LOCUS       NM_000914              15143 bp    mRNA    linear   PRI 01-OCT-2024
DEFINITION  Homo sapiens opioid receptor mu 1 (OPRM1), transcript variant
            MOR-1, mRNA.
ACCESSION   NM_000914
VERSION     NM_000914.5
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 15143)
  AUTHORS   Agullo,L., Escorial,M., Orutno,S., Muriel,J., Sandoval,J.,
            Margarit,C. and Peiro,A.M.
  TITLE     Epigenetic and sex differences in opioid use disorder in chronic
            pain: A real-world study linked with OPRM1 DNA methylation
  JOURNAL   Addict Biol 29 (7), e13422 (2024)
   PUBMED   38949208
  REMARK    GeneRIF: Epigenetic and sex differences in opioid use disorder in
            chronic pain: A real-world study linked with OPRM1 DNA methylation.
REFERENCE   2  (bases 1 to 15143)
  AUTHORS   Kaya-Akyuzlu,D., Ozkan-Kotiloglu,S., Danisman,M. and Bal,C.
  TITLE     OPRM1 rs2075572 has potential to affect plasma buprenorphine level
            in opioid users, but not OPRM1 rs562859
  JOURNAL   Neurosci Lett 834, 137846 (2024)
   PUBMED   38821204
  REMARK    GeneRIF: OPRM1 rs2075572 has potential to affect plasma
            buprenorphine level in opioid users, but not OPRM1 rs562859.
REFERENCE   3  (bases 1 to 15143)
  AUTHORS   Bigliardi,P.L., Lo,S., Bigliardi,E., Dancik,Y., Leblanc-Noblesse,E.
            and Bigliardi-Qi,M.
  TITLE     Delta opioid receptor expression correlates to skin ageing and
            melanin expression in Asian women
  JOURNAL   Exp Dermatol 33 (6), e15096 (2024)
   PUBMED   38922774
  REMARK    GeneRIF: Delta opioid receptor expression correlates to skin ageing
            and melanin expression in Asian women.
REFERENCE   4  (bases 1 to 15143)
  AUTHORS   Andersen,S., Baar,C., Fladvad,T., Laugsand,E.A. and Skorpen,F.
  TITLE     The N-terminally truncated micro3 and micro3-like opioid receptors
            are transcribed from a novel promoter upstream of exon 2 in the
            human OPRM1 gene
  JOURNAL   PLoS One 8 (8), e71024 (2013)
   PUBMED   23951073
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 15143)
  AUTHORS   Kasai,S. and Ikeda,K.
  TITLE     Pharmacogenomics of the human micro-opioid receptor
  JOURNAL   Pharmacogenomics 12 (9), 1305-1320 (2011)
   PUBMED   21919606
  REMARK    GeneRIF: this article summarizes the genetic variations in the
            human OPRM1 gene, which are analyzed with regard to pain
            sensitivity, opioid drug sensitivity and susceptibility to drug
            dependence, and other disorders.[Review]
            Review article
REFERENCE   6  (bases 1 to 15143)
  AUTHORS   Song,K.Y., Kim,C.S., Hwang,C.K., Choi,H.S., Law,P.Y., Wei,L.N. and
            Loh,H.H.
  TITLE     uAUG-mediated translational initiations are responsible for human
            mu opioid receptor gene expression
  JOURNAL   J Cell Mol Med 14 (5), 1113-1124 (2010)
   PUBMED   19438807
  REMARK    GeneRIF: These results indicate that re-initiation in MOR gene
            expression could play an important role in OPRM1 regulation.
REFERENCE   7  (bases 1 to 15143)
  AUTHORS   Xu,J., Xu,M., Hurd,Y.L., Pasternak,G.W. and Pan,Y.X.
  TITLE     Isolation and characterization of new exon 11-associated N-terminal
            splice variants of the human mu opioid receptor gene
  JOURNAL   J Neurochem 108 (4), 962-972 (2009)
   PUBMED   19077058
REFERENCE   8  (bases 1 to 15143)
  AUTHORS   Chuang,T.K., Killam,K.F. Jr., Chuang,L.F., Kung,H.F., Sheng,W.S.,
            Chao,C.C., Yu,L. and Chuang,R.Y.
  TITLE     Mu opioid receptor gene expression in immune cells
  JOURNAL   Biochem Biophys Res Commun 216 (3), 922-930 (1995)
   PUBMED   7488213
REFERENCE   9  (bases 1 to 15143)
  AUTHORS   Mestek,A., Hurley,J.H., Bye,L.S., Campbell,A.D., Chen,Y., Tian,M.,
            Liu,J., Schulman,H. and Yu,L.
