LOCUS       NM_001395002            7970 bp    mRNA    linear   PRI 20-AUG-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase kinase kinase
            4 (MAP4K4), transcript variant 55, mRNA.
ACCESSION   NM_001395002 XM_005264048
VERSION     NM_001395002.1
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 7970)
  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 7970)
  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 7970)
  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 7970)
  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 7970)
  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 7970)
  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 7970)
  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 7970)
  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 7970)
  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 7970)
  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 and AC005035.2.
            
            On May 24, 2021 this sequence version replaced XM_005264048.2.
            
            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].
            
            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##
            RNAseq introns :: single sample supports all introns SAMEA1965299,
                              SAMEA1968540 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            inferred exon combination :: based on alignments, homology
            MANE Ensembl match        :: ENST00000324219.9/ ENSP00000313644.6
            RefSeq Select criteria    :: based on manual assertion,
                                         conservation, longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-431               AC007005.3         56920-57350
            432-497             AC007005.3         57686-57751
            498-554             AC007005.3         149933-149989
            555-680             AC005035.2         15565-15690
            681-791             AC005035.2         16956-17066
            792-882             AC005035.2         21141-21231
            883-1013            AC005035.2         23358-23488
            1014-1068           AC005035.2         26046-26100
            1069-1147           AC005035.2         27537-27615
            1148-1323           AC005035.2         31456-31631
            1324-1396           AC005035.2         34246-34318
            1397-1607           AC005035.2         35738-35948
            1608-1769           AC005035.2         47614-47775
            1770-1856           AC005035.2         50633-50719
            1857-2078           AC005035.2         51280-51501
            2079-2240           AC005035.2         52462-52623
            2241-2471           AC005035.2         55458-55688
            2472-2578           AC005035.2         56567-56673
            2579-2730           AC005035.2         58065-58216
            2731-2828           AC005035.2         58849-58946
            2829-2837           AC005035.2         59666-59674
            2838-3013           AC005035.2         61259-61434
            3014-3134           AC005035.2         61932-62052
            3135-3326           AC005035.2         63131-63322
            3327-3444           AC005035.2         65284-65401
            3445-3615           AC005035.2         65719-65889
            3616-3759           AC005035.2         68640-68783
            3760-3894           AC005035.2         74188-74322
            3895-3995           AC005035.2         76824-76924
            3996-4145           AC005035.2         78725-78874
            4146-4305           AC005035.2         79415-79574
            4306-4445           AC005035.2         80433-80572
            4446-7970           AC005035.2         82803-86327
FEATURES             Location/Qualifiers
     source          1..7970
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q11.2"
