LOCUS       NM_025113              11050 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens rubicon like autophagy enhancer (RUBCNL), transcript
            variant 1, mRNA.
ACCESSION   NM_025113
VERSION     NM_025113.5
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 11050)
  AUTHORS   Li,W., Zhou,C., Yu,L., Hou,Z., Liu,H., Kong,L., Xu,Y., He,J.,
            Lan,J., Ou,Q., Fang,Y., Lu,Z., Wu,X., Pan,Z., Peng,J. and Lin,J.
  TITLE     Tumor-derived lactate promotes resistance to bevacizumab treatment
            by facilitating autophagy enhancer protein RUBCNL expression
            through histone H3 lysine 18 lactylation (H3K18la) in colorectal
            cancer
  JOURNAL   Autophagy 20 (1), 114-130 (2024)
   PUBMED   37615625
  REMARK    GeneRIF: Tumor-derived lactate promotes resistance to bevacizumab
            treatment by facilitating autophagy enhancer protein RUBCNL
            expression through histone H3 lysine 18 lactylation (H3K18la) in
            colorectal cancer.
REFERENCE   2  (bases 1 to 11050)
  AUTHORS   Chen,D., You,H., Xu,X., Liu,D., Shen,M., Pan,Y., Liu,Z., Zhang,L.
            and Wang,H.
  TITLE     MYC-activated CERS6-AS1 sponges miR-6838-5p and regulates the
            expression of RUBCNL in colorectal cancer
  JOURNAL   Cell Mol Biol (Noisy-le-grand) 68 (12), 42-48 (2022)
   PUBMED   37130182
  REMARK    GeneRIF: MYC-activated CERS6-AS1 sponges miR-6838-5p and regulates
            the expression of RUBCNL in colorectal cancer.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 11050)
  AUTHORS   Cheng,X., Ma,X., Zhu,Q., Song,D., Ding,X., Li,L., Jiang,X.,
            Wang,X., Tian,R., Su,H., Shen,Z., Chen,S., Liu,T., Gong,W., Liu,W.
            and Sun,Q.
  TITLE     Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in
            Regulation of Autophagosome Maturation and Lipid Metabolism
  JOURNAL   Mol Cell 73 (4), 788-802 (2019)
   PUBMED   30704899
  REMARK    GeneRIF: mTORC1 and GSK3-TIP60 signaling converge to modulate
            autophagosome maturation and lipid metabolism through Pacer.
REFERENCE   4  (bases 1 to 11050)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Paulo,J.A., Cannon,J.R., Ting,L.,
            Baltier,K., Colby,G., Gebreab,F., Gygi,M.P., Parzen,H., Szpyt,J.,
            Tam,S., Zarraga,G., Pontano-Vaites,L., Swarup,S., White,A.E.,
            Schweppe,D.K., Rad,R., Erickson,B.K., Obar,R.A., Guruharsha,K.G.,
            Li,K., Artavanis-Tsakonas,S., Gygi,S.P. and Harper,J.W.
  TITLE     Architecture of the human interactome defines protein communities
            and disease networks
  JOURNAL   Nature 545 (7655), 505-509 (2017)
   PUBMED   28514442
REFERENCE   5  (bases 1 to 11050)
  AUTHORS   Cheng,X., Ma,X., Ding,X., Li,L., Jiang,X., Shen,Z., Chen,S.,
            Liu,W., Gong,W. and Sun,Q.
  TITLE     Pacer Mediates the Function of Class III PI3K and HOPS Complexes in
            Autophagosome Maturation by Engaging Stx17
  JOURNAL   Mol Cell 65 (6), 1029-1043 (2017)
   PUBMED   28306502
  REMARK    GeneRIF: Pacer localizes to autophagic structures and positively
            regulates autophagosome maturation.
REFERENCE   6  (bases 1 to 11050)
  AUTHORS   Boers,A., Bosgraaf,R.P., van Leeuwen,R.W., Schuuring,E.,
            Heideman,D.A., Massuger,L.F., Verhoef,V.M., Bulten,J.,
            Melchers,W.J., van der Zee,A.G., Bekkers,R.L. and Wisman,G.B.