  TITLE     The human mu opioid receptor: modulation of functional
            desensitization by calcium/calmodulin-dependent protein kinase and
            protein kinase C
  JOURNAL   J Neurosci 15 (3 Pt 2), 2396-2406 (1995)
   PUBMED   7891175
REFERENCE   10 (bases 1 to 15143)
  AUTHORS   Maneckjee,R. and Minna,J.D.
  TITLE     Opioid and nicotine receptors affect growth regulation of human
            lung cancer cell lines
  JOURNAL   Proc Natl Acad Sci U S A 87 (9), 3294-3298 (1990)
   PUBMED   2159143
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL136444.16 and AL132774.20.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Apr 15, 2020 this sequence version replaced NM_000914.4.
            
            Summary: This gene encodes one of at least three opioid receptors
            in humans; the mu opioid receptor (MOR). The MOR is the principal
            target of endogenous opioid peptides and opioid analgesic agents
            such as beta-endorphin and enkephalins. The MOR also has an
            important role in dependence to other drugs of abuse, such as
            nicotine, cocaine, and alcohol via its modulation of the dopamine
            system. The NM_001008503.2:c.118A>G allele has been associated with
            opioid and alcohol addiction and variations in pain sensitivity but
            evidence for it having a causal role is conflicting. Multiple
            transcript variants encoding different isoforms have been found for
            this gene. Though the canonical MOR belongs to the superfamily of
            7-transmembrane-spanning G-protein-coupled receptors some isoforms
            of this gene have only 6 transmembrane domains. [provided by
            RefSeq, Oct 2013].
            
            Sequence Note:.
            
            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 :: L25119.1, FJ041291.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145544, SAMN03267759
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            CDS uses downstream in-frame AUG :: community standard (PMID:
                                                21919606)
            MANE Ensembl match               :: ENST00000330432.12/
                                                ENSP00000328264.7
            RefSeq Select criteria           :: based on manual assertion,
                                                conservation, expression
            regulatory uORF                  :: PMID: 19438807
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-595               AL136444.16        65027-65621         c
            596-948             AL136444.16        14683-15035         c
            949-1469            AL136444.16        13389-13909         c
            1470-15143          AL132774.20        15822-29495
FEATURES             Location/Qualifiers
     source          1..15143
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q25.2"
     gene            1..15143
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /note="opioid receptor mu 1"
                     /db_xref="GeneID:4988"
                     /db_xref="HGNC:HGNC:8156"
                     /db_xref="MIM:600018"
     exon            1..595
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /inference="alignment:Splign:2.1.0"
     regulatory      30..83
                     /regulatory_class="uORF"
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:19438807]"
                     /note="this uORF is predicted to encode a 17 aa peptide
                     (PMID:19438807)"
     regulatory      70..153
