CHD8_RAT
ID CHD8_RAT Reviewed; 2581 AA.
AC Q9JIX5;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Chromodomain-helicase-DNA-binding protein 8 {ECO:0000255|HAMAP-Rule:MF_03071};
DE Short=CHD-8 {ECO:0000255|HAMAP-Rule:MF_03071};
DE EC=3.6.4.12 {ECO:0000255|HAMAP-Rule:MF_03071};
DE AltName: Full=ATP-dependent helicase CHD8 {ECO:0000255|HAMAP-Rule:MF_03071};
DE AltName: Full=Axis duplication inhibitor;
DE Short=Duplin;
GN Name=Chd8 {ECO:0000255|HAMAP-Rule:MF_03071};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND
RP INTERACTION WITH CTNNB1.
RX PubMed=10921920; DOI=10.1074/jbc.m004089200;
RA Sakamoto I., Kishida S., Fukui A., Kishida M., Yamamoto H., Hino S.,
RA Michiue T., Takada S., Asashima M., Kikuchi A.;
RT "A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf
RT activation and axis formation.";
RL J. Biol. Chem. 275:32871-32878(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11744694; DOI=10.1074/jbc.m108433200;
RA Kobayashi M., Kishida S., Fukui A., Michiue T., Miyamoto Y., Okamoto T.,
RA Yoneda Y., Asashima M., Kikuchi A.;
RT "Nuclear localization of Duplin, a beta-catenin-binding protein, is
RT essential for its inhibitory activity on the Wnt signaling pathway.";
RL J. Biol. Chem. 277:5816-5822(2002).
RN [4]
RP FUNCTION, SUMOYLATION AT LYS-609, INTERACTION WITH PIAS3, AND MUTAGENESIS
RP OF LYS-457; LYS-512; LYS-609 AND LYS-654.
RX PubMed=16452319; DOI=10.1093/jb/mvj033;
RA Yamashina K., Yamamoto H., Chayama K., Nakajima K., Kikuchi A.;
RT "Suppression of STAT3 activity by Duplin, which is a negative regulator of
RT the Wnt signal.";
RL J. Biochem. 139:305-314(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1420; SER-1424; SER-1995;
RP SER-1997; SER-2068; SER-2070 AND SER-2223, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: DNA helicase that acts as a chromatin remodeling factor and
CC regulates transcription. Acts as a transcription repressor by
CC remodeling chromatin structure and recruiting histone H1 to target
CC genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1
CC and preventing p53/TP53 transactivation activity. Acts as a negative
CC regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1)
CC activity. Negatively regulates CTNNB1-targeted gene expression by being
CC recruited specifically to the promoter regions of several CTNNB1
CC responsive genes. Involved in both enhancer blocking and epigenetic
CC remodeling at chromatin boundary via its interaction with CTCF. Acts as
CC a suppressor of STAT3 activity by suppressing the LIF-induced STAT3
CC transcriptional activity. Also acts as a transcription activator via
CC its interaction with ZNF143 by participating in efficient U6 RNA
CC polymerase III transcription. {ECO:0000255|HAMAP-Rule:MF_03071,
CC ECO:0000269|PubMed:11744694, ECO:0000269|PubMed:16452319}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03071};
CC -!- SUBUNIT: Interacts with p53/TP53, histone H1 and CTCF. Component of
CC some MLL1/MLL complex, at least composed of the core components
CC KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the
CC facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L,
CC MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A,
CC RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts
CC with CHD7. Interacts with FAM124B (By similarity). Interacts with
CC CTNNB1 (PubMed:10921920). Interacts with PIAS3 (PubMed:16452319).
CC {ECO:0000255|HAMAP-Rule:MF_03071, ECO:0000269|PubMed:10921920,
CC ECO:0000269|PubMed:16452319}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03071,
CC ECO:0000269|PubMed:10921920, ECO:0000269|PubMed:11744694}.
