BIG_ARATH
ID BIG_ARATH Reviewed; 5098 AA.
AC Q9SRU2; F4J4S0;
DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Auxin transport protein BIG;
DE AltName: Full=Protein ATTENUATED SHADE AVOIDANCE 1;
DE AltName: Full=Protein CORYMBOSA1;
DE AltName: Full=Protein DARK OVER-EXPRESSION OF CAB 1;
DE AltName: Full=Protein LOW PHOSPHATE-RESISTANT ROOT 1;
DE AltName: Full=Protein TRANSPORT INHIBITOR RESPONSE 3;
DE AltName: Full=Protein UMBRELLA 1;
GN Name=BIG; Synonyms=ASA1, CRM1, DOC1, GA6, LPR1, TIR3, UMB1;
GN OrderedLocusNames=At3g02260; ORFNames=F14P3.9;
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 [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE,
RP MUTAGENESIS OF CYS-1607, AND TISSUE SPECIFICITY.
RC STRAIN=cv. Columbia;
RX PubMed=11485992; DOI=10.1101/gad.905201;
RA Gil P., Dewey E., Friml J., Zhao Y., Snowden K.C., Putterill J., Palme K.,
RA Estelle M., Chory J.;
RT "BIG: a calossin-like protein required for polar auxin transport in
RT Arabidopsis.";
RL Genes Dev. 15:1985-1997(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=11130713; DOI=10.1038/35048706;
RA Salanoubat M., Lemcke K., Rieger M., Ansorge W., Unseld M., Fartmann B.,
RA Valle G., Bloecker H., Perez-Alonso M., Obermaier B., Delseny M.,
RA Boutry M., Grivell L.A., Mache R., Puigdomenech P., De Simone V.,
RA Choisne N., Artiguenave F., Robert C., Brottier P., Wincker P.,
RA Cattolico L., Weissenbach J., Saurin W., Quetier F., Schaefer M.,
RA Mueller-Auer S., Gabel C., Fuchs M., Benes V., Wurmbach E., Drzonek H.,
RA Erfle H., Jordan N., Bangert S., Wiedelmann R., Kranz H., Voss H.,
RA Holland R., Brandt P., Nyakatura G., Vezzi A., D'Angelo M., Pallavicini A.,
RA Toppo S., Simionati B., Conrad A., Hornischer K., Kauer G., Loehnert T.-H.,
RA Nordsiek G., Reichelt J., Scharfe M., Schoen O., Bargues M., Terol J.,
RA Climent J., Navarro P., Collado C., Perez-Perez A., Ottenwaelder B.,
RA Duchemin D., Cooke R., Laudie M., Berger-Llauro C., Purnelle B., Masuy D.,
RA de Haan M., Maarse A.C., Alcaraz J.-P., Cottet A., Casacuberta E.,
RA Monfort A., Argiriou A., Flores M., Liguori R., Vitale D., Mannhaupt G.,
RA Haase D., Schoof H., Rudd S., Zaccaria P., Mewes H.-W., Mayer K.F.X.,
RA Kaul S., Town C.D., Koo H.L., Tallon L.J., Jenkins J., Rooney T., Rizzo M.,
RA Walts A., Utterback T., Fujii C.Y., Shea T.P., Creasy T.H., Haas B.,
RA Maiti R., Wu D., Peterson J., Van Aken S., Pai G., Militscher J.,
RA Sellers P., Gill J.E., Feldblyum T.V., Preuss D., Lin X., Nierman W.C.,
RA Salzberg S.L., White O., Venter J.C., Fraser C.M., Kaneko T., Nakamura Y.,
RA Sato S., Kato T., Asamizu E., Sasamoto S., Kimura T., Idesawa K.,
RA Kawashima K., Kishida Y., Kiyokawa C., Kohara M., Matsumoto M., Matsuno A.,
RA Muraki A., Nakayama S., Nakazaki N., Shinpo S., Takeuchi C., Wada T.,
RA Watanabe A., Yamada M., Yasuda M., Tabata S.;
RT "Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana.";
RL Nature 408:820-822(2000).
