LOCUS       NM_013381              11047 bp    mRNA    linear   PRI 12-FEB-2025
DEFINITION  Homo sapiens thyrotropin releasing hormone degrading enzyme
            (TRHDE), mRNA.
ACCESSION   NM_013381
VERSION     NM_013381.3
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 11047)
  AUTHORS   Yu,B., Zheng,Y., Alexander,D., Manolio,T.A., Alonso,A.,
            Nettleton,J.A. and Boerwinkle,E.
  TITLE     Genome-wide association study of a heart failure related
            metabolomic profile among African Americans in the Atherosclerosis
            Risk in Communities (ARIC) study
  JOURNAL   Genet Epidemiol 37 (8), 840-845 (2013)
   PUBMED   23934736
REFERENCE   2  (bases 1 to 11047)
  AUTHORS   Freudenberg,J., Lee,H.S., Han,B.G., Shin,H.D., Kang,Y.M.,
            Sung,Y.K., Shim,S.C., Choi,C.B., Lee,A.T., Gregersen,P.K. and
            Bae,S.C.
  TITLE     Genome-wide association study of rheumatoid arthritis in Koreans:
            population-specific loci as well as overlap with European
            susceptibility loci
  JOURNAL   Arthritis Rheum 63 (4), 884-893 (2011)
   PUBMED   21452313
REFERENCE   3  (bases 1 to 11047)
  AUTHORS   Bailey,S.D., Xie,C., Do,R., Montpetit,A., Diaz,R., Mohan,V.,
            Keavney,B., Yusuf,S., Gerstein,H.C., Engert,J.C. and Anand,S.
  CONSRTM   DREAM investigators
  TITLE     Variation at the NFATC2 locus increases the risk of
            thiazolidinedione-induced edema in the Diabetes REduction
            Assessment with ramipril and rosiglitazone Medication (DREAM) study
  JOURNAL   Diabetes Care 33 (10), 2250-2253 (2010)
   PUBMED   20628086
  REMARK    GeneRIF: Observational study of gene-disease association,
            gene-environment interaction, and pharmacogenomic / toxicogenomic.
            (HuGE Navigator)
REFERENCE   4  (bases 1 to 11047)
  AUTHORS   Bozaoglu,K., Curran,J.E., Stocker,C.J., Zaibi,M.S., Segal,D.,
            Konstantopoulos,N., Morrison,S., Carless,M., Dyer,T.D., Cole,S.A.,
            Goring,H.H., Moses,E.K., Walder,K., Cawthorne,M.A., Blangero,J. and
            Jowett,J.B.
  TITLE     Chemerin, a novel adipokine in the regulation of angiogenesis
  JOURNAL   J Clin Endocrinol Metab 95 (5), 2476-2485 (2010)
   PUBMED   20237162
REFERENCE   5  (bases 1 to 11047)
  AUTHORS   Talmud,P.J., Drenos,F., Shah,S., Shah,T., Palmen,J., Verzilli,C.,
            Gaunt,T.R., Pallas,J., Lovering,R., Li,K., Casas,J.P., Sofat,R.,
            Kumari,M., Rodriguez,S., Johnson,T., Newhouse,S.J., Dominiczak,A.,
            Samani,N.J., Caulfield,M., Sever,P., Stanton,A., Shields,D.C.,
            Padmanabhan,S., Melander,O., Hastie,C., Delles,C., Ebrahim,S.,
            Marmot,M.G., Smith,G.D., Lawlor,D.A., Munroe,P.B., Day,I.N.,
            Kivimaki,M., Whittaker,J., Humphries,S.E. and Hingorani,A.D.
  CONSRTM   ASCOT investigators; NORDIL investigators; BRIGHT Consortium
  TITLE     Gene-centric association signals for lipids and apolipoproteins
            identified via the HumanCVD BeadChip
  JOURNAL   Am J Hum Genet 85 (5), 628-642 (2009)
   PUBMED   19913121
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   6  (bases 1 to 11047)
  AUTHORS   Schomburg,L., Turwitt,S., Prescher,G., Lohmann,D., Horsthemke,B.
            and Bauer,K.
