LOCUS       NM_005763               5825 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens aminoadipate-semialdehyde synthase (AASS), mRNA;
            nuclear gene for mitochondrial product.
ACCESSION   NM_005763
VERSION     NM_005763.4
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 5825)
  AUTHORS   Leandro,J., Khamrui,S., Suebsuwong,C., Chen,P.J., Secor,C.,
            Dodatko,T., Yu,C., Sanchez,R., DeVita,R.J., Houten,S.M. and
            Lazarus,M.B.
  TITLE     Characterization and structure of the human lysine-2-oxoglutarate
            reductase domain, a novel therapeutic target for treatment of
            glutaric aciduria type 1
  JOURNAL   Open Biol 12 (9), 220179 (2022)
   PUBMED   36128717
REFERENCE   2  (bases 1 to 5825)
  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 5825)
  AUTHORS   Sasse,S.K., Zuo,Z., Kadiyala,V., Zhang,L., Pufall,M.A., Jain,M.K.,
            Phang,T.L., Stormo,G.D. and Gerber,A.N.
  TITLE     Response Element Composition Governs Correlations between Binding
            Site Affinity and Transcription in Glucocorticoid Receptor
            Feed-forward Loops
  JOURNAL   J Biol Chem 290 (32), 19756-19769 (2015)
   PUBMED   26088140
  REMARK    GeneRIF: GR and KLF15 physically interact via low affinity GR
            binding sites within glucocorticoid response elements (GREs) for
            PRODH and AASS that contribute to combinatorial regulation with
            KLF15.
REFERENCE   4  (bases 1 to 5825)
  AUTHORS   Houten,S.M., Denis,S., Te Brinke,H., Jongejan,A., van Kampen,A.H.,
            Bradley,E.J., Baas,F., Hennekam,R.C., Millington,D.S., Young,S.P.,
            Frazier,D.M., Gucsavas-Calikoglu,M. and Wanders,R.J.
  TITLE     Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes
            dienoyl-CoA reductase deficiency with hyperlysinemia
  JOURNAL   Hum Mol Genet 23 (18), 5009-5016 (2014)
   PUBMED   24847004
  REMARK    GeneRIF: Mitochondrial NADPH is crucial for AASS function
REFERENCE   5  (bases 1 to 5825)
  AUTHORS   Houten,S.M., Te Brinke,H., Denis,S., Ruiter,J.P., Knegt,A.C., de
            Klerk,J.B., Augoustides-Savvopoulou,P., Haberle,J.,
            Baumgartner,M.R., Coskun,T., Zschocke,J., Sass,J.O., Poll-The,B.T.,
            Wanders,R.J. and Duran,M.
  TITLE     Genetic basis of hyperlysinemia
  JOURNAL   Orphanet J Rare Dis 8, 57 (2013)
   PUBMED   23570448
  REMARK    GeneRIF: Hyperlysinemia is caused by mutations in AASS
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 5825)
  AUTHORS   Hendrickson,S.L., Lautenberger,J.A., Chinn,L.W., Malasky,M.,
            Sezgin,E., Kingsley,L.A., Goedert,J.J., Kirk,G.D., Gomperts,E.D.,
            Buchbinder,S.P., Troyer,J.L. and O'Brien,S.J.
  TITLE     Genetic variants in nuclear-encoded mitochondrial genes influence
            AIDS progression
  JOURNAL   PLoS One 5 (9), e12862 (2010)
   PUBMED   20877624
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 5825)
  AUTHORS   Sacksteder,K.A., Biery,B.J., Morrell,J.C., Goodman,B.K.,
            Geisbrecht,B.V., Cox,R.P., Gould,S.J. and Geraghty,M.T.
  TITLE     Identification of the alpha-aminoadipic semialdehyde synthase gene,
            which is defective in familial hyperlysinemia
  JOURNAL   Am J Hum Genet 66 (6), 1736-1743 (2000)
   PUBMED   10775527
REFERENCE   8  (bases 1 to 5825)
  AUTHORS   Papes,F., Kemper,E.L., Cord-Neto,G., Langone,F. and Arruda,P.