  TITLE     DNA methylation analysis in self-sampled brush material as a triage
            test in hrHPV-positive women
  JOURNAL   Br J Cancer 111 (6), 1095-1101 (2014)
   PUBMED   25032730
REFERENCE   7  (bases 1 to 11050)
  AUTHORS   Huisman,C., Wisman,G.B., Kazemier,H.G., van Vugt,M.A., van der
            Zee,A.G., Schuuring,E. and Rots,M.G.
  TITLE     Functional validation of putative tumor suppressor gene C13ORF18 in
            cervical cancer by Artificial Transcription Factors
  JOURNAL   Mol Oncol 7 (3), 669-679 (2013)
   PUBMED   23522960
  REMARK    GeneRIF: Re-activation of C13ORF18 led to partial demethylation of
            the C13ORF18 promoter and decreased repressive histone methylation.
REFERENCE   8  (bases 1 to 11050)
  AUTHORS   Eijsink,J.J., Lendvai,A., Deregowski,V., Klip,H.G., Verpooten,G.,
            Dehaspe,L., de Bock,G.H., Hollema,H., van Criekinge,W.,
            Schuuring,E., van der Zee,A.G. and Wisman,G.B.
  TITLE     A four-gene methylation marker panel as triage test in high-risk
            human papillomavirus positive patients
  JOURNAL   Int J Cancer 130 (8), 1861-1869 (2012)
   PUBMED   21796628
  REMARK    GeneRIF: Data suggest that the four-gene methylation panel might
            provide an alternative triage test after primary high-risk
            papillomavirus (hr-HPV) testing.
REFERENCE   9  (bases 1 to 11050)
  AUTHORS   Yang,N., Eijsink,J.J., Lendvai,A., Volders,H.H., Klip,H.,
            Buikema,H.J., van Hemel,B.M., Schuuring,E., van der Zee,A.G. and
            Wisman,G.B.
  TITLE     Methylation markers for CCNA1 and C13ORF18 are strongly associated
            with high-grade cervical intraepithelial neoplasia and cervical
            cancer in cervical scrapings
  JOURNAL   Cancer Epidemiol Biomarkers Prev 18 (11), 3000-3007 (2009)
   PUBMED   19843677
  REMARK    GeneRIF: Methylation of C13orf18 in cervical scrapings is strongly
            associated with high-grade cervical intraepithelial neoplasia and
            cervical cancer.
REFERENCE   10 (bases 1 to 11050)
  AUTHORS   Ng,D., Hu,N., Hu,Y., Wang,C., Giffen,C., Tang,Z.Z., Han,X.Y.,
            Yang,H.H., Lee,M.P., Goldstein,A.M. and Taylor,P.R.
  TITLE     Replication of a genome-wide case-control study of esophageal
            squamous cell carcinoma
  JOURNAL   Int J Cancer 123 (7), 1610-1615 (2008)
   PUBMED   18649358
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL139801.17 and CD701535.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 20, 2020 this sequence version replaced NM_025113.4.
            
            Summary: This gene encodes a cysteine-rich protein that contains a
            putative zinc-RING and/or ribbon domain. The encoded protein is
            related to Run domain Beclin-1-interacting and cysteine-rich
            domain-containing protein, which plays a role in endocytic
            trafficking and autophagy. In cervical cancer cell lines, this gene
            is expressed at low levels and may function as a tumor suppressor.
            Promoter hypermethylation of this gene is observed in cervical
            cancer cell lines and tissue derived from human patients. [provided
            by RefSeq, Mar 2017].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (a). Variants 1, 2 and 8
            encode the same isoform (a).