                     /regulatory_class="uORF"
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:19438807]"
                     /note="this uORF is predicted to encode a 27 aa peptide
                     (PMID:19438807)"
     regulatory      127..153
                     /regulatory_class="uORF"
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:19438807]"
                     /note="this uORF is predicted to encode an 8 aa peptide
                     (PMID:19438807)"
     CDS             306..1508
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /note="isoform MOR-1 is encoded by transcript variant
                     MOR-1; mu opiate receptor; mu opioid receptor hMOR-1a"
                     /codon_start=1
                     /product="mu-type opioid receptor isoform MOR-1"
                     /protein_id="NP_000905.3"
                     /db_xref="CCDS:CCDS55070.1"
                     /db_xref="GeneID:4988"
                     /db_xref="HGNC:HGNC:8156"
                     /db_xref="MIM:600018"
                     /translation="MDSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDP
                     CGPNRTDLGGRDSLCPPTGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMK
                     TATNIYIFNLALADALATSTLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTL
                     CTMSVDRYIAVCHPVKALDFRTPRNAKIINVCNWILSSAIGLPVMFMATTKYRQGSID
                     CTLTFSHPTWYWENLLKICVFIFAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRN
                     LRRITRMVLVVVAVFIVCWTPIHIYVIIKALVTIPETTFQTVSWHFCIALGYTNSCLN
                     PVLYAFLDENFKRCFREFCIPTSSNIEQQNSTRIRQNTRDHPSTANTVDRTNHQLENL
                     EAETAPLP"
     exon            596..948
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /inference="alignment:Splign:2.1.0"
     exon            949..1469
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /inference="alignment:Splign:2.1.0"
     exon            1470..15143
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /inference="alignment:Splign:2.1.0"
     regulatory      15120..15125
                     /regulatory_class="polyA_signal_sequence"
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /note="hexamer: AATAAA"
     polyA_site      15143
                     /gene="OPRM1"
                     /gene_synonym="LMOR; M-OR-1; MOP; MOR; MOR1; OPRM"
                     /note="major polyA site"
ORIGIN      
        1 ctccctccct tccagcctcc gaatcccgca tggcccacgc tcccctcctg cagcggtgcg
       61 gggcaggtga tgagcctctg tgaactacta aggtgggagg gggctatacg cagaggagaa
      121 tgtcagatgc tcagctcggt cccctccgcc tgacgctcct ctctgtctca gccaggactg
      181 gtttctgtaa gaaacagcag gagctgtggc agcggcgaaa ggaagcggct gaggcgcttg
      241 gaacccgaaa agtctcggtg ctcctggcta cctcgcacag cggtgcccgc ccggccgtca
      301 gtaccatgga cagcagcgct gcccccacga acgccagcaa ttgcactgat gccttggcgt
      361 actcaagttg ctccccagca cccagccccg gttcctgggt caacttgtcc cacttagatg
      421 gcaacctgtc cgacccatgc ggtccgaacc gcaccgacct gggcgggaga gacagcctgt
      481 gccctccgac cggcagtccc tccatgatca cggccatcac gatcatggcc ctctactcca
      541 tcgtgtgcgt ggtggggctc ttcggaaact tcctggtcat gtatgtgatt gtcagataca
      601 ccaagatgaa gactgccacc aacatctaca ttttcaacct tgctctggca gatgccttag
      661 ccaccagtac cctgcccttc cagagtgtga attacctaat gggaacatgg ccatttggaa
      721 ccatcctttg caagatagtg atctccatag attactataa catgttcacc agcatattca
      781 ccctctgcac catgagtgtt gatcgataca ttgcagtctg ccaccctgtc aaggccttag
      841 atttccgtac tccccgaaat gccaaaatta tcaatgtctg caactggatc ctctcttcag
      901 ccattggtct tcctgtaatg ttcatggcta caacaaaata caggcaaggt tccatagatt
