LOCUS       NM_001348945            5586 bp    mRNA    linear   PRI 13-OCT-2024
DEFINITION  Homo sapiens ATP binding cassette subfamily B member 1 (ABCB1),
            transcript variant 1, mRNA.
ACCESSION   NM_001348945
VERSION     NM_001348945.2
KEYWORDS    RefSeq.
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 5586)
  AUTHORS   Jin,S., Zou,X., Xue,X., Chen,S., Wang,X. and Xu,W.
  TITLE     Membrane P-glycoprotein expression in lymphocytes from adult
            patients with refractory glomerulonephritis
  JOURNAL   Int J Clin Pharmacol Ther 62 (9), 395-401 (2024)
   PUBMED   38920082
  REMARK    GeneRIF: Membrane P-glycoprotein expression in lymphocytes from
            adult patients with refractory glomerulonephritis.
REFERENCE   2  (bases 1 to 5586)
  AUTHORS   Girolimetti,G., Balena,B., Cordella,P., Verri,T., Eusebi,L.H.,
            Bozzetti,M.P., Bucci,C. and Guerra,F.
  TITLE     Characterization of Chemoresistance in Pancreatic Cancer: A Look at
            MDR-1 Polymorphisms and Expression in Cancer Cells and Patients
  JOURNAL   Int J Mol Sci 25 (15), 8515 (2024)
   PUBMED   39126083
  REMARK    GeneRIF: Characterization of Chemoresistance in Pancreatic Cancer:
            A Look at MDR-1 Polymorphisms and Expression in Cancer Cells and
            Patients.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5586)
  AUTHORS   Ammour,A., Aberkane,M., Boudjema,A., Boughrara,W. and
            Benchekor,S.M.
  TITLE     The Frequencies distribution of CYP3A5 rs776746 and ABCB1 rs1045642
            polymorphisms in the west Algerian population and relationships
            with pharmacogenetics
  JOURNAL   Afr Health Sci 24 (1), 307-312 (2024)
   PUBMED   38962329
  REMARK    GeneRIF: The Frequencies distribution of CYP3A5 rs776746 and ABCB1
            rs1045642 polymorphisms in the west Algerian population and
            relationships with pharmacogenetics.
REFERENCE   4  (bases 1 to 5586)
  AUTHORS   Kitada,K. and Yamasaki,T.
  TITLE     The MDR1/ABCB1 regional amplification in large inverted repeats
            with asymmetric sequences and microhomologies at the junction sites
  JOURNAL   Cancer Genet Cytogenet 178 (2), 120-127 (2007)
   PUBMED   17954267
  REMARK    GeneRIF: Treatment with the anti-cancer drug paclitaxel have an
            increased copy number in the 7q21.12 region including the
            MDR1/ABCB1 gene.
REFERENCE   5  (bases 1 to 5586)
  AUTHORS   Kioka,N., Yamano,Y., Komano,T. and Ueda,K.
  TITLE     Heat-shock responsive elements in the induction of the multidrug
            resistance gene (MDR1)
  JOURNAL   FEBS Lett 301 (1), 37-40 (1992)
   PUBMED   1360409
REFERENCE   6  (bases 1 to 5586)
  AUTHORS   Safa,A.R., Stern,R.K., Choi,K., Agresti,M., Tamai,I., Mehta,N.D.
            and Roninson,I.B.
  TITLE     Molecular basis of preferential resistance to colchicine in
            multidrug-resistant human cells conferred by Gly-185----Val-185
            substitution in P-glycoprotein
  JOURNAL   Proc Natl Acad Sci U S A 87 (18), 7225-7229 (1990)
   PUBMED   1976255
REFERENCE   7  (bases 1 to 5586)
  AUTHORS   Gekeler,V., Weger,S. and Probst,H.
  TITLE     mdr1/P-glycoprotein gene segments analyzed from various human
            leukemic cell lines exhibiting different multidrug resistance
            profiles
  JOURNAL   Biochem Biophys Res Commun 169 (2), 796-802 (1990)
   PUBMED   1972623
REFERENCE   8  (bases 1 to 5586)
  AUTHORS   Chen,C.J., Clark,D., Ueda,K., Pastan,I., Gottesman,M.M. and
            Roninson,I.B.
  TITLE     Genomic organization of the human multidrug resistance (MDR1) gene
            and origin of P-glycoproteins
  JOURNAL   J Biol Chem 265 (1), 506-514 (1990)
   PUBMED   1967175
REFERENCE   9  (bases 1 to 5586)
  AUTHORS   Kioka,N., Tsubota,J., Kakehi,Y., Komano,T., Gottesman,M.M.,
            Pastan,I. and Ueda,K.
