LOCUS       NM_001242559            7535 bp    mRNA    linear   PRI 20-AUG-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase kinase kinase
            4 (MAP4K4), transcript variant 4, mRNA.
ACCESSION   NM_001242559
VERSION     NM_001242559.2
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 7535)
  AUTHORS   Ampadu,F., Awasthi,V. and Joshi,A.D.
  TITLE     Role of Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4
            Signaling in Liver and Metabolic Diseases
  JOURNAL   J Pharmacol Exp Ther 390 (2), 233-239 (2024)
   PUBMED   38844365
  REMARK    GeneRIF: Role of Mitogen-Activated Protein Kinase Kinase Kinase
            Kinase 4 Signaling in Liver and Metabolic Diseases.
            Review article
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 7535)
  AUTHORS   Chen,Y., Li,S., Guan,B., Yan,X., Huang,C., Du,Y., Yang,F.,
            Zhang,N., Li,Y., Lu,J., Wang,J., Zhang,J., Chen,Z., Chen,C. and
            Kong,X.
  TITLE     MAP4K4 exacerbates cardiac microvascular injury in diabetes by
            facilitating S-nitrosylation modification of Drp1
  JOURNAL   Cardiovasc Diabetol 23 (1), 164 (2024)
   PUBMED   38724987
  REMARK    GeneRIF: MAP4K4 exacerbates cardiac microvascular injury in
            diabetes by facilitating S-nitrosylation modification of Drp1.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 7535)
  AUTHORS   LeClaire,L.L., Rana,M., Baumgartner,M. and Barber,D.L.
  TITLE     The Nck-interacting kinase NIK increases Arp2/3 complex activity by
            phosphorylating the Arp2 subunit
  JOURNAL   J Cell Biol 208 (2), 161-170 (2015)
   PUBMED   25601402
REFERENCE   4  (bases 1 to 7535)
  AUTHORS   Santhana Kumar,K., Tripolitsioti,D., Ma,M., Grahlert,J., Egli,K.B.,
            Fiaschetti,G., Shalaby,T., Grotzer,M.A. and Baumgartner,M.
  TITLE     The Ser/Thr kinase MAP4K4 drives c-Met-induced motility and
            invasiveness in a cell-based model of SHH medulloblastoma
  JOURNAL   Springerplus 4, 19 (2015)
   PUBMED   25625039
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 7535)
  AUTHORS   Ma,M. and Baumgartner,M.
  TITLE     Intracellular Theileria annulata promote invasive cell motility
            through kinase regulation of the host actin cytoskeleton
  JOURNAL   PLoS Pathog 10 (3), e1004003 (2014)
   PUBMED   24626571
  REMARK    Publication Status: Online-Only
REFERENCE   6  (bases 1 to 7535)
  AUTHORS   Machida,N., Umikawa,M., Takei,K., Sakima,N., Myagmar,B.E.,
            Taira,K., Uezato,H., Ogawa,Y. and Kariya,K.
  TITLE     Mitogen-activated protein kinase kinase kinase kinase 4 as a
            putative effector of Rap2 to activate the c-Jun N-terminal kinase
  JOURNAL   J Biol Chem 279 (16), 15711-15714 (2004)
   PUBMED   14966141
  REMARK    GeneRIF: MAP4K4 is a putative effector of Rap2, a Ras family small
            GTP-binding protein, mediating the activation of JNK by Rap2
REFERENCE   7  (bases 1 to 7535)
  AUTHORS   Wright,J.H., Wang,X., Manning,G., LaMere,B.J., Le,P., Zhu,S.,
            Khatry,D., Flanagan,P.M., Buckley,S.D., Whyte,D.B., Howlett,A.R.,
            Bischoff,J.R., Lipson,K.E. and Jallal,B.
  TITLE     The STE20 kinase HGK is broadly expressed in human tumor cells and
            can modulate cellular transformation, invasion, and adhesion
  JOURNAL   Mol Cell Biol 23 (6), 2068-2082 (2003)
   PUBMED   12612079
  REMARK    GeneRIF: The STE20 kinase HGK is broadly expressed in human tumor
            cells and can modulate cellular transformation, invasion, and
            adhesion.
REFERENCE   8  (bases 1 to 7535)
  AUTHORS   Becker,E., Huynh-Do,U., Holland,S., Pawson,T., Daniel,T.O. and
            Skolnik,E.Y.
