LOCUS       NM_001348944            5387 bp    mRNA    linear   PRI 13-OCT-2024
DEFINITION  Homo sapiens ATP binding cassette subfamily B member 1 (ABCB1),
            transcript variant 2, mRNA.
ACCESSION   NM_001348944
VERSION     NM_001348944.2
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 5387)
  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 5387)
  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 5387)
  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 5387)
  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 5387)
  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 5387)
  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 5387)
  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 5387)
  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 5387)
  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 5387)
  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_001348944.1.
            
            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 (2) has multiple differences in
            the coding region but maintains the reading frame, compared to
            variant 1. This variant encodes isoform 2, which is shorter than
            isoform 1. Variants 2, 3, and 4 all encode the same isoform (2).
            
            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##
            Transcript exon combination :: SRR1803613.200562.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-135               AC002457.2         148828-148962       c
            136-241             AC002457.2         36640-36745         c
            242-312             AC002457.2         36422-36492         c
            313-386             AC002457.2         35784-35857         c
            387-435             AC002457.2         31433-31481         c
            436-604             AC002457.2         21179-21347         c
            605-656             AC002457.2         5839-5890           c
            657-848             AC002457.2         2452-2643           c
            849-1020            AC002457.2         1737-1908           c
            1021-1145           AC005068.2         95202-95326         c
            1146-1317           AC005068.2         87700-87871         c
            1318-1431           AC005068.2         84664-84777         c
            1432-1542           AC005068.2         84407-84517         c
            1543-1668           AC005068.2         84110-84235         c
            1669-1872           AC005068.2         83790-83993         c
            1873-2043           AC005068.2         83287-83457         c
            2044-2205           AC005068.2         79802-79963         c
            2206-2382           AC005068.2         78762-78938         c
            2383-2529           AC005068.2         78068-78214         c
            2530-2637           AC005068.2         75296-75403         c
            2638-2715           AC005068.2         73207-73284         c
            2716-2799           AC005068.2         70397-70480         c
            2800-3003           AC005068.2         65233-65436         c
            3004-3104           AC005068.2         54715-54815         c
            3105-3245           AC005068.2         53265-53405         c
            3246-3402           AC005068.2         50448-50604         c
            3403-3600           AC005068.2         49170-49367         c
            3601-3807           AC005068.2         43214-43420         c
            3808-3954           AC005068.2         39836-39982         c
            3955-5387           AC005068.2         36956-38388         c
FEATURES             Location/Qualifiers
     source          1..5387
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q21.12"
     gene            1..5387
                     /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..241
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            242..312
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            313..386
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     CDS             319..4161
                     /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 2 is encoded by transcript variant 2;
                     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 2"
                     /protein_id="NP_001335873.1"
                     /db_xref="CCDS:CCDS5608.1"
                     /db_xref="GeneID:5243"
                     /db_xref="HGNC:HGNC:40"
                     /db_xref="MIM:171050"
                     /translation="MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSN
                     WLDKLYMVVGTLAAIIHGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTG
                     FFMNLEEDMTRYAYYYSGIGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEI
                     GWFDVHDVGELNTRLTDDVSKINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVI
                     LAISPVLGLSAAVWAKILSSFTDKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELER
                     YNKNLEEAKRIGIKKAITANISIGAAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTV
                     FFSVLIGAFSVGQASPSIEAFANARGAAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNL
                     EFRNVHFSYPSRKEVKILKGLNLKVQSGQTVALVGNSGCGKSTTVQLMQRLYDPTEGM
