Homo sapiens L. (human) [HSA]

FULL NAME: Histone-lysine N-methyltransferase MLL


DESCRIPTION:
Histone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation. Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity. Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Required for transcriptional activation of HOXA9. Promotes PPP1R15A-induced apoptosis.
Cleaved into the following 2 chains:
1. MLL cleavage product N320
      Alternative name(s):
      N-terminal cleavage product of 320 kDa
      Short name=p320
2. MLL cleavage product C180
      Alternative name(s):
      C-terminal cleavage product of 180 kDa
      Short name=p180

Tissue specificity: Heart, lung, brain and T- and B-lymphocytes.

MISCELLANEOUS:
Chromosomal aberrations involving MLL are a cause of acute leukemias. Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation t(6;11)(q27;q23) with MLLT4/AF6; translocation t(9;11)(p22;q23) with MLLT3/AF9; translocation t(10;11)(p11.2;q23) with ABI1; translocation t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with CASC5 and ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation t(11;19)(q23;p13.3) with ELL; translocation t(11;19)(q23;p13.3) with MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation t(X;11)(q13;q23) with FOXO4/AFX1. Translocation t(3;11)(q28;q23) with LPP. Translocation t(10;11)(q22;q23) with TET1. Translocation t(9;11)(q34;q23) with DAB2IP. Translocation t(4;11)(p12;q23) with FRYL. Fusion proteins MLL-MLLT1, MLL-MLLT3 and MLL-ELL interact with PPP1R15A and, on the contrary to unfused MLL, inhibit PPP1R15A-induced apoptosis. A chromosomal aberration involving MLL may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with SEPT11.


STRUCTURE SIMILARITY:
Belongs to the histone-lysine methyltransferase family. TRX/MLL subfamily. Contains 3 A.T hook DNA-binding domains. Contains 1 bromo domain. Contains 1 CXXC-type zinc finger. Contains 1 FYR C-terminal domain. Contains 1 FYR N-terminal domain. Contains 3 PHD-type zinc fingers. Contains 1 post-SET domain. Contains 1 SET domain.


SUBUNIT STRUCTURE:
MLL cleavage product N320 heterodimerizes with MLL cleavage product C180 (via SET and FYRC domains). Component of some MLL1/MLL complex, at least composed of the core components MLL, ASH2L, HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative components C17orf49, CHD8, E2F6, HSP70, IN80C, KIAA1267, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with WDR5; the interaction is direct. Interacts with KAT8/MOF; the interaction is direct. Interacts with SBF1 and PPP1R15A. the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. The SET domain structure is atypical and is not in an optimal position to have methyltransferase activity. It requires other components of the MLL1/MLL complex, such as ASH2L or RBBP5, to order the active site and obtain optimal histone methyltransferase activity. The CXXC-type zinc finger binds bind to nonmethyl-CpG dinucleotides.


CATALYTIC ACTIVITY:
S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].


POST-TRANSLATIONAL MODIFICATION:
Proteolytic cleavage by TASP1 generates MLL cleavage product N320 and MLL cleavage product C180, which reassemble through a non-covalent association. 2 cleavage sites exist, cleavage site 1 (CS1) and cleavage site 2 (CS2), to generate MLL cleavage products N320 and C180. CS2 is the major site.


PROTEIN TYPE(S):
histone LYSINE methyltransferase (HKMT)


RELATED PATHWAY(S):
histone modification


RELATED DISEASE(S):
B-cell acute lymphoblastic leukemia (B-ALL)
T-cell acute lymphoblastic leukemia (T-ALL)