  TITLE     Human TRH-degrading ectoenzyme cDNA cloning, functional expression,
            genomic structure and chromosomal assignment
  JOURNAL   Eur J Biochem 265 (1), 415-422 (1999)
   PUBMED   10491199
REFERENCE   7  (bases 1 to 11047)
  AUTHORS   Bodeker,H., Keim,V., Fiedler,F., Dagorn,J.C. and Iovanna,J.L.
  TITLE     PAP I interacts with itself, PAP II, PAP III, and
            lithostathine/regIalpha
  JOURNAL   Mol Cell Biol Res Commun 2 (3), 150-154 (1999)
   PUBMED   10662590
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC087886.11, AC016256.19,
            AC078921.17 and AC133480.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 21, 2020 this sequence version replaced NM_013381.2.
            
            Summary: This gene encodes a member of the peptidase M1 family. The
            encoded protein is an extracellular peptidase that specifically
            cleaves and inactivates the neuropeptide thyrotropin-releasing
            hormone.[provided by RefSeq, Dec 2008].
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF126372.1, AY358765.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968968
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000261180.10/ ENSP00000261180.5
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1188              AC087886.11        111514-112701
            1189-1462           AC087886.11        125825-126098
            1463-1589           AC016256.19        30382-30508
            1590-1744           AC016256.19        122145-122299
            1745-1858           AC016256.19        125454-125567
            1859-1996           AC016256.19        151885-152022
            1997-2062           AC078921.17        30484-30549
            2063-2128           AC078921.17        50358-50423
            2129-2316           AC078921.17        51046-51233
            2317-2405           AC078921.17        56761-56849
            2406-2539           AC078921.17        63448-63581
            2540-2595           AC078921.17        63680-63735
            2596-2743           AC078921.17        107084-107231
            2744-2841           AC133480.2         124529-124626       c
            2842-2949           AC133480.2         123983-124090       c
            2950-3117           AC133480.2         93245-93412         c
            3118-3258           AC133480.2         92578-92718         c
            3259-3340           AC133480.2         88726-88807         c
            3341-11047          AC133480.2         74976-82682         c
FEATURES             Location/Qualifiers
     source          1..11047
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q21.1"
     gene            1..11047
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /note="thyrotropin releasing hormone degrading enzyme"
                     /db_xref="GeneID:29953"
                     /db_xref="HGNC:HGNC:30748"
                     /db_xref="MIM:606950"
     exon            1..1188
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     CDS             275..3484
