LOCUS       NM_003566               9839 bp    mRNA    linear   PRI 08-JUN-2024
DEFINITION  Homo sapiens early endosome antigen 1 (EEA1), mRNA.
ACCESSION   NM_003566
VERSION     NM_003566.4
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 9839)
  AUTHORS   Kamentseva,R., Kosheverova,V., Kharchenko,M., Zlobina,M.,
            Salova,A., Belyaeva,T., Nikolsky,N. and Kornilova,E.
  TITLE     Functional cycle of EEA1-positive early endosome: Direct evidence
            for pre-existing compartment of degradative pathway
  JOURNAL   PLoS One 15 (5), e0232532 (2020)
   PUBMED   32357161
  REMARK    GeneRIF: Here, using EGF/EGFR endocytosis as a model and confocal
            microscopy of fixed and live cells, we provide evidence favoring
            EEA1-vesicles being pre-existed vesicular compartment, that
            maintains its resident proteins' level and is sensitive to
            biosynthetic, but not endocytic pathway disturbance.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 9839)
  AUTHORS   Miller,C.M., Wan,W.B., Seth,P.P. and Harris,E.N.
  TITLE     Endosomal Escape of Antisense Oligonucleotides Internalized by
            Stabilin Receptors Is Regulated by Rab5C and EEA1 During Endosomal
            Maturation
  JOURNAL   Nucleic Acid Ther 28 (2), 86-96 (2018)
   PUBMED   29437530
  REMARK    GeneRIF: Rab5C and EEA1 in the early endosomal pathway, and Rab7A
            and lysobisphosphatidic acid in the late endosomal pathway, are
            important for trafficking of phosphorothioate Antisense
            oligonucleotides and facilitate their escape from endolysosomal
            compartments after Stabilin-mediated internalization.
REFERENCE   3  (bases 1 to 9839)
  AUTHORS   Liu,X., Salokas,K., Tamene,F., Jiu,Y., Weldatsadik,R.G., Ohman,T.
            and Varjosalo,M.
  TITLE     An AP-MS- and BioID-compatible MAC-tag enables comprehensive
            mapping of protein interactions and subcellular localizations
  JOURNAL   Nat Commun 9 (1), 1188 (2018)
   PUBMED   29568061
  REMARK    Publication Status: Online-Only
REFERENCE   4  (bases 1 to 9839)
  AUTHORS   Overton,N.L.D., Brakhage,A.A., Thywissen,A., Denning,D.W. and
            Bowyer,P.
  TITLE     Mutations in EEA1 are associated with allergic bronchopulmonary
            aspergillosis and affect phagocytosis of Aspergillus fumigatus by
            human macrophages
  JOURNAL   PLoS One 13 (3), e0185706 (2018)
   PUBMED   29547649
  REMARK    GeneRIF: identification of allergic bronchopulmonary aspergillosis
            -associated variants in EEA that have functional effects on
            macrophage phagocytosis and phagolysosome acidification of A.
            fumigatus conidia.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 9839)
  AUTHORS   Kosheverova,V.V., Kamentseva,R.S., Kharchenko,M.V. and
            Kornilova,E.S.
  TITLE     EEA1 CARRYING VESICLES ARE NOT AUTOPHAGOSOMES IN SERUM-DEPRIVED
            HeLa CELLS
  JOURNAL   Tsitologiia 58 (5), 370-377 (2016)
   PUBMED   30188634
  REMARK    GeneRIF: This also suggests that this pathway is involved in
            EEA1-vesicles biogenesis.
REFERENCE   6  (bases 1 to 9839)
  AUTHORS   McBride,H.M., Rybin,V., Murphy,C., Giner,A., Teasdale,R. and
            Zerial,M.