      961 gtacactaac attctctcat ccaacctggt actgggaaaa cctgctgaag atctgtgttt
     1021 tcatcttcgc cttcattatg ccagtgctca tcattaccgt gtgctatgga ctgatgatct
     1081 tgcgcctcaa gagtgtccgc atgctctctg gctccaaaga aaaggacagg aatcttcgaa
     1141 ggatcaccag gatggtgctg gtggtggtgg ctgtgttcat cgtctgctgg actcccattc
     1201 acatttacgt catcattaaa gccttggtta caatcccaga aactacgttc cagactgttt
     1261 cttggcactt ctgcattgct ctaggttaca caaacagctg cctcaaccca gtcctttatg
     1321 catttctgga tgaaaacttc aaacgatgct tcagagagtt ctgtatccca acctcttcca
     1381 acattgagca acaaaactcc actcgaattc gtcagaacac tagagaccac ccctccacgg
     1441 ccaatacagt ggatagaact aatcatcagc tagaaaatct ggaagcagaa actgctccgt
     1501 tgccctaaca gggtctcatg ccattccgac cttcaccaag cttagaagcc accatgtatg
     1561 tggaagcagg ttgcttcaag aatgtgtagg aggctctaat tctctaggaa agtgcctgct
     1621 tttaggtcat ccaacctctt tcctctctgg ccactctgct ctgcacatta gagggacagc
     1681 caaaagtaag tggagcattt ggaaggaaag gaatatacca caccgaggag tccagtttgt
     1741 gcaagacacc cagtggaacc aaaacccatc gtggtatgtg aattgaagtc atcataaaag
     1801 gtgacccttc tgtctgtaag attttatttt caagcaaata tttatgacct caacaaagaa
     1861 gaaccatctt ttgttaagtt caccgtagta acacataaag taaatgctac ctctgatcaa
     1921 agcaccttga atggaaggtc cgagtctttt tagtgttttg caagggaatg aatccattat
     1981 tctattttag acttttaact tcaccttaaa attagcatct ggctaaggca tcattttcac
     2041 ctccatttct tggttttgta ttgtttaaaa aaataacatc tctttcatct agctccataa
     2101 ttgcaaggga agagattagc atgaaaggta atctgaaaca cagtcatgtg tcagctgtag
     2161 aaaggttgat tctcatgcac tgcaaatact tccaaagagt catcatgggg gatttttcat
     2221 tcttaggctt tcagtggttt gttcctcagt tttaaatgtg caattttctt gctcctattt
     2281 aagtgttcac aaaaggtaat agtcaatgag ctcatcactt catccatgca ggaagtcaag
     2341 cattaaaatg tactctttat ttctcactgg tttctccata ctgcaggctc cccacatatt
     2401 attttctttt tttaactcag ctcagaatcc ttatgccttt tgaatcagtg tgataaaatg
     2461 acagatgttt ttgttgattg ccagaacagt ttaaactttt tttaaacaat aaatccaata
     2521 aacataatct caagacagac tcatatgacc atacagaaaa gtgtgtcatc tatttttcaa
     2581 tcctgtgtag ttacttggat gtgaaatatt aacaatggcc caaaaatatt ttcctgaaga
     2641 ttgtgtttat ataatgtcat caccaatatt ttggtctttt tgatctctgc taaatgtcaa
     2701 gatttccttt gtaaagtgtc gatcttctaa gtagtttctt taagacaatt ctccgcttta
     2761 actgattttc tttgttgtga aacacagtag agatttggca atcaaccatt ttacttgatc
     2821 taggtagaca gccaagtcag atggcccatg cctagaagct ctccattttg aacttttgtc
     2881 agcattgatt aaaagaatca aataccttgt agttatctat gatgatacaa gtaaaaaact
     2941 aggctgctga cttctgagta ttcctgagcc tacaattgta aaattgtaga ctccattgta
     3001 aaatttgtat tttttcatca atctgacaag gcacaaatat gtgccagata tacaaaagca
     3061 atgtttctag aaaacagcta tcatggatca gaataactga atttactctc agatctattg
     3121 gctatagtta tgtggactca acccacgtat ccagtagatg ggaaaaaaca aaagccaaaa
     3181 taagtttttt agtgtttcct tctgatgaag tttcatgttt gcttgtaata atctccattt
     3241 ctcaaatatt atgttccata atagacatac attatgttta attttttata ttttctgaca
     3301 aaagtaacta aaactaggac cttaaaaaga tttagaatgt taaataagtg tactagggtg
     3361 tatatattta catatataca ctactagagc ttccaaaagt aaaatggata attcaaacag
     3421 aacacaatgt aatatttgta tgtaaataac tgaggaggaa aatccatgct tttcatgggc
     3481 taggatggtt tctcccaaga gatgacatag tattgctttt gctcatcagg ctgtttctca
     3541 gcaatcattg tttctgctta ataccagctc ctagtacgaa ttatctggca tgttgagagc
     3601 aactttgtct tcaagtagga cctgatctat ctttttccac aaatgtcatg tgtgtgaaca
     3661 agtttcttcc atgtcatctt tgagactcta cacagaatac acaataaagg gagttatttt
     3721 taaaataaga cattctaaag taaataataa ataaggtcat tgtcaacgtt tttcattcaa
