LOCUS       NM_004136               6324 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens iron responsive element binding protein 2 (IREB2),
            transcript variant 1, mRNA.
ACCESSION   NM_004136 XM_039114
VERSION     NM_004136.4
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 6324)
  AUTHORS   Zhou,H., Chen,J., Fan,M., Cai,H., Dong,Y., Qiu,Y., Zhuang,Q.,
            Lei,Z., Li,M., Ding,X., Yan,P., Lin,A., Zheng,S. and Yan,Q.
  TITLE     KLF14 regulates the growth of hepatocellular carcinoma cells via
            its modulation of iron homeostasis through the repression of
            iron-responsive element-binding protein 2
  JOURNAL   J Exp Clin Cancer Res 42 (1), 5 (2023)
   PUBMED   36600258
  REMARK    GeneRIF: KLF14 regulates the growth of hepatocellular carcinoma
            cells via its modulation of iron homeostasis through the repression
            of iron-responsive element-binding protein 2.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 6324)
  AUTHORS   Fan,H., Ai,R., Mu,S., Niu,X., Guo,Z. and Liu,L.
  TITLE     MiR-19a suppresses ferroptosis of colorectal cancer cells by
            targeting IREB2
  JOURNAL   Bioengineered 13 (5), 12021-12029 (2022)
   PUBMED   35599631
  REMARK    GeneRIF: MiR-19a suppresses ferroptosis of colorectal cancer cells
            by targeting IREB2.
REFERENCE   3  (bases 1 to 6324)
  AUTHORS   Zhu,L., Zhou,Q., He,L. and Chen,L.
  TITLE     IRP2-Hif1alpha/Hif2alpha signaling: a novel mechanism of metabolic
            switch from aerobic glycolysis to oxidative phosphorylation
  JOURNAL   Acta Biochim Biophys Sin (Shanghai) 52 (10), 1175-1177 (2020)
   PUBMED   32813008
  REMARK    GeneRIF: IRP2-Hif1alpha/Hif2alpha signaling: a novel mechanism of
            metabolic switch from aerobic glycolysis to oxidative
            phosphorylation.
REFERENCE   4  (bases 1 to 6324)
  AUTHORS   Ziolkowska-Suchanek,I., Mosor,M., Gabryel,P., Grabicki,M.,
            Zurawek,M., Fichna,M., Strauss,E., Batura-Gabryel,H.,
            Dyszkiewicz,W. and Nowak,J.
  TITLE     Susceptibility loci in lung cancer and COPD: association of IREB2
            and FAM13A with pulmonary diseases
  JOURNAL   Sci Rep 5, 13502 (2015)
   PUBMED   26310313
  REMARK    GeneRIF: This study confirms that the IREB2 variants contribute to
            an increased risk of lung cancer, whereas FAM13A predisposes to
            increased susceptibility to chronic obstructive pulmonary disease.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 6324)
  AUTHORS   Salahudeen,A.A., Thompson,J.W., Ruiz,J.C., Ma,H.W., Kinch,L.N.,
            Li,Q., Grishin,N.V. and Bruick,R.K.
  TITLE     An E3 ligase possessing an iron-responsive hemerythrin domain is a
            regulator of iron homeostasis
  JOURNAL   Science 326 (5953), 722-726 (2009)
   PUBMED   19762597
REFERENCE   6  (bases 1 to 6324)
  AUTHORS   Samaniego,F., Chin,J., Iwai,K., Rouault,T.A. and Klausner,R.D.
  TITLE     Molecular characterization of a second iron-responsive element
            binding protein, iron regulatory protein 2. Structure, function,
            and post-translational regulation
  JOURNAL   J Biol Chem 269 (49), 30904-30910 (1994)
   PUBMED   7983023
REFERENCE   7  (bases 1 to 6324)
  AUTHORS   Guo,B., Yu,Y. and Leibold,E.A.