  TITLE     P-glycoprotein gene (MDR1) cDNA from human adrenal: normal
            P-glycoprotein carries Gly185 with an altered pattern of multidrug
            resistance
  JOURNAL   Biochem Biophys Res Commun 162 (1), 224-231 (1989)
   PUBMED   2568832
REFERENCE   10 (bases 1 to 5586)
  AUTHORS   Chen,C.J., Chin,J.E., Ueda,K., Clark,D.P., Pastan,I.,
            Gottesman,M.M. and Roninson,I.B.
  TITLE     Internal duplication and homology with bacterial transport proteins
            in the mdr1 (P-glycoprotein) gene from multidrug-resistant human
            cells
  JOURNAL   Cell 47 (3), 381-389 (1986)
   PUBMED   2876781
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC002457.2 and AC005068.2.
            
            On Aug 13, 2020 this sequence version replaced NM_001348945.1.
            
            Summary: The membrane-associated protein encoded by this gene is a
            member of the superfamily of ATP-binding cassette (ABC)
            transporters. ABC proteins transport various molecules across
            extra- and intra-cellular membranes. ABC genes are divided into
            seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20,
            White). This protein is a member of the MDR/TAP subfamily. Members
            of the MDR/TAP subfamily are involved in multidrug resistance. The
            protein encoded by this gene is an ATP-dependent drug efflux pump
            for xenobiotic compounds with broad substrate specificity. It is
            responsible for decreased drug accumulation in multidrug-resistant
            cells and often mediates the development of resistance to
            anticancer drugs. This protein also functions as a transporter in
            the blood-brain barrier. Mutations in this gene are associated with
            colchicine resistance and Inflammatory bowel disease 13.
            Alternative splicing and the use of alternative promoters results
            in multiple transcript variants. [provided by RefSeq, Feb 2017].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on 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##
            RNAseq introns :: partial sample support SAMEA1965299, SAMEA1966682
                              [ECO:0000350]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-135               AC002457.2         148828-148962       c
            136-153             AC002457.2         137308-137325       c
            154-334             AC002457.2         38627-38807         c
            335-440             AC002457.2         36640-36745         c
            441-511             AC002457.2         36422-36492         c
            512-585             AC002457.2         35784-35857         c
            586-634             AC002457.2         31433-31481         c
            635-803             AC002457.2         21179-21347         c
            804-855             AC002457.2         5839-5890           c
            856-1047            AC002457.2         2452-2643           c
            1048-1219           AC002457.2         1737-1908           c
            1220-1344           AC005068.2         95202-95326         c
            1345-1516           AC005068.2         87700-87871         c
            1517-1630           AC005068.2         84664-84777         c
            1631-1741           AC005068.2         84407-84517         c
            1742-1867           AC005068.2         84110-84235         c
            1868-2071           AC005068.2         83790-83993         c
            2072-2242           AC005068.2         83287-83457         c
            2243-2404           AC005068.2         79802-79963         c
            2405-2581           AC005068.2         78762-78938         c
            2582-2728           AC005068.2         78068-78214         c
            2729-2836           AC005068.2         75296-75403         c
            2837-2914           AC005068.2         73207-73284         c
            2915-2998           AC005068.2         70397-70480         c
            2999-3202           AC005068.2         65233-65436         c
            3203-3303           AC005068.2         54715-54815         c
            3304-3444           AC005068.2         53265-53405         c
            3445-3601           AC005068.2         50448-50604         c
            3602-3799           AC005068.2         49170-49367         c
            3800-4006           AC005068.2         43214-43420         c
