatga agctgacctt
      601 ttaaagacat caggaacgct gattagtttt atttacccag cccaaaatcc agagttgcta
      661 aataaacttt cccaaagaaa aactacagtt ctggcaatgg accaggttcc aagagtcaca
      721 attgctcagg gatatgatgc gctaagctcc atggccaaca ttgcgggtta taaggctgtt
      781 gtcctagcag caaatcattt tggacgtttt tttactggtc agatcacagc tgctggaaaa
      841 gttcctccag ctaagattct gatagttggt ggtggtgttg ctgggcttgc ttctgcaggc
      901 gcagcaaagt cgatgggtgc aattgttcga ggatttgaca caagagctgc agctttggaa
      961 cagttcaagt ctcttggtgc tgagcccttg gaggtggact tgaaggaatc tggtgaggga
     1021 caaggaggat atgcaaaaga gatgtccaaa gagttcattg aagctgaaat gaaactcttt
     1081 gctcaacaat gcaaggaggt agacatcctt atcagcacag cacttattcc aggtaaaaaa
     1141 gctccagttt tatttaataa agaaatgatt gagtcaatga aggaaggttc agttgttgtg
     1201 gatttagctg ctgaggctgg tggaaacttt gaaaccacta agccaggaga actctacatt
     1261 cataagggaa ttactcacat aggctacaca gacctgccca gccgaatggc cactcaggcc
     1321 agcaccctat attccaacaa catcaccaaa ctcctgaagg ccatcagccc ggacaaagat
     1381 aatttttatt ttgatgtgaa agatgacttt gactttggta cgatgggtca tgtcattaga
     1441 ggaactgtag tgatgaaaga tggtaaagtg attttcccag ctcccacacc gaaaaatatt
     1501 cctcaaggtg ccccagtaaa acagaagaca gtggctgagc tggaagctga aaaagcagct
     1561 accattacac ccttcaggaa gacaatgtca acggcttctg catatacagc aggtctcaca
     1621 gggatactgg gtttgggcat tgcggctccc aatctagcct tttctcagat ggtgaccact
     1681 tttggcttgg ctggcattgt ggggtatcat accgtctggg gagtgacccc tgctctccac
     1741 tcaccactga tgtctgtgac aaatgcaatc tcagggctga ctgcagttgg tgggttggca
     1801 ctgatgggag gacatttgta tccttccaca acttctcagg gccttgctgc tcttgctgca
     1861 ttcatatcct ctgtcaacat tgcaggtggc tttctggtga ctcagagaat gctggacatg
     1921 ttcaagcgtc ccactgaccc cccagaatac aactacctgt acctgctccc tgccggcacc
     1981 tttgttggtg gatatttagc tgccctctac agtggttata acattgaaca gatcatgtac
     2041 ctaggctcgg gtttgtgctg tgtcggtgcc ttggctggcc tctccaccca gggaacagca
     2101 cgtcttggca atgcactggg catgattggg gttgctggag gactggcagc caccctcgga
     2161 gtcctaaaac cgggcccaga attactagct cagatgtctg gagcgatggc tttgggtggt
     2221 accattggat tgacaattgc caaacgcatc cagatttctg atttacctca attagttgct
     2281 gcttttcaca gtttagtggg tttggcagct gtacttactt gcatagctga gtacattata
     2341 gaatatccac attttgctac ggatgcagca gcaaatctca ccaagattgt ggcctacctc
     2401 ggcacttaca ttggtggcgt cacctttagt gggtctctca ttgcctatgg aaaattgcag
     2461 ggtctcctga aatctgcccc tctcctactg cctggaaggc acttactcaa tgcaggctta
     2521 ctggctgcta gtgtgggcgg gataatccca ttcatggtgg acccaagctt tactactggc
     2581 atcacctgtc tgggttcagt gtctgctctc tctgctgtca tgggtgtgac tttgacagct
     2641 gctattgggg gtgctgacat gcccgtcgtt atcactgtgc tgaacagcta ctcaggctgg
     2701 gccctgtgtg cagagggctt cctgctcaac aacaatctgc tgaccatcgt gggtgcactc
     2761 ataggctcgt ctggtgctat cctgtcatac atcatgtgtg tggcaatgaa tcgctccctg
     2821 gctaatgtga ttcttggagg ctatggcacc acttcaacag ctggtggaaa acccatggaa
     2881 atttctggca cacatacgga aatcaacctt gacaatgcaa ttgacatgat tcgagaagct
     2941 aatagcatta ttattacacc aggctatggt ctctgtgcag ccaaagctca ataccccatt
     3001 gctgatttgg taaagatgct cactgagcaa ggcaaaaaag tcaggtttgg aattcaccca
     3061 gttgcaggcc gaatgcctgg tcagcttaat gtgctgctgg ctgaggctgg tgtgccatat
     3121 gacattgtgt tggaaatgga tgagatcaac catgattttc cagatactga tttggtcctt
     3181 gtaattggag ctaatgacac tgttaattca gcagctcaag aagatcccaa ctctattatt
     3241 gcaggcatgc cagtccttga ggtctggaaa tcaaagcagg tgattgttat gaagaggtct
     3301 ttgggtgttg gctatgctgc agtggacaat ccaatcttct acaaacctaa cacggccatg
     3361 cttctaggtg atgccaagaa aacatgtgac gcgctccagg cgaaagttag agaatcctat
     3421 cagaagtaaa tattaaggat caagctgtta gctaataatg ccacctctgc agttttggga
