LOCUS NM_000161.2 2941 bp mRNA linear PRI 20-AUG-2006 DEFINITION Homo sapiens GTP cyclohydrolase 1 (dopa-responsive dystonia) (GCH1), transcript variant 1, mRNA. ACCESSION NM_000161 GI:66932966 LOCUS:NM_000161 GB:NM_000161 SeqStore:3612084154.5 VERSION NM_000161.2 KEYWORDS . SOURCE human ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 AUTHORS Swick,L.; Kapatos,G. TITLE A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions JOURNAL J. Neurochem. 97 (5), 1447-1455 (2006) REMARK GeneRIF: Aha1 may recruit GCH1 into the endothelial nitric oxide synthase/heat shock protein (eNOS/Hsp90) complex to support changes in endothelial nitric oxide production through the local synthesis of BH4. PUBMED 16696853 REFERENCE 2 AUTHORS Al Sarraj,J.; Vinson,C.; Han,J.; Thiel,G. TITLE Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors JOURNAL J. Cell. Biochem. 96 (5), 1003-1020 (2005) REMARK GeneRIF: GTP cyclohydrolase I gene transcription is regulated by basic region leucine zipper transcription factors PUBMED 16149046 REFERENCE 3 AUTHORS Ohta,E.; Toyoshima,I.; Funayama,M.; Ichinose,H.; Hasegawa,K.; Obata,F. TITLE A new mutation (Thr106Ile) of the GTP cyclohydrolase 1 gene associated with DYT5 dystonia (Segawa disease) JOURNAL Mov. Disord. 20 (8), 1083-1084 (2005) REMARK GeneRIF: A new mutation (Thr106Ile) of the GTP cyclohydrolase 1 gene associated with DYT5 dystonia (Segawa disease). PUBMED 15852365 REFERENCE 4 AUTHORS Kealey,C.; Roche,S.; Claffey,E.; McKeon,P. TITLE Linkage and candidate gene analysis of 14q22-24 in bipolar disorder: support for GCHI as a novel susceptibility gene JOURNAL Am. J. Med. Genet. B Neuropsychiatr. Genet. 136 (1), 75-80 (2005) REMARK GeneRIF: Results suggest that variants within GCHI may contribute to bipolar disorder in the Irish population. PUBMED 15909293 REFERENCE 5 AUTHORS Hagenah,J.; Saunders-Pullman,R.; Hedrich,K.; Kabakci,K.; Habermann,K.; Wiegers,K.; Mohrmann,K.; Lohnau,T.; Raymond,D.; Vieregge,P.; Nygaard,T.; Ozelius,L.J.; Bressman,S.B.; Klein,C. TITLE High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening JOURNAL Neurology 64 (5), 908-911 (2005) REMARK GeneRIF: We tested 23 individuals with dopamine-resistant dystonia for the different GCH1 mutation types by conventional and quantitative PCR analyses and found mutations, including two large exon deletions, in 87%. PUBMED 15753436 REFERENCE 6 AUTHORS Huang,A.; Zhang,Y.Y.; Chen,K.; Hatakeyama,K.; Keaney,J.F. Jr. TITLE Cytokine-stimulated GTP cyclohydrolase I expression in endothelial cells requires coordinated activation of nuclear factor-kappaB and Stat1/Stat3 JOURNAL Circ. Res. 96 (2), 164-171 (2005) REMARK GeneRIF: GTPCH1 induction in endothelial cells is stimulated by cytokines and mediated by Stat1/3, Jak2 and NF-kappaB. PUBMED 15604419 REFERENCE 7 AUTHORS Hynes,S.O.; Smith,L.A.; Richardson,D.M.; Kovesdi,I.; O'Brien,T.; Katusic,Z.S. TITLE In vivo expression and function of recombinant GTPCH I in the rabbit carotid artery JOURNAL Am. J. Physiol. Heart Circ. Physiol. 