  TITLE     Iron regulates cytoplasmic levels of a novel iron-responsive
            element-binding protein without aconitase activity
  JOURNAL   J Biol Chem 269 (39), 24252-24260 (1994)
   PUBMED   7523370
REFERENCE   8  (bases 1 to 6324)
  AUTHORS   Rouault,T.A., Haile,D.J., Downey,W.E., Philpott,C.C., Tang,C.,
            Samaniego,F., Chin,J., Paul,I., Orloff,D., Harford,J.B. et al.
  TITLE     An iron-sulfur cluster plays a novel regulatory role in the
            iron-responsive element binding protein
  JOURNAL   Biometals 5 (3), 131-140 (1992)
   PUBMED   1421965
  REMARK    Review article
REFERENCE   9  (bases 1 to 6324)
  AUTHORS   Kaptain,S., Downey,W.E., Tang,C., Philpott,C., Haile,D.,
            Orloff,D.G., Harford,J.B., Rouault,T.A. and Klausner,R.D.
  TITLE     A regulated RNA binding protein also possesses aconitase activity
  JOURNAL   Proc Natl Acad Sci U S A 88 (22), 10109-10113 (1991)
   PUBMED   1946430
REFERENCE   10 (bases 1 to 6324)
  AUTHORS   Rouault,T.A., Tang,C.K., Kaptain,S., Burgess,W.H., Haile,D.J.,
            Samaniego,F., McBride,O.W., Harford,J.B. and Klausner,R.D.
  TITLE     Cloning of the cDNA encoding an RNA regulatory protein--the human
            iron-responsive element-binding protein
  JOURNAL   Proc Natl Acad Sci U S A 87 (20), 7958-7962 (1990)
   PUBMED   2172968
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC011270.9, AC027228.16 and
            KF459563.2.
            
            On Nov 23, 2018 this sequence version replaced NM_004136.3.
            
            Summary: The protein encoded by this gene is an RNA-binding protein
            that acts to regulate iron levels in the cells by regulating the
            translation and stability of mRNAs that affect iron homeostasis
            under conditions when iron is depleted. When iron levels are low,
            this protein binds to iron-responsive elements (IRES), stem-loop
            structures located either in the 5' or 3' UTRs. Binding to the 5'
            UTR represses translation, while binding to the 3' UTR inhibits
            mRNA degradation. When iron is found in the cell, this protein is
            degraded in a F-box and leucine rich repeat protein 5-dependent
            manner. Variants in this gene have been associated with lung cancer
            and chronic obstructive pulmonary disease (COPD). Alternative
            splicing results in multiple transcript variants encoding different
            isoforms. [provided by RefSeq, Aug 2017].
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data because no single transcript was available
            for the full length of the gene. The extent of this transcript is
            supported by 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 :: SRR1803612.94406.1,
                                           SRR1803617.39535.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000258886.13/ ENSP00000258886.8
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-141               AC011270.9         24264-24404         c
            142-228             AC011270.9         22739-22825         c
            229-394             AC027228.16        133927-134092       c
            395-532             AC027228.16        131626-131763       c
            533-678             KF459563.2         1-146               c
            679-751             AC027228.16        130525-130597       c
            752-821             AC027228.16        126413-126482       c