     3781 aaccattttt taacgtaaat ttgctagaac caccttccaa ttccaaggca aggagagaca
     3841 ttacaaccct gactcaactg gatgggctaa ggtttctgat aaaatctgaa gataaagaaa
     3901 atggaatatt ctgctttttt cttccttcta atttcaccct tgcctaagga tgagatttct
     3961 tcccaggttg gtatcccaga aatgcagact gtagctatgg ggcggaagct ttgtttcttt
     4021 acctgatcac ttgctgtgga aattctagct tattgtgttc caagtagtta gtggtttttc
     4081 tccttcagtc tccactgtta ttttgctcct tcatccctct ttccttgcca atcattagaa
     4141 aggaaagaag aggaaagaga ctcgctggag cactggtgag tctctaggac cctgctatcc
     4201 tatcccaaca gggctgtcag acggagaact cctaatgtgg ccatttgaaa cacttctcaa
     4261 cattgaaata gacagttgaa gttttaaaat aacctcttct aagacacggc tatgagtagg
     4321 taagagagca ttcattccct tcaataatat gactgtgttg ataaaactga taaccattca
     4381 cttgcaaatg ttattattga ataagtctca cttagctcat ttaatattac ccaaaagatg
     4441 ctaacaaatt ctgtttccca cattgtcaca gcatgccctt tacatctcag gatccaggca
     4501 aaagttgaaa ttcagaaaca tagatatgaa atgtaagata caaagaaaac acctctgcaa
     4561 agattccgac cacatttatc aaaaagtccc caaagcattc aaaatcttta cttaagtcaa
     4621 gtctatttat acgtttaaaa gctaaaaaca agatcttttt ggtaatgctt caattaaatg
     4681 ttttatctaa atatgtggaa atgataagat gcgtactgca tctctcatat aataaagata
     4741 atcagtttta tacagacata ttctccatct actggcaatt accaagataa gatggcacta
     4801 gaaatttctc cagcttacgc catgaatact gcagaagctg atactatccg ttgtggtttt
     4861 acaaattcta gagggttcta gccaaagcaa cctaagaata ggacatggta gcttaagttt
     4921 ttcagcttct taactggcca cacacacaca agttgtgttt gtacaattct tgaggtcaat
     4981 cagaaccaaa aaatctgttg ctggaagaaa tattatcctc ttcatagaaa tatccaccag
     5041 cagaaaattg gtttctcaag gaatccctac tgcccttgta gaaacatcaa gattcttgcc
     5101 tggattctca acataagtct ttactcacag gcctattgct tggtttcaga agagtgagaa
     5161 catgaaagtt cataaatgcc tgggccactg caactctaac cactgtgttt cccccagttt
     5221 gatatggttc aggatacata gtcatagaac agggcatgca gattgtattt aagaccactg
     5281 caagtaaggt ctaaggcaaa agtaaattaa tgagtccaac tctggggcat ccatttaaga
     5341 gccatttaat ccatttaatt acaaataatt tcaacccata gtcagtgttc ttcactgtct
     5401 tcaaaaatat aaaaagtaca aggaattgtg tacattacaa actgctccag aaacaaaacc
     5461 aaatgtggat agctttgtga gctgcagtgt gtggcaaatg ttcaaccttt tgttatgcaa
     5521 tatcacccat atcaaatacc attcttaaag cagtagacag atgagtcaag ttcaatttaa
     5581 tgcaaacaat attactgtgt tctaagcgct tctgttactc gaaaggggtc tgatccagac
     5641 cccaaaagag ggttcttgga cctcatgcaa gaaagaattc aggagtaaag tgaaagtgaa
     5701 atgggtcagg atcaatggtc tcattgtcta aggtgttatc cgagctcgtt gtctcacaac
     5761 caagaaaatt aaggagcatg gacacaaagg gtgaggttgg agcaaaagtt taataagcaa
     5821 aagaggaaag ctctctgcag cagagacggg agcccaagtg ggttgctgtt tttacagctg
     5881 aatccaaaag cttttataag aaactcctct catctctgca gctatttgag taacttctct
     5941 tatctgaaaa gctgtctgta caactgcctc tatctatgca gctatggggt gtctctaggc
     6001 gagcacaaag catagcttct cttgttgtat aattgtgggt ttgttttaag taagccactt
     6061 tcctccctgc aagttcccac ggagcagaaa aaaggaggaa actttttcct gggagcccac
     6121 taatcacaca gtgaacaaaa ggcttctatg ctgggcctta ctttctaaca gtgcagcagt
     6181 tatagtctga gttttctcca ggctgctcca tttttgcctg tagctatgat ttttcaggca
     6241 gcctgcttct ccgaggacta gtcttagctg tttacctaac tgattggtcc ttttcttctc
     6301 cctgaaaagc aagtttatta agaaagcaaa ggaataaaga atggctactc cataggcagc
     6361 gtagccccaa gggctgctgg ttggctattt ttgtggttat ttcttgatta tatgctaaac
     6421 aaggggtgga ttattcatgg gttttctggg aaaggagtgg gcaattccca gaactgaggg
     6481 ttcttcccct tttaagaccg catagggcaa cttcctgaca ttgccatggc atttgtaaac
     6541 tgtcgtggta ctggtgggaa tgttttttag catgctaatg caatataatt agtgtataat