286 (2), H570-H574 (2004) REMARK GeneRIF: Genetic transfer into rabbit vascular endothelium in vivo increases intracellular concentration of tetrahydrobiopterin. PUBMED 14551046 REFERENCE 8 AUTHORS Garavaglia,B.; Invernizzi,F.; Carbone,M.L.; Viscardi,V.; Saracino,F.; Ghezzi,D.; Zeviani,M.; Zorzi,G.; Nardocci,N. TITLE GTP-cyclohydrolase I gene mutations in patients with autosomal dominant and recessive GTP-CH1 deficiency: identification and functional characterization of four novel mutations JOURNAL J. Inherit. Metab. Dis. 27 (4), 455-463 (2004) PUBMED 15303002 REFERENCE 9 AUTHORS Zheng,J.S.; Yang,X.Q.; Lookingland,K.J.; Fink,G.D.; Hesslinger,C.; Kapatos,G.; Kovesdi,I.; Chen,A.F. TITLE Gene transfer of human guanosine 5'-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in low renin hypertension JOURNAL Circulation 108 (10), 1238-1245 (2003) REMARK GeneRIF: Gene transfer of human GTPCH I restored arterial GTPCH I activity and BH4 levels, resulting in reduced O2- and improved endothelium-dependent relaxation and basal NO release in DOCA-salt hypertensive rats PUBMED 12925450 REFERENCE 10 AUTHORS Hwu,W.L.; Yeh,H.Y.; Fang,S.W.; Chiang,H.S.; Chiou,Y.W.; Lee,Y.M. TITLE Regulation of GTP cyclohydrolase I by alternative splicing in mononuclear cells JOURNAL Biochem. Biophys. Res. Commun. 306 (4), 937-942 (2003) REMARK GeneRIF: GTP cyclohydrolase I is alternatively spliced in mononuclear cells PUBMED 12821132 REFERENCE 11 AUTHORS Leuzzi,V.; Carducci,C.; Carducci,C.; Cardona,F.; Artiola,C.; Antonozzi,I. TITLE Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome JOURNAL Neurology 59 (8), 1241-1243 (2002) REMARK GeneRIF: A kindred is reported in which GTP-CH deficiency presents as a dopa-responsive myoclonus-dystonia syndrome, documented as a missense mutation in exon 6 of GTP-CH1 gene (K224R). PUBMED 12391354 REFERENCE 12 AUTHORS Muller,U.; Steinberger,D.; Topka,H. TITLE Mutations of GCH1 in Dopa-responsive dystonia JOURNAL J. Neural Transm. 109 (3), 321-328 (2002) REMARK Review article PUBMED 11956954 REFERENCE 13 AUTHORS Dhondt,J.L.; Hayte,J.M. TITLE [Screening of tetrahydrobiopterin deficiency among hyperphenylalaninemic patients] JOURNAL Ann. Biol. Clin. (Paris) 60 (2), 165-171 (2002) PUBMED 11937441 REFERENCE 14 AUTHORS Bader,G.; Schiffmann,S.; Herrmann,A.; Fischer,M.; Gutlich,M.; Auerbach,G.; Ploom,T.; Bacher,A.; Huber,R.; Lemm,T. TITLE Crystal structure of rat GTP cyclohydrolase I feedback regulatory protein, GFRP JOURNAL J. Mol. Biol. 312 (5), 1051-1057 (2001) REMARK GeneRIF: kinetic studies with GFRP PUBMED 11580249 REFERENCE 15 AUTHORS Skrygan,M.; Bartholome,B.; Bonafe,L.; Blau,N.; Bartholome,K. TITLE