  TITLE     Nck-interacting Ste20 kinase couples Eph receptors to c-Jun
            N-terminal kinase and integrin activation
  JOURNAL   Mol Cell Biol 20 (5), 1537-1545 (2000)
   PUBMED   10669731
REFERENCE   9  (bases 1 to 7535)
  AUTHORS   Yao,Z., Zhou,G., Wang,X.S., Brown,A., Diener,K., Gan,H. and
            Tan,T.H.
  TITLE     A novel human STE20-related protein kinase, HGK, that specifically
            activates the c-Jun N-terminal kinase signaling pathway
  JOURNAL   J Biol Chem 274 (4), 2118-2125 (1999)
   PUBMED   9890973
REFERENCE   10 (bases 1 to 7535)
  AUTHORS   Su,Y.C., Han,J., Xu,S., Cobb,M. and Skolnik,E.Y.
  TITLE     NIK is a new Ste20-related kinase that binds NCK and MEKK1 and
            activates the SAPK/JNK cascade via a conserved regulatory domain
  JOURNAL   EMBO J 16 (6), 1279-1290 (1997)
   PUBMED   9135144
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC007005.3, DB086475.1,
            AY212247.1, AC005035.2 and BU625485.1.
            
            On Jun 2, 2019 this sequence version replaced NM_001242559.1.
            
            Summary: The protein encoded by this gene is a member of the
            serine/threonine protein kinase family. This kinase has been shown
            to specifically activate MAPK8/JNK. The activation of MAPK8 by this
            kinase is found to be inhibited by the dominant-negative mutants of
            MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this
            kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase
            cascade, and mediate the TNF-alpha signaling pathway. Alternatively
            spliced transcript variants encoding different isoforms have been
            identified. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (4) uses two alternate in-frame
            splice sites and lacks an alternate in-frame exon in the central
            coding region, compared to variant 2. The encoded isoform (4) is
            shorter than isoform 2. The 5' UTR of this variant is incomplete
            due to a lack of 5'-complete transcripts representing this variant,
            and the presence of splicing ambiguity in the 5' UTR.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript 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 :: AY212247.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-369               AC007005.3         56920-57288
            370-374             DB086475.1         217-221
            375-2889            AY212247.1         1-2515
            2890-2890           AC005035.2         62051-62051
            2891-4166           AY212247.1         2517-3792
            4167-6834           AC005035.2         82959-85626
            6835-7535           BU625485.1         18-718              c
FEATURES             Location/Qualifiers
     source          1..7535
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q11.2"
     gene            1..7535
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="mitogen-activated protein kinase kinase kinase
                     kinase 4"
                     /db_xref="GeneID:9448"
                     /db_xref="HGNC:HGNC:6866"
                     /db_xref="MIM:604666"
     exon            1..431
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     CDS             375..4094
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /EC_number="2.7.11.1"
                     /note="isoform 4 is encoded by transcript variant 4;
                     hepatocyte progenitor kinase-like/germinal center
                     kinase-like kinase; Ste20 group protein kinase HGK;