  TITLE     Oligomeric complexes link Rab5 effectors with NSF and drive
            membrane fusion via interactions between EEA1 and syntaxin 13
  JOURNAL   Cell 98 (3), 377-386 (1999)
   PUBMED   10458612
REFERENCE   7  (bases 1 to 9839)
  AUTHORS   Kutateladze,T.G., Ogburn,K.D., Watson,W.T., de Beer,T., Emr,S.D.,
            Burd,C.G. and Overduin,M.
  TITLE     Phosphatidylinositol 3-phosphate recognition by the FYVE domain
  JOURNAL   Mol Cell 3 (6), 805-811 (1999)
   PUBMED   10394369
REFERENCE   8  (bases 1 to 9839)
  AUTHORS   Callaghan,J., Simonsen,A., Gaullier,J.M., Toh,B.H. and Stenmark,H.
  TITLE     The endosome fusion regulator early-endosomal autoantigen 1 (EEA1)
            is a dimer
  JOURNAL   Biochem J 338 (Pt 2) (Pt 2), 539-543 (1999)
   PUBMED   10024533
REFERENCE   9  (bases 1 to 9839)
  AUTHORS   Simonsen,A., Lippe,R., Christoforidis,S., Gaullier,J.M., Brech,A.,
            Callaghan,J., Toh,B.H., Murphy,C., Zerial,M. and Stenmark,H.
  TITLE     EEA1 links PI(3)K function to Rab5 regulation of endosome fusion
  JOURNAL   Nature 394 (6692), 494-498 (1998)
   PUBMED   9697774
REFERENCE   10 (bases 1 to 9839)
  AUTHORS   Mu,F.T., Callaghan,J.M., Steele-Mortimer,O., Stenmark,H.,
            Parton,R.G., Campbell,P.L., McCluskey,J., Yeo,J.P., Tock,E.P. and
            Toh,B.H.
  TITLE     EEA1, an early endosome-associated protein. EEA1 is a conserved
            alpha-helical peripheral membrane protein flanked by cysteine
            'fingers' and contains a calmodulin-binding IQ motif
  JOURNAL   J Biol Chem 270 (22), 13503-13511 (1995)
   PUBMED   7768953
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC021646.35, AC026111.31 and AC016136.21.
            
            On May 17, 2019 this sequence version replaced NM_003566.3.
            
            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 :: SRR1660809.232910.1,
                                           SRR1660807.4023.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000322349.13/ ENSP00000317955.8
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-253               AC021646.35        15284-15536         c
            254-346             AC026111.31        48341-48433         c
            347-474             AC026111.31        21572-21699         c
            475-529             AC026111.31        14143-14197         c
            530-595             AC026111.31        13987-14052         c
            596-635             AC026111.31        10627-10666         c
            636-749             AC026111.31        9624-9737           c
            750-871             AC026111.31        8887-9008           c
            872-1027            AC026111.31        7823-7978           c
            1028-1144           AC016136.21        173881-173997       c
            1145-1483           AC016136.21        163928-164266       c
            1484-1633           AC016136.21        159328-159477       c
            1634-1753           AC016136.21        157582-157701       c
            1754-1957           AC016136.21        150724-150927       c
            1958-2158           AC016136.21        147616-147816       c