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /EC_number="3.4.19.6"
                     /note="pyroglutamyl-peptidase II; thyroliberinase;
                     TRH-degrading ectoenzyme; pyroglutamyl aminopeptidase II;
                     TRH-specific aminopeptidase"
                     /codon_start=1
                     /product="thyrotropin-releasing hormone-degrading
                     ectoenzyme"
                     /protein_id="NP_037513.2"
                     /db_xref="CCDS:CCDS9004.2"
                     /db_xref="GeneID:29953"
                     /db_xref="HGNC:HGNC:30748"
                     /db_xref="MIM:606950"
                     /translation="MALDGELGEQEEEKKKKKKKKRKKKKEEEEEEEGAEKSSSPFAA
                     AMGEDDAALRAGSRGLSDPWADSVGVRPRTTERHIAVHKRLVLAFAVSLVALLAVTML
                     AVLLSLRFDECGASATPGADGGPSGFPERGGNGSLPGSARRNHHAGGDSWQPEAGGVA
                     SPGTTSAQPPSEEEREPWEPWTQLRLSGHLKPLHYNLMLTAFMENFTFSGEVNVEIAC
                     RNATRYVVLHASRVAVEKVQLAEDRAFGAVPVAGFFLYPQTQVLVVVLNRTLDAQRNY
                     NLKIIYNALIENELLGFFRSSYVLHGERRFLGVTQFSPTHARKAFPCFDEPIYKATFK
                     ISIKHQATYLSLSNMPVETSVFEEDGWVTDHFSQTPLMSTYYLAWAICNFTYRETTTK
                     SGVVVRLYARPDAIRRGSGDYALHITKRLIEFYEDYFKVPYSLPKLDLLAVPKHPYAA
                     MENWGLSIFVEQRILLDPSVSSISYLLDVTMVIVHEICHQWFGDLVTPVWWEDVWLKE
                     GFAHYFEFVGTDYLYPGWNMEKQRFLTDVLHEVMLLDGLASSHPVSQEVLQATDIDRV
                     FDWIAYKKGAALIRMLANFMGHSVFQRGLQDYLTIHKYGNAARNDLWNTLSEALKRNG
                     KYVNIQEVMDQWTLQMGYPVITILGNTTAENRIIITQQHFIYDISAKTKALKLQNNSY
                     LWQIPLTIVVGNRSHVSSEAIIWVSNKSEHHRITYLDKGSWLLGNINQTGYFRVNYDL
                     RNWRLLIDQLIRNHEVLSVSNRAGLIDDAFSLARAGYLPQNIPLEIIRYLSEEKDFLP
                     WHAASRALYPLDKLLDRMENYNIFNEYILKQVATTYIKLGWPKNNFNGSLVQASYQHE
                     ELRREVIMLACSFGNKHCHQQASTLISDWISSNRNRIPLNVRDIVYCTGVSLLDEDVW
                     EFIWMKFHSTTAVSEKKILLEALTCSDDRNLLNRLLNLSLNSEVVLDQDAIDVIIHVA
                     RNPHGRDLAWKFFRDKWKILNTRYGEALFMNSKLISGVTEFLNTEGELKELKNFMKNY
                     DGVAAASFSRAVETVEANVRWKMLYQDELFQWLGKALRH"
     exon            1189..1462
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            1463..1589
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            1590..1744
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            1745..1858
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            1859..1996
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            1997..2062
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2063..2128
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2129..2316
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2317..2405
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2406..2539
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2540..2595
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2596..2743
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2744..2841
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2842..2949