     6601 gagtagtgag gacaaccaga ggtaactttc attgccatct tggttttagt ggggtttggc
     6661 cggcttcttt accacatcct tttatcagta agatcttcgt gacctgtacc ttgtgccaac
     6721 ctcctatctc ttcctgtgac ttggaatgcc taacctcctg ggaatgcagc ccagtaggtc
     6781 tcagccttat tttacccagc ctctattcaa gatggagtcg ctctggttca aacacctctg
     6841 acacttgaat tacaaatata aggaccattg acactgagat tttaagggag gaaaaacaga
     6901 ttgacagtgg actaaaggta cttttgtagc aaggtacttt ccacacaata ttgaataaat
     6961 gcagtgtata catttttaaa ggaattttaa gagctcggaa atcattaaaa ttaagtttat
     7021 caatttttga aagcatcttc tgactcaaat atatgaaaag attattctag accttaggca
     7081 gatattcaga gaaagatcag ttttctatgg gttttttcca tcatgcattt tatacaaatt
     7141 taatatactt tttcaactca ctttgcattt cctgttacct tgtactgaga acttcattaa
     7201 aacctgcact tgaaattgca cttaaacttt acaaaatcac agaagaagtt gttttccata
     7261 ggtgtggggt gggatgttag agctctagac attaattcct aggaatcgca tacctacgga
     7321 aaacagtcct ctgacctcct gtgacacatg gggtgagccc ttcctttttg tctcaatctc
     7381 aaaaaacagt aagtctttaa tccatttgca tcaaaaagta cttcatatgc tcgaaactaa
     7441 agtaaaactt tattgaaata cattaatatg ctcctggaac atactactgg gtctcagaca
     7501 gtgcagaagc tttattgttt atttgggaag agcaaggtaa gaatcaagta gaaatgataa
     7561 agggcaagga aaaaagatga aagcttactc atattaacca ttctaccatt ggaattattt
     7621 gccaacacac cttgctgcta cttagagaaa gtagttcacc tcactacctt ttatccaaag
     7681 aaattatctc taaaagcact cagacatttt gtagagcaag tagcaatcta ttcaaagttg
     7741 taaaggttct gtagaatctc tcagaccagg tacaggacct accaaaggcc acagccaagc
     7801 acaagcagct acattagaca gttttacagc tctgtatttc aggaaaactt ctgtcctgtg
     7861 ggagcaatac aaaactatac cagttttttg ttagtgtaaa aattgcccaa tattaaccag
     7921 agcagcccaa aatatttcag ggtaagaata gatatattta tatttttcag atgatatatc
     7981 ttcattttcg attttgaaag aacagtaata ctaattatat cccatgtaag gggctactga
     8041 caattttgat ggtacctgaa tttgcctcta tcatgcatct caatgatttg ttgtcatcca
     8101 aagctatttc atgaatcaaa tatcgttttc tacctgcccc acaactgtgt acataaaacc
     8161 taaacctctg aagcaataaa cctcttccat tacacaggtt tagattcaga gttttcttgc
     8221 ttaagttcca actaaaagta ttacattctt agcataagta tactcataaa gaaaaataag
     8281 tatttgtttt aggttttaga gagagagcac agagtccctt tgagacagtg gggaaaattc
     8341 atcttcatat tgtcacatgc actgtaatag gaatgtttag caaaaaaaac cttccagaga
     8401 aaggtggttt ccaatattac ctacaacttc ctttgcaatt tgatttttga aaggacctaa
     8461 aagttgaaaa caggctatca catcccattt gctttaaagt ctcttaaact tacgctcttt
     8521 cgcttcaaat gcataaatgt tttatttaag tttgcattgc ccactaaggc tagacatttt
     8581 tttttttttt tttttttttt tttttttgag acagagtctc gctctgtcgc ccaggctgga
     8641 gtacagtggc gggatctcgg ctcactgcaa gctccgcctc ccgggttcac gccattctcc
     8701 tgcctcagcc tcccaagtag ctgggactac aggcgcccgc cactacgccc ggctaatttt
     8761 ttgtattttt agtagagacg gggtttcacc gttttagccg ggatgatctc gatctcctga
     8821 cctcgtgatc cgcccgcctc ggcctcccaa agtgctggga ttacaggcgt gagccaccgc
     8881 gcccggcccg gctagacatt ttttgataaa ttcacagggt tacaaaatac caaacggaaa
     8941 tgagataagt ggtataaacc acagaagata taggagaaga gaaaaaaaaa agaggaaata
     9001 aagaagacaa ctcttttcct aagagtctgg gtaaaattga acatagccat attcactgaa
     9061 caacatgagt gagcttcatt aatttaagca cagcaaaact gctttaatta acaagaccag
     9121 agagaaggga gaggagacta catttgtgtg acctaatggt tgtgatttca ctgtccaaga
     9181 ggacaaagac aaagaaattc tgggaaggag aacaacaatt atattccccc atttcaagaa
     9241 gggcagaagt gtcccaacac tacccaatat ttgcaaaatt caaatgtctc ataggctctt
     9301 cttccctggt tccctcagga gctgggtttc tgggttgcag aagtgctttt catattctgt
     9361 atctggttgt ggtggcaatg tcaccaccct acactgctgt gacaccgaaa caaccaagcc
     9421 tagaatcagc tggtgcctct tttcatctgc agggtagatt tggcttccat ggttgttcac