  TITLE     Lysine degradation through the saccharopine pathway in mammals:
            involvement of both bifunctional and monofunctional
            lysine-degrading enzymes in mouse
  JOURNAL   Biochem J 344 Pt 2 (Pt 2), 555-563 (1999)
   PUBMED   10567240
  REMARK    GeneRIF: Isolation and characterization of the mouse ortholog.
REFERENCE   9  (bases 1 to 5825)
  AUTHORS   Markovitz,P.J., Chuang,D.T. and Cox,R.P.
  TITLE     Familial hyperlysinemias. Purification and characterization of the
            bifunctional aminoadipic semialdehyde synthase with
            lysine-ketoglutarate reductase and saccharopine dehydrogenase
            activities
  JOURNAL   J Biol Chem 259 (19), 11643-11646 (1984)
   PUBMED   6434529
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA995180.1, AF229180.1,
            AC006020.2 and BM669241.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_005763.3.
            
            Summary: This gene encodes a bifunctional enzyme that catalyzes the
            first two steps in the mammalian lysine degradation pathway. The
            N-terminal and the C-terminal portions of this enzyme contain
            lysine-ketoglutarate reductase and saccharopine dehydrogenase
            activity, respectively, resulting in the conversion of lysine to
            alpha-aminoadipic semialdehyde. Mutations in this gene are
            associated with familial hyperlysinemia. [provided by RefSeq, Jul
            2008].
            
            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 alignments.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803617.21373.1,
                                           SRR1660809.102574.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000417368.7/
                                                  ENSP00000403768.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-35                DA995180.1         42-76
            36-3132             AF229180.1         1-3097
            3133-5278           AC006020.2         63051-65196         c
            5279-5825           BM669241.1         22-568              c
FEATURES             Location/Qualifiers
     source          1..5825
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q31.32"
     gene            1..5825
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /note="aminoadipate-semialdehyde synthase"
                     /db_xref="GeneID:10157"
                     /db_xref="HGNC:HGNC:17366"
                     /db_xref="MIM:605113"
     exon            1..89
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            90..314
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     CDS             105..2885
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /EC_number="1.5.1.8"
                     /EC_number="1.5.1.9"
                     /note="lysine-2-oxoglutarate reductase; aminoadipic
                     semialdehyde synthase; lysine-ketoglutarate reductase
                     /saccharopine dehydrogenase; alpha-aminoadipate
                     semialdehyde synthase; saccharopine dehydrogenase (NAD(+),
                     L-glutamate-forming); saccharopine dehydrogenase (NADP(+),
                     L-lysine-forming)"
                     /codon_start=1
                     /product="alpha-aminoadipic semialdehyde synthase,
                     mitochondrial"
                     /protein_id="NP_005754.2"
                     /db_xref="CCDS:CCDS5783.1"
                     /db_xref="GeneID:10157"
                     /db_xref="HGNC:HGNC:17366"