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia;
RX PubMed=8314087; DOI=10.1101/gad.8.3.339;
RA Li H.-M., Altschmied L., Chory J.;
RT "Arabidopsis mutants define downstream branches in the phototransduction
RT pathway.";
RL Genes Dev. 8:339-349(1994).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia;
RX PubMed=9165751; DOI=10.2307/3870429;
RA Ruegger M., Dewey E., Hobbie L., Brown D., Bernasconi P., Turner J.,
RA Muday G., Estelle M.;
RT "Reduced naphthylphthalamic acid binding in the tir3 mutant of Arabidopsis
RT is associated with a reduction in polar auxin transport and diverse
RT morphological defects.";
RL Plant Cell 9:745-757(1997).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. Landsberg erecta;
RX PubMed=9390435; DOI=10.1104/pp.115.3.1009;
RA Sponsel V.M., Schmidt F.W., Porter S.G., Nakayama M., Kohlstruk S.,
RA Estelle M.;
RT "Characterization of new gibberellin-responsive semidwarf mutants of
RT arabidopsis.";
RL Plant Physiol. 115:1009-1020(1997).
RN [7]
RP REVIEW.
RX PubMed=11676938; DOI=10.1016/s0960-9822(01)00497-3;
RA Luschnig C.;
RT "Auxin transport: why plants like to think BIG.";
RL Curr. Biol. 11:R831-R833(2001).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia;
RX PubMed=12834402; DOI=10.1046/j.1365-313x.2003.01779.x;
RA Kanyuka K., Praekelt U., Franklin K.A., Billingham O.E., Hooley R.,
RA Whitelam G.C., Halliday K.J.;
RT "Mutations in the huge Arabidopsis gene BIG affect a range of hormone and
RT light responses.";
RL Plant J. 35:57-70(2003).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia, and cv. Landsberg erecta;
RX PubMed=15634200; DOI=10.1111/j.1365-313x.2004.02287.x;
RA Desgagne-Penix I., Eakanunkul S., Coles J.P., Phillips A.L., Hedden P.,
RA Sponsel V.M.;
RT "The auxin transport inhibitor response 3 (tir3) allele of BIG and auxin
RT transport inhibitors affect the gibberellin status of Arabidopsis.";
RL Plant J. 41:231-242(2005).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia, and cv. Wassilewskija;
RX PubMed=15681664; DOI=10.1104/pp.104.049577;
RA Lopez-Bucio J., Hernandez-Abreu E., Sanchez-Calderon L., Perez-Torres A.,
RA Rampey R.A., Bartel B., Herrera-Estrella L.;
RT "An auxin transport independent pathway is involved in phosphate stress-
RT induced root architectural alterations in Arabidopsis. Identification of
RT BIG as a mediator of auxin in pericycle cell activation.";
RL Plant Physiol. 137:681-691(2005).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RC STRAIN=cv. Columbia, and cv. Landsberg erecta;
RX PubMed=17652113; DOI=10.1093/pcp/pcm094;
RA Yamaguchi N., Suzuki M., Fukaki H., Morita-Terao M., Tasaka M., Komeda Y.;
RT "CRM1/BIG-mediated auxin action regulates Arabidopsis inflorescence
RT development.";
RL Plant Cell Physiol. 48:1275-1290(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=cv. Columbia;
RX PubMed=19245862; DOI=10.1016/j.jprot.2009.02.004;
RA Jones A.M.E., MacLean D., Studholme D.J., Serna-Sanz A., Andreasson E.,
RA Rathjen J.P., Peck S.C.;
RT "Phosphoproteomic analysis of nuclei-enriched fractions from Arabidopsis
RT thaliana.";
RL J. Proteomics 72:439-451(2009).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19176721; DOI=10.1104/pp.108.130369;
RA Contreras-Cornejo H.A., Macias-Rodriguez L., Cortes-Penagos C.,
RA Lopez-Bucio J.;
RT "Trichoderma virens, a plant beneficial fungus, enhances biomass production
RT and promotes lateral root growth through an auxin-dependent mechanism in
RT Arabidopsis.";
RL Plant Physiol. 149:1579-1592(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
CC -!- FUNCTION: Required for auxin efflux and polar auxin transport (PAT)
CC influencing auxin-mediated developmental responses (e.g. cell