     9481 tgctctgtgt taggaaggct cagtgacagg tgtacagcct tcagtaatgc ctcaaaggtt
     9541 ctccaagcag aggtaaacat gtgggtcctg ctggtgacat attagacttc ttactttccc
     9601 caaataaaaa agtgcctgct gggcgcggtg gctcacgcct gtaattccag cactttggga
     9661 ggccgaggcg ggcggaacac aaggtcagga gatcaagacc atcctggcca atatggtaaa
     9721 accccatctc tactaaaaat acaaaattag gaaggcgtgg tggtgcacgc ctgtaatccc
     9781 agctagtcgg gaggctgagg caggagaatt gcttgaactg gggaggcgga agttgcagtg
     9841 agccaagatc gcagcattgc actccagcct gggcaacaga atgagattgt ctcaaaaaaa
     9901 aaaaaaagtg ccacatgcca tgctatgtgc ccaaagtttc cttcacacaa cacagccttg
     9961 agatgcagta ttaaattcta cacttttcct accatagtga tacatgtggc ttttctttgc
    10021 tgtgttctga gatgtcatgc tttgaaatca gtggccatta tcatctaagg attccgccag
    10081 agacttccaa aagaagaggt ctcatttata aagtgaattt gaataaaatg accagttagg
    10141 tgttttcaga aacacctatg ccctacttgc ctactcttca agggtttagg ggcttagggg
    10201 gaggttttgt ttgggttttt tgttgctgtt gcttgtttat ttgtttgttg tgtttaagac
    10261 gttttacttg tccctgaaat gtttgtcatc acacagatac acgctcagga taagaactac
    10321 cagactagat taggaggtcc acaccaccaa ttgagatgta cctgtgctca tgacttgaca
    10381 ttgtggtggg ccggctacaa ccctccccac ccctcgcttt cactaaataa caactctctt
    10441 ctctccatca ttttgactta gagccagtca gaattcaatc tccaatatcc tgactagcac
    10501 aagaaatcca taggttgatt cttgttctcc tgcatctctg caggtggcaa acctgattcc
    10561 taatgcctgt tcctgcctct gcaggggttc attcagaaaa caggaaaata acaaaggctt
    10621 cctgtaattc tctttggctg taatacaatt tgttcccgtc tgcccccagg ctcacccagt
    10681 gctctgtctc agtggtaagc tgtaactgat cactgctgta ttaactcaaa actcatttgc
    10741 tttatggaaa ttcatggccc ttatttctca agggaccaga gaaaaccaat aggcctactc
    10801 cccagctgag tactttccat gcaagctacc gcatctgtat aaattaggtt caaataacag
    10861 agtatttcca ggatttataa attcagtatt acaaatagta atctggcaag tgttctcagg
    10921 atccccttgc tacctgtaat tcaatcatat aacttctgaa tgggctgggg gaaaataaca
    10981 ataagaaaaa ctggtgttta cctgaagatc tgcccagtga tttgtgtgtt ttcttaataa
    11041 actttaccca cttattaaaa gaataaaatg aaggtggagt taattctgac tacgggattc
    11101 ctttttcact tttataatga actccttcct tctaactaaa tcttatcata agcaaatcta
    11161 tgcaccaaat tatttagtac aattcctaat aacagctgaa ggaccattta tttgaagcaa
    11221 tgttcaccat agcaaaattc cagtgaagtc taagaactgg gacagtccgt tgaggatcct
    11281 tgtgccagga tgtatgttgc cccatgaatg tgcacatgca tattaaaata tgggcacctc
    11341 ttttaattct tttttttctc ataataagtt tgaaactcac agtaggaaat tgagagatca
    11401 atttggttac tgttttatca ttgatcctga agacagttga agcaatcata ctggttgttc
    11461 tcgaactagc tggtttccca gagacagctg gagactgagc acataaagac atcattgagg
    11521 aaaaaggcta ccttgtacct catggagagc tgaaggtctg ataaatggga actgccaggt
    11581 aatagctatg ctatttctga cataaattta aaaactagta ttgtttcttc tagctctgtt
    11641 tttgcatagt gcacagagat ctttgtaaaa aacaggaaat taatgttaaa ttggatctat
    11701 aaacataagt caatttggct ctattatgtc aaaagagaat aggagtttta acttatatct
    11761 gtgttttatt aatattttga agtataggaa cctcatggtg tagcaggatg agccacagac
    11821 aaaacctctc agacaccgag ttgtagaagg aagggcttta ttcagctggg agcatcgacc
    11881 agctactgtc tcaaaatcca agctccctga gtacacaatt tctgtccctt ttaagggctc
    11941 acaacactag atttcacatg aaagggtcgt gattgatttg agcaagcaag gggtatgtga
    12001 caggggctgc atgcaccggt ggtctgggag gaacagaaca ggacagggag ttcttctata
    12061 caatagagaa cagaacaatg ttcttctata caatgtaagg aatctatgaa taacatcggc
    12121 ttctaaatca taagttgatt tttaactact gggtttaggc caggcgggcc caggcctggt
    12181 ttcgggcctg gcgctgagct gcctgtattt ggttttactt ccttgttgtt tttactgaat
    12241 atgaaacaat ataaaacaat gtgagagggt ctttctctcc tctcaatgtc aacatcatat