                     VSVDGQDIRTINVRFLREIIGVVSQEPVLFATTIAENIRYGRENVTMDEIEKAVKEAN
                     AYDFIMKLPHKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESE
                     AVVQVALDKARKGRTTIVIAHRLSTVRNADVIAGFDDGVIVEKGNHDELMKEKGIYFK
                     LVTMQTAGNEVELENAADESKSEIDALEMSSNDSRSSLIRKRSTRRSVRGSQAQDRKL
                     STKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAIINGGLQPAFAIIFSKIIGVFT
                     RIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKAGEILTKRLRYMVFRSMLR
                     QDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNIANLGTGIIISFIYGWQ
                     LTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGSGKIATEAIENFRTVVSLTQEQ
                     KFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFGAYLVAHKLMSFE
                     DVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDSYSTEGLMPNT
                     LEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYD
                     PLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVVSQEEIV
                     RAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLDEATS
                     ALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLA
                     QKGIYFSMVSVQAGTKRQ"
     exon            387..435
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            436..604
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            605..656
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            657..848
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            849..1020
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1021..1145
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1146..1317
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1318..1431
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1432..1542
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1543..1668
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1669..1872
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            1873..2043
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2044..2205
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2206..2382
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2383..2529
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2530..2637
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2638..2715
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2716..2799
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            2800..3003
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3004..3104
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3105..3245
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3246..3402
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3403..3600
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3601..3807
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3808..3954
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     exon            3955..5387
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4519..4524
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /note="hexamer: AATAAA"
     regulatory      4525..4530
                     /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      4546
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
                     /note="major polyA site"
     polyA_site      4561
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
     regulatory      5309..5314
                     /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      5331
                     /gene="ABCB1"
                     /gene_synonym="ABC20; CD243; CLCS; ENPAT; GP170; MDR1;
                     p-170; P-GP; PGY1"
     regulatory      5363..5368
                     /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      5387
                     /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 aaaagagagg tgcaacggaa gccagaacat tcctcctgga aattcaacct
      181 gtttcgcagt ttctcgagga atcagcattc agtcaatccg ggccgggagc agtcatctgt
      241 ggtctttcca ctaaagtcgg agtatcttct tccaaaattt cacgtcttgg tggccgttcc
      301 aaggagcgcg aggtcggaat ggatcttgaa ggggaccgca atggaggagc aaagaagaag
      361 aactttttta aactgaacaa taaaagtgaa aaagataaga aggaaaagaa accaactgtc
      421 agtgtatttt caatgtttcg ctattcaaat tggcttgaca agttgtatat ggtggtggga
      481 actttggctg ccatcatcca tggggctgga cttcctctca tgatgctggt gtttggagaa
      541 atgacagata tctttgcaaa tgcaggaaat ttagaagatc tgatgtcaaa catcactaat
      601 agaagtgata tcaatgatac agggttcttc atgaatctgg aggaagacat gaccaggtat
      661 gcctattatt acagtggaat tggtgctggg gtgctggttg ctgcttacat tcaggtttca
      721 ttttggtgcc tggcagctgg aagacaaata cacaaaatta gaaaacagtt ttttcatgct
      781 ataatgcgac aggagatagg ctggtttgat gtgcacgatg ttggggagct taacacccga
      841 cttacagatg atgtctccaa gattaatgaa ggaattggtg acaaaattgg aatgttcttt
      901 cagtcaatgg caacattttt cactgggttt atagtaggat ttacacgtgg ttggaagcta
      961 acccttgtga ttttggccat cagtcctgtt cttggactgt cagctgctgt ctgggcaaag
     1021 atactatctt catttactga taaagaactc ttagcgtatg caaaagctgg agcagtagct
     1081 gaagaggtct tggcagcaat tagaactgtg attgcatttg gaggacaaaa gaaagaactt
     1141 gaaaggtaca acaaaaattt agaagaagct aaaagaattg ggataaagaa agctattaca
