LOCUS       NM_004579               7147 bp    mRNA    linear   PRI 05-DEC-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase kinase kinase
            2 (MAP4K2), transcript variant 1, mRNA.
ACCESSION   NM_004579
VERSION     NM_004579.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 7147)
  AUTHORS   Seo,G., Mckinley,J. and Wang,W.
  TITLE     MAP4K2 connects the Hippo pathway to autophagy in response to
            energy stress
  JOURNAL   Autophagy 20 (3), 704-706 (2024)
   PUBMED   37937799
  REMARK    GeneRIF: MAP4K2 connects the Hippo pathway to autophagy in response
            to energy stress.
REFERENCE   2  (bases 1 to 7147)
  AUTHORS   Zhang,X., Zhao,G., Zhang,Y., Wang,J., Wang,Y., Cheng,L., Sun,M. and
            Rui,Y.
  TITLE     Activation of JNK signaling in osteoblasts is inversely correlated
            with collagen synthesis in age-related osteoporosis
  JOURNAL   Biochem Biophys Res Commun 504 (4), 771-776 (2018)
   PUBMED   30217450
  REMARK    GeneRIF: MAP4K2 was up-regulated and its expression was inversely
            correlated with collagen expression in the osteoblasts from older
            donors.
REFERENCE   3  (bases 1 to 7147)
  AUTHORS   Matthews,J.M., Bhatt,S., Patricelli,M.P., Nomanbhoy,T.K., Jiang,X.,
            Natkunam,Y., Gentles,A.J., Martinez,E., Zhu,D., Chapman,J.R.,
            Cortizas,E., Shyam,R., Chinichian,S., Advani,R., Tan,L., Zhang,J.,
            Choi,H.G., Tibshirani,R., Buhrlage,S.J., Gratzinger,D., Verdun,R.,
            Gray,N.S. and Lossos,I.S.
  TITLE     Pathophysiological significance and therapeutic targeting of
            germinal center kinase in diffuse large B-cell lymphoma
  JOURNAL   Blood 128 (2), 239-248 (2016)
   PUBMED   27151888
  REMARK    GeneRIF: These studies demonstrate, for the first time, that GCK is
            a molecular therapeutic target in DLBCL tumors and that inhibiting
            GCK may significantly extend DLBCL patient survival.
REFERENCE   4  (bases 1 to 7147)
  AUTHORS   Tan,L., Nomanbhoy,T., Gurbani,D., Patricelli,M., Hunter,J.,
            Geng,J., Herhaus,L., Zhang,J., Pauls,E., Ham,Y., Choi,H.G., Xie,T.,
            Deng,X., Buhrlage,S.J., Sim,T., Cohen,P., Sapkota,G., Westover,K.D.
            and Gray,N.S.
  TITLE     Discovery of type II inhibitors of TGFbeta-activated kinase 1
            (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2
            (MAP4K2)
  JOURNAL   J Med Chem 58 (1), 183-196 (2015)
   PUBMED   25075558
  REMARK    GeneRIF: Data indicate 4-substituted 1H-pyrrolo[2,3-b]pyridines as
            potent inhibitors against TGFbeta-activated kinase 1 (TAK1) and
            mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2).
REFERENCE   5  (bases 1 to 7147)
  AUTHORS   Guo,Z., Hou,X., Goody,R.S. and Itzen,A.
  TITLE     Intermediates in the guanine nucleotide exchange reaction of Rab8
            protein catalyzed by guanine nucleotide exchange factors Rabin8 and
            GRAB
  JOURNAL   J Biol Chem 288 (45), 32466-32474 (2013)
   PUBMED   24072714
  REMARK    GeneRIF: Intermediates in the guanine nucleotide exchange reaction
            of Rab8 protein catalyzed by guanine nucleotide exchange factors
            Rabin8 and GRAB.
REFERENCE   6  (bases 1 to 7147)
  AUTHORS   Yuasa,T., Ohno,S., Kehrl,J.H. and Kyriakis,J.M.