            2159-2272           AC016136.21        144396-144509       c
            2273-2428           AC016136.21        142695-142850       c
            2429-2568           AC016136.21        140433-140572       c
            2569-2899           AC016136.21        133820-134150       c
            2900-3001           AC016136.21        133016-133117       c
            3002-3196           AC016136.21        130308-130502       c
            3197-3379           AC016136.21        119283-119465       c
            3380-3565           AC016136.21        113366-113551       c
            3566-3697           AC016136.21        111696-111827       c
            3698-3883           AC016136.21        110531-110716       c
            3884-4122           AC016136.21        109357-109595       c
            4123-4243           AC016136.21        108959-109079       c
            4244-4342           AC016136.21        108260-108358       c
            4343-9839           AC016136.21        102053-107549       c
FEATURES             Location/Qualifiers
     source          1..9839
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q22"
     gene            1..9839
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /note="early endosome antigen 1"
                     /db_xref="GeneID:8411"
                     /db_xref="HGNC:HGNC:3185"
                     /db_xref="MIM:605070"
     exon            1..253
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     CDS             230..4465
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /note="early endosome-associated protein; early endosome
                     antigen 1, 162kD; endosome-associated protein p162; zinc
                     finger FYVE domain-containing protein 2"
                     /codon_start=1
                     /product="early endosome antigen 1"
                     /protein_id="NP_003557.3"
                     /db_xref="CCDS:CCDS31874.1"
                     /db_xref="GeneID:8411"
                     /db_xref="HGNC:HGNC:3185"
                     /db_xref="MIM:605070"
                     /translation="MLRRILQRTPGRVGSQGSDLDSSATPINTVDVNNESSSEGFICP
                     QCMKSLGSADELFKHYEAVHDAGNDSGHGGESNLALKRDDVTLLRQEVQDLQASLKEE
                     KWYSEELKKELEKYQGLQQQEAKPDGLVTDSSAELQSLEQQLEEAQTENFNIKQMKDL
                     FEQKAAQLATEIADIKSKYDEERSLREAAEQKVTRLTEELNKEATVIQDLKTELLQRP
                     GIEDVAVLKKELVQVQTLMDNMTLERERESEKLKDECKKLQSQYASSEATISQLRSEL
                     AKGPQEVAVYVQELQKLKSSVNELTQKNQTLTENLLKKEQDYTKLEEKHNEESVSKKN
                     IQATLHQKDLDCQQLQSRLSASETSLHRIHVELSEKGEATQKLKEELSEVETKYQHLK
                     AEFKQLQQQREEKEQHGLQLQSEINQLHSKLLETERQLGEAHGRLKEQRQLSSEKLMD
                     KEQQVADLQLKLSRLEEQLKEKVTNSTELQHQLDKTKQQHQEQQALQQSTTAKLREAQ
                     NDLEQVLRQIGDKDQKIQNLEALLQKSKENISLLEKEREDLYAKIQAGEGETAVLNQL
                     QEKNHTLQEQVTQLTEKLKNQSESHKQAQENLHDQVQEQKAHLRAAQDRVLSLETSVN
                     ELNSQLNESKEKVSQLDIQIKAKTELLLSAEAAKTAQRADLQNHLDTAQNALQDKQQE
                     LNKITTQLDQVTAKLQDKQEHCSQLESHLKEYKEKYLSLEQKTEELEGQIKKLEADSL
                     EVKASKEQALQDLQQQRQLNTDLELRATELSKQLEMEKEIVSSTRLDLQKKSEALESI