                     /db_xref="MIM:605113"
                     /translation="MLQVHRTGLGRLGVSLSKGLHHKAVLAVRREDVNAWERRAPLAP
                     KHIKGITNLGYKVLIQPSNRRAIHDKDYVKAGGILQEDISEACLILGVKRPPEEKLMS
                     RKTYAFFSHTIKAQEANMGLLDEILKQEIRLIDYEKMVDHRGVRVVAFGQWAGVAGMI
                     NILHGMGLRLLALGHHTPFMHIGMAHNYRNSSQAVQAVRDAGYEISLGLMPKSIGPLT
                     FVFTGTGNVSKGAQAIFNELPCEYVEPHELKEVSQTGDLRKVYGTVLSRHHHLVRKTD
                     AVYDPAEYDKHPERYISRFNTDIAPYTTCLINGIYWEQNTPRLLTRQDAQSLLAPGKF
                     SPAGVEGCPALPHKLVAICDISADTGGSIEFMTECTTIEHPFCMYDADQHIIHDSVEG
                     SGILMCSIDNLPAQLPIEATECFGDMLYPYVEEMILSDATQPLESQNFSPVVRDAVIT
                     SNGTLPDKYKYIQTLRESRERAQSLSMGTRRKVLVLGSGYISEPVLEYLSRDGNIEIT
                     VGSDMKNQIEQLGKKYNINPVSMDICKQEEKLGFLVAKQDLVISLLPYVLHPLVAKAC
                     ITNKVNMVTASYITPALKELEKSVEDAGITIIGELGLDPGLDHMLAMETIDKAKEVGA
                     TIESYISYCGGLPAPEHSNNPLRYKFSWSPVGVLMNVMQSATYLLDGKVVNVAGGISF
                     LDAVTSMDFFPGLNLEGYPNRDSTKYAEIYGISSAHTLLRGTLRYKGYMKALNGFVKL
                     GLINREALPAFRPEANPLTWKQLLCDLVGISPSSEHDVLKEAVLKKLGGDNTQLEAAE
                     WLGLLGDEQVPQAESILDALSKHLVMKLSYGPEEKDMIVMRDSFGIRHPSGHLEHKTI
                     DLVAYGDINGFSAMAKTVGLPTAMAAKMLLDGEIGAKGLMGPFSKEIYGPILERIKAE
                     GIIYTTQSTIKP"
     exon            315..491
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            492..576
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            577..644
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            645..791
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            792..870
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            871..998
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            999..1147
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1148..1270
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1271..1382
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1383..1442
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1443..1510
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1511..1632
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1633..1759
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1760..1870
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1871..1979
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            1980..2120
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            2121..2288
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            2289..2384
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            2385..2500
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            2501..2589
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            2590..2766
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     exon            2767..5825
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5805..5810
                     /regulatory_class="polyA_signal_sequence"
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /note="hexamer: TATAAA"
     polyA_site      5825
                     /gene="AASS"
                     /gene_synonym="LKR/SDH; LKRSDH; LORSDH"
                     /note="major polyA site"
ORIGIN      
        1 agtttcttct aggaattcgg agcctcccct gcagcgactc ggaagattcg aggcggcggg
       61 ggacaagtcg gcgccccaga gcggacgagt caccaggtgt caagatgctg caagtacata
      121 ggactggact gggcaggctg ggggtcagcc tctccaaggg tcttcaccac aaagctgtgt
      181 tggccgtccg gagggaggat gtgaacgcct gggagagaag ggccccgcta gctcccaagc