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            2950..3117
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            3118..3258
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            3259..3340
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     exon            3341..11047
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8583..8588
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /note="hexamer: AATAAA"
     polyA_site      8605
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /note="major polyA site"
     regulatory      10656..10661
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /note="hexamer: AATAAA"
     polyA_site      10684
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
     regulatory      10986..10991
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /note="hexamer: AATAAA"
     polyA_site      11013
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
     regulatory      11028..11033
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
                     /note="hexamer: AATAAA"
     polyA_site      11047
                     /gene="TRHDE"
                     /gene_synonym="PAP-II; PGPEP2; TRH-DE"
ORIGIN      
        1 gagaagtagc gcgcgctggg caagcaagac gctttccaag ttgggcgcgt cccagagctc
       61 acagcccggt gtccagagtg aggcggggct gatgggggtc gcggaagctg ccgtcgcttg
      121 tgtccagaac ccgtcttaaa agaacccggg ccagcatccc cagtcgcgcg ccctcggccc
      181 gcgtgagctc tccgatgcct gctctggctg tggcccgggt ggcccgcccg cggggggtgc
      241 cagagggggc gggggaggag gaggaggcgg tgtgatggcc ctggacggcg agctggggga
      301 gcaagaggag gagaagaaaa agaagaagaa aaagaagagg aagaagaaga aggaggagga
      361 ggaggaggag gagggggccg agaagagcag ctcacccttc gcagccgcga tgggggaaga
      421 cgacgccgcg cttcgggctg gcagcagggg gctctccgac ccgtgggcag actcagtggg
      481 agtgcgaccc cgcaccacgg agcgccacat cgccgtacac aagcggcttg tgctggcctt
      541 cgctgtgtcc ctcgtggcat tgctcgcggt cacaatgctc gctgtgctgc tcagcctgcg
      601 cttcgacgag tgcggggcga gtgccacgcc aggcgccgac ggtggcccct caggctttcc
      661 ggagcgcggc ggcaacggga gcctccctgg atcggcccgg cgcaaccacc acgcaggcgg
      721 ggactcctgg cagcccgagg cgggtggggt ggccagtccg gggaccacgt cggcccagcc
      781 gccgtcggag gaggagcggg agccgtggga gccgtggacg cagctgcgcc tgtcgggcca
      841 cctgaagccg ctgcactaca atctgatgct caccgccttc atggagaact tcaccttctc
      901 cggggaggtc aacgtggaga tcgcgtgccg gaacgccacc cgctacgtag tgctgcacgc
      961 ttcccgagtg gcggtggaga aagtgcagct ggccgaggac cgggcgttcg gggctgtccc
     1021 tgtagccggt tttttcctct acccgcaaac ccaggtctta gtggtggtgc tgaataggac
     1081 actggacgcg cagaggaatt acaatctgaa gattatctac aacgcgctca tcgagaatga
     1141 gctcctgggc ttcttccgca gctcctatgt gctccacggg gagagaagat tccttggtgt
     1201 tactcagttt tcgcctacac atgccagaaa ggcatttcct tgttttgatg agccaatcta
     1261 caaggctact ttcaaaatca gcatcaagca tcaagcaacc tatttatctt tatctaatat
     1321 gccagtggaa acttccgtgt ttgaggaaga tggatgggtt acggatcact tttcacagac
     1381 ccctctcatg tccacatatt atttagcctg ggcaatttgc aacttcacat acagagaaac