Amino acids sequence

        10         20         30         40         50         60
MAHSCRWRFP ARPGTTGGGG GGGRRGLGGA PRQRVPALLL PPGPPVGGGG PGAPPSPPAV
        70         80         90        100        110        120
AAAAAAAGSS GAGVPGGAAA ASAASSSSAS SSSSSSSSAS SGPALLRVGP GFDAALQVSA
       130        140        150        160        170        180
AIGTNLRRFR AVFGESGGGG GSGEDEQFLG FGSDEEVRVR SPTRSPSVKT SPRKPRGRPR
       190        200        210        220        230        240
SGSDRNSAIL SDPSVFSPLN KSETKSGDKI KKKDSKSIEK KRGRPPTFPG VKIKITHGKD
       250        260        270        280        290        300
ISELPKGNKE DSLKKIKRTP SATFQQATKI KKLRAGKLSP LKSKFKTGKL QIGRKGVQIV
       310        320        330        340        350        360
RRRGRPPSTE RIKTPSGLLI NSELEKPQKV RKDKEGTPPL TKEDKTVVRQ SPRRIKPVRI
       370        380        390        400        410        420
IPSSKRTDAT IAKQLLQRAK KGAQKKIEKE AAQLQGRKVK TQVKNIRQFI MPVVSAISSR
       430        440        450        460        470        480
IIKTPRRFIE DEDYDPPIKI ARLESTPNSR FSAPSCGSSE KSSAASQHSS QMSSDSSRSS
       490        500        510        520        530        540
SPSVDTSTDS QASEEIQVLP EERSDTPEVH PPLPISQSPE NESNDRRSRR YSVSERSFGS
       550        560        570        580        590        600
RTTKKLSTLQ SAPQQQTSSS PPPPLLTPPP PLQPASSISD HTPWLMPPTI PLASPFLPAS
       610        620        630        640        650        660
TAPMQGKRKS ILREPTFRWT SLKHSRSEPQ YFSSAKYAKE GLIRKPIFDN FRPPPLTPED
       670        680        690        700        710        720
VGFASGFSAS GTAASARLFS PLHSGTRFDM HKRSPLLRAP RFTPSEAHSR IFESVTLPSN
       730        740        750        760        770        780
RTSAGTSSSG VSNRKRKRKV FSPIRSEPRS PSHSMRTRSG RLSSSELSPL TPPSSVSSSL
       790        800        810        820        830        840
SISVSPLATS ALNPTFTFPS HSLTQSGESA EKNQRPRKQT SAPAEPFSSS SPTPLFPWFT
       850        860        870        880        890        900
PGSQTERGRN KDKAPEELSK DRDADKSVEK DKSRERDRER EKENKRESRK EKRKKGSEIQ
       910        920        930        940        950        960
SSSALYPVGR VSKEKVVGED VATSSSAKKA TGRKKSSSHD SGTDITSVTL GDTTAVKTKI
       970        980        990       1000       1010       1020
LIKKGRGNLE KTNLDLGPTA PSLEKEKTLC LSTPSSSTVK HSTSSIGSML AQADKLPMTD
      1030       1040       1050       1060       1070       1080
KRVASLLKKA KAQLCKIEKS KSLKQTDQPK AQGQESDSSE TSVRGPRIKH VCRRAAVALG
      1090       1100       1110       1120       1130       1140
RKRAVFPDDM PTLSALPWEE REKILSSMGN DDKSSIAGSE DAEPLAPPIK PIKPVTRNKA
      1150       1160       1170       1180       1190       1200
PQEPPVKKGR RSRRCGQCPG CQVPEDCGVC TNCLDKPKFG GRNIKKQCCK MRKCQNLQWM
      1210       1220       1230       1240       1250       1260
PSKAYLQKQA KAVKKKEKKS KTSEKKDSKE SSVVKNVVDS SQKPTPSARE DPAPKKSSSE
      1270       1280       1290       1300       1310       1320
PPPRKPVEEK SEEGNVSAPG PESKQATTPA SRKSSKQVSQ PALVIPPQPP TTGPPRKEVP
      1330       1340       1350       1360       1370       1380
KTTPSEPKKK QPPPPESGPE QSKQKKVAPR PSIPVKQKPK EKEKPPPVNK QENAGTLNIL
      1390       1400       1410       1420       1430       1440
STLSNGNSSK QKIPADGVHR IRVDFKEDCE AENVWEMGGL GILTSVPITP RVVCFLCASS
      1450       1460       1470       1480       1490       1500
GHVEFVYCQV CCEPFHKFCL EENERPLEDQ LENWCCRRCK FCHVCGRQHQ ATKQLLECNK
      1510       1520       1530       1540       1550       1560
CRNSYHPECL GPNYPTKPTK KKKVWICTKC VRCKSCGSTT PGKGWDAQWS HDFSLCHDCA
      1570       1580       1590       1600       1610       1620
KLFAKGNFCP LCDKCYDDDD YESKMMQCGK CDRWVHSKCE NLSGTEDEMY EILSNLPESV
      1630       1640       1650       1660       1670       1680
AYTCVNCTER HPAEWRLALE KELQISLKQV LTALLNSRTT SHLLRYRQAA KPPDLNPETE
      1690       1700       1710       1720       1730       1740
ESIPSRSSPE GPDPPVLTEV SKQDDQQPLD LEGVKRKMDQ GNYTSVLEFS DDIVKIIQAA
      1750       1760       1770       1780       1790       1800
INSDGGQPEI KKANSMVKSF FIRQMERVFP WFSVKKSRFW EPNKVSSNSG MLPNAVLPPS
      1810       1820       1830       1840       1850       1860
LDHNYAQWQE REENSHTEQP PLMKKIIPAP KPKGPGEPDS PTPLHPPTPP ILSTDRSRED
      1870       1880       1890       1900       1910       1920
SPELNPPPGI EDNRQCALCL TYGDDSANDA GRLLYIGQNE WTHVNCALWS AEVFEDDDGS
      1930       1940       1950       1960       1970       1980
LKNVHMAVIR GKQLRCEFCQ KPGATVGCCL TSCTSNYHFM CSRAKNCVFL DDKKVYCQRH