     gene            1..7970
                     /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..4529
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /EC_number="2.7.11.1"
                     /note="isoform 55 is encoded by transcript variant 55;
                     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 55"
                     /protein_id="NP_001381931.1"
                     /db_xref="CCDS:CCDS92821.1"
                     /db_xref="GeneID:9448"
                     /db_xref="HGNC:HGNC:6866"
                     /db_xref="MIM:604666"
                     /translation="MANDSPAKSLVDIDLSSLRDPAGIFELVEVVGNGTYGQVYKGRH
                     VKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYSHHRNIATYYGAFIKKSPPGHDDQLW
                     LVMEFCGAGSITDLVKNTKGNTLKEDWIAYISREILRGLAHLHIHHVIHRDIKGQNVL
                     LTENAEVKLVDFGVSAQLDRTVGRRNTFIGTPYWMAPEVIACDENPDATYDYRSDLWS
                     CGITAIEMAEGAPPLCDMHPMRALFLIPRNPPPRLKSKKWSKKFFSFIEGCLVKNYMQ
                     RPSTEQLLKHPFIRDQPNERQVRIQLKDHIDRTRKKRGEKDETEYEYSGSEEEEEEVP
                     EQEGEPSSIVNVPGESTLRRDFLRLQQENKERSEALRRQQLLQEQQLREQEEYKRQLL
                     AERQKRIEQQKEQRRRLEEQQRREREARRQQEREQRRREQEEKRRLEELERRRKEEEE
                     RRRAEEEKRRVEREQEYIRRQLEEEQRHLEVLQQQLLQEQAMLLECRWREMEEHRQAE
                     RLQRQLQQEQAYLLSLQHDHRRPHPQHSQQPPPPQQERSKPSFHAPEPKAHYEPADRA
                     REVEDRFRKTNHSSPEAQSKQTGRVLEPPVPSRSESFSNGNSESVHPALQRPAEPQVQ
                     WSHLASLKNNVSPVSRSHSFSDPSPKFAHHHLRSQDPCPPSRSEVLSQSSDSKSEAPD
                     PTQKAWSRSDSDEVPPRVPVRTTSRSPVLSRRDSPLQGSGQQNSQAGQRNSTSSIEPR
                     LLWERVEKLVPRPGSGSSSGSSNSGSQPGSHPGSQSGSGERFRVRSSSKSEGSPSQRL
                     ENAVKKPEDKKEVFRPLKPAGEVDLTALAKELRAVEDVRPPHKVTDYSSSSEESGTTD
                     EEDDDVEQEGADESTSGPEDTRAASSLNLSNGETESVKTMIVHDDVESEPAMTPSKEG
                     TLIVRQSTVDQKRASHHESNGFAGRIHLLPDLLQQSHSSSTSSTSSSPSSSQPTPTMS
                     PQTPQDKLTANETQSASSTLQKHKSSSSFTPFIDPRLLQISPSSGTTVTSVVGFSCDG
                     MRPEAIRQDPTRKGSVVNVNPTNTRPQSDTPEIRKYKKRFNSEILCAALWGVNLLVGT
                     ESGLMLLDRSGQGKVYPLINRRRFQQMDVLEGLNVLVTISGKKDKLRVYYLSWLRNKI
                     LHNDPEVEKKQGWTTVGDLEGCVHYKVVKYERIKFLVIALKSSVEVYAWAPKPYHKFM
                     AFKSFGELVHKPLLVDLTVEEGQRLKVIYGSCAGFHAVDVDSGSVYDIYLPTHIQCSI
                     KPHAIIILPNTDGMELLVCYEDEGVYVNTYGRITKDVVLQWGEMPTSVAYIRSNQTMG
                     WGEKAIEIRSVETGHLDGVFMHKRAQRLKFLCERNDKVFFASVRSGGSSQVYFMTLGR
                     TSLLSW"
     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..2471
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2472..2578
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2579..2730
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2731..2828
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2829..2837
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            2838..3013
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3014..3134
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3135..3326
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3327..3444
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3445..3615
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3616..3759
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3760..3894
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3895..3995
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            3996..4145
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            4146..4305
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            4306..4445
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     exon            4446..7970
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4734..4739
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="hexamer: AATAAA"
     polyA_site      4776