A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping JOURNAL J. Inherit. Metab. Dis. 24 (3), 345-351 (2001) PUBMED 11486899 REFERENCE 16 AUTHORS Golderer,G.; Werner,E.R.; Heufler,C.; Strohmaier,W.; Grobner,P.; Werner-Felmayer,G. TITLE GTP cyclohydrolase I mRNA: novel splice variants in the slime mould Physarum polycephalum and in human monocytes (THP-1) indicate conservation of mRNA processing JOURNAL Biochem. J. 355 (PT 2), 499-507 (2001) PUBMED 11284739 REFERENCE 17 AUTHORS Hong,K.M.; Kim,Y.S.; Paik,M.K. TITLE A novel nonsense mutation of the GTP cyclohydrolase I gene in a family with dopa-responsive dystonia JOURNAL Hum. Hered. 52 (1), 59-60 (2001) PUBMED 11359069 REFERENCE 18 AUTHORS Auerbach,G.; Herrmann,A.; Bracher,A.; Bader,G.; Gutlich,M.; Fischer,M.; Neukamm,M.; Garrido-Franco,M.; Richardson,J.; Nar,H.; Huber,R.; Bacher,A. TITLE Zinc plays a key role in human and bacterial GTP cyclohydrolase I JOURNAL Proc. Natl. Acad. Sci. U.S.A. 97 (25), 13567-13572 (2000) PUBMED 11087827 REFERENCE 19 AUTHORS Hwu,W.L.; Wang,P.J.; Hsiao,K.J.; Wang,T.R.; Chiou,Y.W.; Lee,Y.M. TITLE Dopa-responsive dystonia induced by a recessive GTP cyclohydrolase I mutation JOURNAL Hum. Genet. 105 (3), 226-230 (1999) PUBMED 10987649 REFERENCE 20 AUTHORS Steinberger,D.; Topka,H.; Fischer,D.; Muller,U. TITLE GCH1 mutation in a patient with adult-onset oromandibular dystonia JOURNAL Neurology 52 (4), 877-879 (1999) PUBMED 10078749 REFERENCE 21 AUTHORS Brique,S.; Destee,A.; Lambert,J.C.; Mouroux,V.; Delacourte,A.; Amouyel,P.; Chartier-Harlin,M.C. TITLE A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form JOURNAL Neuroreport 10 (3), 487-491 (1999) PUBMED 10208576 REFERENCE 22 AUTHORS Furukawa,Y.; Kish,S.J.; Bebin,E.M.; Jacobson,R.D.; Fryburg,J.S.; Wilson,W.G.; Shimadzu,M.; Hyland,K.; Trugman,J.M. TITLE Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations JOURNAL Ann. Neurol. 44 (1), 10-16 (1998) PUBMED 9667588 REFERENCE 23 AUTHORS Tamaru,Y.; Hirano,M.; Ito,H.; Kawamura,J.; Matsumoto,S.; Imai,T.; Ueno,S. TITLE Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene JOURNAL J. Neurol. Neurosurg. Psychiatr. 64 (4), 469-473 (1998) PUBMED 9576537 REFERENCE 24 AUTHORS Katusic,Z.S.; Stelter,A.; Milstien,S. TITLE Cytokines stimulate GTP cyclohydrolase I gene expression in cultured human umbilical vein endothelial cells JOURNAL Arterioscler. Thromb. Vasc. Biol. 18 (1), 27-32 (1998) PUBMED 9445252 REFERENCE 25 AUTHORS Weber,Y.; Steinberger,D.; Deuschl,G.; Benecke,R.; Muller,U. TITLE Two previously unrecognized splicing mutations of GCH1 in Dopa-responsive dystonia: exon skipping and one base insertion JOURNAL Neurogenetics 1 (2), 125-127 (1997) PUBMED 10732814 REFERENCE 26 AUTHORS Thony,B.; Blau,N. TITLE Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes JOURNAL Hum. Mutat. 