CC elongation, apical dominance, lateral root production, inflorescence
CC architecture, general growth and development). Controls the elongation
CC of the pedicels and stem internodes through auxin action. Involved in
CC the expression modulation of light-regulated genes. Represses CAB1 and
CC CAB3 genes expression in etiolated seedlings. Confers sensitivity to
CC the auxin transport inhibitors N-1-naphthylphthalamic acid (NPA), 2-
CC carboxyphenyl-3-phenylpropane-l,2-dione (CPD), and methyl-2-chloro-9-
CC hydroxyfluorene-9-carboxylate (CFM). Influences the polarized
CC subcellular distribution of the auxin transporter PIN1 in response to
CC auxin transport inhibitors. Plays a role in the regulation of responses
CC to phytohormones such as auxin, cytokinins, ethylene and gibberellic
CC acid (GA), particularly during light-mediated stimuli (e.g. shade
CC ovoidance, etiolation). Required for pericycle cell activation to form
CC lateral root primordia (LRP) in both high and low phosphate P
CC conditions. Necessary for the plant-growth promotion and lateral root
CC development mediated by the fungus Trichoderma virens.
CC {ECO:0000269|PubMed:11485992, ECO:0000269|PubMed:12834402,
CC ECO:0000269|PubMed:15634200, ECO:0000269|PubMed:15681664,
CC ECO:0000269|PubMed:17652113, ECO:0000269|PubMed:19176721,
CC ECO:0000269|PubMed:8314087, ECO:0000269|PubMed:9165751,
CC ECO:0000269|PubMed:9390435}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Constitutively expressed in roots, rosette leaves,
CC inflorescence stems, and flowers. Present in inflorescence meristems,
CC floral meristems and vascular tissues. {ECO:0000269|PubMed:11485992,
CC ECO:0000269|PubMed:17652113}.
CC -!- DISRUPTION PHENOTYPE: Altered expression of light-regulated genes;
CC overexpression of CAB (photosystem II type I chlorophyll a/b-binding
CC proteins) genes in the dark (e.g. CAB1 and CAB3). Reduced auxin
CC transport. Under long-day growth conditions (18 hr light/6 hr dark),
CC reduced apical dominance in mature plants. Reduced plant growth under
CC both short-day (9 hr light/15 hr dark) and long-day conditions
CC resulting in shorter plants. Strong deficiency in lateral root
CC production. Reduced cell elongation in siliques, pedicels, roots, and
CC the inflorescence leading to a compact rosette, more secondary corymb-
CC like inflorescence, and small seeds. Delayed flowering. Reduced
CC sensitivity to auxin transport inhibitors N-1-naphthylphthalamic acid
CC (NPA), 2-carboxyphenyl-3-phenylpropane-l,2-dione (CPD), and methyl-2-
CC chloro-9-hydroxyfluorene-9-carboxylate (CFM). Organ-specific defect in
CC response to cytokinins, ethylene and gibberellic acid (GA). Increased
CC expression of auxin transporters PIN1 and PIN6. Reduced growth-
CC promotion and lateral root development stimulation mediated by the
CC fungus T.virens. {ECO:0000269|PubMed:11485992,
CC ECO:0000269|PubMed:12834402, ECO:0000269|PubMed:15634200,
CC ECO:0000269|PubMed:15681664, ECO:0000269|PubMed:17652113,
CC ECO:0000269|PubMed:19176721, ECO:0000269|PubMed:8314087,
CC ECO:0000269|PubMed:9165751, ECO:0000269|PubMed:9390435}.
CC -!- MISCELLANEOUS: May be or regulate a N-1-naphthylphthalamic acid (NPA)
CC binding protein (NBP), an auxin transport inhibitor.
CC -!- SIMILARITY: Belongs to the UBR4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF02112.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAM77595.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF507018; AAM77595.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC009755; AAF02112.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002686; AEE73785.1; -; Genomic_DNA.
DR RefSeq; NP_186875.2; NM_111093.2.
DR BioGRID; 5732; 3.