                     epididymis secretory protein Li 31; MEK kinase kinase 4;
                     nck-interacting kinase; HPK/GCK-like kinase HGK; MAPK/ERK
                     kinase kinase kinase 4"
                     /codon_start=1
                     /product="mitogen-activated protein kinase kinase kinase
                     kinase 4 isoform 4"
                     /protein_id="NP_001229488.1"
                     /db_xref="CCDS:CCDS56130.1"
                     /db_xref="GeneID:9448"
                     /db_xref="HGNC:HGNC:6866"
                     /db_xref="MIM:604666"
                     /translation="MANDSPAKSLVDIDLSSLRDPAGIFELVEVVGNGTYGQVYKGRH
                     VKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYSHHRNIATYYGAFIKKSPPGHDDQLW
                     LVMEFCGAGSITDLVKNTKGNTLKEDWIAYISREILRGLAHLHIHHVIHRDIKGQNVL
                     LTENAEVKLVDFGVSAQLDRTVGRRNTFIGTPYWMAPEVIACDENPDATYDYRSDLWS
                     CGITAIEMAEGAPPLCDMHPMRALFLIPRNPPPRLKSKKWSKKFFSFIEGCLVKNYMQ
                     RPSTEQLLKHPFIRDQPNERQVRIQLKDHIDRTRKKRGEKDETEYEYSGSEEEEEEVP
                     EQEGEPSSIVNVPGESTLRRDFLRLQQENKERSEALRRQQLLQEQQLREQEEYKRQLL
                     AERQKRIEQQKEQRRRLEEQQRREREARRQQEREQRRREQEEKRRLEELERRRKEEEE
                     RRRAEEEKRRVEREQEYIRRQLEEEQRHLEVLQQQLLQEQAMLLECRWREMEEHRQAE
                     RLQRQLQQEQAYLLSLQHDHRRPHPQHSQQPPPPQQERSKPSFHAPEPKAHYEPADRA
                     REVEDRFRKTNHSSPEAQSKQTGRVLEPPVPSRSESFSNGNSESVHPALQRPAEPQVP
                     VRTTSRSPVLSRRDSPLQGSGQQNSQAGQRNSTSIEPRLLWERVEKLVPRPGSGSSSG
                     SSNSGSQPGSHPGSQSGSGERFRVRSSSKSEGSPSQRLENAVKKPEDKKEVFRPLKPA
                     DLTALAKELRAVEDVRPPHKVTDYSSSSEESGTTDEEDDDVEQEGADESTSGPEDTRA
                     ASSLNLSNGETESVKTMIVHDDVESEPAMTPSKEGTLIVRQTQSASSTLQKHKSSSSF
                     TPFIDPRLLQISPSSGTTVTSVVGFSCDGMRPEAIRQDPTRKGSVVNVNPTNTRPQSD
                     TPEIRKYKKRFNSEILCAALWGVNLLVGTESGLMLLDRSGQGKVYPLINRRRFQQMDV
                     LEGLNVLVTISGKKDKLRVYYLSWLRNKILHNDPEVEKKQGWTTVGDLEGCVHYKVVK
                     YERIKFLVIALKSSVEVYAWAPKPYHKFMAFKSFGELVHKPLLVDLTVEEGQRLKVIY
                     GSCAGFHAVDVDSGSVYDIYLPTHIQCSIKPHAIIILPNTDGMELLVCYEDEGVYVNT
                     YGRITKDVVLQWGEMPTSVAYIRSNQTMGWGEKAIEIRSVETGHLDGVFMHKRAQRLK
                     FLCERNDKVFFASVRSGGSSQVYFMTLGRTSLLSW"
     exon            432..497
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            498..554
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            555..680
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            681..791
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            792..882
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            883..1013
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            1014..1068
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            1069..1147
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            1148..1323
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            1324..1396
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            1397..1607
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            1608..1769
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            1770..1856
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            1857..2078
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2079..2240
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2241..2347
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2348..2496
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2497..2594
