ROS1_ARATH
ID ROS1_ARATH Reviewed; 1393 AA.
AC Q9SJQ6; Q7Y1X6;
DT 16-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=DNA glycosylase/AP lyase ROS1 {ECO:0000305};
DE EC=4.2.99.18 {ECO:0000269|PubMed:25240767};
DE AltName: Full=DEMETER-like protein 1 {ECO:0000303|PubMed:12150995};
DE AltName: Full=Protein REPRESSOR OF SILENCING 1 {ECO:0000303|PubMed:12526807};
DE Short=Protein ROS1 {ECO:0000303|PubMed:12526807};
GN Name=ROS1 {ECO:0000303|PubMed:12526807};
GN Synonyms=DML1 {ECO:0000303|PubMed:12150995};
GN OrderedLocusNames=At2g36490 {ECO:0000312|Araport:AT2G36490};
GN ORFNames=F1O11.12 {ECO:0000312|EMBL:AAD24633.1};
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF ASP-1309, FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=cv. C24;
RX PubMed=12526807; DOI=10.1016/s0092-8674(02)01133-9;
RA Gong Z., Morales-Ruiz T., Ariza R.R., Roldan-Arjona T., David L.,
RA Zhu J.-K.;
RT "ROS1, a repressor of transcriptional gene silencing in Arabidopsis,
RT encodes a DNA glycosylase/lyase.";
RL Cell 111:803-814(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=10617197; DOI=10.1038/45471;
RA Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D.,
RA Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V.,
RA Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L., Moffat K.S.,
RA Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L., Tallon L.J.,
RA Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., Goodman H.M.,
RA Somerville C.R., Copenhaver G.P., Preuss D., Nierman W.C., White O.,
RA Eisen J.A., Salzberg S.L., Fraser C.M., Venter J.C.;
RT "Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.";
RL Nature 402:761-768(1999).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [4]
RP NOMENCLATURE.
RX PubMed=12150995; DOI=10.1016/s0092-8674(02)00807-3;
RA Choi Y., Gehring M., Johnson L., Hannon M., Harada J.J., Goldberg R.B.,
RA Jacobsen S.E., Fischer R.L.;
RT "DEMETER, a DNA glycosylase domain protein, is required for endosperm gene
RT imprinting and seed viability in Arabidopsis.";
RL Cell 110:33-42(2002).
RN [5]
RP INTERACTION WITH RPA2A.
RX PubMed=16271867; DOI=10.1016/j.cub.2005.09.013;
RA Kapoor A., Agarwal M., Andreucci A., Zheng X., Gong Z., Hasegawa P.M.,
RA Bressan R.A., Zhu J.-K.;
RT "Mutations in a conserved replication protein suppress transcriptional gene
RT silencing in a DNA-methylation-independent manner in Arabidopsis.";
RL Curr. Biol. 15:1912-1918(2005).
RN [6]
RP INTERACTION WITH RPA2A.
RX PubMed=16326925; DOI=10.1105/tpc.105.037507;
RA Xia R., Wang J., Liu C., Wang Y., Wang Y., Zhai J., Liu J., Hong X.,
RA Cao X., Zhu J.-K., Gong Z.;
RT "ROR1/RPA2A, a putative replication protein A2, functions in epigenetic
RT gene silencing and in regulation of meristem development in Arabidopsis.";
RL Plant Cell 18:85-103(2006).
RN [7]
RP FUNCTION.
RX PubMed=16624880; DOI=10.1073/pnas.0601109103;
RA Morales-Ruiz T., Ortega-Galisteo A.P., Ponferrada-Marin M.I.,
RA Martinez-Macias M.I., Ariza R.R., Roldan-Arjona T.;
RT "DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA
RT glycosylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:6853-6858(2006).
RN [8]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-901, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=cv. Landsberg erecta;
RX PubMed=17272265; DOI=10.1074/mcp.m600408-mcp200;
RA Maor R., Jones A., Nuehse T.S., Studholme D.J., Peck S.C., Shirasu K.;
RT "Multidimensional protein identification technology (MudPIT) analysis of
RT ubiquitinated proteins in plants.";
RL Mol. Cell. Proteomics 6:601-610(2007).
RN [9]
RP FUNCTION.