      1990       2000       2010       2020       2030       2040
RDLIKGEVVP ENGFEVFRRV FVDFEGISLR RKFLNGLEPE NIHMMIGSMT IDCLGILNDL
      2050       2060       2070       2080       2090       2100
SDCEDKLFPI GYQCSRVYWS TTDARKRCVY TCKIVECRPP VVEPDINSTV EHDENRTIAH
      2110       2120       2130       2140       2150       2160
SPTSFTESSS KESQNTAEII SPPSPDRPPH SQTSGSCYYH VISKVPRIRT PSYSPTQRSP
      2170       2180       2190       2200       2210       2220
GCRPLPSAGS PTPTTHEIVT VGDPLLSSGL RSIGSRRHST SSLSPQRSKL RIMSPMRTGN
      2230       2240       2250       2260       2270       2280
TYSRNNVSSV STTGTATDLE SSAKVVDHVL GPLNSSTSLG QNTSTSSNLQ RTVVTVGNKN
      2290       2300       2310       2320       2330       2340
SHLDGSSSSE MKQSSASDLV SKSSSLKGEK TKVLSSKSSE GSAHNVAYPG IPKLAPQVHN
      2350       2360       2370       2380       2390       2400
TTSRELNVSK IGSFAEPSSV SFSSKEALSF PHLHLRGQRN DRDQHTDSTQ SANSSPDEDT
      2410       2420       2430       2440       2450       2460
EVKTLKLSGM SNRSSIINEH MGSSSRDRRQ KGKKSCKETF KEKHSSKSFL EPGQVTTGEE
      2470       2480       2490       2500       2510       2520
GNLKPEFMDE VLTPEYMGQR PCNNVSSDKI GDKGLSMPGV PKAPPMQVEG SAKELQAPRK
      2530       2540       2550       2560       2570       2580
RTVKVTLTPL KMENESQSKN ALKESSPASP LQIESTSPTE PISASENPGD GPVAQPSPNN
      2590       2600       2610       2620       2630       2640
TSCQDSQSNN YQNLPVQDRN LMLPDGPKPQ EDGSFKRRYP RRSARARSNM FFGLTPLYGV
      2650       2660       2670       2680       2690       2700
RSYGEEDIPF YSSSTGKKRG KRSAEGQVDG ADDLSTSDED DLYYYNFTRT VISSGGEERL
      2710       2720       2730       2740       2750       2760
ASHNLFREEE QCDLPKISQL DGVDDGTESD TSVTATTRKS SQIPKRNGKE NGTENLKIDR
      2770       2780       2790       2800       2810       2820
PEDAGEKEHV TKSSVGHKNE PKMDNCHSVS RVKTQGQDSL EAQLSSLESS RRVHTSTPSD
      2830       2840       2850       2860       2870       2880
KNLLDTYNTE LLKSDSDNNN SDDCGNILPS DIMDFVLKNT PSMQALGESP ESSSSELLNL
      2890       2900       2910       2920       2930       2940
GEGLGLDSNR EKDMGLFEVF SQQLPTTEPV DSSVSSSISA EEQFELPLEL PSDLSVLTTR
      2950       2960       2970       2980       2990       3000
SPTVPSQNPS RLAVISDSGE KRVTITEKSV ASSESDPALL SPGVDPTPEG HMTPDHFIQG
      3010       3020       3030       3040       3050       3060
HMDADHISSP PCGSVEQGHG NNQDLTRNSS TPGLQVPVSP TVPIQNQKYV PNSTDSPGPS
      3070       3080       3090       3100       3110       3120
QISNAAVQTT PPHLKPATEK LIVVNQNMQP LYVLQTLPNG VTQKIQLTSS VSSTPSVMET
      3130       3140       3150       3160       3170       3180
NTSVLGPMGG GLTLTTGLNP SLPTSQSLFP SASKGLLPMS HHQHLHSFPA ATQSSFPPNI
      3190       3200       3210       3220       3230       3240
SNPPSGLLIG VQPPPDPQLL VSESSQRTDL STTVATPSSG LKKRPISRLQ TRKNKKLAPS
      3250       3260       3270       3280       3290       3300
STPSNIAPSD VVSNMTLINF TPSQLPNHPS LLDLGSLNTS SHRTVPNIIK RSKSSIMYFE
      3310       3320       3330       3340       3350       3360
PAPLLPQSVG GTAATAAGTS TISQDTSHLT SGSVSGLASS SSVLNVVSMQ TTTTPTSSAS
      3370       3380       3390       3400       3410       3420
VPGHVTLTNP RLLGTPDIGS ISNLLIKASQ QSLGIQDQPV ALPPSSGMFP QLGTSQTPST
      3430       3440       3450       3460       3470       3480
AAITAASSIC VLPSTQTTGI TAASPSGEAD EHYQLQHVNQ LLASKTGIHS SQRDLDSASG
      3490       3500       3510       3520       3530       3540
PQVSNFTQTV DAPNSMGLEQ NKALSSAVQA SPTSPGGSPS SPSSGQRSAS PSVPGPTKPK
      3550       3560       3570       3580       3590       3600
PKTKRFQLPL DKGNGKKHKV SHLRTSSSEA HIPDQETTSL TSGTGTPGAE AEQQDTASVE
      3610       3620       3630       3640       3650       3660
QSSQKECGQP AGQVAVLPEV QVTQNPANEQ ESAEPKTVEE EESNFSSPLM LWLQQEQKRK
      3670       3680       3690       3700       3710       3720
ESITEKKPKK GLVFEISSDD GFQICAESIE DAWKSLTDKV QEARSNARLK QLSFAGVNGL
      3730       3740       3750       3760       3770       3780
RMLGILHDAV VFLIEQLSGA KHCRNYKFRF HKPEEANEPP LNPHGSARAE VHLRKSAFDM
      3790       3800       3810       3820       3830       3840
FNFLASKHRQ PPEYNPNDEE EEEVQLKSAR RATSMDLPMP MRFRHLKKTS KEAVGVYRSP
      3850       3860       3870       3880       3890       3900
IHGRGLFCKR NIDAGEMVIE YAGNVIRSIQ TDKREKYYDS KGIGCYMFRI DDSEVVDATM
      3910       3920       3930       3940       3950       3960
HGNAARFINH SCEPNCYSRV INIDGQKHIV IFAMRKIYRG EELTYDYKFP IEDASNKLPC
      3970
NCGAKKCRKF LN    