                     KQKLTKQEEEKKILKQDFETLSQETKIQHEELNNRIQTTVTELQKVKMEKEALMTELS
                     TVKDKLSKVSDSLKNSKSEFEKENQKGKAAILDLEKTCKELKHQLQVQMENTLKEQKE
                     LKKSLEKEKEASHQLKLELNSMQEQLIQAQNTLKQNEKEEQQLQGNINELKQSSEQKK
                     KQIEALQGELKIAVLQKTELENKLQQQLTQAAQELAAEKEKISVLQNNYEKSQETFKQ
                     LQSDFYGRESELLATRQDLKSVEEKLSLAQEDLISNRNQIGNQNKLIQELKTAKATLE
                     QDSAKKEQQLQERCKALQDIQKEKSLKEKELVNEKSKLAEIEEIKCRQEKEITKLNEE
                     LKSHKLESIKEITNLKDAKQLLIQQKLELQGKADSLKAAVEQEKRNQQILKDQVKKEE
                     EELKKEFIEKEAKLHSEIKEKEVGMKKHEENEAKLTMQITALNENLGTVKKEWQSSQR
                     RVSELEKQTDDLRGEIAVLEATVQNNQDERRALLERCLKGEGEIEKLQTKVLELQRKL
                     DNTTAAVQELGRENQSLQIKHTQALNRKWAEDNEVQNCMACGKGFSVTVRRHHCRQCG
                     NIFCAECSAKNALTPSSKKPVRVCDACFNDLQG"
     exon            254..346
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            347..474
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            475..529
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            530..595
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            596..635
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            636..749
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            750..871
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            872..1027
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            1028..1144
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            1145..1483
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            1484..1633
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            1634..1753
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            1754..1957
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            1958..2158
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            2159..2272
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            2273..2428
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            2429..2568
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            2569..2899
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            2900..3001
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            3002..3196
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            3197..3379
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            3380..3565
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            3566..3697
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            3698..3883
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            3884..4122
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            4123..4243
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            4244..4342
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     exon            4343..9839
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      7943..7948
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /note="hexamer: ATTAAA"
     polyA_site      7964
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /note="major polyA site"