     1441 taccaccaag agtggggttg tagtacgatt atatgcaaga cctgatgcta tcagaagagg
     1501 atccggggac tatgctctcc atataacaaa gagattaata gaattttatg aagactactt
     1561 taaagtgccc tattccttgc caaaactaga tcttttagct gtgcctaagc atccgtatgc
     1621 tgctatggag aactggggac taagtatttt tgtggaacaa agaatactgc tggatcccag
     1681 tgtttcatct atttcttatt tgctggatgt caccatggtc attgttcatg agatatgtca
     1741 ccagtggttt ggtgaccttg tgacgcctgt gtggtgggaa gacgtgtggc tgaaggaagg
     1801 gtttgctcac tactttgaat ttgttggtac agactacctc tatcctggct ggaacatgga
     1861 aaagcagagg tttctgaccg atgttctgca tgaagtgatg ctgctggacg gtttggccag
     1921 ttcccatcca gtatcacagg aagtgctgca ggcaacagat attgacaggg tgtttgactg
     1981 gatcgcatat aaaaagggtg ctgctttaat aagaatgctg gctaatttta tgggccattc
     2041 agttttccag aggggtttgc aagattattt aaccattcat aagtatggta atgcagccag
     2101 aaatgatctc tggaatacat tatcggaggc tttaaaaaga aatgggaaat atgtaaatat
     2161 acaagaagta atggatcagt ggacactcca gatgggttat cctgttatca ccatcttggg
     2221 aaacacaaca gcagaaaata gaataataat tacccaacag cattttatct atgatatcag
     2281 tgctaaaact aaagcactta aacttcagaa taacagttac ctgtggcaga ttccattaac
     2341 tattgtggta ggaaatagaa gccatgtgtc ttcagaagca attatttggg tgtctaacaa
     2401 atcagagcac cacagaataa cttatttgga caaaggaagc tggctgctgg ggaacatcaa
     2461 tcaaactggc tattttagag tcaactatga cctaaggaac tggagattat taattgatca
     2521 attaatccgg aatcatgagg ttctttctgt cagtaaccga gcgggcttga tcgatgatgc
     2581 cttcagccta gccagggctg gctatttgcc tcagaatatt cctctggaga ttatcagata
     2641 cctgtctgag gagaaggatt ttcttccttg gcatgctgcc agccgagctc tttatcctct
     2701 agataaatta ctggaccgca tggaaaacta caacattttc aatgaatata ttttaaagca
     2761 agttgcaaca acatatatca agcttgggtg gccgaaaaat aattttaatg gatctcttgt
     2821 tcaagcatcc taccaacatg aagaactacg tagagaagtt ataatgctgg cctgcagttt
     2881 tggcaacaag cactgtcacc aacaggcatc aacacttatt tcagattgga tttccagcaa
     2941 caggaacaga ataccactaa atgttagaga catcgtatac tgtacaggag tgtcactact
     3001 ggatgaggat gtctgggaat tcatatggat gaaattccat tccaccacag cagtttctga
     3061 gaagaaaata ttattggaag ccttaacttg cagtgatgac aggaatttat taaacaggct
     3121 tctaaatctg tcactgaatt ctgaggtggt gctggatcaa gatgcaattg atgtcataat
     3181 ccatgtagct cgaaatccac atggtcgaga ccttgcctgg aagtttttca gggataaatg
     3241 gaagatatta aataccaggt atggagaagc attgtttatg aattccaaac tcatcagtgg
     3301 tgtcacagaa tttcttaata ctgaaggtga actcaaagag ctcaagaact tcatgaaaaa
     3361 ctatgatggg gtagctgctg cttctttctc acgagctgtg gaaactgtcg aagccaatgt
     3421 gcgctggaaa atgctttacc aagacgagct tttccaatgg ttaggaaaag ctctaagaca
     3481 ctaatatatg tatcttataa acaaacaatt caactcagaa gtttatgaga agacacgctt
     3541 tttgtggaat gaggaaaatg tactacctag aaaatggcca gattttcagt gttaacgtgt
     3601 gggaggaatt ttttttttag tttttatttt ttggttttgg gggatatttt ttatttgttt
     3661 cattcattct gttctgtttc tctactgggt gttcctctct aaagaaactc ttgcaagtga
     3721 aactagccat gattgcttca gctgtacatt ccttgctgta caggaccaaa tatgatagtg
     3781 atgcatgttg atgttacagt caatttggaa aaacatattc agaatatctg tgcatggata