Encoded by MLL gene

FULL NAME: myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila)


OTHER NAME(S):
ALL-1
CXXC7
FLJ11783
HRX
HTRX1
KMT2A
MLL/GAS7
MLL1A
TET1-MLL
TRX1


DESCRIPTION:
This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 (H3K4) methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. This protein is processed by the enzyme Taspase 1 into two fragments, MLL-C and MLL-N. These fragments reassociate and further assemble into different multiprotein complexes that regulate the transcription of specific target genes, including many of the HOX genes. Multiple chromosomal translocations involving this gene are the cause of certain acute lymphoid leukemias and acute myeloid leukemias. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]


Nucleic acid sequence

        10         20         30         40         50         60
atggcgcaca gctgtcggtg gcgcttcccc gcccgacccg ggaccaccgg gggcggcggc
        70         80         90        100        110        120
ggcggggggc gccggggcct agggggcgcc ccgcggcaac gcgtcccggc cctgctgctt
       130        140        150        160        170        180
ccccccgggc ccccggtcgg cggtggcggc cccggggcgc ccccctcccc cccggctgtg
       190        200        210        220        230        240
gcggccgcgg cggcggcggc gggaagcagc ggggctgggg ttccaggggg agcggccgcc
       250        260        270        280        290        300
gcctcagcag cctcctcgtc gtccgcctcg tcttcgtctt cgtcatcgtc ctcagcctct
       310        320        330        340        350        360
tcagggccgg ccctgctccg ggtgggcccg ggcttcgacg cggcgctgca ggtctcggcc
       370        380        390        400        410        420
gccatcggca ccaacctgcg ccggttccgg gccgtgtttg gggagagcgg cgggggaggc
       430        440        450        460        470        480
ggcagcggag aggatgagca attcttaggt tttggctcag atgaagaagt cagagtgcga
       490        500        510        520        530        540
agtcccacaa ggtctccttc agttaaaact agtcctcgaa aacctcgtgg gagacctaga
       550        560        570        580        590        600
agtggctctg accgaaattc agctatcctc tcagatccat ctgtgttttc ccctctaaat
       610        620        630        640        650        660
aaatcagaga ccaaatctgg agataagatc aagaagaaag attctaaaag tatagaaaag
       670        680        690        700        710        720
aagagaggaa gacctcccac cttccctgga gtaaaaatca aaataacaca tggaaaggac
       730        740        750        760        770        780
atttcagagt taccaaaggg aaacaaagaa gatagcctga aaaaaattaa aaggacacct
       790        800        810        820        830        840
tctgctacgt ttcagcaagc cacaaagatt aaaaaattaa gagcaggtaa actctctcct
       850        860        870        880        890        900
ctcaagtcta agtttaagac agggaagctt caaataggaa ggaagggggt acaaattgta
       910        920        930        940        950        960
cgacggagag gaaggcctcc atcaacagaa aggataaaga ccccttcggg tctcctcatt
       970        980        990       1000       1010       1020
aattctgaac tggaaaagcc ccagaaagtc cggaaagaca aggaaggaac acctccactt
      1030       1040       1050       1060       1070       1080
acaaaagaag ataagacagt tgtcagacaa agccctcgaa ggattaagcc agttaggatt
      1090       1100       1110       1120       1130       1140
attccttctt caaaaaggac agatgcaacc attgctaagc aactcttaca gagggcaaaa
      1150       1160       1170       1180       1190       1200
aagggggctc aaaagaaaat tgaaaaagaa gcagctcagc tgcagggaag aaaggtgaag
      1210       1220       1230       1240       1250       1260
acacaggtca aaaatattcg acagttcatc atgcctgttg tcagtgctat ctcctcgcgg
      1270       1280       1290       1300       1310       1320
atcattaaga cccctcggcg gtttatagag gatgaggatt atgaccctcc aattaaaatt
      1330       1340       1350       1360       1370       1380
gcccgattag agtctacacc gaatagtaga ttcagtgccc cgtcctgtgg atcttctgaa
      1390       1400       1410       1420       1430       1440
aaatcaagtg cagcttctca gcactcctct caaatgtctt cagactcctc tcgatctagt
      1450       1460       1470       1480       1490       1500
agccccagtg ttgatacctc cacagactct caggcttctg aggagattca ggtacttcct
      1510       1520       1530       1540       1550       1560
gaggagcgga gcgatacccc tgaagttcat cctccactgc ccatttccca gtccccagaa
      1570       1580       1590       1600       1610       1620
aatgagagta atgataggag aagcagaagg tattcagtgt cggagagaag ttttggatct
      1630       1640       1650       1660       1670       1680
agaacgacga aaaaattatc aactctacaa agtgcccccc agcagcagac ctcctcgtct
      1690       1700       1710       1720       1730       1740
ccacctccac ctctgctgac tccaccgcca ccactgcagc cagcctccag tatctctgac
      1750       1760       1770       1780       1790       1800
cacacacctt ggcttatgcc tccaacaatc cccttagcat caccattttt gcctgcttcc
      1810       1820       1830       1840       1850       1860
actgctccta tgcaagggaa gcgaaaatct attttgcgag aaccgacatt taggtggact
      1870       1880       1890       1900       1910       1920
tctttaaagc attctaggtc agagccacaa tacttttcct cagcaaagta tgccaaagaa
      1930       1940       1950       1960       1970       1980
ggtcttattc gcaaaccaat atttgataat ttccgacccc ctccactaac tcccgaggac
      1990       2000       2010       2020       2030       2040
gttggctttg catctggttt ttctgcatct ggtaccgctg cttcagcccg attgttttcg
      2050       2060       2070       2080       2090       2100
ccactccatt ctggaacaag gtttgatatg cacaaaagga gccctcttct gagagctcca