RX PubMed=18845569; DOI=10.1093/pcp/pcn152;
RA Douet J., Blanchard B., Cuvillier C., Tourmente S.;
RT "Interplay of RNA Pol IV and ROS1 during post-embryonic 5S rDNA chromatin
RT remodeling.";
RL Plant Cell Physiol. 49:1783-1791(2008).
RN [10]
RP FUNCTION, AND SUBSTRATE SPECIFICITY.
RX PubMed=19443451; DOI=10.1093/nar/gkp390;
RA Ponferrada-Marin M.I., Roldan-Arjona T., Ariza R.R.;
RT "ROS1 5-methylcytosine DNA glycosylase is a slow-turnover catalyst that
RT initiates DNA demethylation in a distributive fashion.";
RL Nucleic Acids Res. 37:4264-4274(2009).
RN [11]
RP FUNCTION, AND DOMAIN.
RX PubMed=20489198; DOI=10.1074/jbc.m110.124578;
RA Ponferrada-Marin M.I., Martinez-Macias M.I., Morales-Ruiz T.,
RA Roldan-Arjona T., Ariza R.R.;
RT "Methylation-independent DNA binding modulates specificity of Repressor of
RT Silencing 1 (ROS1) and facilitates demethylation in long substrates.";
RL J. Biol. Chem. 285:23032-23039(2010).
RN [12]
RP INTERACTION WITH ZDP, AND ACTIVITY REGULATION.
RX PubMed=22325353; DOI=10.1016/j.molcel.2011.11.034;
RA Martinez-Macias M.I., Qian W., Miki D., Pontes O., Liu Y., Tang K., Liu R.,
RA Morales-Ruiz T., Ariza R.R., Roldan-Arjona T., Zhu J.K.;
RT "A DNA 3' phosphatase functions in active DNA demethylation in
RT Arabidopsis.";
RL Mol. Cell 45:357-370(2012).
RN [13]
RP INTERACTION WITH XRCC1, AND ACTIVITY REGULATION.
RX PubMed=23316050; DOI=10.1074/jbc.m112.427617;
RA Martinez-Macias M.I., Cordoba-Canero D., Ariza R.R., Roldan-Arjona T.;
RT "The DNA repair protein XRCC1 functions in the plant DNA demethylation
RT pathway by stimulating cytosine methylation (5-meC) excision, gap
RT tailoring, and DNA ligation.";
RL J. Biol. Chem. 288:5496-5505(2013).
RN [14]
RP FUNCTION, INDUCTION BY UV-B, AND DISRUPTION PHENOTYPE.
RX PubMed=24155752; DOI=10.3389/fpls.2013.00420;
RA Queesta J.I., Fina J.P., Casati P.;
RT "DDM1 and ROS1 have a role in UV-B induced- and oxidative DNA damage in A.
RT thaliana.";
RL Front. Plant Sci. 4:420-420(2013).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-971, AND DOMAIN.
RX PubMed=25240767; DOI=10.1016/j.jmb.2014.09.010;
RA Hong S., Hashimoto H., Kow Y.W., Zhang X., Cheng X.;
RT "The carboxy-terminal domain of ROS1 is essential for 5-methylcytosine DNA
RT glycosylase activity.";
RL J. Mol. Biol. 426:3703-3712(2014).
RN [16]
RP FUNCTION.
RX PubMed=25228464; DOI=10.1093/nar/gku834;
RA Lee J., Jang H., Shin H., Choi W.L., Mok Y.G., Huh J.H.;
RT "AP endonucleases process 5-methylcytosine excision intermediates during
RT active DNA demethylation in Arabidopsis.";
RL Nucleic Acids Res. 42:11408-11418(2014).
RN [17]
RP INTERACTION WITH MBD7; IDM1; IDM2 AND IDM3.
RX PubMed=25684209; DOI=10.1016/j.molcel.2015.01.009;
RA Lang Z., Lei M., Wang X., Tang K., Miki D., Zhang H., Mangrauthia S.K.,
RA Liu W., Nie W., Ma G., Yan J., Duan C.G., Hsu C.C., Wang C., Tao W.A.,
RA Gong Z., Zhu J.K.;
RT "The methyl-CpG-binding protein MBD7 facilitates active DNA demethylation
RT to limit DNA hyper-methylation and transcriptional gene silencing.";
RL Mol. Cell 57:971-983(2015).