10 (1), 11-20 (1997) REMARK Review article PUBMED 9222755 REFERENCE 27 AUTHORS Ichinose,H.; Ohye,T.; Matsuda,Y.; Hori,T.; Blau,N.; Burlina,A.; Rouse,B.; Matalon,R.; Fujita,K.; Nagatsu,T. TITLE Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency JOURNAL J. Biol. Chem. 270 (17), 10062-10071 (1995) PUBMED 7730309 REFERENCE 28 AUTHORS Nomura,T.; Ohtsuki,M.; Matsui,S.; Sumi-Ichinose,C.; Nomura,H.; Hagino,Y.; Iwase,K.; Ichinose,H.; Fujita,K.; Nagatsu,T. TITLE Isolation of a full-length cDNA clone for human GTP cyclohydrolase I type 1 from pheochromocytoma JOURNAL J. Neural Transm. Gen. Sect. 101 (1-3), 237-242 (1995) PUBMED 8695054 REFERENCE 29 AUTHORS Imazumi,K.; Sasaki,T.; Takahashi,K.; Takai,Y. TITLE Identification of a rabphilin-3A-interacting protein as GTP cyclohydrolase I in PC12 cells JOURNAL Biochem. Biophys. Res. Commun. 205 (2), 1409-1416 (1994) PUBMED 7802677 REFERENCE 30 AUTHORS Ichinose,H.; Ohye,T.; Takahashi,E.; Seki,N.; Hori,T.; Segawa,M.; Nomura,Y.; Endo,K.; Tanaka,H.; Tsuji,S. et al. TITLE Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene JOURNAL Nat. Genet. 8 (3), 236-242 (1994) PUBMED 7874165 REFERENCE 31 AUTHORS Gutlich,M.; Jaeger,E.; Rucknagel,K.P.; Werner,T.; Rodl,W.; Ziegler,I.; Bacher,A. TITLE Human GTP cyclohydrolase I: only one out of three cDNA isoforms gives rise to the active enzyme JOURNAL Biochem. J. 302 (PT 1), 215-221 (1994) PUBMED 8068008 REFERENCE 32 AUTHORS Nygaard,T.G.; Wilhelmsen,K.C.; Risch,N.J.; Brown,D.L.; Trugman,J.M.; Gilliam,T.C.; Fahn,S.; Weeks,D.E. TITLE Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q JOURNAL Nat. Genet. 5 (4), 386-391 (1993) PUBMED 8298648 REFERENCE 33 AUTHORS Gutlich,M.; Schott,K.; Werner,T.; Bacher,A.; Ziegler,I. TITLE Species and tissue specificity of mammalian GTP cyclohydrolase I messenger RNA JOURNAL Biochim. Biophys. Acta 1171 (2), 133-140 (1992) PUBMED 1482676 REFERENCE 34 AUTHORS Togari,A.; Ichinose,H.; Matsumoto,S.; Fujita,K.; Nagatsu,T. TITLE Multiple mRNA forms of human GTP cyclohydrolase I JOURNAL Biochem. Biophys. Res. Commun. 187 (1), 359-365 (1992) PUBMED 1520321 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from CR589979.1, U19523.1, U66097.1 and BM971258.1. On Jun 3, 2005 this sequence version replaced gi:4503948. Summary: This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. Transcript Variant: This variant (1), also known as Type I, represents the longest transcript. Variants 1 and 2 encode the longest isoform (1), which is the active enzyme. COMPLETENESS: complete on the 3' end. FEATURES Location/Qualifiers source 1..2941 /mol_type="mRNA" /map="14q22.1-q22.2" /db_xref="taxon:9606" /chromosome="14" /organism="Homo sapiens" gene 1..2941 /db_xref="GeneID:2643" /db_xref="HGNC:4193" /db_xref="HPRD:HPRD_02573" /db_xref="MIM:600225" /gene="GCH1" /note="synonyms: GCH, DYT5, GTPCH1, GTP-CH-1" CDS 162..914 /go_function="hydrolase activity [goid 0016787] [evidence IEA]" /go_function="protein binding [goid 0005515] [evidence IPI] [pmid 16696853]" /go_function="GTP cyclohydrolase I activity [goid 0003934] [evidence TAS] [pmid 8702680]" /protein_id="NP_000152.1" /gene="GCH1" /go_process="L-phenylalanine catabolism [goid 0006559] [evidence IEA]" /go_process="nitric oxide biosynthesis [goid 0006809] [evidence TAS] [pmid 8702680]" /go_process="aromatic compound biosynthesis [goid 0019438] [evidence IEA]" /go_process="neurotransmitter metabolism [goid 0042133] [evidence TAS] [pmid 8702680]" /go_process="tetrahydrobiopterin biosynthesis [goid 0006729] [evidence IEA]" /note="isoform 1 is encoded by transcript variant 1; guanosine 5'-triphosphate cyclohydrolase I" /db_xref="GI:4503949" /db_xref="CCDS:CCDS9720.1" /db_xref="GeneID:2643" /db_xref="HGNC:4193" /db_xref="HPRD:HPRD_02573" /db_xref="MIM:600225" /codon_start=1 /go_component="cytoplasm [goid 0005737] [evidence IEA]" /product="GTP cyclohydrolase 1 isoform 1" /translation="MEKGPVRAPAEKPRGARCSNGFPERDPPRPGPSRPAEKPPRPEA KSAQPADGWKGERPRSEEDNELNLPNLAAAYSSILSSLGENPQRQGLLKTPWRAASAM QFFTKGYQETISDVLNDAIFDEDHDEMVIVKDIDMFSMCEHHLVPFVGKVHIGYLPNK QVLGLSKLARIVEIYSRRLQVQERLTKQIAVAITEALRPAGVGVVVEATHMCMVMRGV QKMNSKTVTSTMLGVFREDPKTREEFLTLIRS" /EC_number="3.5.4.16" misc_feature 408..911 /db_xref="CDD:29763" /gene="GCH1" /note="GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin triphosphate; Region: GTP_cyclohydro1; cd00642" STS 944..1281 /db_xref="UniSTS:34488" /gene="GCH1" /standard_name="D14S1260" variation 1157 /db_xref="dbSNP:841" /replace="c" /replace="t" /gene="GCH1" variation complement(1591) /db_xref="dbSNP:10136966" /replace="a" /replace="g" /gene="GCH1" variation complement(1797) /db_xref="dbSNP:34156666" /replace="" /replace="ttc" /gene="GCH1" variation complement(1799) /db_xref="dbSNP:34808879" /replace="" /replace="ctt" /gene="GCH1" STS 1903..2036 /db_xref="UniSTS:33272" /gene="GCH1" /standard_name="D14S1190" variation complement(2056) /db_xref="dbSNP:10151500" /replace="a" /replace="g" /gene="GCH1" polyA_signal 2896..2901 /gene="GCH1" polyA_site 2915 /gene="GCH1" polyA_site 2926 /gene="GCH1" BASE COUNT 773 a 597 c 658 g 913 t ORIGIN 1 cctgtggccg ctcccggctc ggagtgtgat ctaagcaggt tgcgtacctt cctcaggtga 61 ctccggccac agcccattgt ccgcggccac cggcggagtt tagccgcaga cctcgaagcg 121 ccccggggtc cttcccgaac ggcagcggct gcggcgggtc catggagaag ggccctgtgc 181 gggcaccggc ggagaagccg cggggcgcca ggtgcagcaa tgggttcccc gagcgggatc 241 cgccgcggcc cgggcccagc aggccggcgg agaagccccc gcggcccgag gccaagagcg 301 cgcagcccgc ggacggctgg aagggcgagc ggccccgcag cgaggaggat aacgagctga 361 acctccctaa cctggcagcc gcctactcgt ccatcctgag ctcgctgggc gagaaccccc 421 agcggcaagg gctgctcaag acgccctgga gggcggcctc ggccatgcag ttcttcacca 481 agggctacca ggagaccatc tcagatgtcc taaacgatgc tatatttgat gaagatcatg 541 