      2110       2120       2130       2140       2150       2160
agatttactc caagtgaggc tcactctaga atatttgagt ctgtaacctt gcctagtaat
      2170       2180       2190       2200       2210       2220
cgaacttctg ctggaacatc ttcttcagga gtatccaata gaaaaaggaa aagaaaagtg
      2230       2240       2250       2260       2270       2280
tttagtccta ttcgatctga accaagatct ccttctcact ccatgaggac aagaagtgga
      2290       2300       2310       2320       2330       2340
aggcttagta gttctgagct ctcacctctc acccccccgt cttctgtctc ttcctcgtta
      2350       2360       2370       2380       2390       2400
agcatttctg ttagtcctct tgccactagt gccttaaacc caacttttac ttttccttct
      2410       2420       2430       2440       2450       2460
cattccctga ctcagtctgg ggaatctgca gagaaaaatc agagaccaag gaagcagact
      2470       2480       2490       2500       2510       2520
agtgctccgg cagagccatt ttcatcaagt agtcctactc ctctcttccc ttggtttacc
      2530       2540       2550       2560       2570       2580
ccaggctctc agactgaaag agggagaaat aaagacaagg cccccgagga gctgtccaaa
      2590       2600       2610       2620       2630       2640
gatcgagatg ctgacaagag cgtggagaag gacaagagta gagagagaga ccgggagaga
      2650       2660       2670       2680       2690       2700
gaaaaggaga ataagcggga gtcaaggaaa gagaaaagga aaaagggatc agaaattcag
      2710       2720       2730       2740       2750       2760
agtagttctg ctttgtatcc tgtgggtagg gtttccaaag agaaggttgt tggtgaagat
      2770       2780       2790       2800       2810       2820
gttgccactt catcttctgc caaaaaagca acagggcgga agaagtcttc atcacatgat
      2830       2840       2850       2860       2870       2880
tctgggactg atattacttc tgtgactctt ggggatacaa cagctgtcaa aaccaaaata
      2890       2900       2910       2920       2930       2940
cttataaaga aagggagagg aaatctggaa aaaaccaact tggacctcgg cccaactgcc
      2950       2960       2970       2980       2990       3000
ccatccctgg agaaggagaa aaccctctgc ctttccactc cttcatctag cactgttaaa
      3010       3020       3030       3040       3050       3060
cattccactt cctccatagg ctccatgttg gctcaggcag acaagcttcc aatgactgac
      3070       3080       3090       3100       3110       3120
aagagggttg ccagcctcct aaaaaaggcc aaagctcagc tctgcaagat tgagaagagt
      3130       3140       3150       3160       3170       3180
aagagtctta aacaaaccga ccagcccaaa gcacagggtc aagaaagtga ctcatcagag
      3190       3200       3210       3220       3230       3240
acctctgtgc gaggaccccg gattaaacat gtctgcagaa gagcagctgt tgcccttggc
      3250       3260       3270       3280       3290       3300
cgaaaacgag ctgtgtttcc tgatgacatg cccaccctga gtgccttacc atgggaagaa
      3310       3320       3330       3340       3350       3360
cgagaaaaga ttttgtcttc catggggaat gatgacaagt catcaattgc tggctcagaa
      3370       3380       3390       3400       3410       3420
gatgctgaac ctcttgctcc acccatcaaa ccaattaaac ctgtcactag aaacaaggca
      3430       3440       3450       3460       3470       3480
ccccaggaac ctccagtaaa gaaaggacgt cgatcgaggc ggtgtgggca gtgtcccggc
      3490       3500       3510       3520       3530       3540
tgccaggtgc ctgaggactg tggtgtttgt actaattgct tagataagcc caagtttggt
      3550       3560       3570       3580       3590       3600
ggtcgcaata taaagaagca gtgctgcaag atgagaaaat gtcagaatct acaatggatg
      3610       3620       3630       3640       3650       3660
ccttccaaag cctacctgca gaagcaagct aaagctgtga aaaagaaaga gaaaaagtct
      3670       3680       3690       3700       3710       3720
aagaccagtg aaaagaaaga cagcaaagag agcagtgttg tgaagaacgt ggtggactct
      3730       3740       3750       3760       3770       3780
agtcagaaac ctaccccatc agcaagagag gatcctgccc caaagaaaag cagtagtgag
      3790       3800       3810       3820       3830       3840
cctcctccac gaaagcccgt cgaggaaaag agtgaagaag ggaatgtctc ggcccctggg
      3850       3860       3870       3880       3890       3900
cctgaatcca aacaggccac cactccagct tccaggaagt caagcaagca ggtctcccag
      3910       3920       3930       3940       3950       3960
ccagcactgg tcatcccgcc tcagccacct actacaggac cgccaagaaa agaagttccc
      3970       3980       3990       4000       4010       4020
aaaaccactc ctagtgagcc caagaaaaag cagcctccac caccagaatc aggtccagag
      4030       4040       4050       4060       4070       4080
cagagcaaac agaaaaaagt ggctccccgc ccaagtatcc ctgtaaaaca aaaaccaaaa
      4090       4100       4110       4120       4130       4140
gaaaaggaaa aaccacctcc ggtcaataag caggagaatg caggcacttt gaacatcctc
      4150       4160       4170       4180       4190       4200
agcactctct ccaatggcaa tagttctaag caaaaaattc cagcagatgg agtccacagg
      4210       4220       4230       4240       4250       4260
atcagagtgg actttaagga ggattgtgaa gcagaaaatg tgtgggagat gggaggctta
      4270       4280       4290       4300       4310       4320
ggaatcttga cttctgttcc tataacaccc agggtggttt gctttctctg tgccagtagt
      4330       4340       4350       4360       4370       4380
gggcatgtag agtttgtgta ttgccaagtc tgttgtgagc ccttccacaa gttttgttta
      4390       4400       4410       4420       4430       4440
gaggagaacg agcgccctct ggaggaccag ctggaaaatt ggtgttgtcg tcgttgcaaa
      4450       4460       4470       4480       4490       4500
ttctgtcacg tttgtggaag gcaacatcag gctacaaagc agctgctgga gtgtaataag
      4510       4520       4530       4540       4550       4560
tgccgaaaca gctatcaccc tgagtgcctg ggaccaaact accccaccaa acccacaaag