     3841 tattgtcctg cctgtgttcc agcatgctta tttcaaacgt ccagtgttgt gtgtgaatat
     3901 gtgttacacc taggatgggc attatgcaaa agcacaaaga ttatatatga caatcagtat
     3961 tgcaatgaaa gaaaaactaa aaacagaaat gatattctca attttgggca atgtgagagg
     4021 taaaatagcc cttgacatga tgaacatcac ttatttcagc acttggattg tctggcaatg
     4081 attactgtgt tgctaactca ttttctttga gttaaagctg tgtatacatt ttaaaaggca
     4141 tatagatagt gtatgcatat gtatatgtac atagggaagc cccatatgta tatagtatgt
     4201 tgtacactgc acatgtacaa agaatgtctt cagatcaaag aaaatttatc tctttttata
     4261 aacttaagga cagttgcaaa aggcttcaag gaatttatct caacattatt ctttctatgt
     4321 cctaactaaa tttctcaact gttatgaatt tttcatctac ttcttgaaca gtggtctatt
     4381 ctgctacatg aagatgaata caaacaaaat ttttgtataa actactattc cagttctcct
     4441 gtgtcagtct tgcctataga ttttgccatc gttttctgtc aaagttcctt ttgcatgaaa
     4501 caattatgca aacttataat tattagtgct gaaaaagagt ttattttcca tcttgtttgt
     4561 tttcctacct tatgctgagt agtccagaga gttaaaaaaa ttctctgcat gttggtcttt
     4621 taagtctgtt ttgctctaat cctccattaa gcgagcatac ctcaagtggg tctattagca
     4681 tttaatgacc ttttgtgcca gttgtgccat cccttaagat gaaaagttcc ttttcttgtg
     4741 ttaatgtaca aagcttttct tttggcactg acaactgtgt tctacctggg aattttgaat
     4801 agccattttc atggctgtgt gttgtgtaac acaaatgttt ttaaatggta ttctcaccca
     4861 gtaggccagc tctccaaacg ttgcttagat gcttcaaaat tagcatattt taagtttacc
     4921 agtataaaat accaatgcaa ctactctaca tagccaaatg tttgtaaatc acgtcttatt
     4981 ttcctgaggt ttttcactcc accaaatctt acaaatcatt gaaagaaata tattctaaca
     5041 gtacgcactg aatagtgaaa ataattagac attttaagaa ccagagccat agaattattt
     5101 taaattagta gaaaagagga gctatttccg aatctataga ataaagtacc acctaaaact
     5161 gaattttatc atataagcaa gtaataccta ttagtcatac ctaaattttt cagcacttca
     5221 ttcaattaaa atacatgaat tttaaatatt ttacatgatg tgaataggca tgataatact
     5281 tttagtataa aatctaaact ttttccattt atcagaaatg ataaaatcca gttaccacat
     5341 atcacgttta taaaatcctt aattaaatga gtaacttcta aaatataaca atactaaata
     5401 tcacactgcg atggaggtcc caaatatgtg gtctatcacc actgaattca tgtaatagat
     5461 aagaaaaaaa ttagaggtgg atgtcttgtt ttgtgtcatg aattactaaa atctcttagt
     5521 agttgtggta tatttttgag taaaattacc atttccagat ttgagtttga agggctttta
     5581 tagttgtatt ttcctcctca ctgttaataa tcataatcct ttttcagtat tttagtggcc
     5641 ttgaacaact ggtttatcta caatctcaaa tcctaagtgt ataattatgt gcaatgttca
     5701 atacctcata taatacttgc tcaacagtat agtggtacca atggcattaa gatggtgttt
     5761 ttgttctaca tatttttcaa taatttattc tttctaatgt tgaaattata tcaggcttta
     5821 ccggtttttt tagttgttta aataagtaat attttcaaaa gaataaaata accaatgata
     5881 tctcttggaa taatctgtaa aacgtagtta taaaattcta ttttctactt agagttttta
     5941 tcttttcttt tttgtcggct ttacaaatta tatgtatgca tgaaataact aactgttgaa
     6001 agtgtccaac ctccagccat agcaatttgc tgtgccaata tgtgtacaaa aaagtagttt
     6061 caattagaaa ggacaacatt atttatcaca ttgagtatta aacatttcca ggtaactcgt
     6121 aaataaaaag atttccccat ttttacacat tttttcttaa aatttttcta taatctttga
     6181 agtttctaaa atacacaatc tcaacctcta agactaacat ctacaatact aggtctattc