            
            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 :: SRR11853561.8242.1,
                                           SRR14038196.1564557.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000429979.6/ ENSP00000396935.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-119               AL139801.17        10359-10477
            120-235             AL139801.17        19606-19721
            236-892             AL139801.17        25014-25670
            893-975             AL139801.17        28796-28878
            976-1183            AL139801.17        29362-29569
            1184-1282           AL139801.17        34398-34496
            1283-1343           AL139801.17        35013-35073
            1344-1476           AL139801.17        36038-36170
            1477-1622           AL139801.17        37980-38125
            1623-1687           AL139801.17        41115-41179
            1688-1926           AL139801.17        47260-47498
            1927-1988           AL139801.17        48264-48325
            1989-2142           AL139801.17        52011-52164
            2143-2233           AL139801.17        52780-52870
            2234-3476           AL139801.17        54114-55356
            3477-3992           CD701535.1         30-545
            3993-11050          AL139801.17        55873-62930
FEATURES             Location/Qualifiers
     source          1..11050
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="13"
                     /map="13q14.13"
     gene            1..11050
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="rubicon like autophagy enhancer"
                     /db_xref="GeneID:80183"
                     /db_xref="HGNC:HGNC:20420"
                     /db_xref="MIM:620175"
     exon            1..119
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            120..235
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            236..892
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     CDS             358..2346
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="isoform a is encoded by transcript variant 1;
                     KIAA0226 like; protein RUBCNL-like; protein associated
                     with UVRAG as autophagy enhancer; RUN and cysteine rich
                     domain containing beclin 1 interacting protein like;
                     rubicon like autophagy regulator; protein Rubicon-like"
                     /codon_start=1
                     /product="protein associated with UVRAG as autophagy
                     enhancer isoform a"
                     /protein_id="NP_079389.2"
                     /db_xref="CCDS:CCDS31970.2"
                     /db_xref="GeneID:80183"
                     /db_xref="HGNC:HGNC:20420"
                     /db_xref="MIM:620175"
                     /translation="MVSQSTVRQDSPVEPWEGISDHSGIIDGSPRLLNTDHPPCQLDI
                     RLMRHKAVWINPQDVQQQPQDLQSQVPAAGNSGTHFVTDAASPSGPSPSCLGDSLAET
                     TLSEDTTDSVGSASPHGSSEKSSSFSLSSTEVHMVRPGYSHRVSLPTSPGILATSPYP
                     ETDSAFFEPSHLTSAADEGAVQVSRRTISSNSFSPEVFVLPVDVEKENAHFYVADMII
                     SAMEKMKCNILSQQQTESWSKEVSGLLGSDQPDSEMTFDTNIKQESGSSTSSYSGYEG
                     CAVLQVSPVTETRTYHDVKEICKCDVDEFVILELGDFNDITETCSCSCSSSKSVTYEP