      4570       4580       4590       4600       4610       4620
aagaagaaag tctggatctg taccaagtgt gttcgctgta agagctgtgg atccacaact
      4630       4640       4650       4660       4670       4680
ccaggcaaag ggtgggatgc acagtggtct catgatttct cactgtgtca tgattgcgcc
      4690       4700       4710       4720       4730       4740
aagctctttg ctaaaggaaa cttctgccct ctctgtgaca aatgttatga tgatgatgac
      4750       4760       4770       4780       4790       4800
tatgagagta agatgatgca atgtggaaag tgtgatcgct gggtccattc caaatgtgag
      4810       4820       4830       4840       4850       4860
aatctttcag gtacagaaga tgagatgtat gagattctat ctaatctgcc agaaagtgtg
      4870       4880       4890       4900       4910       4920
gcctacactt gtgtgaactg tactgagcgg caccctgcag agtggcgact ggcccttgaa
      4930       4940       4950       4960       4970       4980
aaagagctgc agatttctct gaagcaagtt ctgacagctt tgttgaattc tcggactacc
      4990       5000       5010       5020       5030       5040
agccatttgc tacgctaccg gcaggctgcc aagcctccag acttaaatcc cgagacagag
      5050       5060       5070       5080       5090       5100
gagagtatac cttcccgcag ctcccccgaa ggacctgatc caccagttct tactgaggtc
      5110       5120       5130       5140       5150       5160
agcaaacagg atgatcagca gcctttagat ctagaaggag tcaagaggaa gatggaccaa
      5170       5180       5190       5200       5210       5220
gggaattaca catctgtgtt ggagttcagt gatgatattg tgaagatcat tcaagcagcc
      5230       5240       5250       5260       5270       5280
attaattcag atggaggaca gccagaaatt aaaaaagcca acagcatggt caagtccttc
      5290       5300       5310       5320       5330       5340
ttcattcggc aaatggaacg tgtttttcca tggttcagtg tcaaaaagtc caggttttgg
      5350       5360       5370       5380       5390       5400
gagccaaata aagtatcaag caacagtggg atgttaccaa acgcagtgct tccaccttca
      5410       5420       5430       5440       5450       5460
cttgaccata attatgctca gtggcaggag cgagaggaaa acagccacac tgagcagcct
      5470       5480       5490       5500       5510       5520
cctttaatga agaaaatcat tccagctccc aaacccaaag gtcctggaga accagactca
      5530       5540       5550       5560       5570       5580
ccaactcctc tgcatcctcc tacaccacca attttgagta ctgataggag tcgagaagac
      5590       5600       5610       5620       5630       5640
agtccagagc tgaacccacc cccaggcata gaagacaata gacagtgtgc gttatgtttg
      5650       5660       5670       5680       5690       5700
acttatggtg atgacagtgc taatgatgct ggtcgtttac tatatattgg ccaaaatgag
      5710       5720       5730       5740       5750       5760
tggacacatg taaattgtgc tttgtggtca gcggaagtgt ttgaagatga tgacggatca
      5770       5780       5790       5800       5810       5820
ctaaagaatg tgcatatggc tgtgatcagg ggcaagcagc tgagatgtga attctgccaa
      5830       5840       5850       5860       5870       5880
aagccaggag ccaccgtggg ttgctgtctc acatcctgca ccagcaacta tcacttcatg
      5890       5900       5910       5920       5930       5940
tgttcccgag ccaagaactg tgtctttctg gatgataaaa aagtatattg ccaacgacat
      5950       5960       5970       5980       5990       6000
cgggatttga tcaaaggcga agtggttcct gagaatggat ttgaagtttt cagaagagtg
      6010       6020       6030       6040       6050       6060
tttgtggact ttgaaggaat cagcttgaga aggaagtttc tcaatggctt ggaaccagaa
      6070       6080       6090       6100       6110       6120
aatatccaca tgatgattgg gtctatgaca atcgactgct taggaattct aaatgatctc
      6130       6140       6150       6160       6170       6180
tccgactgtg aagataagct ctttcctatt ggatatcagt gttccagggt atactggagc
      6190       6200       6210       6220       6230       6240
accacagatg ctcgcaagcg ctgtgtatat acatgcaaga tagtggagtg ccgtcctcca
      6250       6260       6270       6280       6290       6300
gtcgtagagc cggatatcaa cagcactgtt gaacatgatg aaaacaggac cattgcccat
      6310       6320       6330       6340       6350       6360
agtccaacat cttttacaga aagttcatca aaagagagtc aaaacacagc tgaaattata
      6370       6380       6390       6400       6410       6420
agtcctccat caccagaccg acctcctcat tcacaaacct ctggctcctg ttattatcat
      6430       6440       6450       6460       6470       6480
gtcatctcaa aggtccccag gattcgaaca cccagttatt ctccaacaca gagatcccct
      6490       6500       6510       6520       6530       6540
ggctgtcgac cgttgccttc tgcaggaagt cctaccccaa ccactcatga aatagtcaca
      6550       6560       6570       6580       6590       6600
gtaggtgatc ctttactctc ctctggactt cgaagcattg gctccaggcg tcacagtacc
      6610       6620       6630       6640       6650       6660
tcttccttat caccccagcg gtccaaactc cggataatgt ctccaatgag aactgggaat
      6670       6680       6690       6700       6710       6720
acttactcta ggaataatgt ttcctcagtc tccaccaccg ggaccgctac tgatcttgaa
      6730       6740       6750       6760       6770       6780
tcaagtgcca aagtagttga tcatgtctta gggccactga attcaagtac tagtttaggg
      6790       6800       6810       6820       6830       6840
caaaacactt ccacctcttc aaatttgcaa aggacagtgg ttactgtagg caataaaaac
      6850       6860       6870       6880       6890       6900
agtcacttgg atggatcttc atcttcagaa atgaagcagt ccagtgcttc agacttggtg
      6910       6920       6930       6940       6950       6960
tccaagagct cctctttaaa gggagagaag accaaagtgc tgagttccaa gagctcagag
      6970       6980       6990       7000       7010       7020
ggatctgcac ataatgtggc ttaccctgga attcctaaac tggccccaca ggttcataac