     regulatory      8208..8213
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
                     /note="hexamer: TATAAA"
     polyA_site      8234
                     /gene="EEA1"
                     /gene_synonym="MST105; MSTP105; ZFYVE2"
ORIGIN      
        1 ggaggcgctc gcaggctgcc tagtcgttcg ctcgctctct ctcgcgtgct ccctctcgcc
       61 gcctgtgggg aagtcggggc cgcccgagcg gccgtcgcca ccgcctcgcc ccgacctcct
      121 tcccggtccc ctcccggccc agtccctccc gcccgcgcac cccgagtagt gagtggcccc
      181 gcgcagggtc tggagagtca ccgcggcggc gccgggtggt ggttaaacca tgttaaggag
      241 gattttacag aggactcctg ggagagttgg ctctcaaggt tctgatttag attcatcagc
      301 aactcctata aacacagtgg acgtcaataa tgaaagctct tcagagggtt tcatatgtcc
      361 ccagtgtatg aaatctcttg gatctgctga tgaacttttc aaacattatg aagctgttca
      421 tgatgctggt aatgactcag gtcatggagg agagtctaat cttgctttga agcgagatga
      481 tgtaacactg ctcagacaag aggtccaaga cctacaggct tcacttaagg aagaaaaatg
      541 gtactcggaa gaattaaaga aggaattaga aaaatatcaa gggctgcagc agcaagaggc
      601 caaacctgat gggttggtga ctgattcatc agcagaacta cagtctttgg aacagcaatt
      661 agaagaagcc caaacagaaa attttaatat taagcaaatg aaagacttat ttgaacagaa
      721 agcagcccaa cttgctactg aaattgcaga tataaagtca aagtatgatg aagaaaggag
      781 tcttcgagaa gctgctgaac aaaaagtgac acgtctgaca gaagaattaa acaaagaggc
      841 aactgtaatt caagatctga agacggaact gcttcagaga cctggtatag aagatgttgc
      901 cgtgctaaag aaagaactgg tccaagttca aacactaatg gataacatga ccttggaacg
      961 tgagcgagaa tctgaaaaac tcaaagatga atgcaaaaaa ttgcagtcac aatatgctag
     1021 ctcagaggcc acaataagcc agctaaggag tgaacttgcc aaaggccccc aggaagttgc
     1081 tgtatatgta caggaactac aaaaactgaa aagttcagtt aatgaattaa cacaaaaaaa
     1141 tcagaccttg acagaaaact tgctgaaaaa agaacaagac tatactaagt tagaggagaa
     1201 acataatgaa gaatctgtga gtaaaaagaa tattcaggca acccttcatc aaaaagacct
     1261 agattgtcaa cagcttcagt caagattgtc tgcatctgaa acctcactgc atagaataca
     1321 tgtagaacta agtgaaaaag gagaagctac tcaaaagctc aaagaagaat tatctgaggt
     1381 agagaccaag taccagcatc taaaggcgga gtttaagcag ctacaacaac agagagaaga
     1441 aaaggagcag catgggttac aactccaaag tgaaattaat caattacata gcaaacttct
     1501 ggagacagag cgccaactag gggaagctca tggtaggctg aaggaacaga gacagctttc
     1561 aagtgaaaag ttgatggata aagaacaaca agtggctgat ttacaactca aactttctcg
     1621 gttagaagag cagttgaagg aaaaagttac aaattctaca gaattgcagc atcaattaga
     1681 taaaacaaag caacagcatc aagaacaaca ggctcttcag caaagcacca cggcaaaact
     1741 tcgagaagct cagaatgatt tggaacaagt tctacgtcaa attggcgata aggaccaaaa
     1801 gatccagaac cttgaagctt tattacagaa gagtaaagaa aatatttcat tactagaaaa
     1861 agaaagagaa gatctttatg caaaaattca ggctggtgaa ggagagactg ctgttcttaa
     1921 ccagttacaa gaaaaaaacc atacactaca ggagcaagta actcaactaa cagagaagct
     1981 gaagaatcag tcagaaagtc ataaacaagc ccaggagaat ttgcatgacc aggtacaaga
     2041 gcagaaggca catcttagag ctgcacaaga ccgtgtcctt tccctagaaa ctagtgtcaa
     2101 tgaattaaat agtcaattaa atgaaagcaa ggagaaggtc tcccagcttg acatacagat
     2161 taaagccaaa accgaactat tactatcagc agaagcagca aaaactgctc aaagagctga
     2221 tcttcagaat catttggaca cagctcaaaa tgcattacaa gataaacagc aggagttaaa