                     DFNSAELLAKELYRVFQKCWILSVVNSQLAGSLSAAGSIVVNEECVRKDFESSMNVVQ
                     EIKFKSRIRGTEDWAPPRFQIIFNIHPPLKRDLVVAAQNFFCAGCGTPVEPKFVKRLR
                     YCEYLGKYFCDCCHSYAESCIPARILMMWDFKKYYVSNFSKQLLDSIWHQPIFNLLSI
                     GQSLYAKAKELDRVKEIQEQLFHIKKLLKTCRFANSALKEFEQVPGHLTDELHLFSLE
                     DLVRIKKGLLAPLLKDILKASLAHVAGCELCQGKGFICEFCQNTTVIFPFQTATCRRC
                     SACRACFHKQCFQSSECPRCARITARRKLLESVASAAT"
     exon            893..975
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            976..1183
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            1184..1282
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            1283..1343
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            1344..1476
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            1477..1622
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            1623..1687
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            1688..1926
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            1927..1988
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            1989..2142
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            2143..2233
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     exon            2234..11050
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2748..2753
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="hexamer: AACAAA"
     polyA_site      2767
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="major polyA site"
     regulatory      3180..3185
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="hexamer: ATTAAA"
     regulatory      3202..3207
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="hexamer: AATAAG"
     polyA_site      3217
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
     polyA_site      3225
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
     regulatory      3469..3474
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="hexamer: AATAAA"
     polyA_site      3504
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
     regulatory      3712..3717
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="hexamer: AATAAA"
     polyA_site      3733
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
     regulatory      10966..10971
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
                     /note="hexamer: ATTAAA"
     polyA_site      10992
                     /gene="RUBCNL"
                     /gene_synonym="C13orf18; KIAA0226L; PACER"
ORIGIN      
        1 cccctttctg ctgttaccgg gagcgcggtg gccacggaac gctgcccgga gccgcgcgag
       61 ggaggacccg acgcgcggcg tttacccagc gcagcgttcc accgctcggg tttggctgga
      121 taaaataaaa aatggggata ttgacctcct gtcactactg catggacttt gatggtttcc
      181 aatcattact ttctcctctg tgtcaatctg cctcttcgag aaattcatac tcctgaatag
      241 ctctccagac ccccagctgg ccatgtggtg agttcagggc ccaaatcaag tagtaccagc
      301 aatcagggaa ctcctatctg ttttgaatgg attcacacca gccacaagcc tggaaagatg
      361 gtgtcacaat ctacagtcag gcaggattct cctgtggagc cctgggaagg gatcagcgat
      421 cactctggca ttattgatgg ttcgcccaga ctcctgaaca ctgaccatcc tccttgccaa
      481 ttagacatca ggctcatgag gcacaaagct gtctggatta acccccagga tgtgcagcaa
      541 cagccgcagg acttgcaatc tcaggtgcca gcagcaggga acagtgggac ccattttgtg