RN [18]
RP INTERACTION WITH APE1L, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=25569774; DOI=10.1371/journal.pgen.1004905;
RA Li Y., Cordoba-Canero D., Qian W., Zhu X., Tang K., Zhang H., Ariza R.R.,
RA Roldan-Arjona T., Zhu J.K.;
RT "An AP endonuclease functions in active DNA dimethylation and gene
RT imprinting in Arabidopsis.";
RL PLoS Genet. 11:E1004905-E1004905(2015).
CC -!- FUNCTION: Bifunctional DNA glycosylase/lyase, which excises 5-
CC methylcytosine (5-meC) and 5-hydroxymethylcytosine (5-hmeC), leaving an
CC apyrimidinic (AP) site that is subsequently incised by the lyase
CC activity (PubMed:25240767). Generates 3'-phosphor-alpha,beta-
CC unsaturated aldehyde (3'-PUA) as a primary 5-meC excision intermediate
CC (PubMed:25228464). Prevents DNA hypermethylation, specifically in the
CC promoter of otherwise silenced loci. May be involved in DNA repair
CC through its nicking activity on methylated DNA. Binds with similar
CC affinity to both methylated and non-methylated DNA. Highly distributive
CC behavior on DNA substrates containing multiple 5-meC residues. Involved
CC with Pol IV in the remodeling of the 5S rDNA chromatin via DNA
CC methylation modifications during the first days of development post-
CC germination. Participates in UV-B induced- and oxidative DNA damage
CC repair (PubMed:24155752). {ECO:0000269|PubMed:12526807,
CC ECO:0000269|PubMed:16624880, ECO:0000269|PubMed:18845569,
CC ECO:0000269|PubMed:19443451, ECO:0000269|PubMed:20489198,
CC ECO:0000269|PubMed:24155752, ECO:0000269|PubMed:25228464,
CC ECO:0000269|PubMed:25240767}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)-2'-
CC deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3-
CC dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-monophospho-
CC 2'-deoxyribonucleoside-DNA + H(+); Xref=Rhea:RHEA:66592, Rhea:RHEA-
CC COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695,
CC ChEBI:CHEBI:167181; EC=4.2.99.18;
CC Evidence={ECO:0000269|PubMed:25240767};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P0AB83};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a
CC role in catalysis, but is probably involved in the proper positioning
CC of the enzyme along the DNA strand. {ECO:0000250|UniProtKB:P0AB83};
CC -!- ACTIVITY REGULATION: Stimulated by ZDP (PubMed:22325353). Stimulated by
CC XRCC1 (PubMed:23316050). {ECO:0000269|PubMed:22325353,
CC ECO:0000269|PubMed:23316050}.
CC -!- SUBUNIT: Interacts (via the central region) with ZDP (PubMed:22325353).
CC Binds to RPA2A (PubMed:16271867, PubMed:16326925). Interacts with XRCC1
CC (PubMed:23316050). Interacts probably with a complex made of MBD7,
CC IDM1, IDM2 and IDM3 (Probable). Interacts with APE1L (PubMed:25569774).
CC {ECO:0000269|PubMed:16271867, ECO:0000269|PubMed:16326925,
CC ECO:0000269|PubMed:22325353, ECO:0000269|PubMed:23316050,
CC ECO:0000269|PubMed:25569774, ECO:0000305|PubMed:25684209}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12526807,
CC ECO:0000269|PubMed:25569774}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:25569774}. Note=Co-localizes in nucleoplasmic foci
CC with APE1L and ZDP, two components of the DNA demethylase machinery.
CC {ECO:0000269|PubMed:25569774}.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously in both vegetative and
CC reproductive organs. {ECO:0000269|PubMed:12526807}.
CC -!- INDUCTION: Down-regulated by UV-B. {ECO:0000269|PubMed:24155752}.
CC -!- DOMAIN: The N-terminal lysine-rich domain (112-260) is required for
CC non-specific binding to DNA and for efficient activity on 5-meC.
CC {ECO:0000269|PubMed:20489198}.
CC -!- DOMAIN: The glycosylase domain (510-1073) is inactive on 5-meC and 5-
CC hmeC excisions but retains residual AP activity. Addition of the C-
CC terminal domain (1077-1393) restored partial base excision activity and
CC increases the AP lyase activity. {ECO:0000269|PubMed:25240767}.