            4007-4153           AC005068.2         39836-39982         c
            4154-5586           AC005068.2         36956-38388         c
FEATURES             Location/Qualifiers
     source          1..5586
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q21.12"
     gene            1..5586
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /note="ATP binding cassette subfamily B member 1"
                     /db_xref="GeneID:5243"
                     /db_xref="HGNC:HGNC:40"
                     /db_xref="MIM:171050"
     exon            1..135
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            136..153
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            154..334
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     CDS             308..4360
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /EC_number="7.6.2.2"
                     /EC_number="7.6.2.1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     colchicin sensitivity; doxorubicin resistance;
                     phospholipid transporter ABCB1; P-glycoprotein 1;
                     multidrug resistance protein 1; ATP-binding cassette,
                     sub-family B (MDR/TAP), member 1; ATP-dependent
                     translocase ABCB1"
                     /codon_start=1
                     /product="ATP-dependent translocase ABCB1 isoform 1"
                     /protein_id="NP_001335874.1"
                     /db_xref="GeneID:5243"
                     /db_xref="HGNC:HGNC:40"
                     /db_xref="MIM:171050"
                     /translation="MSVNLQGDQRGATEARTFLLEIQPVSQFLEESAFSQSGPGAVIC
                     GLSTKVGVSSSKISRLGGRSKEREVGMDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKP
                     TVSVFSMFRYSNWLDKLYMVVGTLAAIIHGAGLPLMMLVFGEMTDIFANAGNLEDLMS
                     NITNRSDINDTGFFMNLEEDMTRYAYYYSGIGAGVLVAAYIQVSFWCLAAGRQIHKIR
                     KQFFHAIMRQEIGWFDVHDVGELNTRLTDDVSKINEGIGDKIGMFFQSMATFFTGFIV
                     GFTRGWKLTLVILAISPVLGLSAAVWAKILSSFTDKELLAYAKAGAVAEEVLAAIRTV
                     IAFGGQKKELERYNKNLEEAKRIGIKKAITANISIGAAFLLIYASYALAFWYGTTLVL
                     SGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARGAAYEIFKIIDNKPSIDSYSK
                     SGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSGQTVALVGNSGCGKSTTVQ
                     LMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLFATTIAENIRYGRENVT
                     MDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLL
                     DEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAGFDDGVIVEKGNH
                     DELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRSSLIRKRSTRR
                     SVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAIINGGLQPAF
                     AIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKAGEILTK
                     RLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNIANLG
                     TGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGSGKIATEAIE
                     NFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFG
                     AYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLI
                     DSYSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGK
                     STVVQLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYG
                     DNSRVVSQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVR
                     QPHILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGR
                     VKEHGTHQQLLAQKGIYFSMVSVQAGTKRQ"
     exon            335..440
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            441..511
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            512..585
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            586..634
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            635..803
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            804..855
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            856..1047
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1048..1219
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1220..1344
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1345..1516
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1517..1630
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1631..1741
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1742..1867