     6241 ttgagtttca ataacatgta ttttagttgg gtcataaact tgcattattt tatattatct
     6301 ccaggacaat tatatcatag gactaagatt tttgtgatag tattatttac aaatattata
     6361 agtataatat cttgtgaggc tattattaag gttatgccat gtattgataa aatgcattgc
     6421 tttctcaaag aactgttaca cattttgttt tatttgactc atcacaaaaa cataataaat
     6481 gttgtgagcc ctaatattct gatgagaaaa ctggggctca ggtagcaaca tgagctattt
     6541 aaaactacaa aatagggctg ggcacagtgg ctcatgcctg taatcccagc actttgggag
     6601 gctgagggtg ggaggatcac ttgagcccag gggtttgaga ccagtctggg aaacatattg
     6661 aggccccatt tctataaaaa taaaaatgaa aactagccag gcatggtggt gtgcacctgt
     6721 tgtcccagct actggggagg ctgaggtggg agaattattt aagtccaaaa gttcagtgct
     6781 ctagtgagct atgatcactg tactccagcc tgggtgacag agtgagatcc tgtctctaaa
     6841 aaaataaaat aaaatcacaa tgtttgttgt tattttggga accaatataa caacctaagt
     6901 ctatcacaac atcattcccc aactaaaata taaatatatg ttgaaaatat ctctatcgat
     6961 tgcattaatt ggagattttc caaatactag accagcatca aaatacacag ttaaatatat
     7021 ttgcaataat tccattgttt gttaactttt gcatttctaa tttgcaggat gttaaacaac
     7081 tggatgaaat gttatgattt aatttggtca gtataaataa tcaaatattg ggacaaataa
     7141 tttaattcat ttagtttatt aattatattt cctgtctgta tcttttattg aacattgttt
     7201 aaacataacc ttaaagtact gataatttgc ttaattttca acacaaattt atctgacaaa
     7261 ttctgtctat agtaacagat ggtcagaatg cagataaatt gtgtgcatct caatcagtaa
     7321 aaataatatt cagtaaaatg tctataaatc tatgcagatt aagttgtgaa aaacaatgca
     7381 attttagtac tactggatta gatgcagtaa aggaatccct aaggaagttt acaataatat
     7441 atttaattaa aatctactgg caattagaat tttaaggaat tcttttctaa gaagttggag
     7501 aacctaaaat agcttgctta ttcgcctggg tactctcatg aagtaaccat gtacacctaa
     7561 taaagaaata gtaaaagcac atataatgaa aaataattaa gatttcttac acctgatttt
     7621 ttcattatca gagataatta tcagagataa tttttcatta tcagagatca tagctgaatt
     7681 atcatttgac aatacataag aatatatatt gtatagatac aatatataac tatacttaaa
     7741 gaaatattta ttgagcatct tttatttcac aaggcactta gtgagggaaa ggaatacaga
     7801 gatgaatatg gcctgaagga atgaactcat attacaataa atgaaaaaga aaaagaaata
     7861 atgaaccaag ggaatgaggg caacaggaaa aataattcct tgctacagac gggaagtcaa
     7921 tcatttttag gtatacataa tattatacaa ctatttttgt acactagttc tcaaaacatt
     7981 tatgatacct agtataattt ttattgtttg atttcctagt gcttacttgt gttttacaga
     8041 aatatgttac attttgaaat tataataaaa taatagagtt taaactctaa taattggaat
     8101 ataaattggg atggaattta tccttaagaa aagctgttta aacaatttag tagtattagt
     8161 aagttgcagg aatactttaa tctacttacg aaaaagtagt tcaagttttc taaaatggtt
     8221 tcagcatact atcggtatct cacaatgtgt taattttaag ttaattatat attctttaaa
     8281 gcagattaaa taatacttgt cctaagcata atttatttgt tgaaattagt atatgtgaac
     8341 ttatgaaaaa atgttcttgt aaattattct agaatcccaa attttaatta tataagaaca
     8401 accttttgtt caattgcttt gaactaatga tgaagttttt taaaatatta agtattttat
     8461 ttaatgtgat atagattcag gaaaagtcta acaaaaatgt acttcagtag ttttattttt
     8521 attttgtgaa attttatttt aaagtttagg taaggaaagt ttttaaactg tcttaaatat
     8581 ttaataaaag cagttgttaa aaatatatgt tctaatgtta actatatgac atatatgcca