CC -!- DOMAIN: The DEMETER domain, which is present in proteins of the
CC subfamily, is related to the J-domain, but lacks some important
CC conserved residues. {ECO:0000269|PubMed:20489198}.
CC -!- DISRUPTION PHENOTYPE: Decreased response to UV-B radiation
CC (PubMed:24155752). No visible phenotype (PubMed:25569774).
CC {ECO:0000269|PubMed:24155752, ECO:0000269|PubMed:25569774}.
CC -!- MISCELLANEOUS: Although strongly related to DNA glycosylase proteins,
CC it differs from these proteins. The DNA repair function may not exist.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: MBD7 binds to chromatin at high mCG density regions and
CC then recruits IDM2 and IDM3, thus bringing IDM1 to the methylated DNA.
CC The specific histone H3 acetylation marks produced by IDM1 create a
CC chromatin environment that facilitate the binding of ROS1 to erase DNA
CC methylation. {ECO:0000305|PubMed:25684209}.
CC -!- SIMILARITY: Belongs to the DNA glycosylase family. DEMETER subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD24633.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY286009; AAP37178.1; -; mRNA.
DR EMBL; AC006919; AAD24633.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002685; AEC09263.1; -; Genomic_DNA.
DR PIR; D84781; D84781.
DR RefSeq; NP_181190.3; NM_129207.5.
DR AlphaFoldDB; Q9SJQ6; -.
DR SMR; Q9SJQ6; -.
DR BioGRID; 3568; 12.
DR STRING; 3702.AT2G36490.1; -.
DR iPTMnet; Q9SJQ6; -.
DR PaxDb; Q9SJQ6; -.
DR PRIDE; Q9SJQ6; -.
DR ProteomicsDB; 227970; -.
DR EnsemblPlants; AT2G36490.1; AT2G36490.1; AT2G36490.
DR GeneID; 818224; -.
DR Gramene; AT2G36490.1; AT2G36490.1; AT2G36490.
DR KEGG; ath:AT2G36490; -.
DR Araport; AT2G36490; -.
DR TAIR; locus:2044923; AT2G36490.
DR eggNOG; ENOG502QQKH; Eukaryota.
DR HOGENOM; CLU_000567_3_1_1; -.
DR InParanoid; Q9SJQ6; -.
DR OMA; EAENCTH; -.
DR OrthoDB; 164157at2759; -.
DR PhylomeDB; Q9SJQ6; -.
DR PRO; PR:Q9SJQ6; -.
DR Proteomes; UP000006548; Chromosome 2.
DR ExpressionAtlas; Q9SJQ6; baseline and differential.
DR Genevisible; Q9SJQ6; AT.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:TAIR.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0140078; F:class I DNA-(apurinic or apyrimidinic site) endonuclease activity; IEA:UniProtKB-EC.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0035514; F:DNA demethylase activity; IEA:InterPro.
DR GO; GO:0019104; F:DNA N-glycosylase activity; IDA:TAIR.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:TAIR.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006284; P:base-excision repair; IEA:InterPro.
DR GO; GO:0050832; P:defense response to fungus; IMP:TAIR.
DR GO; GO:0080111; P:DNA demethylation; IMP:TAIR.
DR GO; GO:0006306; P:DNA methylation; IDA:TAIR.
DR GO; GO:0006281; P:DNA repair; IMP:TAIR.
DR CDD; cd00056; ENDO3c; 1.
DR Gene3D; 1.10.1670.10; -; 1.
DR InterPro; IPR044811; DME/ROS1.
DR InterPro; IPR011257; DNA_glycosylase.
DR InterPro; IPR003651; Endonuclease3_FeS-loop_motif.
DR InterPro; IPR003265; HhH-GPD_domain.
DR InterPro; IPR023170; HhH_base_excis_C.
DR InterPro; IPR028924; Perm-CXXC.
DR InterPro; IPR028925; RRM_DME.
DR PANTHER; PTHR46213; PTHR46213; 1.
DR Pfam; PF15629; Perm-CXXC; 1.
DR Pfam; PF15628; RRM_DME; 1.
DR SMART; SM00478; ENDO3c; 1.
DR SMART; SM00525; FES; 1.