CC Note=Localizes to the promoter regions of several CTNNB1-responsive
CC genes. Also present at known CTCF target sites. {ECO:0000255|HAMAP-
CC Rule:MF_03071}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JIX5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JIX5-2; Sequence=VSP_036678, VSP_036679;
CC -!- PTM: Sumoylated. {ECO:0000255|HAMAP-Rule:MF_03071,
CC ECO:0000269|PubMed:16452319}.
CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. CHD8 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03071}.
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DR EMBL; AF169825; AAF89678.1; -; mRNA.
DR EMBL; CH474040; EDL88472.1; -; Genomic_DNA.
DR RefSeq; NP_001334590.1; NM_001347661.1. [Q9JIX5-1]
DR RefSeq; XP_006251973.1; XM_006251911.3. [Q9JIX5-1]
DR AlphaFoldDB; Q9JIX5; -.
DR SMR; Q9JIX5; -.
DR STRING; 10116.ENSRNOP00000022593; -.
DR iPTMnet; Q9JIX5; -.
DR PhosphoSitePlus; Q9JIX5; -.
DR PaxDb; Q9JIX5; -.
DR PRIDE; Q9JIX5; -.
DR Ensembl; ENSRNOT00000096813; ENSRNOP00000096922; ENSRNOG00000025011. [Q9JIX5-2]
DR GeneID; 65027; -.
DR KEGG; rno:65027; -.
DR UCSC; RGD:620696; rat. [Q9JIX5-1]
DR CTD; 57680; -.
DR RGD; 620696; Chd8.
DR VEuPathDB; HostDB:ENSRNOG00000025011; -.
DR eggNOG; KOG0384; Eukaryota.
DR GeneTree; ENSGT00940000153649; -.
DR HOGENOM; CLU_000315_5_2_1; -.
DR InParanoid; Q9JIX5; -.
DR OMA; IFSDPQF; -.
DR OrthoDB; 7181at2759; -.
DR PhylomeDB; Q9JIX5; -.
DR TreeFam; TF313572; -.
DR Reactome; R-RNO-3769402; Deactivation of the beta-catenin transactivating complex.
DR PRO; PR:Q9JIX5; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Proteomes; UP000234681; Chromosome 15.
DR Bgee; ENSRNOG00000025011; Expressed in spleen and 19 other tissues.
DR Genevisible; Q9JIX5; RN.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0071339; C:MLL1 complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0070016; F:armadillo repeat domain binding; IPI:RGD.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140658; F:ATP-dependent chromatin remodeler activity; ISS:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0002039; F:p53 binding; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0048565; P:digestive tract development; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0060134; P:prepulse inhibition; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0035176; P:social behavior; ISO:RGD.
DR GO; GO:0001964; P:startle response; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.40.5.120; -; 1.
DR Gene3D; 3.40.50.10810; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_03071; CHD8; 1.
DR InterPro; IPR006576; BRK_domain.
DR InterPro; IPR037259; BRK_sf.
DR InterPro; IPR034724; CHD8.
DR InterPro; IPR016197; Chromo-like_dom_sf.
DR InterPro; IPR000953; Chromo/chromo_shadow_dom.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR038718; SNF2-like_sf.
DR InterPro; IPR000330; SNF2_N.
DR Pfam; PF07533; BRK; 1.
DR Pfam; PF00385; Chromo; 2.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF00176; SNF2-rel_dom; 1.
DR SMART; SM00592; BRK; 2.
DR SMART; SM00298; CHROMO; 2.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF160481; SSF160481; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF54160; SSF54160; 2.
DR PROSITE; PS50013; CHROMO_2; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; ATP-binding; Chromatin regulator;
KW DNA-binding; Helicase; Hydrolase; Isopeptide bond; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation;
KW Wnt signaling pathway.