            822-1005            AC027228.16        125090-125273       c
            1006-1145           AC027228.16        123633-123772       c
            1146-1317           AC027228.16        120655-120826       c
            1318-1418           AC027228.16        118617-118717       c
            1419-1535           AC027228.16        113580-113696       c
            1536-1695           AC027228.16        112094-112253       c
            1696-1831           AC027228.16        111174-111309       c
            1832-1916           AC027228.16        109197-109281       c
            1917-2073           AC027228.16        108678-108834       c
            2074-2198           AC027228.16        108243-108367       c
            2199-2303           AC027228.16        106488-106592       c
            2304-2446           AC027228.16        106253-106395       c
            2447-2594           AC027228.16        102958-103105       c
            2595-2717           AC027228.16        102750-102872       c
            2718-2903           AC027228.16        99703-99888         c
            2904-6324           AC027228.16        95561-98981         c
FEATURES             Location/Qualifiers
     source          1..6324
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q25.1"
     gene            1..6324
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /note="iron responsive element binding protein 2"
                     /db_xref="GeneID:3658"
                     /db_xref="HGNC:HGNC:6115"
                     /db_xref="MIM:147582"
     exon            1..141
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     CDS             123..3014
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /note="isoform 1 is encoded by transcript variant 1; iron
                     regulatory protein 2"
                     /codon_start=1
                     /product="iron-responsive element-binding protein 2
                     isoform 1"
                     /protein_id="NP_004127.2"
                     /db_xref="CCDS:CCDS10302.1"
                     /db_xref="GeneID:3658"
                     /db_xref="HGNC:HGNC:6115"
                     /db_xref="MIM:147582"
                     /translation="MDAPKAGYAFEYLIETLNDSSHKKFFDVSKLGTKYDVLPYSIRV
                     LLEAAVRNCDGFLMKKEDVMNILDWKTKQSNVEVPFFPARVLLQDFTGIPAMVDFAAM
                     REAVKTLGGDPEKVHPACPTDLTVDHSLQIDFSKCAIQNAPNPGGGDLQKAGKLSPLK
                     VQPKKLPCRGQTTCRGSCDSGELGRNSGTFSSQIENTPILCPFHLQPVPEPETVLKNQ
                     EVEFGRNRERLQFFKWSSRVFKNVAVIPPGTGMAHQINLEYLSRVVFEEKDLLFPDSV
                     VGTDSHITMVNGLGILGWGVGGIETEAVMLGLPVSLTLPEVVGCELTGSSNPFVTSID
                     VVLGITKHLRQVGVAGKFVEFFGSGVSQLSIVDRTTIANMCPEYGAILSFFPVDNVTL
                     KHLEHTGFSKAKLESMETYLKAVKLFRNDQNSSGEPEYSQVIQINLNSIVPSVSGPKR
                     PQDRVAVTDMKSDFQACLNEKVGFKGFQIAAEKQKDIVSIHYEGSEYKLSHGSVVIAA
                     VISCTNNCNPSVMLAAGLLAKKAVEAGLRVKPYIRTSLSPGSGMVTHYLSSSGVLPYL
                     SKLGFEIVGYGCSICVGNTAPLSDAVLNAVKQGDLVTCGILSGNKNFEGRLCDCVRAN
                     YLASPPLVVAYAIAGTVNIDFQTEPLGTDPTGKNIYLHDIWPSREEVHRVEEEHVILS
                     MFKALKDKIEMGNKRWNSLEAPDSVLFPWDLKSTYIRCPSFFDKLTKEPIALQAIENA
                     HVLLYLGDSVTTDHISPAGSIARNSAAAKYLTNRGLTPREFNSYGARRGNDAVMTRGT
                     FANIKLFNKFIGKPAPKTIHFPSGQTLDVFEAAELYQKEGIPLIILAGKKYGSGNSRD
                     WAAKGPYLLGVKAVLAESYEKIHKDHLIGIGIAPLQFLPGENADSLGLSGRETFSLTF