    12301 atgattggag acttccacat aattgagttt tagtgcccac tgttacagaa aatcataatg
    12361 gaaaaactaa aatgtcaata ataatttcag atgtgtattt tagttctcat aagaacatct
    12421 acattcattt gaaaaatagt tctatatcta ttcttgaaac atatttcttt agttcaaggt
    12481 ctgatgagct cccagactgt tggggattgc tctacagctg ctcaagcttt tgaagactcc
    12541 tgtgattttt ttaaatggct ggtttggttg aagtttctct tatcagtcag gcactttgca
    12601 ttttaagcgt actttaccac cgacaccctc cccccccagc acacacacac acacacacac
    12661 acacacacac acaacatagt gaaatggacc cgtgggaatt atatgatagt tgtaatcaaa
    12721 ataaaatgca atcaatacta aaatacaatt taccaaaggc ttacctcctt atttgaaact
    12781 ccagcatcaa taatttactt gcactcttgt tatttacatt tgtactctgg aagtaaactt
    12841 aaaatgaaaa ttagaatttg ctttcaatta tactatctct atctaaatct taatttgaaa
    12901 tttaaattat tttgtctcta cccaaaccat cgatttcatg gaaatgttta aattttcttt
    12961 tttttttttt tttttgatgg agtctcactc tgtcgcccag gctggagtgc agtggctcaa
    13021 tcttggctca ctgcaacctc tgcctcccgg gttcacacca ttctcctgct tcagcctcct
    13081 gagtagctgg gactacaggt gcccgccaca acacctggct aattttttgt atttttagta
    13141 gagatggggt ttcaccacgt tagccaggat ggtttcgatc tcctgacctc gtgatctgcc
    13201 tgcctcggcc tcccaaagtg ttgggattac aggtgtgagc cactgcgcct ggccagaaat
    13261 gtttaaaatt tcataaatct tgaatccata aaattcaatg ctaccattta taatttaata
    13321 ctcctaccat aaaaatttct gtgttaggca tagctatatg aatatttgcc tataaatccc
    13381 catcaattta ataggaatta agttagaaat actagtatat atattccctt tatatactaa
    13441 ttgtatatcc atataaaagc attagtacca ttatatgaaa gtatatatgc cattccataa
    13501 aaatatatct accaatataa atagaatata taaagggaat atatatatac caatataaat
    13561 gggaatttat attggcacat acatttccat tattttaatg ggaattaaag aaaaaatgcc
    13621 tgttttcact aagtcatcct tcccctggca atacatttcc tgaactttta catacttaaa
    13681 tagccagtta tgaaaatgta aaacaatgag tgatcttgtt gttttcattt tattatgtta
    13741 tatgaaaaaa agaaaccttg taagtgcaga tttattttaa aaaattgaaa aactactctg
    13801 tcaaacatag caaataggaa agttaaaaaa aagtaagtct aaagattagg tgctctgtca
    13861 cttgtcatta cattttttta taacattaat gacacatttt ttgctatcca aatataattt
    13921 ccactagaaa agaaaagatg tcctccatgt tttaaattgc atttgaaatt caggtaacta
    13981 ataacccttg gttttaaaag atacatataa tgtttccgta ggaaaaaaat caaaatattg
    14041 taaagaatct gagtaaatga gagcctctca tggttgatta agttcagaca ttttaaacag
    14101 actcctgccc acaaactatt tttcctctcc aggaataaga atggcaactg aattgttcct
    14161 tctttattct atagctttaa gtcaaaccta acataagcaa tcaacccttc cacccattgt
    14221 cctctttcta gctgcttata ttcctgagtc tgaaagaagg gcagaattaa ttcgtttcct
    14281 tgacagtgtt gggggtgaaa taaaagatag acccctgctg ctctgcacgt agattcagtt
    14341 tgtatgccag ggtgacattt taatttacag tagtccagac acctaaacag gacatagaaa
    14401 tgtcaactgg tcatattaaa ataaaaaagt atagaatagt ttctgtttta cggattttgt
    14461 atccaagtaa atgaaaacac aatcaccttt caaaacatgg tatgaaatcc acagttgtaa
    14521 cagtgagcac aacatgcttt ctgtgtgtgt ttttaagctc tttccccaca tctgcttttc
    14581 aaaaatattt gcctggaaac ctgtatttcg cctatagaga caaatacata tattgtttgt
    14641 tgtgataatg cacaaaaagg aatgttaaaa aaaaacacac aacattgttt tccttttgat
    14701 ggtctgggag tttttctata agtttttggt tttttttttt ttttctcttc attagtgtgt
    14761 tagttccatc atcatgtctg tttactattg aaaaataaat atcttcattt aaagtagaga
    14821 caaagctact atttcacatt tccaggtagg acaggatgat cagatgcagc tttcaaaaga
    14881 actacctgct aaatcataat ggtctcatgt gcagatcaaa atgtcaacta gtatatcaaa
    14941 cagtgagcaa ttcactaaat tatttttaca ttactcctat ttgactgttt cagatagttg
    15001 tatataaaaa atataaattt ttgcattgta ttgttcttga tgtaccagca tacataaaca
    15061 tattaggctg tattgtaagt ttcctgcatg taatatgtaa tgtgtaatta tatgtgataa
    15121 ataaaaccta aaactgatac aaa
//