FT CHAIN 1..2581
FT /note="Chromodomain-helicase-DNA-binding protein 8"
FT /id="PRO_0000367311"
FT DOMAIN 642..709
FT /note="Chromo 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT DOMAIN 724..790
FT /note="Chromo 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT DOMAIN 823..997
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT DOMAIN 1137..1288
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT REGION 22..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 596..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1692..1713
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1789..2302
FT /note="Interaction with FAM124B"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT REGION 1988..2016
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2047..2118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2179..2221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2484..2581
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 948..951
FT /note="DEAH box"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT COMPBIAS 43..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 357..371
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..521
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 560..584
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1692..1710
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2074..2093
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2094..2116
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2491..2511
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2515..2531
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2537..2553
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 836..843
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 1420
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1976
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 1978
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 1993
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 1995
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1997
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2008
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 2068
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2070
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2182
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 2200
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 2202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q09XV5"
FT MOD_RES 2204
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q09XV5"
FT MOD_RES 2211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT MOD_RES 2215
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q09XV5"
FT MOD_RES 2223
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2519
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT CROSSLNK 609
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03071"
FT CROSSLNK 2025
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT CROSSLNK 2256
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9HCK8"
FT VAR_SEQ 743..749
FT /note="PVIYYLV -> VSWAQRV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10921920"
FT /id="VSP_036678"
FT VAR_SEQ 750..2581
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10921920"
FT /id="VSP_036679"
FT MUTAGEN 457