     3481 acaggcaaat aaagtatcag tatacatggt gatgtacatc tgtagcaaag ctcttggaga
     3541 aaatgaagac tgaagaaagc aaagcaaaaa ctgtatagag agatttttca aaagcagtaa
     3601 tccctcaatt ttaaaaaagg attgaaaatt ctaaatgtct ttctgtgcat attttttgtg
     3661 ttaggaatca aaagtatttt ataaaaggag aaagaacagc ctcattttag atgtagtcct
     3721 gttggatttt ttatgcctcc tcagtaacca gaaatgtttt aaaaaactaa gtgtttagga
     3781 tttcaagaca acattataca tggctctgaa atatctgaca caatgtaaac attgcaggca
     3841 cctgcatttt atgttttttt tttcaacaaa tgtgactaat ttgaaacttt tatgaacttc
     3901 tgagctgtcc ccttgcaatt caaccgcagt ttgaattaat catatcaaat cagttttaat
     3961 tttttaaatt gtacttcaga gtctatattt caagggcaca ttttctcact actattttaa
     4021 tacattaaag gactaaataa tctttcagag atgctggaaa caaatcattt gctttatatg
     4081 tttcattaga ataccaatga aacatacaac ttgaaaatta gtaatagtat ttttgaagat
     4141 cccatttcta attggagatc tctttaattt cgatcaactt ataatgtgta gtactatatt
     4201 aagtgcactt gagtggaatt caacatttga ctaataaaat gagttcatca tgttggcaag
     4261 tgatgtggca attatctctg gtgacaaaag agtaaaatca aatatttctg cctgttacaa
     4321 atatcaagga agacctgcta ctatgaaata gatgacatta atctgtcttc actgtttata
     4381 atacggatgg attttttttc aaatcagtgt gtgttttgag gtcttatgta attgatgaca
     4441 tttgagagaa atggtggctt tttttagcta cctctttgtt catttaagca ccagtaaaga
     4501 tcatgtcttt ttatagaagt gtagattttc tttgtgactt tgctatcgtg cctaaagctc
     4561 taaatatagg tgaatgtgtg atgaatactc agattatttg tctctctata taattagttt
     4621 ggtactaagt ttctcaaaaa attattaaca catgaaagac aatctctaaa ccagaaaaag
     4681 aagtagtaca aattttgtta ctgtaatgct cgcgtttagt gagtttaaaa cacacagtat
     4741 cttttggttt tataatcagt ttctattttg ctgtgcctga gattaagatc tgtgtatgtg
     4801 tgtgtgtgtg tgtgtgcgtt tgtgtgttaa agcagaaaag acttttttaa aagttttaag
     4861 tgataaatgc aatttgttaa ttgatcttag atcactagta aactcagggc tgaattatac
     4921 catgtatatt ctattagaag aaagtaaaca ccatctttat tcctgccctt tttcttctct
     4981 caaagtagtt gtagttatat ctagaaagaa gcaattttga tttcttgaaa aggtagttcc
     5041 tgcactcagt ttaaactaaa aataatcata cttggatttt atttattttt gtcatagtaa
     5101 aaattttaat ttatatatat ttttatttag tattatctta ttctttgcta tttgccaatc
     5161 ctttgtcatc aattgtgtta aatgaattga aaattcatgc cctgttcatt ttattttact
     5221 ttattggtta ggatatttaa aggatttttg tatatataat ttcttaaatt aatattccaa
     5281 aaggttagtg gacttagatt ataaattatg gcaaaaatct aaaaacaaca aaaatgattt
     5341 ttatacattc tatttcatta ttcctctttt tccaataagt catacaattg gtagatatga
     5401 cttattttat ttttgtatta ttcactatat ctttatgata tttaagtata aataattaaa
     5461 aaaatttatt gtaccttata gtctgtcacc aaaaaaaaaa aattatctgt aggtagtgaa
     5521 atgctaatgt tgatttgtct ttaagggctt gttaactatc ctttattttc tcatttgtct
     5581 taaattagga gtttgtgttt aaattactca tctaagcaaa aaatgtatat aaatcccatt
     5641 actgggtata tacccaaagg attataaatc atgctgctat aaagacacat gcacacgtat
     5701 gtttattgca gcactattca caatagcaaa gacttggaac caacccaaat gtccatcaat
     5761 gatagacttg attaagaaaa tgtgcacata tacaccatgg aatactatgc agccataaaa
     5821 aaggatgagt tcatgtcctt tgtagggaca tggataaagc tggaaaccat cattctgagc
     5881 aaactattgc aaggacagaa aaccaaacac tgcatgttct cactcatagg tgggaattga
     5941 acaatgagaa cacttggaca caaggtgggg aacaccacac accagggcct gtcatggggt
     6001 ggggggagtg gggagggata gcattaggag atatacctaa tgtaaatgat gagttaatgg
     6061 gtgcagcaca ccaacatggc acatgtatac atatgtagca aacctgcacg ttgtgcacat
     6121 gtaccctaga acttaaagta taattaaaaa aaaaaagaaa acagaagcta tttataaaga
     6181 agttatttgc tgaaataaat gtgatctttc ccattaaaaa aataaagaaa ttttggggta
     6241 aaaaaacaca atatattgta ttcttgaaaa attctaagag agtggatgtg aagtgttctc
     6301 accacaaaag tgataactaa ttgaggtaat gcacatatta attagaaaga ttttgtcatt
     6361 ccacaatgta tatatactta aaaatatgtt atacacaata aatacataca ttaaaaaata
     6421 a
//