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="major polyA site"
     regulatory      6064..6069
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="hexamer: AATAAA"
     polyA_site      6084
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
     regulatory      7949..7954
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP4K4"
                     /gene_synonym="FLH21957; HEL-S-31; HGK; MEKKK4; NIK"
                     /note="hexamer: AATAAA"
     polyA_site      7970
                     /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 gtacagtggt cccacctggc atctctcaag aacaatgttt
     2281 cccctgtctc gcgatcccat tccttcagtg acccttctcc caaatttgca caccaccatc
     2341 ttcgttctca ggacccatgt ccaccttccc gcagtgaggt gctcagtcag agctctgact
     2401 ctaagtcaga ggcgcctgac cctacccaaa aggcttggtc tagatcagac agtgacgagg
     2461 tgcctccaag ggttcctgtg agaacaacat ctcgctcccc tgttctgtcc cgtcgagatt
     2521 ccccactgca gggcagtggg cagcagaata gccaggcagg acagagaaac tccaccagca
     2581 gtattgagcc caggcttctg tgggagagag tggagaagct ggtgcccaga cctggcagtg
     2641 gcagctcctc agggtccagc aactcaggat cccagcccgg gtctcaccct gggtctcaga
     2701 gtggctccgg ggaacgcttc agagtgagat catcatccaa gtctgaaggc tctccatctc
     2761 agcgcctgga aaatgcagtg aaaaaacctg aagataaaaa ggaagttttc agacccctca
     2821 agcctgctgg cgaagtggat ctgaccgcac tggccaaaga gcttcgagca gtggaagatg
     2881 tacggccacc tcacaaagta acggactact cctcatccag tgaggagtcg gggacgacgg
     2941 atgaggagga cgacgatgtg gagcaggaag gggctgacga gtccacctca ggaccagagg
     3001 acaccagagc agcgtcatct ctgaatttga gcaatggtga aacggaatct gtgaaaacca
     3061 tgattgtcca tgatgatgta gaaagtgagc cggccatgac cccatccaag gagggcactc
     3121 taatcgtccg ccagagtaca gttgaccaaa agcgtgccag ccatcatgag agcaatggct
     3181 ttgccggtcg cattcacctc ttgccagatc tcttacagca aagccattcc tcctccactt
     3241 cctccacctc ctcctcccca tcctccagcc agccgacacc caccatgtcc ccacagacac
     3301 cccaggacaa gctcactgct aatgagactc agtccgctag tagcacactc cagaaacaca
     3361 aatcttcctc ctcctttaca ccttttatag accccagatt actacagatt tctccatcta
     3421 gcggaacaac agtgacatct gtggtgggat tttcctgtga tgggatgaga ccagaagcca
     3481 taaggcaaga tcctacccgg aaaggctcag tggtcaatgt gaatcctacc aacactaggc
     3541 cacagagtga caccccggag attcgtaaat acaagaagag gtttaactct gagattctgt
     3601 gtgctgcctt atggggagtg aatttgctag tgggtacaga gagtggcctg atgctgctgg
     3661 acagaagtgg ccaagggaag gtctatcctc ttatcaaccg aagacgattt caacaaatgg
     3721 acgtacttga gggcttgaat gtcttggtga caatatctgg caaaaaggat aagttacgtg
     3781 tctactattt gtcctggtta agaaataaaa tacttcacaa tgatccagaa gttgagaaga
     3841 agcagggatg gacaaccgta ggggatttgg aaggatgtgt acattataaa gttgtaaaat
     3901 atgaaagaat caaatttctg gtgattgctt tgaagagttc tgtggaagtc tatgcgtggg
     3961 caccaaagcc atatcacaaa tttatggcct ttaagtcatt tggagaattg gtacataagc
     4021 cattactggt ggatctcact gttgaggaag gccagaggtt gaaagtgatc tatggatcct
     4081 gtgctggatt ccatgctgtt gatgtggatt caggatcagt ctatgacatt tatctaccaa
     4141 cacatatcca gtgtagcatc aaaccccatg caatcatcat cctccccaat acagatggaa
     4201 tggagcttct ggtgtgctat gaagatgagg gggtttatgt aaacacatat ggaaggatca
     4261 ccaaggatgt agttctacag tggggagaga tgcctacatc agtagcatat attcgatcca
     4321 atcagacaat gggctgggga gagaaggcca tagagatccg atctgtggaa actggtcact
     4381 tggatggtgt gttcatgcac aaaagggctc aaagactaaa attcttgtgt gaacgcaatg
     4441 acaaggtgtt ctttgcctct gttcggtctg gtggcagcag tcaggtttat ttcatgacct
     4501 taggcaggac ttctcttctg agctggtaga agcagtgtga tccagggatt actggcctcc
     4561 agagtcttca agatcctgag aacttggaat tccttgtaac tggagctcgg agctgcaccg
     4621 agggcaacca ggacagctgt gtgtgcagac ctcatgtgtt gggttctctc ccctccttcc
     4681 tgttcctctt atataccagt ttatccccat tctttttttt tttcttactc caaaataaat
     4741 caaggctgca atgcagctgg tgctgttcag attctaccat caggtgctat aagtgtttgg
     4801 gattgagcat catactggaa agcaaacacc tttcctccag ctccagaatt ccttgtctct
     4861 gaatgactct gtcttgtggg tgtctgacag tggcgacgat gaacatgccg ttggttttat