      7030       7040       7050       7060       7070       7080
acaacatcta gagaactgaa tgttagtaaa atcggctcct ttgctgaacc ctcttcagtg
      7090       7100       7110       7120       7130       7140
tcgttttctt ctaaagaggc cctctccttc ccacacctcc atttgagagg gcaaaggaat
      7150       7160       7170       7180       7190       7200
gatcgagacc aacacacaga ttctacccaa tcagcaaact cctctccaga tgaagatact
      7210       7220       7230       7240       7250       7260
gaagtcaaaa ccttgaagct atctggaatg agcaacagat catccattat caacgaacat
      7270       7280       7290       7300       7310       7320
atgggatcta gttccagaga taggagacag aaagggaaaa aatcctgtaa agaaactttc
      7330       7340       7350       7360       7370       7380
aaagaaaagc attccagtaa atcttttttg gaacctggtc aggtgacaac tggtgaggaa
      7390       7400       7410       7420       7430       7440
ggaaacttga agccagagtt tatggatgag gttttgactc ctgagtatat gggccaacga
      7450       7460       7470       7480       7490       7500
ccatgtaaca atgtttcttc tgataagatt ggtgataaag gcctttctat gccaggagtc
      7510       7520       7530       7540       7550       7560
cccaaagctc cacccatgca agtagaagga tctgccaagg aattacaggc accacggaaa
      7570       7580       7590       7600       7610       7620
cgcacagtca aagtgacact gacacctcta aaaatggaaa atgagagtca atccaaaaat
      7630       7640       7650       7660       7670       7680
gccctgaaag aaagtagtcc tgcttcccct ttgcaaatag agtcaacatc tcccacagaa
      7690       7700       7710       7720       7730       7740
ccaatttcag cctctgaaaa tccaggagat ggtccagtgg cccaaccaag ccccaataat
      7750       7760       7770       7780       7790       7800
acctcatgcc aggattctca aagtaacaac tatcagaatc ttccagtaca ggacagaaac
      7810       7820       7830       7840       7850       7860
ctaatgcttc cagatggccc caaacctcag gaggatggct cttttaaaag gaggtatccc
      7870       7880       7890       7900       7910       7920
cgtcgcagtg cccgtgcacg ttctaacatg ttttttgggc ttaccccact ctatggagta
      7930       7940       7950       7960       7970       7980
agatcctatg gtgaagaaga cattccattc tacagcagct caactgggaa gaagcgaggc
      7990       8000       8010       8020       8030       8040
aagagatcag ctgaaggaca ggtggatggg gccgatgact taagcacttc agatgaagac
      8050       8060       8070       8080       8090       8100
gacttatact attacaactt cactagaaca gtgatttctt caggtggaga ggaacgactg
      8110       8120       8130       8140       8150       8160
gcatcccata atttatttcg ggaggaggaa cagtgtgatc ttccaaaaat ctcacagttg
      8170       8180       8190       8200       8210       8220
gatggtgttg atgatgggac agagagtgat actagtgtca cagccacaac aaggaaaagc
      8230       8240       8250       8260       8270       8280
agccagattc caaaaagaaa tggtaaagaa aatggaacag agaacttaaa gattgataga
      8290       8300       8310       8320       8330       8340
cctgaagatg ctggggagaa agaacatgtc actaagagtt ctgttggcca caaaaatgag
      8350       8360       8370       8380       8390       8400
ccaaagatgg ataactgcca ttctgtaagc agagttaaaa cacagggaca agattccttg
      8410       8420       8430       8440       8450       8460
gaagctcagc tcagctcatt ggagtcaagc cgcagagtcc acacaagtac cccctccgac
      8470       8480       8490       8500       8510       8520
aaaaatttac tggacaccta taatactgag ctcctgaaat cagattcaga caataacaac
      8530       8540       8550       8560       8570       8580
agtgatgact gtgggaatat cctgccttca gacattatgg actttgtact aaagaatact
      8590       8600       8610       8620       8630       8640
ccatccatgc aggctttggg tgagagccca gagtcatctt catcagaact cctgaatctt
      8650       8660       8670       8680       8690       8700
ggtgaaggat tgggtcttga cagtaatcgt gaaaaagaca tgggtctttt tgaagtattt
      8710       8720       8730       8740       8750       8760
tctcagcagc tgcctacaac agaacctgtg gatagtagtg tctcttcctc tatctcagca
      8770       8780       8790       8800       8810       8820
gaggaacagt ttgagttgcc tctagagcta ccatctgatc tgtctgtctt gaccacccgg
      8830       8840       8850       8860       8870       8880
agtcccactg tccccagcca gaatcccagt agactagctg ttatctcaga ctcaggggag
      8890       8900       8910       8920       8930       8940
aagagagtaa ccatcacaga aaaatctgta gcctcctctg aaagtgaccc agcactgctg
      8950       8960       8970       8980       8990       9000
agcccaggag tagatccaac tcctgaaggc cacatgactc ctgatcattt tatccaagga
      9010       9020       9030       9040       9050       9060
cacatggatg cagaccacat ctctagccct ccttgtggtt cagtagagca aggtcatggc
      9070       9080       9090       9100       9110       9120
aacaatcagg atttaactag gaacagtagc acccctggcc ttcaggtacc tgtttcccca
      9130       9140       9150       9160       9170       9180
actgttccca tccagaacca gaagtatgtg cccaattcta ctgatagtcc tggcccgtct
      9190       9200       9210       9220       9230       9240
cagatttcca atgcagctgt ccagaccact ccaccccacc tgaagccagc cactgagaaa
      9250       9260       9270       9280       9290       9300
ctcatagttg ttaaccagaa catgcagcca ctttatgttc tccaaactct tccaaatgga
      9310       9320       9330       9340       9350       9360
gtgacccaaa aaatccaatt gacctcttct gttagttcta cacccagtgt gatggagaca
      9370       9380       9390       9400       9410       9420
aatacttcag tattgggacc catgggaggt ggtctcaccc ttaccacagg actaaatcca
      9430       9440       9450       9460       9470       9480
agcttgccaa cttctcaatc tttgttccct tctgctagca aaggattgct acccatgtct