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2595..2770
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2771..2891
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2892..3009
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3010..3180
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3181..3324
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3325..3459
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3460..3560
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3561..3710
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3711..3870
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3871..4010
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            4011..7535
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4299..4304
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="hexamer: AATAAA"
     polyA_site      4341
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="major polyA site"
     regulatory      5629..5634
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="hexamer: AATAAA"
     polyA_site      5649
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
     regulatory      7514..7519
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="hexamer: AATAAA"
     polyA_site      7535
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
ORIGIN      
        1 actcgctcaa ctcggcgccg ccgcggcccc acgctccggg cccgtcctcg aggcgcgcgg
       61 cgcggggcgc gggcgccggg gcctgaggcg gcgggcgacg cccgggggcc tgacggccgg
      121 ccccgcgcca tggtgtgagc gccgccgccc gtgcacgctc cgtccgccct ccgcgcggcc
      181 cggccggcag agagccccga gcggcccgag agcgcagccg agcccgccgc cgccgcccgc
      241 ggccccgcga ggagagtacc gggccggctc ggctgccgcg cgaggagcgc ggtcggcggc
      301 ctggtctgcg gctgagatac acagagcgac agagacattt attgttattt gttttttggt
      361 ggcaaaaagg gaaaatggcg aacgactccc ctgcaaaaag tctggtggac atcgacctct
      421 cctccctgcg ggatcctgct gggatttttg agctggtgga agtggttgga aatggcacct
      481 atggacaagt ctataagggt cgacatgtta aaacgggtca gttggcagcc atcaaagtta
      541 tggatgtcac tgaggatgaa gaggaagaaa tcaaactgga gataaatatg ctaaagaaat
      601 actctcatca cagaaacatt gcaacatatt atggtgcttt catcaaaaag agccctccag
      661 gacatgatga ccaactctgg cttgttatgg agttctgtgg ggctgggtcc attacagacc
      721 ttgtgaagaa caccaaaggg aacacactca aagaagactg gatcgcttac atctccagag
      781 aaatcctgag gggactggca catcttcaca ttcatcatgt gattcaccgg gatatcaagg
      841 gccagaatgt gttgctgact gagaatgcag aggtgaaact tgttgacttt ggtgtgagtg
      901 ctcagctgga caggactgtg gggcggagaa atacgttcat aggcactccc tactggatgg
      961 ctcctgaggt catcgcctgt gatgagaacc cagatgccac ctatgattac agaagtgatc
     1021 tttggtcttg tggcattaca gccattgaga tggcagaagg tgctccccct ctctgtgaca
     1081 tgcatccaat gagagcactg tttctcattc ccagaaaccc tcctccccgg ctgaagtcaa
     1141 aaaaatggtc gaagaagttt tttagtttta tagaagggtg cctggtgaag aattacatgc
     1201 agcggccctc tacagagcag cttttgaaac atccttttat aagggatcag ccaaatgaaa
     1261 ggcaagttag aatccagctt aaggatcata tagatcgtac caggaagaag agaggcgaga
     1321 aagatgaaac tgagtatgag tacagtggga gtgaggaaga agaggaggaa gtgcctgaac
     1381 aggaaggaga gccaagttcc attgtgaacg tgcctggtga gtctactctt cgccgagatt
     1441 tcctgagact gcagcaggag aacaaggaac gttccgaggc tcttcggaga caacagttac
     1501 tacaggagca acagctccgg gagcaggaag aatataaaag gcaactgctg gcagagagac
     1561 agaagcggat tgagcagcag aaagaacaga ggcgacggct agaagagcaa caaaggagag
     1621 agcgggaagc tagaaggcag caggaacgtg aacagcgaag gagagaacaa gaagaaaaga
     1681 ggcgtctaga ggagttggag agaaggcgca aagaagaaga ggagaggaga cgggcagaag
     1741 aagaaaagag gagagttgaa agagaacagg agtatatcag gcgacagcta gaagaggagc