  TITLE     Tumor necrosis factor signaling to stress-activated protein kinase
            (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center
            kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase
            kinase 1 and SAPK while receptor interacting protein associates
            with a mitogen-activated protein kinase kinase kinase upstream of
            MKK6 and p38
  JOURNAL   J Biol Chem 273 (35), 22681-22692 (1998)
   PUBMED   9712898
REFERENCE   7  (bases 1 to 7147)
  AUTHORS   Guru,S.C., Agarwal,S.K., Manickam,P., Olufemi,S.E., Crabtree,J.S.,
            Weisemann,J.M., Kester,M.B., Kim,Y.S., Wang,Y., Emmert-Buck,M.R.,
            Liotta,L.A., Spiegel,A.M., Boguski,M.S., Roe,B.A., Collins,F.S.,
            Marx,S.J., Burns,L. and Chandrasekharappa,S.C.
  TITLE     A transcript map for the 2.8-Mb region containing the multiple
            endocrine neoplasia type 1 locus
  JOURNAL   Genome Res 7 (7), 725-735 (1997)
   PUBMED   9253601
REFERENCE   8  (bases 1 to 7147)
  AUTHORS   Ren,M., Zeng,J., De Lemos-Chiarandini,C., Rosenfeld,M., Adesnik,M.
            and Sabatini,D.D.
  TITLE     In its active form, the GTP-binding protein rab8 interacts with a
            stress-activated protein kinase
  JOURNAL   Proc Natl Acad Sci U S A 93 (10), 5151-5155 (1996)
   PUBMED   8643544
REFERENCE   9  (bases 1 to 7147)
  AUTHORS   Pombo,C.M., Kehrl,J.H., Sanchez,I., Katz,P., Avruch,J., Zon,L.I.,
            Woodgett,J.R., Force,T. and Kyriakis,J.M.
  TITLE     Activation of the SAPK pathway by the human STE20 homologue
            germinal centre kinase
  JOURNAL   Nature 377 (6551), 750-754 (1995)
   PUBMED   7477268
REFERENCE   10 (bases 1 to 7147)
  AUTHORS   Katz,P., Whalen,G. and Kehrl,J.H.
  TITLE     Differential expression of a novel protein kinase in human B
            lymphocytes. Preferential localization in the germinal center
  JOURNAL   J Biol Chem 269 (24), 16802-16809 (1994)
   PUBMED   7515885
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BM458161.1, U07349.1,
            AW574847.1, BU844790.1 and AP001462.3.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_004579.4.
            
            Summary: The protein encoded by this gene is a member of the
            serine/threonine protein kinase family. Although this kinase is
            found in many tissues, its expression in lymphoid follicles is
            restricted to the cells of germinal centre, where it may
            participate in B-cell differentiation. This kinase can be activated
            by TNF-alpha, and has been shown to specifically activate MAP
            kinases. This kinase is also found to interact with TNF
            receptor-associated factor 2 (TRAF2), which is involved in the
            activation of MAP3K1/MEKK1. Alternative splicing results in
            multiple transcript variants. [provided by RefSeq, Apr 2015].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: SRR14038196.841145.1, U07349.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000294066.7/ ENSP00000294066.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-745               BM458161.1         28-772
            746-2548            U07349.1           717-2519
            2549-2928           AW574847.1         17-396              c
            2929-2964           BU844790.1         297-332
            2965-7147           AP001462.3         69193-73375         c
FEATURES             Location/Qualifiers
     source          1..7147
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q13.1"