                     PEELSPGITLNIQTSTGKVFSVIASFEDDVEITLYKHGGLLNFVARKFS"
     exon            142..228
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            229..394
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            395..532
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            533..751
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            752..821
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            822..1005
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            1006..1145
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            1146..1317
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            1318..1418
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            1419..1535
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            1536..1695
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            1696..1831
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            1832..1916
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            1917..2073
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            2074..2198
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            2199..2303
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            2304..2446
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            2447..2594
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            2595..2717
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            2718..2903
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     exon            2904..6324
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3300..3305
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /note="hexamer: AATAAA"
     polyA_site      3323
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /note="major polyA site"
     regulatory      3369..3374
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /note="hexamer: AATAAA"
     polyA_site      3390
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
     regulatory      6301..6306
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /note="hexamer: AATAAA"
     polyA_site      6324
                     /gene="IREB2"
                     /gene_synonym="ACO3; IRE-BP 2; IRE-BP2; IRP2; IRP2AD;
                     NDCAMA"
                     /note="major polyA site"
ORIGIN      
        1 gagcctgctt ccttctttcc tcccttgcca gtccgcctgt cttcctcccc gtcttccctg
       61 cccggcctcc cccttcttcc cccgctggcc ccctccccgg agggataata tggtctccgg
      121 cgatggacgc cccaaaagca ggatacgcct ttgagtacct tattgaaaca ttaaatgaca
      181 gttcacataa gaagttcttc gatgtatcta aacttggcac caagtatgat gttctgcctt
      241 actcaatacg ggtcttgttg gaagctgctg tacgaaattg tgatggcttt ttaatgaaga
      301 aggaagatgt tatgaacatt ttagactgga aaaccaaaca aagcaatgtt gaagtgccct
      361 ttttccctgc ccgtgttctt cttcaagatt ttactggaat accagcaatg gtggattttg
      421 ctgctatgag ggaggcagtg aaaactcttg gaggtgatcc tgagaaagtc catcctgctt
      481 gtccgacaga tcttacagtt gaccattctt tacaaattga cttcagtaaa tgtgcaatac
      541 agaatgcacc aaatcctgga ggtggtgacc tgcagaaagc aggaaagctc tctccactta
      601 aagtgcagcc taagaagctt ccctgcagag gccagactac ctgccgagga tcttgtgatt
      661 ctggagaact aggccgaaac tcaggaacat tttcttcgca gattgagaat acacccatcc
      721 tgtgtccttt tcatttgcaa ccagtgcctg aacctgaaac agtgttaaaa aatcaagaag
      781 tagaattcgg cagaaatcga gagaggcttc agttttttaa gtggagttca agagttttta