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1868..2071
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2072..2242
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2243..2404
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2405..2581
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2582..2728
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2729..2836
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2837..2914
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2915..2998
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2999..3202
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3203..3303
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3304..3444
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3445..3601
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3602..3799
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3800..4006
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            4007..4153
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            4154..5586
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4718..4723
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /note="hexamer: AATAAA"
     regulatory      4724..4729
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /note="hexamer: ACTAAA"
     polyA_site      4745
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /note="major polyA site"
     polyA_site      4760
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
     regulatory      5508..5513
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /note="hexamer: AATAAA"
     polyA_site      5530
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
     regulatory      5562..5567
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /note="hexamer: AATAAA"
     polyA_site      5586
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
ORIGIN      
        1 atcattactc tttacctgtg aagagtagaa catgaagaaa tctactttat tcagatattc
       61 tccagattcc taaagattag agatcatttc tcattctcct aggagtactc acttcaggaa
      121 gcaaccagat aaaagatcaa aactcactaa atgatacata tagaacagac tgcagcagag
      181 aggcaaatct ttaatgttgt cagagtatag acaagttggt gaaatggcta catgagagcg
      241 gaggacaaga aggtgcagat tgtggcagtc acttcaaatg gaaatatcac cgcttgaatg
      301 aaggtatatg agtgtcaact tgcaagggga ccagagaggt gcaacggaag ccagaacatt
      361 cctcctggaa attcaacctg tttcgcagtt tctcgaggaa tcagcattca gtcaatccgg
      421 gccgggagca gtcatctgtg gtctttccac taaagtcgga gtatcttctt ccaaaatttc
      481 acgtcttggt ggccgttcca aggagcgcga ggtcggaatg gatcttgaag gggaccgcaa
      541 tggaggagca aagaagaaga acttttttaa actgaacaat aaaagtgaaa aagataagaa
      601 ggaaaagaaa ccaactgtca gtgtattttc aatgtttcgc tattcaaatt ggcttgacaa
      661 gttgtatatg gtggtgggaa ctttggctgc catcatccat ggggctggac ttcctctcat
      721 gatgctggtg tttggagaaa tgacagatat ctttgcaaat gcaggaaatt tagaagatct
      781 gatgtcaaac atcactaata gaagtgatat caatgataca gggttcttca tgaatctgga
      841 ggaagacatg accaggtatg cctattatta cagtggaatt ggtgctgggg tgctggttgc
      901 tgcttacatt caggtttcat tttggtgcct ggcagctgga agacaaatac acaaaattag
      961 aaaacagttt tttcatgcta taatgcgaca ggagataggc tggtttgatg tgcacgatgt
     1021 tggggagctt aacacccgac ttacagatga tgtctccaag attaatgaag gaattggtga
     1081 caaaattgga atgttctttc agtcaatggc aacatttttc actgggttta tagtaggatt
     1141 tacacgtggt tggaagctaa cccttgtgat tttggccatc agtcctgttc ttggactgtc
     1201 agctgctgtc tgggcaaaga tactatcttc atttactgat aaagaactct tagcgtatgc
     1261 aaaagctgga gcagtagctg aagaggtctt ggcagcaatt agaactgtga ttgcatttgg
     1321 aggacaaaag aaagaacttg aaaggtacaa caaaaattta gaagaagcta aaagaattgg
     1381 gataaagaaa gctattacag ccaatatttc tataggtgct gctttcctgc tgatctatgc
     1441 atcttatgct ctggccttct ggtatgggac caccttggtc ctctcagggg aatattctat
     1501 tggacaagta ctcactgtat tcttttctgt attaattggg gcttttagtg ttggacaggc
     1561 atctccaagc attgaagcat ttgcaaatgc aagaggagca gcttatgaaa tcttcaagat
     1621 aattgataat aagccaagta ttgacagcta ttcgaagagt gggcacaaac cagataatat
     1681 taagggaaat ttggaattca gaaatgttca cttcagttac ccatctcgaa aagaagttaa
     1741 gatcttgaag ggtctgaacc tgaaggtgca gagtgggcag acggtggccc tggttggaaa
     1801 cagtggctgt gggaagagca caacagtcca gctgatgcag aggctctatg accccacaga
     1861 ggggatggtc agtgttgatg gacaggatat taggaccata aatgtaaggt ttctacggga
     1921 aatcattggt gtggtgagtc aggaacctgt attgtttgcc accacgatag ctgaaaacat
     1981 tcgctatggc cgtgaaaatg tcaccatgga tgagattgag aaagctgtca aggaagccaa