     gene            1..7147
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /note="mitogen-activated protein kinase kinase kinase
                     kinase 2"
                     /db_xref="GeneID:5871"
                     /db_xref="HGNC:HGNC:6864"
                     /db_xref="MIM:603166"
     exon            1..161
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     CDS             66..2528
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /EC_number="2.7.11.1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     germinal centre kinase (GC kinase); B lymphocyte
                     serine/threonine protein kinase; Rab8 interacting protein;
                     MEKKK 2; MEK kinase kinase 2; MAPK/ERK kinase kinase
                     kinase 2"
                     /codon_start=1
                     /product="mitogen-activated protein kinase kinase kinase
                     kinase 2 isoform 1"
                     /protein_id="NP_004570.2"
                     /db_xref="CCDS:CCDS8082.1"
                     /db_xref="GeneID:5871"
                     /db_xref="HGNC:HGNC:6864"
                     /db_xref="MIM:603166"
                     /translation="MALLRDVSLQDPRDRFELLQRVGAGTYGDVYKARDTVTSELAAV
                     KIVKLDPGDDISSLQQEITILRECRHPNVVAYIGSYLRNDRLWICMEFCGGGSLQEIY
                     HATGPLEERQIAYVCREALKGLHHLHSQGKIHRDIKGANLLLTLQGDVKLADFGVSGE
                     LTASVAKRRSFIGTPYWMAPEVAAVERKGGYNELCDVWALGITAIELGELQPPLFHLH
                     PMRALMLMSKSSFQPPKLRDKTRWTQNFHHFLKLALTKNPKKRPTAEKLLQHPFTTQQ
                     LPRALLTQLLDKASDPHLGTPSPEDCELETYDMFPDTIHSRGQHGPAERTPSEIQFHQ
                     VKFGAPRRKETDPLNEPWEEEWTLLGKEELSGSLLQSVQEALEERSLTIRSASEFQEL
                     DSPDDTMGTIKRAPFLGPLPTDPPAEEPLSSPPGTLPPPPSGPNSSPLLPTAWATMKQ
                     REDPERSSCHGLPPTPKVHMGACFSKVFNGCPLRIHAAVTWIHPVTRDQFLVVGAEEG
                     IYTLNLHELHEDTLEKLISHRCSWLYCVNNVLLSLSGKSTHIWAHDLPGLFEQRRLQQ
                     QVPLSIPTNRLTQRIIPRRFALSTKIPDTKGCLQCRVVRNPYTGATFLLAALPTSLLL
                     LQWYEPLQKFLLLKNFSSPLPSPAGMLEPLVLDGKELPQVCVGAEGPEGPGCRVLFHV
                     LPLEAGLTPDILIPPEGIPGSAQQVIQVDRDTILVSFERCVRIVNMQGEPTATLAPEL
                     TFDFPIETVVCLQDSVLAFWSHGMQGRSLDTNEVTQEITDETRIFRVLGAHRDIILES
                     IPTDNPEAHSNLYILTGHQSTY"
     exon            162..219
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            220..310
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            311..375
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            376..431
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            432..479
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            480..522
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            523..595
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            596..727
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            728..790
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            791..872
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            873..980
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            981..1059
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1060..1118
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1119..1162
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1163..1201
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1202..1235
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1236..1341