DR SUPFAM; SSF48150; SSF48150; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Activator; DNA-binding; Iron; Iron-sulfur; Isopeptide bond; Lyase;
KW Metal-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..1393
FT /note="DNA glycosylase/AP lyase ROS1"
FT /id="PRO_0000102246"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 98..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 528..626
FT /note="DEMETER"
FT REGION 653..722
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 789..830
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..130
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..155
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 653..670
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 684..698
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 699..722
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1038
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P0AB83"
FT BINDING 1045
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P0AB83"
FT BINDING 1048
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P0AB83"
FT BINDING 1054
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P0AB83"
FT CROSSLNK 901
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:17272265"
FT MUTAGEN 971
FT /note="D->N: Abolishes the base excision activity, but not
FT the AP lyase activity."
FT /evidence="ECO:0000269|PubMed:25240767"
FT MUTAGEN 1309
FT /note="D->N: In ros1-2; loss of activity inducing a
FT transcriptional gene silencing."
FT /evidence="ECO:0000269|PubMed:12526807"
SQ SEQUENCE 1393 AA; 156547 MW; DA6D5136C76CEA8E CRC64;
MEKQRREESS FQQPPWIPQT PMKPFSPICP YTVEDQYHSS QLEERRFVGN KDMSGLDHLS
FGDLLALANT ASLIFSGQTP IPTRNTEVMQ KGTEEVESLS SVSNNVAEQI LKTPEKPKRK
KHRPKVRREA KPKREPKPRA PRKSVVTDGQ ESKTPKRKYV RKKVEVSKDQ DATPVESSAA
VETSTRPKRL CRRVLDFEAE NGENQTNGDI REAGEMESAL QEKQLDSGNQ ELKDCLLSAP
STPKRKRSQG KRKGVQPKKN GSNLEEVDIS MAQAAKRRQG PTCCDMNLSG IQYDEQCDYQ
KMHWLYSPNL QQGGMRYDAI CSKVFSGQQH NYVSAFHATC YSSTSQLSAN RVLTVEERRE
GIFQGRQESE LNVLSDKIDT PIKKKTTGHA RFRNLSSMNK LVEVPEHLTS GYCSKPQQNN
KILVDTRVTV SKKKPTKSEK SQTKQKNLLP NLCRFPPSFT GLSPDELWKR RNSIETISEL
LRLLDINREH SETALVPYTM NSQIVLFGGG AGAIVPVTPV KKPRPRPKVD LDDETDRVWK
LLLENINSEG VDGSDEQKAK WWEEERNVFR GRADSFIARM HLVQGDRRFT PWKGSVVDSV
VGVFLTQNVS DHLSSSAFMS LASQFPVPFV PSSNFDAGTS SMPSIQITYL DSEETMSSPP
DHNHSSVTLK NTQPDEEKDY VPSNETSRSS SEIAISAHES VDKTTDSKEY VDSDRKGSSV
EVDKTDEKCR VLNLFPSEDS ALTCQHSMVS DAPQNTERAG SSSEIDLEGE YRTSFMKLLQ
GVQVSLEDSN QVSPNMSPGD CSSEIKGFQS MKEPTKSSVD SSEPGCCSQQ DGDVLSCQKP
TLKEKGKKVL KEEKKAFDWD CLRREAQARA GIREKTRSTM DTVDWKAIRA ADVKEVAETI
KSRGMNHKLA ERIQGFLDRL VNDHGSIDLE WLRDVPPDKA KEYLLSFNGL GLKSVECVRL
LTLHHLAFPV DTNVGRIAVR LGWVPLQPLP ESLQLHLLEM YPMLESIQKY LWPRLCKLDQ
KTLYELHYQM ITFGKVFCTK SKPNCNACPM KGECRHFASA FASARLALPS TEKGMGTPDK
NPLPLHLPEP FQREQGSEVV QHSEPAKKVT CCEPIIEEPA SPEPETAEVS IADIEEAFFE
DPEEIPTIRL NMDAFTSNLK KIMEHNKELQ DGNMSSALVA LTAETASLPM PKLKNISQLR
TEHRVYELPD EHPLLAQLEK REPDDPCSYL LAIWTPGETA DSIQPSVSTC IFQANGMLCD
EETCFSCNSI KETRSQIVRG TILIPCRTAM RGSFPLNGTY FQVNEVFADH ASSLNPINVP
RELIWELPRR TVYFGTSVPT IFKGLSTEKI QACFWKGYVC VRGFDRKTRG PKPLIARLHF
PASKLKGQQA NLA