      601 acagatgctg cctctccctc aggcccttca ccttcgtgcc tcggggactc cctggcagag
      661 acaacgttgt ctgaggatac cacagactcc gttggcagcg cttctcccca tggctcgagt
      721 gaaaagagta gcagcttctc tctgtcctca acagaggtac acatggtccg cccaggatac
      781 tctcatcggg tgtctctgcc cacaagccct gggattttgg ccacctcccc atatcctgag
      841 actgacagtg ctttttttga gccttcccat ctgacatctg ctgctgatga aggtgctgtt
      901 caagtcagta gaagaaccat ttcttcgaat tccttctcac cagaggtatt tgtgctgcct
      961 gttgatgtag aaaaggaaaa tgcccacttt tatgttgcag atatgattat atcagcaatg
     1021 gagaaaatga agtgtaacat tctgagtcaa cagcagacag agagctggag taaagaagtc
     1081 agtgggttac ttgggagtga tcagcctgac tctgaaatga cttttgatac caacataaag
     1141 caagagtctg ggtcttctac ttcttcatac agtggctatg aaggttgtgc tgtgttacag
     1201 gtcagcccag tgactgaaac acgtacttac catgatgtga aagagatttg caaatgcgat
     1261 gttgatgaat ttgttatttt agagcttgga gattttaatg atatcacaga aacctgtagc
     1321 tgttcctgca gctcctctaa gagtgtcact tatgagccag acttcaattc tgcagaacta
     1381 ttagccaaag agctgtaccg cgtgttccag aagtgctgga tactgtcagt agttaattct
     1441 cagctggcag gttccctgag tgcagctggc tcgatagtcg taaatgaaga gtgtgtccga
     1501 aaagactttg aatccagtat gaatgtagta caggaaatta aatttaagtc taggatcaga
     1561 gggactgaag actgggctcc tcctagattt caaatcatat ttaatattca tccaccactc
     1621 aagagggacc ttgtggtggc agcccagaat tttttctgtg ccggctgtgg aactccagta
     1681 gagcctaagt ttgtgaagcg gctccggtac tgcgaatacc tagggaagta tttctgtgac
     1741 tgctgccact catatgcaga gtcgtgcatc cctgcccgaa tcctgatgat gtgggacttc
     1801 aagaagtact acgtcagcaa tttctccaaa cagctgctcg acagcatatg gcaccagccc
     1861 attttcaatt tgctgagcat cggccaaagc ctgtatgcga aagccaagga gctggacaga
     1921 gtgaaggaaa ttcaggagca gctcttccat atcaagaagc tgttgaagac ctgtaggttt
     1981 gctaacagtg cattaaagga gttcgagcag gtgccgggac acttgactga tgagctccac
     2041 ctgttctccc ttgaggacct ggtcaggatc aagaaagggc tgctggcacc cttactcaag
     2101 gacattctga aagcttccct tgcacatgtg gctggctgtg agctgtgtca aggaaagggc
     2161 tttatttgtg aattttgcca gaatacgact gtcatcttcc catttcagac agcaacatgt
     2221 agaagatgtt cagcgtgcag ggcttgcttt cacaaacagt gcttccagtc ctccgagtgc
     2281 ccccggtgtg cgaggatcac agcgaggaga aaacttctgg aaagtgtggc ctctgcagca
     2341 acatgatgcc cctgagtact gtgaaaaaga ctgttcaaca tgccttatga taacaccgat
     2401 ttgtgtctat tattggtgac attgttttag atattgggta ttgtatatta aggaaaaaga
     2461 tggtctatat tctctttatt gcatatactt aatgtttcaa aagaatgcag attctgtgtt
     2521 taagcacagg gctgatagtt gtggttttgt ttacaaatgt tctgttttgg ctgctattgg
     2581 ttttttaaag aggtttttta tacttttgta tttgaatagt tatgtttcac tgatgctgag
     2641 ccagtttgta tgtgtgtgca tatatgtgaa ctgtaactga caagatgaat tactcagttt
     2701 ctctttctct aaagcttgtt tgatgaaact ggttggtcct ttcagtgaac aaaaatatga
     2761 ccccaaatct gtttgctctg gcttttattt cttcaggaag cagacttcca cttaaatgcc
     2821 attttgtgat tgtgtcaatc atacacattt tatttacttc agagtttgaa tagagagtac
     2881 acatttcttc tgcagattta tttcatgatg agtttgagtt gcttagcagg gcgtgtgggt
     2941 cccgttgaag tgcagtttga agcaactgct tctagatggc actctttcag gtggcacaaa
     3001 ttgaacctgt atttgtcatc tctgttccac acactgcaat gtcaagggat gcagaagtga
     3061 gtagaattcc atccctgccc ttgaggatct tgctttaaca gatgtaaaac tgaacataag
     3121 gtatttgcag atttaaacga actgggggaa ataatgaaca gtgtgattct agtaataaca