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1342..1430
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1431..1472
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1473..1557
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1558..1637
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1638..1698
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1699..1816
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1817..1875
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1876..1979
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            1980..2157
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            2158..2226
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            2227..2313
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            2314..2384
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            2385..2440
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     exon            2441..7147
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2909..2914
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /note="hexamer: ATTAAA"
     polyA_site      2928
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /note="major polyA site"
     polyA_site      2964
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
     regulatory      7125..7130
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
                     /note="hexamer: AATAAA"
     polyA_site      7147
                     /gene="MAP4K2"
                     /gene_synonym="BL44; GCK; RAB8IP"
ORIGIN      
        1 gcgccgcccc gcgccggctc cgcagctcgc gcccgcccgc ctgccggccc gcccggcgcc
       61 gggccatggc gctgctgcgg gatgtgtcgc tgcaggaccc gcgggaccgc ttcgagctgc
      121 tgcagcgcgt gggggccggg acctatggcg acgtctacaa ggcccgcgac acggtcacgt
      181 ccgaactggc cgccgtgaag atagtcaagc tagacccagg ggacgacatc agctccctcc
      241 agcaggaaat caccatcctg cgtgagtgcc gccaccccaa tgtggtggcc tacattggca
      301 gctacctcag gaatgaccgc ttgtggatct gcatggagtt ctgcggaggg ggctccctgc
      361 aggagattta ccatgccact gggcccctgg aggagcggca gattgcctac gtctgccgag
      421 aggcactgaa ggggctccac cacctgcatt ctcaggggaa gatccacaga gacatcaagg
      481 gagccaacct tctcctcact ctccagggag atgtcaaact ggctgacttt ggggtgtcag
      541 gcgagctgac agcgtctgtg gccaagagga ggtctttcat tgggactccc tactggatgg
      601 ctcccgaggt ggctgctgtg gagcgcaaag gtggctacaa tgagctatgt gacgtctggg
      661 ccctgggcat cactgccatt gagctgggcg agctgcagcc ccctctgttc cacctgcacc
      721 ccatgagggc cctgatgctc atgtcgaaga gcagcttcca gccgcccaaa ctgagagata
      781 agactcgctg gacccagaat ttccaccact ttctcaaact ggccctgacc aagaatccta
      841 agaagaggcc gacagcagag aagctcctgc agcacccgtt cacgactcag cagctccctc
      901 gggccctcct cacacagctg ctggacaaag ccagtgaccc tcatctgggg accccctccc
      961 ctgaggactg tgagctggag acctatgaca tgtttccaga caccattcac tcccgggggc
     1021 agcacggccc agccgagagg accccctcgg agatccagtt tcaccaggtg aaatttggcg
     1081 ccccacgcag gaaggaaact gacccactga atgagccgtg ggaggaagag tggacactac
     1141 tgggaaagga agagttgagt gggagcctgc tgcagtcggt ccaggaggcc ctggaggaaa
     1201 ggagtctgac tattcggtca gcctcagaat tccaggagct ggactcccca gacgatacca
     1261 tgggaaccat caagcgggcc ccgttcctag ggccactccc cactgaccct ccagcagagg
     1321 agcctctgtc cagtccccca ggaaccctgc ccccacctcc ttcaggcccc aacagctccc
     1381 cactgctgcc cacggcctgg gccaccatga agcagcggga ggatcctgag aggtcatcct
     1441 gccacgggct ccccccaact cccaaggtgc atatgggcgc ctgcttctcc aaggtcttca
     1501 atggctgccc cctgcggatc cacgctgctg tcacctggat tcaccctgtt actcgggacc