      841 agaatgtggc agtgatccct cctggaactg gaatggctca tcaaataaac ttagaatatt
      901 tgtcaagagt ggtttttgaa gaaaaagacc tcctcttccc agacagtgta gtcggcacag
      961 attcacacat aacgatggtg aatggtttag ggattctggg gtggggggtt ggaggcattg
     1021 aaacagaagc agttatgctt ggtctgccag tttctcttac tttaccagag gtggttggat
     1081 gtgagttaac tgggtcatca aacccttttg ttacatccat agatgttgtt cttggtatta
     1141 caaagcacct caggcaagta ggagtggctg gaaagtttgt tgagtttttt ggaagtggag
     1201 tttcacaatt atctatagtt gatcgaacta caatagcaaa catgtgtccg gaatatggtg
     1261 ctatcctcag ctttttccct gttgacaatg tgacattaaa acatttagaa catacaggtt
     1321 ttagcaaagc caaactcgaa tcaatggaaa cataccttaa agctgtgaaa ttgtttcgaa
     1381 atgaccagaa ttcttcagga gaacctgaat actcccaggt gatccagatt aatctgaatt
     1441 caatagttcc atctgttagt ggtccaaaaa gacctcagga tagagttgct gtgacagata
     1501 tgaaaagcga tttccaggct tgcttaaatg aaaaggttgg atttaaaggc ttccaaattg
     1561 cagctgaaaa acaaaaggat attgtctcca ttcattatga aggaagtgaa tataagctgt
     1621 ctcatggatc agtggtcatt gctgcagtta tcagttgtac caataattgc aatccatctg
     1681 tcatgcttgc tgcaggtctt ttggctaaaa aggctgttga agctggtctg cgtgttaaac
     1741 cttatataag aacaagttta tctccaggca gtgggatggt tacacattac ctcagttcaa
     1801 gtggagtatt accatatcta agtaagcttg gatttgaaat cgttggctat ggatgttcaa
     1861 tttgtgtggg aaatacagca cccttatcag acgcagtttt aaatgcagta aaacagggtg
     1921 atttggttac ctgtggaatt ttatctggaa acaaaaattt tgaaggtcgt ctttgtgatt
     1981 gtgttcgtgc caattatctt gcctctccac ccttagtggt agcttatgcc atagcaggca
     2041 cagtgaatat agatttccag acagaacctt taggtactga ccccaccggc aagaacattt
     2101 acctgcatga tatttggcct agtcgagaag aagttcatcg agtagaggaa gaacatgtta
     2161 tactatccat gtttaaagca ttaaaagata aaatagaaat ggggaataaa cggtggaatt
     2221 ccttagaagc accggattca gttttgtttc catgggactt aaagtctact tatatcagat
     2281 gcccttcatt ttttgataaa cttaccaaag agccaattgc actccaggct attgaaaatg
     2341 cccatgtctt attatatttg ggagactctg tcacaacaga tcatatatca cctgcaggaa
     2401 gtatcgctag gaatagtgct gccgctaagt atttgacaaa cagaggcctt acccctcgtg
     2461 aattcaactc ttacggagct cgaagaggta atgatgctgt aatgacaaga ggcacttttg
     2521 caaatatcaa gctttttaat aagtttattg gaaaaccagc tcctaaaaca attcattttc
     2581 catcaggaca gacgctagat gtatttgagg ctgcagagct gtaccagaaa gaaggtatcc
     2641 cactgattat tttagcagga aagaaatatg gttcaggaaa ctccagagac tgggctgcca
     2701 aaggaccgta tttactgggt gtgaaagctg ttttggccga aagttatgaa aaaatacaca
     2761 aagatcattt gattggaatt ggcatagctc cacttcagtt ccttccagga gaaaatgcag
     2821 attccttggg cctctccggt agagaaacat tttctttaac atttcctgaa gaactgtctc
     2881 ctggaattac attgaatata cagacaagca ctggaaaagt attcagcgtg attgcttcgt
     2941 ttgaagatga tgtggaaata acattataca aacatggagg attattaaac tttgtggcac
     3001 gaaaattctc atagtatcta cttaccatag atacctttca taactggtaa ctgcaaagcc
     3061 ttttgtgctg gacccaggaa tccttaccat ggagcagcag atagtcccag tatactcact
     3121 tatctcatcc atggatgtaa atgatgatga atcaacatag taactgaaat gaaatcttct
     3181 tgattttaaa taatatacga atggtgctat taatattgct aaaatcaacg tgtgaagtgt
     3241 gttgtggaag agacctgtaa gtatgggggg ggggcgatat tttatcagac cattttgtaa
     3301 ataaaggcag aatttgtgtt gaagattctt atatgaataa ccttcctgga tttgtttagt
     3361 tttgcaccaa taaaactgtg tactactgtt tgttggttta agagtagcag attgaaatat
     3421 aagaagccag attagactct aaaattgtgg ccattggaat ctcatttata aatggacctt
     3481 ttaagtatat taattcctct tcagaattga gctggacaca tttggcattc ttagtttgtc
     3541 atataaccag gtttatcctt agtctaactg caagggatgg aacctgcccc aggtcacaat