     3181 ttaaaatcat agacattgac taataaggtt aaatgaatca caaaaccttt atgaatttct
     3241 tttttctaat agttcttata tgttttcctg aaacatgtga gcctattctt ttttcttcta
     3301 ctttctatat actttctccc acttgagaaa ggggccttga ggctgggtcc cttcatggta
     3361 tacctttaga ctgaacggtt tgcaacctag ggcttgggca ttacattccc tgggattcac
     3421 atgccctaac taaacctacc ttgattttct cagacagcac aggcaggcaa taaagcgtca
     3481 cagattgtcc cctaacccca tccagccatg tgtatgagtg tgttttattc aatgggatag
     3541 tactgagcac atgaaagaaa tgaatgactt ctgtcaatct cttttcattc agtcttctca
     3601 ttctgtcaat tgttttctca tccgcagtgc ctctgccaga actgtgctca catccattat
     3661 ttaagccaga tcttttctaa gtattataga agtgtagagg cacatagaat aaataaaacc
     3721 agacttcaaa caatgtttca ttcttgccca ttgctcctat tccctgttaa gaatcaaggg
     3781 taagagtggt atgttcacat tcctttctga ggcagatgtc tatatctcca tttacaggca
     3841 aggaaactga ggcctagaga agagaaataa ctttcctagg ttcccacagg aagtgcatga
     3901 tggagctggg gttgacattc aagtccacct gcctccaaag cccatgctta ggccctgctt
     3961 cttttgtggt gtcttttcaa gacaaaggag taaaaacaac cttaactggt aagtgttgct
     4021 ccaacttgca gaagtggcat tgggcagagt gttttctcac atcagtgttg atttaaggca
     4081 gctgctatgg ctcaagcatt gcttgaaggg ctctgtgctc agggtttgta tgtttgtaag
     4141 gcactgatga gcctgtgtgt gttacatatc tttgatatta aggaagagtg cacagcagtt
     4201 gccaggaagt gatgcttttg attttctatt ttgaggaaga atgaggtcat ttaaataact
     4261 gcagtatggg atttgtctga gactttgttc ctctccaatg tgataataga ggcttcttcc
     4321 caggaaggca cctgttaggg aagtgatctt cagcccacat ggagcacccc ataaggaagt
     4381 aattagttgt ggcatatata gctgtttaat gggtcttcct gattgtgtgg gttttctgtt
     4441 caactcttcc ttggctgccg gaaagaagat gaatgcttgg tcagaccatt acccactgtg
     4501 aggcatcagt tgcagtgctg taaaggtcag tgattcattt tctgcctctg cactcttcac
     4561 atgggcaatt ccagtagtgt gtcatttaca gtcatgattc tcaactgcag ggaggaagtt
     4621 acaccatctc aaggcagagg ctataggatg aggaggagca agccatccca aagatgtctg
     4681 gtgtgttgac ctgggtgaga attattggcc acaacttcag attagatccc aaatatgcca
     4741 ctttctacct acccatggtg acttggtgct ctagtttggc ttgtttgact cctgcaaacc
     4801 tcatggtgaa atttgatccc cagtgttgaa ggtaggccta ataagaggtg tttgggtcat
     4861 gcgggtggat ccctcaagaa tagcttggtg gcacctttgt ggtgatgagt gagttctcac
     4921 tcttagttcc catgagagct ggttgttatg aagcctggca cctccctgcc ctctctttgc
     4981 ctcctctgtt tccatacaag gggagtctgc acacgcaggc tccccttccc ctccaccatg
     5041 agtggaagca gccacaagtc ctaaccagaa gcagatattg gtgcgatgct tgtacagccc
     5101 gcagaaccat aagccaaatt aacctctttt ctttataaat cacccagcct caggtattcc
     5161 tttatagcaa cacaaataga ctcagacact ggggaagcca tttaaattat ctaagcctct
     5221 gtttgtaaaa tgagggatat gactctctgc agttgagata aggattagaa atgaaaatga
     5281 agcacccact aaaaggcctg gtacaagcaa gggcaaatgg taataatgag gtctagacag
     5341 attacaaact gagtcatacc ccttattttc tgtatctctg ggtaagttac tccctgggtc
     5401 tcagtttata atctgtaata caaggattag aacaatagct actgttgtgg gttgaattgt
     5461 gtcccatgaa agaatatgtt aaaggtctat gctggtgtct gtgctgtggc cttttgggaa
     5521 gtagggtctt tgcagaggtg gttaagttag gatgaggaca tagtgcatta ggatgagttt
     5581 tgatctagtg actggtgtcc ttataagaaa agggaaattg agagaagaga gaagatgcag
     5641 ggaagaaaaa aagcagaggt tggggtgatg catctacaag ccaaggagca ccaagaattg
     5701 ctggcagccc ccagaagccg gagagaggca gggggcagat tcttcctcag agccttaaaa
     5761 aaaaaaccca acatggctga ccccttgatt tcaaacttct gacattgaga attatgagag