     2041 tgcctatgac tttatcatga aactgcctca taaatttgac accctggttg gagagagagg
     2101 ggcccagttg agtggtgggc agaagcagag gatcgccatt gcacgtgccc tggttcgcaa
     2161 ccccaagatc ctcctgctgg atgaggccac gtcagccttg gacacagaaa gcgaagcagt
     2221 ggttcaggtg gctctggata aggccagaaa aggtcggacc accattgtga tagctcatcg
     2281 tttgtctaca gttcgtaatg ctgacgtcat cgctggtttc gatgatggag tcattgtgga
     2341 gaaaggaaat catgatgaac tcatgaaaga gaaaggcatt tacttcaaac ttgtcacaat
     2401 gcagacagca ggaaatgaag ttgaattaga aaatgcagct gatgaatcca aaagtgaaat
     2461 tgatgccttg gaaatgtctt caaatgattc aagatccagt ctaataagaa aaagatcaac
     2521 tcgtaggagt gtccgtggat cacaagccca agacagaaag cttagtacca aagaggctct
     2581 ggatgaaagt atacctccag tttccttttg gaggattatg aagctaaatt taactgaatg
     2641 gccttatttt gttgttggtg tattttgtgc cattataaat ggaggcctgc aaccagcatt
     2701 tgcaataata ttttcaaaga ttataggggt ttttacaaga attgatgatc ctgaaacaaa
     2761 acgacagaat agtaacttgt tttcactatt gtttctagcc cttggaatta tttcttttat
     2821 tacatttttc cttcagggtt tcacatttgg caaagctgga gagatcctca ccaagcggct
     2881 ccgatacatg gttttccgat ccatgctcag acaggatgtg agttggtttg atgaccctaa
     2941 aaacaccact ggagcattga ctaccaggct cgccaatgat gctgctcaag ttaaaggggc
     3001 tataggttcc aggcttgctg taattaccca gaatatagca aatcttggga caggaataat
     3061 tatatccttc atctatggtt ggcaactaac actgttactc ttagcaattg tacccatcat
     3121 tgcaatagca ggagttgttg aaatgaaaat gttgtctgga caagcactga aagataagaa
     3181 agaactagaa ggttctggga agatcgctac tgaagcaata gaaaacttcc gaaccgttgt
     3241 ttctttgact caggagcaga agtttgaaca tatgtatgct cagagtttgc aggtaccata
     3301 cagaaactct ttgaggaaag cacacatctt tggaattaca ttttccttca cccaggcaat
     3361 gatgtatttt tcctatgctg gatgtttccg gtttggagcc tacttggtgg cacataaact
     3421 catgagcttt gaggatgttc tgttagtatt ttcagctgtt gtctttggtg ccatggccgt
     3481 ggggcaagtc agttcatttg ctcctgacta tgccaaagcc aaaatatcag cagcccacat
     3541 catcatgatc attgaaaaaa cccctttgat tgacagctac agcacggaag gcctaatgcc
     3601 gaacacattg gaaggaaatg tcacatttgg tgaagttgta ttcaactatc ccacccgacc
     3661 ggacatccca gtgcttcagg gactgagcct ggaggtgaag aagggccaga cgctggctct
     3721 ggtgggcagc agtggctgtg ggaagagcac agtggtccag ctcctggagc ggttctacga
     3781 ccccttggca gggaaagtgc tgcttgatgg caaagaaata aagcgactga atgttcagtg
     3841 gctccgagca cacctgggca tcgtgtccca ggagcccatc ctgtttgact gcagcattgc
     3901 tgagaacatt gcctatggag acaacagccg ggtggtgtca caggaagaga ttgtgagggc
     3961 agcaaaggag gccaacatac atgccttcat cgagtcactg cctaataaat atagcactaa
     4021 agtaggagac aaaggaactc agctctctgg tggccagaaa caacgcattg ccatagctcg
     4081 tgcccttgtt agacagcctc atattttgct tttggatgaa gccacgtcag ctctggatac
     4141 agaaagtgaa aaggttgtcc aagaagccct ggacaaagcc agagaaggcc gcacctgcat
     4201 tgtgattgct caccgcctgt ccaccatcca gaatgcagac ttaatagtgg tgtttcagaa
     4261 tggcagagtc aaggagcatg gcacgcatca gcagctgctg gcacagaaag gcatctattt
     4321 ttcaatggtc agtgtccagg ctggaacaaa gcgccagtga actctgactg tatgagatgt
     4381 taaatacttt ttaatatttg tttagatatg acatttattc aaagttaaaa gcaaacactt
     4441 acagaattat gaagaggtat ctgtttaaca tttcctcagt caagttcaga gtcttcagag
     4501 acttcgtaat taaaggaaca gagtgagaga catcatcaag tggagagaaa tcatagttta
     4561 aactgcatta taaattttat aacagaatta aagtagattt taaaagataa aatgtgtaat
     4621 tttgtttata ttttcccatt tggactgtaa ctgactgcct tgctaaaaga ttatagaagt
     4681 agcaaaaagt attgaaatgt ttgcataaag tgtctataat aaaactaaac tttcatgtga
     4741 ctggagtcat cttgtccaaa ctgcctgtga atatatcttc tctcaattgg aatattgtag
     4801 ataacttctg ctttaaaaaa gttttcttta aatataccta ctcatttttg tgggaatggt
     4861 taagcagttt aaataattcc tgttgtatat gtctattcac attgggtctt acagaaccat
     4921 ctggcttcat tcttcttgga cttgatcctg ctgattcttg catttccaca ttaaggtggc
     4981 tctcaaaccc aaaacacaga tcgatataag attttaggag gtggggtgag gcacaattat
     5041 gaagtgcata ttattcagat gtatagtaaa tactttgcat tgcttttata aagggttctt
     5101 taaggatttt ttaagatttt tacacttcca aagtacattt actttttgtc ttgataatga
     5161 atcacttttg ccagtaattg gcctcttcca aaagtgatcc ttctgactta cagatgttta
     5221 aaatgtgcca tgagtttaac tacatcttga tacaaacatg ataaaaaaag aaaaaaatat
     5281 attccaaagg ttgggactct ggacgacaaa tttttttaaa ttagccaaaa agcattatta
     5341 acattataaa ctatatttac tataaacaat tgctatctta aataagcaac ttctaaaaat
     5401 aaaaaaaaga agccatcacc tccaggaaaa aaaaatagga aaggatataa tcaggtaatt
     5461 ctcaaagaag aaatgcatga gaaaaatgta tacagtttca acaatcaaat aaatgcaaat
     5521 taaaacaaaa tatcattttt ttgccttgta atttaatgat gaataaaaaa atctaatgtg
     5581 acattc
//