     3601 cattctgtcc aatccagcca aggttccctc cacatatgaa gatggaccat ggcaggatac
     3661 aactgattgt gtggcaccat gtattagcag tgggaatatg tatcacatat gatgcagcct
     3721 ttcatatttc agcagtttgc cactgtgact gtctggcaag cccccagatg gcgttatatt
     3781 aattggatta gattattttg ctcaccttat gtaatactgt aacttcctat aacctaatat
     3841 tttcggtatc attaaccaaa atttcacact catagttgct aaagagaatg ttattcaatc
     3901 attaaactct gaactgattt cttctataca tttaaattat ccaccctcaa taatacgggt
     3961 gctcaaccct atgcattttt taagtgttgc tatttcttaa ttaaattgat ttcctgtcat
     4021 tttgaatcat ttatcacctg cgatgcatga ttctattaat tttgttatgt tactgtttta
     4081 accaaagctg accgtaagga taaaacactt aagttgttgc tgagtactat atatcctcaa
     4141 tatgcatgtc tgcccatcac atcaaatgtt ctgtcaacaa gatgtttggt aatttttttt
     4201 aaaaaggttg gaaaattaat tatagaaggt tctatactgt ttttttaatt aagaaactaa
     4261 gtctagcagg ctaaaggtta attgtagtga ttttttttca catagatatc tttctatgac
     4321 ctagttagtt actgcaattc agaattagtt cacattgcat aaagaattac ttgttgtaag
     4381 caaaatgctg aaactaccaa accagtggat gaagaccact aagaactttg cacataatca
     4441 tacaatcttt tgaaaatatt ttgcaaatat gtgtttagac aataagatgg actagagttc
     4501 gacaaaatga tttctttatt taaattttgt ataagtattt tcttcgacac tttcaaatta
     4561 tattgtgttc ttgatatatg ctgtatattt atttgttagt gcatgtgttt ttaatttaca
     4621 tgaaaacatg agttaggaga aattacaggt tgaaagatga aatgcctgta tgtgctctga
     4681 agaaatggta attccagatt gtgcaggggg aaacaaatct attttgtttt gttttgtttt
     4741 ttgagacgga gtcttgccct gtggctgggc tggagtgcaa tggcgcgatc ttggctcact
     4801 gcaacctccg cctcccgggt tcaggggatt ctcctgcctc agcctcctga gtagctggga
     4861 ctacaagcat gcaccaccac gcccagctaa tttttgtagt tttagtagag atggggtttc
     4921 accatgttgg ccagatgatc tgaatctctt gacctcgtga tccgcccgcc ttggcctcca
     4981 caagtgctgg gattacaggt gtgagccacc acacccggcc tatattgttt tgaaagcata
     5041 ctctatatat agttatgggc agaggcacag gcatcctcag cagctgattc aggagatgat
     5101 ggtaaagcta gctaactatg aattaaacat tcacatatcc agtctacctg gtccagtaat
     5161 aatacaagca aatcttgtat ttcaggaaca aatcaaggtt ctcttaattt tttggcttat
     5221 atacaatgaa gtaaaaactt gataaacatg gtttcaaatt gaggaggaga gtcttggatg
     5281 tatgttttaa tatgtatacc ttataattct gcctctagcc aaatgctatg tttgcaaaat
     5341 gtggcatctg ttagttttta ttgtctgtgt cttctttgtt tactatacct tgggtaattt
     5401 tgtgttacca aaaaaaaaaa aaaaaaaagg aagtgtaatg tcagacacac aagaaaagca
     5461 aatcagtgtt gtaagcttaa agtacaattt caaaggtcac taccaacagc agggtttttt
     5521 ttatactttg aaaacattat gctacatatc attgccattt tcatattttg gggttttgct
     5581 actcttatac aatggaatca atggaaatgt catccagcca ctgaattgcc attattatat
     5641 ctaaaaagtt tctaagatga cagttatcac tattttgttt tatctccatg ctgacatttg
     5701 aaagaaggta ctagtatccc tctagccaga ttgcttagtt tttcgttggt aatcaaacaa
     5761 cagttgtact aaaggaaagt aaagctagga cctaaatcag aatcatagtt gcctgcatat
     5821 atggtaacaa ggtcgtgtgc atttgctttc acagtgatga gtgagaggat gagaagaaat
     5881 tatttgacat ttttctgtgg ttgaatagaa gacacctttc ttttgtcttt aggtttagga
     5941 ggagatacta agatactgga tgtttatcct atcttagttt ggttggagta ataagagaga
     6001 agaagagggt ggactttggc ttttcagtgt tttttcccct aaagagtgat attgctgacg
     6061 tttctatcaa ttttacacat aatatgtggc tatgaaacca tatatctcac ttaagtaaca
     6121 aagtaatcac tttgtctatc actaagtaat agacaaaaat cattgtctat tatttaaagc
     6181 caacaaaaca gtgtaacagt tttaagttca ataatgttaa gtattgtata gaaatatatt
     6241 ggaggcaaag ttcagttgat gacaattgtg tatatgttac tgatgctgta aattattttt
     6301 aataaagaaa attgtattat caca
//