     5821 aataaattcc tggggttttt ttgttttgtt ttgtttttgt ttttgttttt ttgaaatgga
     5881 gtcttgctct gtcacccagg ctatagtgca gtggtgcgat ctcagctcac ttcaacctcc
     5941 gccacctggg ttcaagtgat tttcctgtct caccctcccg agtagctggg attgcaggcg
     6001 cacgccacca ggcctggata atttttgtat ttttagtaga gacgggtttt caccatgttg
     6061 gcaaggctgg tctctaaccc ctgacctcag gtgatctgcc tgcttcggct tccaaaagtg
     6121 ctgggattac aggcctgagc cactgcgcct gaccctgttg ttttaaacca cccagagtgt
     6181 ggtcatttgt ctgagacttc ggaattcaaa cctgctggaa ggaacgtggt agacatgtca
     6241 ggaaggggtt tgacattcag tttctgcccc caggtctgag cctgcatggc tggcttagcc
     6301 accgtcagat gctacctgca ggaagccttc ctgaactcat cgccaaagga gggtgaagtg
     6361 tgtcattttt agaagcgtgc ttccttaaaa caagcattta aggatctctg tctttaaata
     6421 atttctcaac tggtatggga aggaaaaccg tagttcccct ttttcacttc actagaaact
     6481 aaaacaatac ttttatgagt aatgctgagg tagcaggctg cagacacaat tgggaagctt
     6541 cagcacaaac atgagaaatc gagaaccttt gcatcctcgc atatctgggc agctctccaa
     6601 gccaagggga ctgaggattg aagagcttaa ccacataggt taagcaaatt gtgtattttt
     6661 ccttgcactt tttttttttt ttttgagaca gggtctcgct ctgtcgccca ggctggagtg
     6721 cagttggcgt gatctcagtt cactgcagcc tctgcttccc ggttcaagcg attttcctgc
     6781 ctcagcttcc ctagtagctg ggaccacagg catgtgccac catgcccagc taattttttt
     6841 ctgtttttgg tagagacggg gtttcgccat gttggccagg ctggtctcag aagtgatcta
     6901 cccgcctcgg cctcccaaag tgcttggatt acaggtgtga gccaccgcgc ccagcccttc
     6961 cttgaacatt ttctggcctc tgcttgtgct tccaggcttc tttctcccca gggctgcccc
     7021 ctcttttcta gtcctgccgt gttcctgcct ccatggtctt gttcttcttg catcccttgc
     7081 ctgggatcag gactgccctt tcatcctgga aagaggccct gctctggcct tcctcgggct
     7141 acgtacatcc ccattggtga ggagacaaag ggcaagcgca cccaaagccc ccacccctcc
     7201 tgttagatca aatggagccc cagacagaat cccctgccct gtggtctcaa ccccactttt
     7261 agggctgctc aggtctttcc cctggtccag cctcctgaaa gtgaactgcg ctgctaagac
     7321 caagaggcag ccaaggggca gctgcttgta ggatggagcc aaagtgggaa gagagagggg
     7381 caggggttgg cccaatgcta gctatacctg agccaccatg ctccagagca gagcagtgag
     7441 gagtcaaaga tttcaaaatt caaacctgct ttctcgggtc ctgatgaagg gatattcacc
     7501 atggtaggaa gataaaacat atttcaaatt ttaaatactt ggatatatgg catgtggacc
     7561 tgtatttgta ctcttgcatg ggctctgcag atgggagtgg tgggcgcttc cccttttcat
     7621 ctccctcccg atcttgccca ttcttcagcg tactgcacgt gcacacacat gctcccttct
     7681 ccttacactc tgatatctgc atttacctca ttattctact ggggacagct ctctgaactt
     7741 ttggcagcct ttgatccttt ctatctgccc ttgaaagtct cttggaagct atgagagaga
     7801 ctttattctc cctttgctcc tgcagcccct gaaggtccac attcctgagg gccctaccca
     7861 gctccctgag tgattgtttg aaatagaact actcaggagt gcggtgcctg cattggactt
     7921 tttacaagca agaataaacc tttattttgt tcagttcctg agatttttgt ggggctggtt
     7981 cctacagtgt aacccaccct actctgacta acataagatg tcctgatacc tgttgtccag
     8041 gggatgagta ctgagggaac aggtttgtca ctgtcgtagt ctgtttaggc tgctataata
     8101 aaatacctta cgctaggtgg ataataaaca acagaaactt actgctaaca gttctggagg
     8161 ctaggaagtc caagatcaag acaacagcag atttgatgtc tattgaggga ccacttcctg
     8221 gttcatagat ggcactatct cactgtatcc ttacatggta gaaaggagag agagcggacc
     8281 aggcacggtg gctcacactt gtaatcccag cactcccaaa gttgagatat atgcctcagg
     8341 ctgagacagg catatcacga ggtcaggaga ttgagaccat cctggccaac atggtgaaac
     8401 ccagtcttta ctaaaaatac aaaaattagg tgtggtcgca agtgcctgta atcccagcta