     2281 taagattact actcagttgg atcaggtcac tgcaaagtta caagacaagc aagaacattg
     2341 cagtcagctg gaaagtcatc ttaaagaata taaagagaaa tacctctctt tagaacagaa
     2401 aaccgaagag ctagaaggtc aaattaagaa actagaagct gatagtcttg aagttaaagc
     2461 aagcaaggag caggctttgc aagatctaca acagcaaaga cagctgaaca cagatttaga
     2521 gctcagagcc acagaattga gtaaacaact tgaaatggag aaggaaatag tatccagtac
     2581 aagattggat ctacagaaaa aatctgaagc ccttgaaagt atcaagcaaa agcttaccaa
     2641 gcaagaggaa gaaaaaaaaa tcctgaaaca agattttgaa actttaagtc aagaaacaaa
     2701 gattcagcat gaggaattga ataacagaat tcaaacaaca gtaacagaac tacaaaaagt
     2761 gaaaatggag aaagaagctt taatgacaga gctttctaca gtaaaggaca aactatcaaa
     2821 agtttctgat tctttgaaaa actctaaaag tgaatttgaa aaggagaatc agaaaggaaa
     2881 agccgctata ttagacttgg aaaaaacttg caaagaatta aagcatcaac ttcaagtgca
     2941 gatggaaaac acacttaagg aacagaagga actgaaaaag tcacttgaaa aagagaagga
     3001 ggcttctcat cagttgaaat tggaactcaa ttcaatgcag gaacaactta tacaggccca
     3061 gaatacttta aaacaaaatg aaaaagaaga gcaacaactt caggggaaca taaatgagct
     3121 aaagcaatca agtgaacaga agaaaaaaca aattgaagca ctccaaggag agcttaaaat
     3181 tgctgtttta cagaagacag agcttgagaa taaactacag cagcagttaa cacaggcagc
     3241 ccaggaactt gcagcagaga aagagaaaat atcagtatta caaaacaact atgaaaaaag
     3301 tcaggaaact ttcaaacagc ttcaatctga tttctatggg agggaatctg aacttctagc
     3361 caccaggcaa gatcttaagt ctgtagaaga gaagctttct ctagcacagg aggacttgat
     3421 ttcaaacaga aatcaaattg gaaatcaaaa taaattgatt caagaactga agactgccaa
     3481 ggctacattg gagcaggatt cagcaaagaa agaacagcaa ttgcaggagc gatgtaaagc
     3541 actacaagac attcagaaag aaaagtcact gaaagaaaaa gaactggtaa atgagaagtc
     3601 taaattggca gagatagaag aaattaaatg tagacaagaa aaagaaatca ctaaactaaa
     3661 cgaagaactc aagtcccaca aactagaaag cataaaggag ataacaaatc ttaaagatgc
     3721 taaacagctt ctaattcagc agaaattaga acttcaagga aaagcggact ccctgaaggc
     3781 agctgttgaa caggagaaga gaaatcagca gatactaaaa gaccaggtga aaaaggaaga
     3841 agaggagctg aagaaagaat ttattgagaa agaagctaag ttgcattccg aaataaaaga
     3901 aaaggaagta ggaatgaaga agcatgaaga aaatgaggct aaacttacca tgcagattac
     3961 agcattaaat gaaaacttag gcactgtgaa gaaggagtgg caatctagtc aacggagagt
     4021 tagtgagctt gagaaacaaa cggatgactt acggggtgaa attgcagtat tagaagcaac
     4081 ggttcagaat aatcaagatg aaaggagagc actactggaa agatgtctta aaggagaagg
     4141 tgaaatagaa aagcttcaaa ccaaagtatt agaattgcaa agaaagctgg ataatacaac
     4201 tgcagcagtg caggagctgg gcagagaaaa ccaatcactt cagatcaaac atacacaagc
     4261 gttgaataga aagtgggccg aagacaatga agtacaaaac tgtatggcct gtgggaaagg
     4321 cttttcagta acagtgagac ggcatcactg ccgacagtgt ggaaatatct tctgtgctga
     4381 atgttcagcc aaaaatgcct taactccttc ctccaagaag cctgttcgtg tctgtgatgc
     4441 atgtttcaat gacttgcaag gataatgggt tatcacaact tcagagtaat attacactaa
     4501 cattagattt ttaataaatg tacttaatag aggtcttgga ctactatttg gtttggacac
     4561 tggttgcaat actagaccaa ataggaatta gtatattttg gaatgttatg gatatcaagt
     4621 aaaactcttc tatttttgtg agacttgggc ttatcatctt tcattacttt tttcccattt
     4681 agcccctgga atagctttca tgccaagttt agaattagcc aatgaaatgt aaataaactt
     4741 tggacagaaa atagcaatgt atttttttaa tataatttca ttattcacaa atgaagaatg