     1801 agcggcactt ggaagtcctt cagcagcagc tgctccagga gcaggccatg ttactggagt
     1861 gccgatggcg ggagatggag gagcaccggc aggcagagag gctccagagg cagttgcaac
     1921 aagaacaagc atatctcctg tctctacagc atgaccatag gaggccgcac ccgcagcact
     1981 cgcagcagcc gccaccaccg cagcaggaaa ggagcaagcc aagcttccat gctcccgagc
     2041 ccaaagccca ctacgagcct gctgaccgag cgcgagaggt ggaagataga tttaggaaaa
     2101 ctaaccacag ctcccctgaa gcccagtcta agcagacagg cagagtattg gagccaccag
     2161 tgccttcccg atcagagtct ttttccaatg gcaactccga gtctgtgcat cccgccctgc
     2221 agagaccagc ggagccacag gttcctgtga gaacaacatc tcgctcccct gttctgtccc
     2281 gtcgagattc cccactgcag ggcagtgggc agcagaatag ccaggcagga cagagaaact
     2341 ccaccagtat tgagcccagg cttctgtggg agagagtgga gaagctggtg cccagacctg
     2401 gcagtggcag ctcctcaggg tccagcaact caggatccca gcccgggtct caccctgggt
     2461 ctcagagtgg ctccggggaa cgcttcagag tgagatcatc atccaagtct gaaggctctc
     2521 catctcagcg cctggaaaat gcagtgaaaa aacctgaaga taaaaaggaa gttttcagac
     2581 ccctcaagcc tgctgatctg accgcactgg ccaaagagct tcgagcagtg gaagatgtac
     2641 ggccacctca caaagtaacg gactactcct catccagtga ggagtcgggg acgacggatg
     2701 aggaggacga cgatgtggag caggaagggg ctgacgagtc cacctcagga ccagaggaca
     2761 ccagagcagc gtcatctctg aatttgagca atggtgaaac ggaatctgtg aaaaccatga
     2821 ttgtccatga tgatgtagaa agtgagccgg ccatgacccc atccaaggag ggcactctaa
     2881 tcgtccgcca gactcagtcc gctagtagca cactccagaa acacaaatct tcctcctcct
     2941 ttacaccttt tatagacccc agattactac agatttctcc atctagcgga acaacagtga
     3001 catctgtggt gggattttcc tgtgatggga tgagaccaga agccataagg caagatccta
     3061 cccggaaagg ctcagtggtc aatgtgaatc ctaccaacac taggccacag agtgacaccc
     3121 cggagattcg taaatacaag aagaggttta actctgagat tctgtgtgct gccttatggg
     3181 gagtgaattt gctagtgggt acagagagtg gcctgatgct gctggacaga agtggccaag
     3241 ggaaggtcta tcctcttatc aaccgaagac gatttcaaca aatggacgta cttgagggct
     3301 tgaatgtctt ggtgacaata tctggcaaaa aggataagtt acgtgtctac tatttgtcct
     3361 ggttaagaaa taaaatactt cacaatgatc cagaagttga gaagaagcag ggatggacaa
     3421 ccgtagggga tttggaagga tgtgtacatt ataaagttgt aaaatatgaa agaatcaaat
     3481 ttctggtgat tgctttgaag agttctgtgg aagtctatgc gtgggcacca aagccatatc
     3541 acaaatttat ggcctttaag tcatttggag aattggtaca taagccatta ctggtggatc
     3601 tcactgttga ggaaggccag aggttgaaag tgatctatgg atcctgtgct ggattccatg
     3661 ctgttgatgt ggattcagga tcagtctatg acatttatct accaacacat atccagtgta
     3721 gcatcaaacc ccatgcaatc atcatcctcc ccaatacaga tggaatggag cttctggtgt
     3781 gctatgaaga tgagggggtt tatgtaaaca catatggaag gatcaccaag gatgtagttc
     3841 tacagtgggg agagatgcct acatcagtag catatattcg atccaatcag acaatgggct
     3901 ggggagagaa ggccatagag atccgatctg tggaaactgg tcacttggat ggtgtgttca
     3961 tgcacaaaag ggctcaaaga ctaaaattct tgtgtgaacg caatgacaag gtgttctttg
     4021 cctctgttcg gtctggtggc agcagtcagg tttatttcat gaccttaggc aggacttctc
     4081 ttctgagctg gtagaagcag tgtgatccag ggattactgg cctccagagt cttcaagatc
     4141 ctgagaactt ggaattcctt gtaactggag ctcggagctg caccgagggc aaccaggaca
     4201 gctgtgtgtg cagacctcat gtgttgggtt ctctcccctc cttcctgttc ctcttatata
     4261 ccagtttatc cccattcttt ttttttttct tactccaaaa taaatcaagg ctgcaatgca
     4321 gctggtgctg ttcagattct accatcaggt gctataagtg tttgggattg agcatcatac
     4381 tggaaagcaa acacctttcc tccagctcca gaattccttg tctctgaatg actctgtctt
     4441 gtgggtgtct gacagtggcg acgatgaaca tgccgttggt tttattggca gtgggcacaa
     4501 ggaggtgaga agtggtggta aaaggagcgg agtgctgaag cagagagcag atttaatata
     4561 gtaacattaa cagtgtattt aattgacatt tcttttttgt aatgtgacga tatgtggaca
     4621 aagaagaaga tgcaggttta agaagttaat atttataaaa tgtgaaagac acagttacta