     8641 ttgcatgcat tttgtttttt aaataggttt ttcaccactg gccccactag tagatgattt
     8701 taccccagat tttgaaaaca taccacttta atggccttta tttcaaatac ttcgtacttt
     8761 agggatagta ttttgaagat gtttatcttt tgtacattcc tagttcattt attaatgtac
     8821 taagaaaaag aaaacaaaat gactgattct tttgttttga attaaatgtt tgtgctgtat
     8881 taatgttaag tgagttaaga taaagggaag ctacaaaaat ttgaatgcct actaaatgct
     8941 aggcacttta taggtgtctt ctaatatatg tctattggta tcacatcaat taataaccct
     9001 gtgaaatgtc attagctcta attcaccaaa gagtagatgg aggcagagtt gttatcagtt
     9061 tacataatta attagtggta ttcacttgga ttcaaaactc tgcaaactga agccttatat
     9121 agctcaaact agtcattaat ctgccctcag catgtatgaa aacataatgt ttatccgtac
     9181 agaccattct ctatagcaga tttgaatagg tacttagcac actttatcat tgtcactggc
     9241 tctttcgaaa gaagtattaa tttgtgcatt ctggtttacc attcatttct taacaaagtt
     9301 gctttatacg ttccataaaa agttttcatg aaaacatttt acattagcat gttgtgtagt
     9361 gggttttaag ttataacagg taattaacag atatttcggc caacgagaca cacacacaca
     9421 tgaaaaaaat aagtgaaaag acagaataaa ttgcaaaggt tttacgagtg gaccacaaag
     9481 ttaaggttaa acttctgtct ttgcatgtgg aggagacata ttagtctagc cagaactttc
     9541 cttttgctta gcagtgaggt cagagaagta tctctgtcat tctgcttaga agtatacatg
     9601 gactgcaatt gcttaattta cttaaactta acattttcaa tgggtttgct gtgtgaagat
     9661 acagtctaag ataagtgctt tgacttgcct ctgcagaggt caacttattt ctcatcacac
     9721 acatttttct tatgtcatat aagtaaagga aagagtgaaa cgttttatag aaaatattac
     9781 agtggagtta agaacatctg cctcaaatgt acagtgcatt tactttttaa gttaatcatt
     9841 tagtagctac ccttttaacc tctactatgt tcacagtatt gcatttgctc ttgtaaacaa
     9901 ttttgttccc acctttacat agcgtatgac ctactcagtg agaacattca ttattaagtt
     9961 tttgctatta attttcattt aaaataggtt tattaactag caaatctcaa atgcaaaaca
    10021 tttttgagtg aatttttcct caaatgttgt attctacctt tcaaaatatt gtgtaacagc
    10081 aattccacat tatccttttg aatgctacct atatattgcc acatataaag atatttttca
    10141 tttttcattt ttcattgcta tcttttaatc cctttgcatt ttgataatat cgaaaacaga
    10201 ttagggctga aaaactaaaa aagattaggg cttgtattat gcattgtcta gttacttgaa
    10261 caataagaga aattctatct ttgagctttc ataattggct ttctggacac cactgagttt
    10321 attagataat ctttaaaaat attatgaact attttgagtg gacctaaatt tattcagtaa
    10381 taaagtttac tttcctaaat ccattcccca agtgaacagg cttatttaaa atatgtcata
    10441 taaaagcact tttcctttct aacattttat gatttaggaa ttaaaaagta gctgttcttt
    10501 cagtaaataa gtgttaataa agcagtgacc aaataaataa ccttttgtta gtttagcaga
    10561 taaatgtttt caatgtatgc ctttaaaatt attcagtaaa aattgaatta gtacgtattc
    10621 aacatgaaat ttttagtctt ttctgaccaa gcactaataa aattgatttc cctaaatgag
    10681 aaaatttgtc ttctgtattt taagcagaaa aaatatgaat tctgcctctg ataatcaaat
    10741 tttgtacagc aatgtgtaat gtgtcacaat ttaaaaagtt ttaattttct gacatgcaga
    10801 taaggccaaa ataaataata ccatctgttt ttttcacttg aaaatacatt tttaaaattt
    10861 tgagtatata tattatagag gtccatgcaa atggaaaaaa attattctct tctgacatgg
    10921 actttttcat gactatacac atgctgaggc tagaataaaa acatatattt gtgctatatt
    10981 gtaaaaataa aaacaatttg ttctcctttc taattatatg cctttagaat aaatgaaatg
    11041 atctgca
//