     1561 agttcctggt ggtaggggcc gaggaaggca tctacacact caacctgcat gaactgcatg
     1621 aggatacgct ggagaagctg atttcacatc gctgctcctg gctctactgc gtgaacaacg
     1681 tgctgctgtc actctcaggg aaatccacgc acatctgggc ccatgacctc ccaggcctgt
     1741 ttgagcagcg gaggctacag caacaggttc ccctctccat ccccaccaac cgcctcaccc
     1801 agcgcatcat ccccaggcgc tttgctctgt ccaccaagat tcctgacacc aaaggctgct
     1861 tgcagtgtcg tgtggtgcgg aacccctaca cgggtgccac cttcctgctg gccgccctgc
     1921 ccaccagcct gctcctgctg cagtggtatg agccgctgca gaagtttctg ctgctgaaga
     1981 acttctccag ccctctgccc agcccagctg ggatgctgga gccgctggtg ctggatggga
     2041 aggagctgcc gcaggtgtgt gttggggccg aggggcctga ggggcccggc tgccgcgtcc
     2101 tgttccatgt cctgcccctg gaggctggcc tgacgcccga catcctcatc ccacctgagg
     2161 ggatcccagg ctcggcccag caggtgatcc aggtggacag ggacacaatc ctagtcagct
     2221 ttgaacgctg tgtgaggatt gtcaacatgc agggcgagcc cacggccaca ctggcacctg
     2281 agctgacctt tgatttcccc atcgagactg tggtgtgcct gcaggacagt gtgctggcct
     2341 tctggagcca tgggatgcaa ggccgaagcc tggataccaa tgaggtgacc caggagatca
     2401 cagatgaaac aaggatcttc cgagtgcttg gggcccacag agacatcatc ctggagagca
     2461 ttcccactga caacccagag gcgcacagca acctctacat cctcacgggc caccagagca
     2521 cctactaaga gcagcgggcc tgtccagggg ctccccgccc caccccacgc cttagctgca
     2581 ggcccttttg ggcaaagggg cccatcctag accagaggag cccaggccct ggccctgctg
     2641 gggctgaagg tcagaagtaa tcctgagaaa tgtttcaggc ctggggaggg aggggagccc
     2701 ccgacgcctc tgcaataact ggaccagggg gagctgctgt cactccccca tccccgaggc
     2761 agcccagtcc ctagtgccca aggcagggac cctgggcctg ggccatccat tccattttgt
     2821 tccacatttc ctttctactc tttctgccaa gagcctgccc ctgcatttgt cctgggaaac
     2881 acggtattta agagagaact atattggtat taaagctggt ttgttttagt cctctggtcc
     2941 ctctgggtag ggggagtgaa cccacctcat ctcccgcctc cttccctcca acacacgttt
     3001 ctgtgggcac cacagaaggg cagggccccc agggttttgg agaagccagg tagaggtgac
     3061 aggaggccat ggcccccagc agccttctag gggcactgtg ccttcccctg catccttgct
     3121 cagaactgac cctcagcttt gcagtttgag ggctctgctg tagtttagca ccccaaggac
     3181 tcatgcagat ggggggacct caacaaaggg actctcatcc agggcaccct tgccccacgt
     3241 aggatctcac tgggtgaccc ctggaagggc ccaggaggag cccccagagg gctgttccct
     3301 ccattcccat ggaggctgct gcccatggag gtagcctgtg tgacctgtat cccctgcctc
     3361 cacctactgc ctaggtgtta gaccaggaac atcagatgac agcacgatca tcagattgga
     3421 tgggaaggct agcctgtgtc cgtctaccag actcccaagg gctgcctcag tgccaggccc
     3481 tggggtcact accagaaaca gaccagcccc cagggagggc gtcctccttg ctggagcctg
     3541 catcttgagg gcatggccat tctcctgtag cttgtgctta cgctgtcatt ctccaagggt
     3601 ctgtctgctc agctctgaat gccagggccc ccagggctgg gcatcctctt ttgccccagg
     3661 cactgatcag ccgctcttga ctggagcctt tgggcagctg cagcccagga ggcaggatgg
     3721 gaactgcctt gagggcccac agctgggggg ctgggaaggt gggggcaggg tggggggaac
     3781 agctggagca aaggccccat ggtcacccct acattcaagg caggtgttgg aggaagacct
     3841 ttgcacctgg tgggtggcaa taaagacttg cggagtgacg tggtaggtgg atggcagcca
     3901 tgcgagtagg ctcagtggtt cccagggtgt cacactgtcc cctcagccac cctccagcag
     3961 agtttcaact gttctgactc tgtccagtga ctgggagggt ttcttggctg gaatggggag
     4021 ccagcccagg ggagggaaca catctcttca caccaggcat tcacacccat gttcccgtga
     4081 gccccaagga gggtgagggg caccttccaa attggggtcg gtggtaacag ggatacaaag
     4141 tgaattccta acttccaatt ttccagattt ctcggaggaa tgttgggacc agggtggggt
     4201 aagtggggac agggaggtga gctcctgctc agcaaaggcc ctgaccaaag gcgccctggg
     4261 gaggactggc tttccgttca ccaaccggcc agcagcagac agtgcctcct tgtggcggat
     4321 cttcccggac ctcagattca gtctggaaac ggggtttgga ctgcagagtg taaactgcca