     4681 ggataacttt tttgtgggtg gggcttggga gatggggtgg ggtgggttaa ggggtcccat
     4741 tttgtttctt tggatttggg gtgggggtcc tggccaagaa ctcagtcatt tttctgtgta
     4801 ccaggttgcc taaatcatgt gcagatggtt ctaaaaaaaa aaaaaaaaaa aaaaaaaaaa
     4861 ggaaaaaaaa aaagaaaaag aaaacgtgtg cattttgtat aatggccaga actttgtcgt
     4921 gtgacagtat tagcactgcc tcagttaaag gtttaatttt tgtttaaacc tagacgtgca
     4981 acaaaagttt taccacagtc tgcacttgca gaagaaagaa aaaaattcaa accacatgtt
     5041 tatttttttt ttgcctacct cattgttctt aatgcattga gaggtgattt agtttatatg
     5101 tttttggaag aaaccattaa tgtttaattt aatcttaata ccaaaacgac cagattgaag
     5161 tttgactttt attgtcacaa atcagcaggc acaagaactg tccatgaaga tgggaaatag
     5221 ccttaaggct gatgcagttt acttacaagt ttagaaacca gaatgctttg tttttaccag
     5281 attcaccatt agaggttgat ggggcaactg cagcccatga cacaagatct cattgttctc
     5341 gatgtagagg ggttggtagc agacaggtgg ttacattaga atagtcacac aaactgttca
     5401 gtgttgcagg aaccttttct tgggggtggg ggagtttccc ttttctaaaa atgcaatgca
     5461 ctaaaactat tttaagaatg tagttaattc tgcttattca taaagtgggc atcttctgtg
     5521 ttttaggtgt aatatcgaag tcctggcttt tctcgttttc tcacttgctc tcttgttctc
     5581 tgttttttta aaccaatttt actttatgaa tatattcatg acatttgtaa taaatgtctt
     5641 gagaaagaat ttgtttcatg gcttcatggt catcactcaa gctcccgtaa ggatattacc
     5701 gtctcaggaa aggatcagga ctccatgtca cagtcctgcc atcttacttt cctcttgtcg
     5761 agttctgagt ggaaataact gcattatggc tgctttaacc tcagtcatca aaagaaactt
     5821 gctgtttttt aggcttgatc tttttccttt gtggttaatt ttcctgtata ttgtgaaaat
     5881 gggggatttt ccctctgctc ccacccacct aaacacagca gccatttgta cctgtttgct
     5941 tcccatccca cttggcaccc actctgacct cttgtcagtt tcctgttcct ggttccatct
     6001 ttttgaaaaa ggccctcctt tgagctacaa acatctggta agacaagtac atccactcat
     6061 gaatgcagac acagcagctg gtggttttgt gtatacctgt aaagacaagc tgagaagctt
     6121 actttttggg gaagtaaaag aagatggaaa tggatgtttc atttgtatga gtttggagca
     6181 gtgctgaagg ccaaagccgc ctactggttt gtagttaacc tagagaaggt tgaaaaatta
     6241 atcctacctt taaagggatt tgaggtaggc tggattccat cgccacagga ctttagttag
     6301 aattaaattc ctgcttgtaa tttatatcca tgtttaggct tttcataaga tgaaacatgc
     6361 cacagtgaac acactcgtgt acatatcaag agaagaagga aaggcacagg tggagaacag
     6421 taaaaggtgg gcagatgtct ttgaagaaat gctcaatgtc tgatgctaag tgggagaagg
     6481 cagagaacaa aggatgtggc ataatggtct taacattatc caaagacttg aagctccatg
     6541 tctgtaagtc aaatgttaca caaaaaaaaa tgcaaatggt gtttcattgg aattaccaag
     6601 tgcttagaac ttgctggctt tcccataggt ggtaaagggg tctgagctca caccgagttg
     6661 tgcttggctt gcttgtgcag ctccaggcac ccggtgggca ctctggtggt gtttgtggtg
     6721 aactgaattg aatccattgt tgggcttaag ttactgaaat tggaacaccc tttgtccttc
     6781 tcggcggggg cttcctggtc tgtgctttac ttggcttttt tccttcccgt cttagcctca
     6841 cccccttgtc aaccagattg agttgctata gcttgatgca gggacccagt gaagtttctc
     6901 cgttaaagat tgggagtcgt cgaaatgttt agattctttt aggaaaggaa ttattttccc
     6961 cccttttaca gggtagtaac ttctccacag aagtgccaat atggcaaaat tacacaagaa
     7021 aacagtattg caatgacacc attacataag gaacattgaa ctgttagagg agtgctcttc
     7081 caaacaaaac aaaaatgtct ctaggtttag tcagagcttt cacaagtaat aacctttctg
     7141 tattaaaatc agagtaaccc tttctgtatt gagtgcagtg ttttttactc ttttctcatg
     7201 cacatgttac gttggagaaa atgtttacaa aaatggtttt gttacactaa tgcgcaccac
     7261 atatttatgg tttattttaa gtgacttttt atgggttatt taggttttcg tcttagttgt
     7321 agcacactta ccctaatttt gccaattatt aatttgctaa atagtaatac aaatgacaaa
     7381 ctgcattaaa tttactaatt ataaaagctg caaagcagac tggtggcaag tacacagccc
     7441 ttttttttgc agtgctaact tgtctactgt gtattatgaa aattactgtt gtccccccac
     7501 ccttttttcc ttaaataaag taaaaatgac accta
//