     1201 gccaatattt ctataggtgc tgctttcctg ctgatctatg catcttatgc tctggccttc
     1261 tggtatggga ccaccttggt cctctcaggg gaatattcta ttggacaagt actcactgta
     1321 ttcttttctg tattaattgg ggcttttagt gttggacagg catctccaag cattgaagca
     1381 tttgcaaatg caagaggagc agcttatgaa atcttcaaga taattgataa taagccaagt
     1441 attgacagct attcgaagag tgggcacaaa ccagataata ttaagggaaa tttggaattc
     1501 agaaatgttc acttcagtta cccatctcga aaagaagtta agatcttgaa gggtctgaac
     1561 ctgaaggtgc agagtgggca gacggtggcc ctggttggaa acagtggctg tgggaagagc
     1621 acaacagtcc agctgatgca gaggctctat gaccccacag aggggatggt cagtgttgat
     1681 ggacaggata ttaggaccat aaatgtaagg tttctacggg aaatcattgg tgtggtgagt
     1741 caggaacctg tattgtttgc caccacgata gctgaaaaca ttcgctatgg ccgtgaaaat
     1801 gtcaccatgg atgagattga gaaagctgtc aaggaagcca atgcctatga ctttatcatg
     1861 aaactgcctc ataaatttga caccctggtt ggagagagag gggcccagtt gagtggtggg
     1921 cagaagcaga ggatcgccat tgcacgtgcc ctggttcgca accccaagat cctcctgctg
     1981 gatgaggcca cgtcagcctt ggacacagaa agcgaagcag tggttcaggt ggctctggat
     2041 aaggccagaa aaggtcggac caccattgtg atagctcatc gtttgtctac agttcgtaat
     2101 gctgacgtca tcgctggttt cgatgatgga gtcattgtgg agaaaggaaa tcatgatgaa
     2161 ctcatgaaag agaaaggcat ttacttcaaa cttgtcacaa tgcagacagc aggaaatgaa
     2221 gttgaattag aaaatgcagc tgatgaatcc aaaagtgaaa ttgatgcctt ggaaatgtct
     2281 tcaaatgatt caagatccag tctaataaga aaaagatcaa ctcgtaggag tgtccgtgga
     2341 tcacaagccc aagacagaaa gcttagtacc aaagaggctc tggatgaaag tatacctcca
     2401 gtttcctttt ggaggattat gaagctaaat ttaactgaat ggccttattt tgttgttggt
     2461 gtattttgtg ccattataaa tggaggcctg caaccagcat ttgcaataat attttcaaag
     2521 attatagggg tttttacaag aattgatgat cctgaaacaa aacgacagaa tagtaacttg
     2581 ttttcactat tgtttctagc ccttggaatt atttctttta ttacattttt ccttcagggt
     2641 ttcacatttg gcaaagctgg agagatcctc accaagcggc tccgatacat ggttttccga
     2701 tccatgctca gacaggatgt gagttggttt gatgacccta aaaacaccac tggagcattg
     2761 actaccaggc tcgccaatga tgctgctcaa gttaaagggg ctataggttc caggcttgct
     2821 gtaattaccc agaatatagc aaatcttggg acaggaataa ttatatcctt catctatggt
     2881 tggcaactaa cactgttact cttagcaatt gtacccatca ttgcaatagc aggagttgtt
     2941 gaaatgaaaa tgttgtctgg acaagcactg aaagataaga aagaactaga aggttctggg
     3001 aagatcgcta ctgaagcaat agaaaacttc cgaaccgttg tttctttgac tcaggagcag
     3061 aagtttgaac atatgtatgc tcagagtttg caggtaccat acagaaactc tttgaggaaa
     3121 gcacacatct ttggaattac attttccttc acccaggcaa tgatgtattt ttcctatgct
     3181 ggatgtttcc ggtttggagc ctacttggtg gcacataaac tcatgagctt tgaggatgtt
     3241 ctgttagtat tttcagctgt tgtctttggt gccatggccg tggggcaagt cagttcattt
     3301 gctcctgact atgccaaagc caaaatatca gcagcccaca tcatcatgat cattgaaaaa
     3361 acccctttga ttgacagcta cagcacggaa ggcctaatgc cgaacacatt ggaaggaaat
     3421 gtcacatttg gtgaagttgt attcaactat cccacccgac cggacatccc agtgcttcag
     3481 ggactgagcc tggaggtgaa gaagggccag acgctggctc tggtgggcag cagtggctgt
     3541 gggaagagca cagtggtcca gctcctggag cggttctacg accccttggc agggaaagtg
     3601 ctgcttgatg gcaaagaaat aaagcgactg aatgttcagt ggctccgagc acacctgggc
     3661 atcgtgtccc aggagcccat cctgtttgac tgcagcattg ctgagaacat tgcctatgga
     3721 gacaacagcc gggtggtgtc acaggaagag attgtgaggg cagcaaagga ggccaacata
     3781 catgccttca tcgagtcact gcctaataaa tatagcacta aagtaggaga caaaggaact
     3841 cagctctctg gtggccagaa acaacgcatt gccatagctc gtgcccttgt tagacagcct
     3901 catattttgc ttttggatga agccacgtca gctctggata cagaaagtga aaaggttgtc
     3961 caagaagccc tggacaaagc cagagaaggc cgcacctgca ttgtgattgc tcaccgcctg
     4021 tccaccatcc agaatgcaga cttaatagtg gtgtttcaga atggcagagt caaggagcat
     4081 ggcacgcatc agcagctgct ggcacagaaa ggcatctatt tttcaatggt cagtgtccag
     4141 gctggaacaa agcgccagtg aactctgact gtatgagatg ttaaatactt tttaatattt
     4201 gtttagatat gacatttatt caaagttaaa agcaaacact tacagaatta tgaagaggta
     4261 tctgtttaac atttcctcag tcaagttcag agtcttcaga gacttcgtaa ttaaaggaac
     4321 agagtgagag acatcatcaa gtggagagaa atcatagttt aaactgcatt ataaatttta
     4381 taacagaatt aaagtagatt ttaaaagata aaatgtgtaa ttttgtttat attttcccat
     4441 ttggactgta actgactgcc ttgctaaaag attatagaag tagcaaaaag tattgaaatg
     4501 tttgcataaa gtgtctataa taaaactaaa ctttcatgtg actggagtca tcttgtccaa
     4561 actgcctgtg aatatatctt ctctcaattg gaatattgta gataacttct gctttaaaaa
     4621 agttttcttt aaatatacct actcattttt gtgggaatgg ttaagcagtt taaataattc
     4681 ctgttgtata tgtctattca cattgggtct tacagaacca tctggcttca ttcttcttgg
     4741 acttgatcct gctgattctt gcatttccac attaaggtgg ctctcaaacc caaaacacag
     4801 atcgatataa gattttagga ggtggggtga ggcacaatta tgaagtgcat attattcaga
     4861 tgtatagtaa atactttgca ttgcttttat aaagggttct ttaaggattt tttaagattt
     4921 ttacacttcc aaagtacatt tactttttgt cttgataatg aatcactttt gccagtaatt
     4981 ggcctcttcc aaaagtgatc cttctgactt acagatgttt aaaatgtgcc atgagtttaa
     5041 ctacatcttg atacaaacat gataaaaaaa gaaaaaaata tattccaaag gttgggactc
     5101 tggacgacaa atttttttaa attagccaaa aagcattatt aacattataa actatattta
     5161 ctataaacaa ttgctatctt aaataagcaa cttctaaaaa taaaaaaaag aagccatcac
     5221 ctccaggaaa aaaaaatagg aaaggatata atcaggtaat tctcaaagaa gaaatgcatg
     5281 agaaaaatgt atacagtttc aacaatcaaa taaatgcaaa ttaaaacaaa atatcatttt
     5341 tttgccttgt aatttaatga tgaataaaaa aatctaatgt gacattc
//