     8461 ctcgggaggc tgaggcagaa gaatcgcttg aaccagggag ttgaaggttg cggtgagctg
     8521 agatcacgcc actgtactcc agcctgacaa cagagtgaga cttggtcccc cctccctgcc
     8581 cccaaaaaaa gaaaaaggaa aagagagaga gagagaaccc cctggggtct gttttacaag
     8641 ggcactaatt ccctttgtga gggcctcacc ctcatgacct aatcaccacc taaaggctcc
     8701 acctcctaat actgtcacaa ttgggggtta ggtcttcaac acatgacttt tgaggagata
     8761 taaatattca gtccataaca gtcatgcaga catcaaaaac tattctactc ctctgagtta
     8821 tccatattat ctagtattcc ttacattaaa aaataaagga atatgcagag agaaaaaaat
     8881 tctttaacct cacattcctt tccagttcta cctctatgat cttcttcaca gcaacatttt
     8941 tgaaagaaca gtttttaatg tttgccatcg cttccacacc tctttcttcc tttacctaca
     9001 acaatagcat ttccatctca accattctac ccaaaccgtc aaggtcacta gcaatatcta
     9061 aattcagtag tcactgtatt gtcttcacct acctctctac cacagttgct tgcattcttc
     9121 ttaacaaaag agaatactgt tttataataa aatataataa aataaaaaag tctagctaag
     9181 aaaagctaga ctataatgaa tttcatcata ttgtggtggt gattatctct gtatagtggg
     9241 attagaataa ttttcaaaaa ttttctttgt aaattttacc atatagacta gatatcattt
     9301 taaataaatg atagatcatt taaactaatg acaaattaca gatgataaat gagatcagta
     9361 ctatacaact tttaagagta atggttgcat ttctactgtc catgcccaca gtggagaaat
     9421 cagattagct gttggggacc acctgaaact ccatcttcgt agagtctgat gatggaggtg
     9481 ctgcctggta cccaaagctc ctggttttct tggttattta gtaaattact aaagaccacg
     9541 tgaaccaaaa agaacagggc cggctgtcag atagaccaga tggatggatg caaccattca
     9601 ccttcctcct ggaagctttg gaacccggaa acatcatgac atttgtgatt tctccccttc
     9661 ctctgtagac agtggtctct tttcttggtc tcctttgtag gttttcctct tctttctctg
     9721 tccatctcta aataaagaca gagattccag ggctcagttt tgccatctct tttcttctct
     9781 tgggatggtc ttatccagtg aaatagcttt gaatgactct aaatttgtag cttcagccca
     9841 gaggctggta ctcagcagcc cactgatagc tgtgcttgta ttagtatttc tttacaggct
     9901 tttccatctc agaaaatggc accaccatag acccagtcgc ttaagccaaa cacctaggag
     9961 tcatcctttc cctttccctc actccccaga tccagtccat cagtaacttc tgtcagctct
    10021 acctacaaaa tatatcttag ttgatggctc accacagcca ctgacattat tacagtacaa
    10081 gccaccatct ctctcctgaa cttctattag attgaactac gtagcattgc tgctatttta
    10141 taattgttga gctaccaagt ggcaatttca tgtgtggttc aacctaatta aaaacctcct
    10201 atctcctctt tccacacttg cccctctata gtccattctc cacacaacac cagaatgttt
    10261 ataaagcata aatcagatcg tctatctccg tggattaaac cctctgaaga cttaatttaa
    10321 aattaagttg ggtgggtgct ggctcgtgtc tgtaatccca gcactttggg aggccaatgc
    10381 aggaggatga cttgagccca ggagtttgtg accagcctgt gcaacatagc gagaccctgt
    10441 ctcttaaaaa aaaaaaaaaa aaaaaaaaaa caacaacaac aacaacaaaa agacacaaat
    10501 tagctgggca caatggtgtg tgccagtatt cccagctacc caggaggctg aggtgggagg
    10561 atcgatcgag cccaggagtt tgaggctgta gtgaggcatg atcccgccac tgcattccag
    10621 cctgggtgac agagtgagac cccatctcaa aaaaaaaaaa gtccaaattc tttacccaag
    10681 taggtttcct gttgggcttg acctgcacca cttcctgagc tgttcctctc ttccctccat
    10741 caggaacctc tttaaaaatt cctcttgccc ttagtatacc cccaaatctt cccccacttt
    10801 cctttggggt acagtgagtc taagtgatcc agaatttaga gccagaagca cttggatcct
    10861 ttcacttcta gtcctgtgat ttgtgataag ttgctcaaat ttcttaagac tccggtttcc
    10921 tatttgtaaa atgctgacaa tctgtctcac aaggttgtcg tacagattaa atgatataag
    10981 ttatgaaaag tatgtttagc atcttgtcta tcactttgtg tataaaattc agtgtttttt
    11041 ttccccctgg
//