FT /note="K->R: Does not affect sumoylation status."
FT /evidence="ECO:0000269|PubMed:16452319"
FT MUTAGEN 512
FT /note="K->R: Does not affect sumoylation status."
FT /evidence="ECO:0000269|PubMed:16452319"
FT MUTAGEN 609
FT /note="K->R: Induces a decrease in sumoylation status."
FT /evidence="ECO:0000269|PubMed:16452319"
FT MUTAGEN 654
FT /note="K->R: Does not affect sumoylation status."
FT /evidence="ECO:0000269|PubMed:16452319"
SQ SEQUENCE 2581 AA; 290692 MW; 4E2BBE55D7A2CD3D CRC64;
MADPIMDLFD DPNLFGLDSL TDDSFNQVTQ DPIEEALGLP SSLDSLDQMN QDGGSGDVGN
SSASDLVPPP EETASTELPK ESTAPAPESL TLHDYTTQPT SQEQPAQPVL QTSTPTSGLL
QVSKSQEILS QGNPFMGVSA TAVSPSNTGG QPSQSAPKIV ILKAPPNSSV TGAHVAQIQA
QGITSTAQPL VAGTANGGKV TFTKVLTGTP LRPGVSIVSG NTVLATKVPG NQAAVQRIVQ
PSRPVKQLVL QPVKGSAPAG NPGATGPPLK PAVTLTSTPA QGESKRITLV LQQPQSGGPQ
GHRHVVLGSL PGKIVLQGNQ LAALTQAKSA QGQPAKVVTI QLQVQQPQQK IQIVPQPPSS
QPQPQPPPSA QPLTLSSVQQ AQIMGPGQNP GQRLSVPLKM VLQPQAGSSQ GASSGLSVVK
VLSASEVAAL SSPASCAPHT AGKTGMEENR RLEHQKKQEK ANRIVAEAIA RARARGEQNI
PRVLNEDELP SVRPEEEGEK KRRKKSSGER LKEEKPKKSK TAAASKTKGK SKLNTITPVV
GKKRKRNTSS DNSDVEVMPA QSPREDEESS IQKRRSNRQV KRKKYTEDLD IKITDDEEEE
EVDVTGPIKP EPILPEPVPE PDGETLPSMQ FFVENPSEED AAIVDKVLSM RVVKKELPSG
QYTEAEEFFV KYKNYSYLHC EWATISQLEK DKRIHQKLKR FKTKMAQMRH FFHEDEEPFN
PDYVEVDRIL DESHSVDKDN GEPVIYYLVK WCSLPYEDST WELKEDVDEG KIREFKRIQS
RHPELKRVNR PQANAWKKLE LSHEYKNRNQ LREYQLEGVN WLLFNWYNRQ NCILADEMGL
GKTIQSIAFL QEVYNVGIHG PFLVIAPLST ITNWEREFNT WTEMNTIVYH GSLASRQMIQ
QYEMYCKDSR GRLIPGAYKF DALITTFEMI LSDCPELREI EWRCVIIDEA HRLKNRNCKL
LDSLKHMDLE HKVLLTGTPL QNTVEELFSL LHFLEPSQFP SESEFLKDFG DLKTEEQVQK
LQAILKPMML RRLKEDVEKN LAPKQETIIE VELTNIQKKY YRAILEKNFS FLSKGAGHTN
MPNLLNTMME LRKCCNHPYL INGAEEKILM EFREACHIIP QDFHLQAMVR SAGKLVLIDK
LLPKLKAGGH KVLIFSQMVR CLDILEDYLI QRRYLYERID GRVRGNLRQA AIDRFSKPDS
DRFVFLLCTR AGGLGINLTA ADTCIIFDSD WNPQNDLQAQ ARCHRIGQSK AVKVYRLITR
NSYEREMFDK ASLKLGLDKA VLQSMSGRDG NITGIQQFSK KEIEDLLRKG AYAAIMEEDD
EGSKFCEEDI DQILLRRTTT ITIESEGKGS TFAKASFVAS ENRTDISLDD PNFWQKWAKK
ADLDMDLLNS KNNLVIDTPR VRKQTRHFST LKDDDLVEFS DLESEDDERP RSRRHDRHHT
YGRTDCFRVE KHLLVYGWGR WRDILSHGRF KRRMTERDVE TICRAILVYC LLHYRGDENI
KSFIWDLISP AENGKTKELQ NHSGLSIPVP RGRKGKKVKS QSTFDIHKAD WIRKYNPDTL
FQDESYKKHL KHQCNKVLLR VRMLYYLRQE VIGDQAEKVL GGAIASEIDI WFPVVDQLEV
PTTWWDSEAD KSLLIGVFKH GYEKYNTMRA DPALCFLEKA GRPDDKAIAA EHRVLDNFSD
LVEGIDFDKD CEDPEYKPLQ GPPKDPDDEG DPLMMMDEEI SVIDGDEAPV TQQPGHLFWP
PGSALTARLR RLVTAYQRSY KREQMKIEAA ERGDRRRRRC EAAFKLKEIA RREKQQRWTR
REQTDFYRVV STFGVEYDPD NMQFHWDRFR TFARLDKKTD ESLTKYFHGF VAMCRQVCRL
PPAAGDEPPD PNLFIEPITE ERASRTLYRI ELLRRLREQV LCHPLLEDRL ALCQPPGLEL
PKWWEPVRHD GELLRGAARH GVSQTDCNIM QDPDFSFLAA RMNYMQNHQA GASAASLSRC
STPLLHQQCT SRTASPSPLR PDVPAEKSPE ENAVQVPSLD SLTLKLEDEV VARSRLTPQD
YEIRVASSDT APLSRSVPPV KLEDDDDSDS ELDLSKLSPS SSSSSSSSSS SSSSDESEDE
KEEKLTADRS RPKLYDEESL LSLTMSQDGF PNEDGEQMTP ELLLLQERQR ASEWPKDRVL
INRIDLVCQA VLSGKWPSNR RSQEMTTGGI LGPGNHLLDS PSLTPGEYGD SPVPTPRSSS
AASMVEEEAS AVTTAAAQFT KLRRGMDEKE FTVQIKDEEG LKLTFQKHRL MANGVMGDGH
PLFHKKKGNR KKLVELEVEC MEEPNHLDVD LETRIPVINK VDGTLLVGDE APRRAELDMW
LQGHPEFAVD PRFLAYMEER RKQKWQRCKK NNKTELNCLG MEPVQPANSR NGKKGHYAET
AFNRVLPGPI APENSKKRVR RTRPDLSKMM ALMQGGSTGS LSLHNTFQHS SSNLQSVSSL
GHSSATSASL PFMPFVMGGA AAPPHVDSST MLHHHHHHPH PHHHHHHHPG LRTTGYPSSP
ATTTSGTALR LPTLQHEDDD EEEDEDDDDL SQGYDSSERD FSLIDDPMMP ANSDSSDDAD
D