     4801 caattccata gcttacttct ttctcctaaa tttaatgtac aaaaatgtac atggatgata
     4861 ttatcacttg ttgctgtttt tgttgcacaa tagcacatta attatattaa atattctctt
     4921 tgtgaagtta tgcacagaac tgtaacactt tcctctgcct ttttctctta tatgtgggtt
     4981 catggttcag ttgcattgtt atgttatgaa tttactactt gggtgttcta aatacagttt
     5041 atcttaaaat atgtagtaat atgaattcaa aaatggtttt tgttttaaca atattaatta
     5101 aattttcttg ggtggatttt ataaaaacct ctgtaaaatc aatttgttta cttatagtta
     5161 tctggggttg tattgcaaag aatagggtta atttttcttt ttgtcttttt ctgtctcttt
     5221 cttaaactcc cacgcattgt ccatttagaa tcttagaaag cttcttaccc tcgctgtcag
     5281 ttggaggatg aataataaac attgtataat gttcttattc tcggtttctt gtaagtggga
     5341 agtcttttga gatcagcctt catatcatac ccttattttg tctctctagc atcttcagga
     5401 acctgagttt gctttttaca tagatctgat tttttccttt atttggttta acattttcaa
     5461 gcatagatca gcttcatgta tttgttttat aattttgcat cttaaagcta gtaactaata
     5521 ttgctgtggt cttattggtg aaaacaaaat ataaaatgat aagaagacat taaatatttt
     5581 actttctatt tcttacccta ttgggaagaa tttttaaaag ttgtaaaatt gacttaaagt
     5641 taaaatggtt ctgaatttgg tgttccatgt caactgttcc cagttttaat tttaactttg
     5701 caaaaataat gttgtgaaat tccctttaag taactaacac ctagaaatag agtatcacca
     5761 aaaacaaatg tatttaggaa tcccagttac aataaaaact gaaacagcat ggctaagcat
     5821 cttaaggata attaagaaat tagcttattt gtatgctgaa caatggaatc gaactttaat
     5881 ttagcatagt cttattaatt tggaaaattg taaaacatct caagagagaa gttattaata
     5941 ttggtttatt aatctttcta gagaagaagt gtagttatac attcattcag tgcaatcatt
     6001 ttataacagt agttaatatt tcatttataa tagttcttaa tatacatttg ctttcaaata
     6061 ttctgaaatg aaattatatt catgctatac ctacagtgta tgtaaactaa agagatcact
     6121 acatatttgt ttaattattt aaaaaaaaat ttaagtaaac cctgttgtca ttagctatta
     6181 agaacattga ttaagtccct ggacttggat aaacatatat ccttgaacat atataatgaa
     6241 gaaatacagt ggctctttat taaaaataat agttggataa tataaactga actatttatg
     6301 catttttata tacttataaa tccttccaaa tagttttaat tctatccttt tacatataaa
     6361 taacttaata agtgtgctgg aaaaacacag atattcacag caccactgtt tttttttttt
     6421 ttttgagata ataaattcca tgagaaatct gggtttgaat atttgtttac tttgtctcct
     6481 aattgaacac cactccaggc cttctgtctg tctccccttt acccccaaaa tactcacaaa
     6541 aaaattttaa gacaacaagt aaccatatat aggtgtttga atgattttct catttttatc
     6601 taatttcatt tcataagtcc cgagtaattt acctaccata ggctactata ctgataatat
     6661 aaatgaaacc gaacattttt tgctactaac tctccccaat ttaatgtgtt ttcgaaataa
     6721 aaatttaaat ttttttcctt ttaattaaaa agtcatcttt gaagtcctta ttggctgtac
     6781 attttacatg tttgctggta ctattatttt gtcagtcagt taaagctggc atgtacagct
     6841 cttggcttta atgaaaagca cattgacata atgttagtaa attccaaacc ccggcacaga
     6901 atgtgagtta aaattaagtc ttgctgggtt agtgtacaat aaactatacc tacagacttt
     6961 tttttaatag aaagaagaca aagctgctgg tataggattt gttcctttga agaaaaaatg
     7021 agggaaacaa acacaaaaac ctcaatgcag tgtataaata acattttgtt caactacctc
     7081 ttaatgtgga attatctact ttaatagttt cctgacagta atgttaaata gtaactgcca
     7141 aatttgttat tttcccatct ctcttaaaaa agtctttatg attattttat atagttttga
     7201 gaactttaaa gccacttttt tttaacctta catttgcata aaaatgttta gcttttaagt
     7261 agagagcaaa ttatgatcat atattttgat attcatgacc tgtttgacta taggagtttt