atgagatggt gattgtgaag gacatagaca tgttttccat gtgtgagcat cacttggttc 601 catttgttgg aaaggtccat attggttatc ttcctaacaa gcaagtcctt ggcctcagca 661 aacttgcgag gattgtagaa atctatagta gaagactaca agttcaggag cgccttacaa 721 aacaaattgc tgtagcaatc acggaagcct tgcggcctgc tggagtcggg gtagtggttg 781 aagcaacaca catgtgtatg gtaatgcgag gtgtacagaa aatgaacagc aaaactgtga 841 ccagcacaat gttgggtgtg ttccgggagg atccaaagac tcgggaagag ttcctgactc 901 tcattaggag ctgagcttca ttcagtgtgt gtgcgttggt tgccgatcgt actgccagta 961 gcattgtctg tctgtccggt cttgtttgta cattccattt tcaattgtta cagatgtgaa 1021 ctttattcct tgtcactaat tatatttaaa attatttcta ggaagtcaaa taaatataat 1081 aaagggttga gccctctact ttcttcttgc cacctttttg tggcaatatt aaagtgaact 1141 gctaatagtg taagtacgtg cacaaaacca ctgccagata accagagggg cctgggaagg 1201 gagaagaatt agtgtatttt tttcaaatag tacagtaatt tgcctcataa gcataggagc 1261 attgggaatg agagggaact gtgcccagta tactgttttt tttcttcctc caataaaagt 1321 ggtgtagtgc cgaaagtgct aaaatattta gtgcggtatt gctctgtgaa ttcaagttca 1381 acagacttca ctttggtcat gtttattaaa ccaccagtga catttaaaaa tatattttta 1441 gcagtcgtaa tgttagtcac caagggaagg tggtggaatg tctatgtttt tgattttact 1501 gtgagttaaa aaggcacatt tctaccttct attgttttta aattcaagaa tagggaatta 1561 gttcctggtg ttgtttacga gtgtattctc gtgtcaacat acagggattt agacatttaa 1621 ctctctgtgc cttgataaga atatcattta gagtgtagat acttttgcct ttttaaaaaa 1681 gccattattt tatgagactt agtactcaca ctgcaaataa ctagtcagct cagttttaac 1741 tttataggtt tattgagttt cctttgtgtg atccatgtag atgcctcaaa atgtttcttc 1801 ttcttctttt ttttaatctt ataagatatt tttctaagta tttccagaaa catttgagag 1861 tgcccatcat tttcaggtct gcagaaccat agcttccacg cacctgaacg agcacagaat 1921 gaactgacgg tggaagacat tatgagctgt gtccaacgtt ttaaccaaag cgtatcgtac 1981 caacgatctg tgaaaatgca ctggaagctt ctggtcccgg tttcctttgt ggtctatgtg 2041 ggtcttgtcc tcattgtaac tccgtataga tggtataggt attttaatcc tggaagctgt 2101 tgccttatta atgattatct taaaatttcc tccattgggg cagcgtgggc caaattaaaa 2161 caaacaaaac cgcaactcct ccacagaaac acaaacacag ttattccatg aagtttagta 2221 tttggttgac atagtgctct tcaaattcat cccattaccc taaaagtaat aactttgatg 2281 cttgctttaa ctttagtccc atctctgcca ctttgatgct atttgggtta tgatggggca 2341 agatggcaga ggtattgggt ttttttgttt ttttccattc ctctctactt ctgtttccta 2401 gctttttctt tctggagttt aagtacagtg atggttggct tgagtacctt tttaaatcta 2461 gcccagtata aacattagcc tgcttaatat ttagacattt ataggtagaa ttctgagcac 2521 tcaactcatg tttggcattt taaagtaaaa acaagtgtga cttcgaggac caaagaaatt 2581 gtcagctata catttatctt tatgaactca tttatattcc tttttaatga ctcgttgttc 2641 taacatttcc tagaagtgtt cttataaagg tctaatgtat ccacaggctg ttgtcttatt 2701 agtaaatgca aagtaatgac tttgtctgtt ttactctagt ctttagtact tcaaaattac 2761 cttttcatat ccatgatctt gagtccattt gggggatttt taagaatttg atgtatttca 2821 atacactgtt caaaattaaa ttgtttaatt ttatgtatga gtatgtatgt tcctgaagtt 2881 ggtcctattt aaattattaa actattgtaa ctttgttctt gtgaaaaaaa aaaaaaaaaa 2941 a //