     4381 aagtgggggc ctcccataaa acgcttgctg ccagcaaagg caggccaaga gcaaagaaag
     4441 gccgagaaac cagggaatat gcactgagag actaacactt taaattttat ttatgtattt
     4501 ttaaatgcgt aacctttgcc catggtacat atttttttaa atacagcaga gatataatga
     4561 agtctccctc ttaccccgtc cccagccacc ctggtctcag ttacttatga acccttctag
     4621 aagtattttg cgtatttaag caatttggta tattttattc ttggcgattt tttatatacg
     4681 tattaacata ttccacatac tgtactgacc ttgcccttta aaaatatatc ctggggggcc
     4741 aggtgtggtg gctcacacct gtaatccaag cactttggga ggccgaggcg ggcgaatcac
     4801 gaggtcaggg gttcgagacc agcctggcca acatggtgaa accccgtctc tactaaaaat
     4861 acaaaaaatt agctgggcat ggtggcgagt gcctgtaatc ccagctactc gggaggctga
     4921 ggcaggagaa tcgcttgaac ctgggaggcg gaggttgcag tgagcctaga acatgccact
     4981 gcactccagc ctgggcgaca gtgcaagact ccgtctcaaa aaaaaaaaaa agagaaaaaa
     5041 atatatatat atcctggaga atatgaatgt attaaattat cacatgcacc ctgaaaagat
     5101 atgtatatat cctggagagt tttgcgttaa agatctccct ttaaaaaaaa attttttttt
     5161 ttttacagct agtggtattc cattgtgtat gtttcccata acaaatgtta atgacctgca
     5221 gtgagatccc tattggtgga aatttgagtt gtttttacta cttttatatt acaaacaatg
     5281 ctgcaataaa tattattagg ctagtgcccc tctgtacata ttcaagcact tctagaagat
     5341 aagttcctgg aagcagcatt aatgagttag cggtggctac atatgccgtg gtgatagctg
     5401 ctgtccagtt gcccctccat gggcagaaac ctgtgggagg gtcagaccag actctttaag
     5461 tcattcttga ggacaagtag aagggacgtg ggccccccca ggatgttcag gtaactggcc
     5521 catacccgga gtcatcctgg tgaaagtcaa ggggagcacc atgatgtgtg cttcgggacg
     5581 gcggaggatc tgccgtgttc cctgtggcat gtccagcacc tgctcactac cagtgctcag
     5641 gagaccctca cgagtaaggg aatggacaag atgtggtgaa gaggagtccc tgcaatctgc
     5701 ccttggactg ggtgagccac cccagctcgc tgagctttac tttccttagg tttaccatat
     5761 ccaaagccaa ctgcagggct gtcaggagga tcagaaatac tgtaacagac ataatgcaat
     5821 aacatagatg actcttagag gtaaattaaa acagcacttt atgcacagta cgatagcata
     5881 ttataaagct caaaaacaaa atgaaaccat ctattgttta gcaatacatg cccaagatac
     5941 aaccctatta aaaaatcatg ggaaggaaaa gcacaaaatc tgagatggtc gtccctgaga
     6001 ggagtgtggg atgggataag gaaggagccc aggaattttt aaaggtattg gtaatatctt
     6061 agctctcagg tttggtggta ggttcatggg tatttaagtt ataactcagt tcctaactca
     6121 cataaggtgc cacacatcct tttgtatgta tcaaatatta tgtcataaaa ttttagtttg
     6181 ggcatggtgg ttcatgtctg taatcccagc actttgggaa actgaggcag gcagatcact
     6241 tgaacccagg agttctagac cagcctgggc aacatgacaa aaccctgtct ctacaaaaga
     6301 tacacaaatt agctggacat ggtggcactc gcctgcagtc ccagctactc tggaggctaa
     6361 ggtgggagga ttgcttgagc ctaggagttc aaggctgcag tgagctatga acttgccact
     6421 gcactccagc ctgggtgaca gagtgagaac ctgtctcaaa aagaaaaaaa aaaaaaggaa
     6481 aaaaattttt aaaaaatatt taaaagtaat caccgaaaaa atagaactcg cttgaaagac
     6541 aagaccaaaa acgaagagga cgtttcccta gatggtgaaa acaagtgggg cggaatcact
     6601 gcagcgtcct gcacagaact ctggaattgc cactttgcag ttgctgcctt ctagtgtgta
     6661 ttgttgaaag acagttttat tgaggcataa ttggcataca ataagctgca tataaaaatg
     6721 tgtacgtgat gacttttgac atacgtgtac acccgtgaag ctatttccac aatcaagata
     6781 atcaccatcc ccttcactct ggaaagtttc ccatgccctt ggtaagccca ccctcctgct
     6841 tcttgcctcc catccccaag taacaactgt gctgctttct gtcactacag gttaatctgc
     6901 actttctaga atgtatgtaa atagaatcac acagtatgta cttgtgtttt gtctggcttc
     6961 ttgcttagct gagcataagg atttgcgagt catccctgtt gcatgcatta atattttatt
     7021 cctttttatt gccaagtagt attccattgt ttggatgcac cagtttggtt agctgttcac
     7081 ctgttgatgg acatttggac catgttccgt tgtgaactat tacaaataaa gctgctataa
     7141 acattca
//