      241 acatcaaagg catcaccaat ctgggataca aggtcttgat acagccttcg aatcggcggg
      301 ccattcatga taaggactat gtcaaagctg gtggcattct tcaggaggat atttctgaag
      361 cttgtctaat tttaggagtt aaaagacctc cagaggaaaa attaatgtcc aggaagactt
      421 atgcattttt ctcccacaca ataaaagctc aggaggccaa tatgggcttg ttggatgaga
      481 ttctaaaaca ggaaattcgc cttattgatt atgagaaaat ggtggatcat agaggagtac
      541 gggtagtggc atttggacag tgggctggtg tggcaggaat gatcaacatt ttacatggaa
      601 tgggtttaag gctccttgct ttgggacatc acacaccttt tatgcacatt ggcatggctc
      661 ataactacag gaatagcagt caggctgtgc aagctgtccg tgatgctggc tatgaaatat
      721 ctttgggttt gatgcctaag tcaataggac ccttaacatt tgtgttcaca ggaactggta
      781 atgtttctaa gggagcccaa gcaatcttta atgagctacc ttgtgaatat gtggagcccc
      841 atgaattaaa agaagtttcc caaactggag acctcagaaa agtgtatggg acggtgttaa
      901 gtcgtcatca tcatcttgtc aggaaaacag atgctgtgta tgatcctgca gagtatgaca
      961 aacatccgga gcgctacata agtcgtttta atactgatat tgcaccctat acaacttgct
     1021 taattaatgg aatctactgg gaacaaaaca ctcctcgcct cctaacccgc caagatgctc
     1081 agagtctcct ggctccgggc aagttctcac ctgctggtgt ggaaggctgc cctgcattac
     1141 cacacaaact cgtggcaata tgtgacattt cagctgacac aggagggtct atagagttta
     1201 tgactgagtg tacaacaata gagcatccct tttgcatgta tgatgcagac cagcatatta
     1261 ttcatgacag tgttgaaggc tcggggatcc tgatgtgttc cattgacaat ttgccggcac
     1321 agctcccaat tgaagctaca gaatgctttg gagacatgct ttacccttat gttgaagaaa
     1381 tgatattatc agacgcgaca cagcctcttg aaagtcagaa tttttctcct gtggtgagag
     1441 atgcagtgat tacatccaac ggtacattac ctgataaata taaatatatc cagacactcc
     1501 gggagagcag ggaacgtgct cagtcacttt caatgggcac caggagaaag gttttggttc
     1561 ttggatctgg ctacatatct gagcctgtat tagaatattt atcaagagat ggcaatatag
     1621 aaataacagt aggatctgac atgaagaatc aaattgaaca gttaggcaag aaatataata
     1681 ttaatcctgt tagcatggac atttgtaaac aagaagagaa gctgggcttc ttggtggcaa
     1741 aacaggatct tgtcatcagc ttgttgcctt atgtattgca ccctcttgtg gccaaggcct
     1801 gcatcacaaa caaagttaac atggtcactg caagctacat cacaccagca ctaaaagaat
     1861 tggaaaagag tgtggaagat gctggcatca caatcattgg tgaattggga ttggaccctg
     1921 gtctggatca catgttagca atggaaacaa tagataaagc caaggaagtg ggagccacga
     1981 ttgaatcata tatttcctac tgtggtgggc ttccagcccc tgaacattca aacaatccat
     2041 tgagatataa atttagctgg agtccagtgg gagttttgat gaatgtaatg cagtctgcca
     2101 cctatctgct cgatggaaag gttgtgaatg ttgcaggagg catctccttt cttgatgccg
     2161 ttacgtccat ggattttttt ccaggattaa atttggaagg ctatcctaac agagacagta
     2221 cgaaatatgc tgagatttat ggcatttctt ctgctcacac tttgttgcgg gggacactga
     2281 gatataaggg atatatgaaa gctttgaatg gatttgtaaa attaggtctt ataaacagag
     2341 aagcgcttcc tgcctttaga cctgaggcca accctctcac ctggaaacaa ctcctctgtg
     2401 acctagttgg gatttcaccc tcctctgagc atgatgtgtt gaaggaagct gttcttaaga
     2461 aactaggagg agacaatacc cagttggagg ctgctgaatg gttgggctta cttggggatg
     2521 aacaagttcc tcaggcagag tccattctgg atgccctctc caagcatttg gtcatgaagc
     2581 tttcctatgg tcctgaagaa aaagatatga ttgtgatgag agacagcttt ggaatcagac
     2641 atccttctgg acatttagaa cataaaacga ttgatcttgt ggcttatggg gacatcaatg
     2701 gcttttcagc catggctaaa accgtggggt tacccaccgc catggcagcc aaaatgttgc
     2761 ttgatggtga aattggagcc aaaggcctaa tggggccctt ttcaaaggag atctatggac
     2821 caatattgga gcgaattaaa gcagaaggca ttatatatac tacacagagt acaattaaac
     2881 cataattggg aattatattt tgtttttttc ttcccaggca atacacctct gaacatgtgt
     2941 gtgataaatg ggtttgctaa tgtgctgttt taaagtataa agcataatat gttttggtta