     4921 tggcagtggg cacaaggagg tgagaagtgg tggtaaaagg agcggagtgc tgaagcagag
     4981 agcagattta atatagtaac attaacagtg tatttaattg acatttcttt tttgtaatgt
     5041 gacgatatgt ggacaaagaa gaagatgcag gtttaagaag ttaatattta taaaatgtga
     5101 aagacacagt tactaggata acttttttgt gggtggggct tgggagatgg ggtggggtgg
     5161 gttaaggggt cccattttgt ttctttggat ttggggtggg ggtcctggcc aagaactcag
     5221 tcatttttct gtgtaccagg ttgcctaaat catgtgcaga tggttctaaa aaaaaaaaaa
     5281 aaaaaaaaaa aaaaaggaaa aaaaaaaaga aaaagaaaac gtgtgcattt tgtataatgg
     5341 ccagaacttt gtcgtgtgac agtattagca ctgcctcagt taaaggttta atttttgttt
     5401 aaacctagac gtgcaacaaa agttttacca cagtctgcac ttgcagaaga aagaaaaaaa
     5461 ttcaaaccac atgtttattt tttttttgcc tacctcattg ttcttaatgc attgagaggt
     5521 gatttagttt atatgttttt ggaagaaacc attaatgttt aatttaatct taataccaaa
     5581 acgaccagat tgaagtttga cttttattgt cacaaatcag caggcacaag aactgtccat
     5641 gaagatggga aatagcctta aggctgatgc agtttactta caagtttaga aaccagaatg
     5701 ctttgttttt accagattca ccattagagg ttgatggggc aactgcagcc catgacacaa
     5761 gatctcattg ttctcgatgt agaggggttg gtagcagaca ggtggttaca ttagaatagt
     5821 cacacaaact gttcagtgtt gcaggaacct tttcttgggg gtgggggagt ttcccttttc
     5881 taaaaatgca atgcactaaa actattttaa gaatgtagtt aattctgctt attcataaag
     5941 tgggcatctt ctgtgtttta ggtgtaatat cgaagtcctg gcttttctcg ttttctcact
     6001 tgctctcttg ttctctgttt ttttaaacca attttacttt atgaatatat tcatgacatt
     6061 tgtaataaat gtcttgagaa agaatttgtt tcatggcttc atggtcatca ctcaagctcc
     6121 cgtaaggata ttaccgtctc aggaaaggat caggactcca tgtcacagtc ctgccatctt
     6181 actttcctct tgtcgagttc tgagtggaaa taactgcatt atggctgctt taacctcagt
     6241 catcaaaaga aacttgctgt tttttaggct tgatcttttt cctttgtggt taattttcct
     6301 gtatattgtg aaaatggggg attttccctc tgctcccacc cacctaaaca cagcagccat
     6361 ttgtacctgt ttgcttccca tcccacttgg cacccactct gacctcttgt cagtttcctg
     6421 ttcctggttc catctttttg aaaaaggccc tcctttgagc tacaaacatc tggtaagaca
     6481 agtacatcca ctcatgaatg cagacacagc agctggtggt tttgtgtata cctgtaaaga
     6541 caagctgaga agcttacttt ttggggaagt aaaagaagat ggaaatggat gtttcatttg
     6601 tatgagtttg gagcagtgct gaaggccaaa gccgcctact ggtttgtagt taacctagag
     6661 aaggttgaaa aattaatcct acctttaaag ggatttgagg taggctggat tccatcgcca
     6721 caggacttta gttagaatta aattcctgct tgtaatttat atccatgttt aggcttttca
     6781 taagatgaaa catgccacag tgaacacact cgtgtacata tcaagagaag aaggaaaggc
     6841 acaggtggag aacagtaaaa ggtgggcaga tgtctttgaa gaaatgctca atgtctgatg
     6901 ctaagtggga gaaggcagag aacaaaggat gtggcataat ggtcttaaca ttatccaaag
     6961 acttgaagct ccatgtctgt aagtcaaatg ttacacaaaa aaaaatgcaa atggtgtttc
     7021 attggaatta ccaagtgctt agaacttgct ggctttccca taggtggtaa aggggtctga
     7081 gctcacaccg agttgtgctt ggcttgcttg tgcagctcca ggcacccggt gggcactctg
     7141 gtggtgtttg tggtgaactg aattgaatcc attgttgggc ttaagttact gaaattggaa
     7201 caccctttgt ccttctcggc gggggcttcc tggtctgtgc tttacttggc ttttttcctt
     7261 cccgtcttag cctcaccccc ttgtcaacca gattgagttg ctatagcttg atgcagggac
     7321 ccagtgaagt ttctccgtta aagattggga gtcgtcgaaa tgtttagatt cttttaggaa
     7381 aggaattatt ttcccccctt ttacagggta gtaacttctc cacagaagtg ccaatatggc
     7441 aaaattacac aagaaaacag tattgcaatg acaccattac ataaggaaca ttgaactgtt
     7501 agaggagtgc tcttccaaac aaaacaaaaa tgtctctagg tttagtcaga gctttcacaa
     7561 gtaataacct ttctgtatta aaatcagagt aaccctttct gtattgagtg cagtgttttt
     7621 tactcttttc tcatgcacat gttacgttgg agaaaatgtt tacaaaaatg gttttgttac
     7681 actaatgcgc accacatatt tatggtttat tttaagtgac tttttatggg ttatttaggt
     7741 tttcgtctta gttgtagcac acttacccta attttgccaa ttattaattt gctaaatagt
     7801 aatacaaatg acaaactgca ttaaatttac taattataaa agctgcaaag cagactggtg
     7861 gcaagtacac agcccttttt tttgcagtgc taacttgtct actgtgtatt atgaaaatta
     7921 ctgttgtccc cccacccttt tttccttaaa taaagtaaaa atgacaccta
//