     7321 tttaaaaaaa tgcactttgg ctataaaacc atggatgatt tgatccataa gatttaaatg
     7381 tgccaccatt atagtattcc tagacatgag cttgatgaat ggtattctgt aattataacg
     7441 tgccacacat tattgtgtct taattgccct tagcctgaat tttaatgatc aatttgttat
     7501 tgttgcagat gtgaatattg tgcataaact tactaaattt atgtaaaatt gtataaaata
     7561 gaattagaag tcactaagtt ctttctgtgt agaagtaata aatttattgt aacacaatgc
     7621 agttgtgtat atgacattct gtaattcctt gaactggatc atatattcat aagttctgta
     7681 gatacttatg catgaacatt ttctcattta gtttttgggt tcattatttg tattgtgttt
     7741 actacttgtg atcatgtagt tgtgccttac tttgtgagaa aggttagctc agtaaatact
     7801 gcaatttcta aactcagtga ttggaaggtt attaattata aatgtaactg ataaagtacg
     7861 tgacagcatt taaatctgta taaagaacaa tggaaggatc cttattgaat tgttgctttt
     7921 ttttaatatg tttaaatatt atattaaaaa catttctttc taaactagtt gtattctgtg
     7981 actataaatt gttttgtcta acaaaagaga gaacactgta ttaaccattt tgcattaatt
     8041 tatttacaga atattaggac tttgcacttg gatatagaca gtggtgtttt aatgttgttc
     8101 aatttcgaat agtaattaaa ttcctgatct caagagaaat tattaatgcc attttgcctt
     8161 agacattcca tttaatattg tagagaatta acaaaactaa aaacaaatat aaaaaatatg
     8221 taattaaccc cttatttcat tgtgtgtctg catttaatac ccagatgacc atttaaagat
     8281 acttaaaaca ttatttattt atttatttat ttatttttct ccctcccctc cccaaagata
     8341 ctttttggaa ggcccaatgt gccattgttt tttgctattt tttcttcctg ggagccacgg
     8401 ttctagaatg gtttttgttc tgacccccgt gatcccttca ttcgaatgtg cttcattcta
     8461 aaccctccaa agagtttaat gtgcatatcc tcaaacatct aatatattgt atattagaca
     8521 tgttactttg tgagctttat agaattccag tttatgtaca gcatattctt gagctgtttt
     8581 atatattttg ttaatttagt cagtctgtct ctccctttaa tgagattcag agggagaaaa
     8641 ctacctttat acatgtaagt ctgtggttgc tggattcatg ggactaaagg aatttgagag
     8701 gccacctcat cctagtccac tgctcacctc cgaggttagt ttatatctaa acatttgcaa
     8761 gatgattgtt aatgtaaaaa ttttttttaa ccagaaattt ctttataaaa tcttctcttg
     8821 cataatctat attgtattct cctggacata actgctttca gtcccatcca gatgccatct
     8881 ctaggaattc acttgaagct tgaagtctat tctccccttt ttctcccctc cacctcattt
     8941 attcttagct attaacaata gttactgtcc tccagatttt cctttttttc ttctattaaa
     9001 tttctgacat tattataaag aggttattag tctccattct aatagtgctt gccttgtaca
     9061 aaagcctttc tgctgcactt gtctttactg ctttgtttgc atagtgaaat ttcaccttcc
     9121 tcaaggaatt actgggcaca tgacttgccc aaacattatc ctctctaccc cattcttcag
     9181 cttaacaaaa tcagctaagg cttcagttgt cttgcagcca aatttgataa atttactact
     9241 ttcactttgc aaattgcaaa aggtacgatt ctgaaatgga agtttgtgga cttccctttg
     9301 atgcaataat ctgaccctaa gaactagttc cttgaatgta gttaatagta tatatcctgc
     9361 catgataata attattcaaa ctgcctttca tgataaaaat tctgaagaaa tttgaagtcc
     9421 tgccaaataa aattaagtga ctgtactgtg ctaacacaca cacacacaca cacacacacc
     9481 aatcaaaacc agaaagtatt tttatggcaa acaccatcat tcttcaaaaa ataaagttaa
     9541 gagacagata ccttactatg tctatgaaaa tctgtacact tcacaacagg ccaagaaaag
     9601 ccatgcaaaa gtgttaactg gtgaaagcca gatttttttt ttcttcctat cttaaagtaa
     9661 tggaatttag tctttgggat tttctacttc cacgttagag tactatatac ctgagatgag
     9721 tttgagaata ggaattttaa aactgctact taaatgtagt ccctatttat tgctttgtat
     9781 attaaaagaa caatcaagct ttgtatctaa agatttatca ttatgtttga ggtaggact
//