     3001 acacaatgta ctttttgaac tataaatctt tattttaata tggaaatgtt tggaacagga
     3061 gatgcaagcc actaacagag aactttaata attctaccct gtattttata aatacgtatg
     3121 tgaaagtgat gatcatgcta tttgttaatt tattgtgcca ctttttttct tttgtttttt
     3181 ttttgttgtt gttgtttttt gagatggagt ctcgctctgt cacccaggct ggagtgcagt
     3241 ggcgcgatct cggctcactg caagctccgc ctcctgggtt cacgccattc tcctgcctca
     3301 gcctcccaag tagctgggac tacaggcacc cgccaccacg cccggctaaa ttttttgtat
     3361 ttttcagtag agacggggtt tcaccatgtt agccaggatg tccacttttt tcttaaatga
     3421 acatattgtc ttataaccag caaatgaagt tttacttttt tagtcagaaa aaatttcgtc
     3481 ataaagctat atttttatat ttttaaaatt gatacagtta gataccttca gattacctaa
     3541 gttaagtttt tgccaaaatg ctattttatg ccctttttgt aaagttatga tttattttgt
     3601 aaatatagtt ccttatagtt ttctcttgag tgtttggaca tgagaataga taagattaaa
     3661 ttacaattta caagatcact tcattaggca caggaaaagt atttaacaaa attcaacacc
     3721 ctttcacaat aaaaaataaa aaataaaaaa ccctcaacaa actaggaata gaaggaaact
     3781 tcctcaacct gataaagggc atctatgaag aacccatggt tagcatcata cttaatggtg
     3841 aaggactgga ttatttcccc ctgagatcag aaacaagaca aggatgtctg ctttggccat
     3901 ttctattcaa cttgtactgg acagtcaaga aagggcaatt aggcaagaaa ataaaataaa
     3961 agtcatctag gttggaaagg aagaagtata actaaataga gatgggagac gatatggtgg
     4021 ttttgtgcat agtaatccaa gggaaaacta tagaaaatcc aaaggcatga tttattaata
     4081 aataaattca gcaaagttac aggatacagg attaaatatg cagaaattgg ttatctttca
     4141 atatagtatc aatgaataaa tcaaaaatga tgttaagaaa acaatttaat tttcaacaat
     4201 ggtcaagctt ggtggcttgt gcctgtaatc ccaacacttt gggagtctga ggcagaaaga
     4261 ctgctagagg ccaggagacc agcctgggaa acagtgagat cccatctcta caaaaacaaa
     4321 caaacaaaaa acaacaagca aacaaaaaac agctggatgt gatgacactc atctgtcgtc
     4381 tcagctactc agaggctgag gtgtaaggat ggcttgagcc ccaaagttcg aagctgcaat
     4441 gagctataac tgggtcactg caatccagcc tggatgacag agttagacct tgactcaaaa
     4501 aaaacaaaaa agaaaagaaa aaaattgaca gcatcagaaa gagtaaaata ccaatataat
     4561 tgagggtcca gaaatattga tcacatttat catcaactga cttttgaaaa tagtgctaag
     4621 acaattcaat gggggcaaaa tagtcttttt cattaaatga tgcttggaaa catggatatc
     4681 cacatgcaaa ataatgaaat tggactccta cctcatattg catataaaaa ttaactcaaa
     4741 gttgacctaa gatctaaatg taagagctaa tattgtaagt atcttcaaag aaaacatggc
     4801 gtaaatcttt ctgactttga attaggcaat gatttcttaa ataaatgaca ctaaaaacac
     4861 aagcaacaaa agaagaaaat aggtaaatta aaattaaaac catttgtgtt tccaaggaca
     4921 atatcaagaa agcaaaaata caacccacag aatgagataa ttttttttaa aatcatgtat
     4981 tagttaaggg aggaatttgt atttagaata tgtaaagaac tgttacaata ataattaaaa
     5041 ggcatataat tcaattttta aaaatcaaca agagatctga attaacagtt ctccaaagaa
     5101 gatacacaaa aggccaataa gcacatgaaa aggttctcaa catcactagc catcagggaa
     5161 atgcaaatga gatctacaat gagatatcac ttaacactca ctggaataga tatataatca
     5221 aagtgataat atcaagtgtt ggtgaggatg cagagaaatt ggaaccctca tgcactgttg
     5281 gtggataccc acgtgatata aaaacaaatg tctacacaaa aacttgtgca cagatgttct
     5341 ttgcagcatt atttataata gcccaaaatt gaaacagccc taatttctat caactaacaa
     5401 gtgaataaac aaaacgtggc atatccatac aaggaatatt attcagcaat aaaaaaagag
     5461 atgaagtact gatatgcacc acaacatgga aaaaccttga aaacatatca agtgaagaat
     5521 gccagacatg aaaggccaca tattatatga tttcatttat atgaaatgtc cagaacaggc
     5581 gaatatatat agagagaagg cagattagtg gttgcttagg ctgaagggtt ggggaggaca
     5641 aaggggtgac tgctaattag tatggggttt cttttttggg gtgatgtaaa cgttgtaaag
     5701 ttgattgtgg taatggtggc acaactctga atatactaaa aaccactgaa ttgtatactt
     5761 tgaatgtttg aactgtgtgg tatgtagatt ttatctcaag ttgttataaa aaattaaatt
     5821 acaaa
//