      9490       9500       9510       9520       9530       9540
catcaccagc acttacattc cttccctgca gctactcaaa gtagtttccc accaaacatc
      9550       9560       9570       9580       9590       9600
agcaatcctc cttcaggcct gcttattggg gttcagcctc ctccggatcc ccaacttttg
      9610       9620       9630       9640       9650       9660
gtttcagaat ccagccagag gacagacctc agtaccacag tagccactcc atcctctgga
      9670       9680       9690       9700       9710       9720
ctcaagaaaa gacccatatc tcgtctacag acccgaaaga ataaaaaact tgctccctct
      9730       9740       9750       9760       9770       9780
agtacccctt caaacattgc cccttctgat gtggtttcta atatgacatt gattaacttc
      9790       9800       9810       9820       9830       9840
acaccctccc agcttcctaa tcatccaagt ctgttagatt tggggtcact taatacttca
      9850       9860       9870       9880       9890       9900
tctcaccgaa ctgtccccaa catcataaaa agatctaaat ctagcatcat gtattttgaa
      9910       9920       9930       9940       9950       9960
ccggcacccc tgttaccaca gagtgtggga ggaactgctg ccacagcggc aggcacatca
      9970       9980       9990      10000      10010      10020
acaataagcc aggatactag ccacctcaca tcagggtctg tgtctggctt ggcatccagt
     10030      10040      10050      10060      10070      10080
tcctctgtct tgaatgttgt atccatgcaa actaccacaa cccctacaag tagtgcgtca
     10090      10100      10110      10120      10130      10140
gttccaggac acgtcacctt aaccaaccca aggttgcttg gtaccccaga tattggctca
     10150      10160      10170      10180      10190      10200
ataagcaatc ttttaatcaa agctagccag cagagcctgg ggattcagga ccagcctgtg
     10210      10220      10230      10240      10250      10260
gctttaccgc caagttcagg aatgtttcca caactgggga catcacagac cccctctact
     10270      10280      10290      10300      10310      10320
gctgcaataa cagcggcatc tagcatctgt gtgctcccct ccactcagac tacgggcata
     10330      10340      10350      10360      10370      10380
acagccgctt caccttctgg ggaagcagac gaacactatc agcttcagca tgtgaaccag
     10390      10400      10410      10420      10430      10440
ctccttgcca gcaaaactgg gattcattct tcccagcgtg atcttgattc tgcttcaggg
     10450      10460      10470      10480      10490      10500
ccccaggtat ccaactttac ccagacggta gacgctccta atagcatggg actggagcag
     10510      10520      10530      10540      10550      10560
aacaaggctt tatcctcagc tgtgcaagcc agccccacct ctcctggggg ttctccatcc
     10570      10580      10590      10600      10610      10620
tctccatctt ctggacagcg gtcagcaagc ccttcagtgc cgggtcccac taaacccaaa
     10630      10640      10650      10660      10670      10680
ccaaaaacca aacggtttca gctgcctcta gacaaaggga atggcaagaa gcacaaagtt
     10690      10700      10710      10720      10730      10740
tcccatttgc ggaccagttc ttctgaagca cacattccag accaagaaac gacatccctg
     10750      10760      10770      10780      10790      10800
acctcaggca cagggactcc aggagcagag gctgagcagc aggatacagc tagcgtggag
     10810      10820      10830      10840      10850      10860
cagtcctccc agaaggagtg tgggcaacct gcagggcaag tcgctgttct tccggaagtt
     10870      10880      10890      10900      10910      10920
caggtgaccc aaaatccagc aaatgaacaa gaaagtgcag aacctaaaac agtggaagaa
     10930      10940      10950      10960      10970      10980
gaggaaagta atttcagctc cccactgatg ctttggcttc agcaagaaca aaagcggaag
     10990      11000      11010      11020      11030      11040
gaaagcatta ctgagaaaaa acccaagaaa ggacttgttt ttgaaatttc cagtgatgat
     11050      11060      11070      11080      11090      11100
ggctttcaga tctgtgcaga aagtattgaa gatgcctgga agtcattgac agataaagtc
     11110      11120      11130      11140      11150      11160
caggaagctc gatcaaatgc ccgcctaaag cagctctcat ttgcaggtgt taacggtttg
     11170      11180      11190      11200      11210      11220
aggatgctgg ggattctcca tgatgcagtt gtgttcctca ttgagcagct gtctggtgcc
     11230      11240      11250      11260      11270      11280
aagcactgtc gaaattacaa attccgtttc cacaagccag aggaggccaa tgaacccccc
     11290      11300      11310      11320      11330      11340
ttgaaccctc acggctcagc cagggctgaa gtccacctca ggaagtcagc atttgacatg
     11350      11360      11370      11380      11390      11400
tttaacttcc tggcttctaa acatcgtcag cctcctgaat acaaccccaa tgatgaagaa
     11410      11420      11430      11440      11450      11460
gaggaggagg tacagctgaa gtcagctcgg agggcaacta gcatggatct gccaatgccc
     11470      11480      11490      11500      11510      11520
atgcgcttcc ggcacttaaa aaagacttct aaggaggcag ttggtgtcta caggtctccc
     11530      11540      11550      11560      11570      11580
atccatggcc ggggtctttt ctgtaagaga aacattgatg caggtgagat ggtgattgag
     11590      11600      11610      11620      11630      11640
tatgccggca acgtcatccg ctccatccag actgacaagc gggaaaagta ttacgacagc
     11650      11660      11670      11680      11690      11700
aagggcattg gttgctatat gttccgaatt gatgactcag aggtagtgga tgccaccatg
     11710      11720      11730      11740      11750      11760
catggaaatg ctgcacgctt catcaatcac tcgtgtgagc ctaactgcta ttctcgggtc
     11770      11780      11790      11800      11810      11820
atcaatattg atgggcagaa gcacattgtc atctttgcca tgcgtaagat ctaccgagga
     11830      11840      11850      11860      11870      11880
gaggaactca cttacgacta taagttcccc attgaggatg ccagcaacaa gctgccctgc
     11890      11900      11910
aactgtggcg ccaagaaatg ccggaagttc ctaaactaa  

Last modification date: Nov. 10, 2011