DR STRING; 3702.AT3G02260.1; -.
DR iPTMnet; Q9SRU2; -.
DR PaxDb; Q9SRU2; -.
DR PRIDE; Q9SRU2; -.
DR ProteomicsDB; 240620; -.
DR EnsemblPlants; AT3G02260.1; AT3G02260.1; AT3G02260.
DR GeneID; 820398; -.
DR Gramene; AT3G02260.1; AT3G02260.1; AT3G02260.
DR KEGG; ath:AT3G02260; -.
DR Araport; AT3G02260; -.
DR TAIR; locus:2076487; AT3G02260.
DR eggNOG; KOG1776; Eukaryota.
DR HOGENOM; CLU_223526_0_0_1; -.
DR InParanoid; Q9SRU2; -.
DR OrthoDB; 717at2759; -.
DR PRO; PR:Q9SRU2; -.
DR Proteomes; UP000006548; Chromosome 3.
DR ExpressionAtlas; Q9SRU2; baseline and differential.
DR Genevisible; Q9SRU2; AT.
DR GO; GO:0005829; C:cytosol; HDA:TAIR.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009506; C:plasmodesma; HDA:TAIR.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0009926; P:auxin polar transport; IDA:TAIR.
DR GO; GO:0009734; P:auxin-activated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0048281; P:inflorescence morphogenesis; IMP:UniProtKB.
DR GO; GO:0010311; P:lateral root formation; IMP:UniProtKB.
DR GO; GO:0009640; P:photomorphogenesis; IMP:TAIR.
DR GO; GO:0009733; P:response to auxin; IMP:TAIR.
DR GO; GO:0009620; P:response to fungus; IMP:UniProtKB.
DR GO; GO:0048364; P:root development; IMP:TAIR.
DR GO; GO:0009826; P:unidimensional cell growth; IMP:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 3.30.60.90; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR025704; E3_Ub_ligase_UBR4_C.
DR InterPro; IPR045189; UBR4-like.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR003126; Znf_UBR.
DR InterPro; IPR000433; Znf_ZZ.
DR InterPro; IPR043145; Znf_ZZ_sf.
DR PANTHER; PTHR21725; PTHR21725; 1.
DR Pfam; PF13764; E3_UbLigase_R4; 1.
DR Pfam; PF00569; ZZ; 1.
DR SMART; SM00396; ZnF_UBR1; 1.
DR SMART; SM00291; ZnF_ZZ; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS51157; ZF_UBR; 1.
DR PROSITE; PS01357; ZF_ZZ_1; 1.
DR PROSITE; PS50135; ZF_ZZ_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Auxin signaling pathway; Coiled coil; Developmental protein;
KW Membrane; Metal-binding; Reference proteome; Transmembrane;
KW Transmembrane helix; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..5098
FT /note="Auxin transport protein BIG"
FT /id="PRO_0000410727"
FT TRANSMEM 1150..1170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1458..1478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2813..2833
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 1573..1644
FT /note="UBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00508"
FT ZN_FING 2613..2672
FT /note="ZZ-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT ZN_FING 3464..3504
FT /note="MYND-type; degenerate"
FT REGION 1539..1562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3149..3174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4891..4915
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 3537..3557
FT /evidence="ECO:0000255"
FT COILED 4313..4333
FT /evidence="ECO:0000255"
FT COMPBIAS 1539..1560
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 2618
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2621
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2633
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2636
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2642
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2645
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2658
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2662
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MUTAGEN 1607
FT /note="C->Y: In doc1-1; altered expression of multiple
FT light-regulated genes."
FT /evidence="ECO:0000269|PubMed:11485992"
SQ SEQUENCE 5098 AA; 567888 MW; 43F7EADD65B23133 CRC64;
MADDLANLCR FLFDDTAFPS LSSSASSDLF SRRLRSDDSI KRGLRSFYLL LRWGVAPIGG
DDADSSGKLR FETWSDSQLQ ALVSISQAIL LLSRSLLGTD LTLNQGLVDQ LEPIVLGVIQ
EVMEFSLSFL EKSSFRQNDL KMEINMEILL EIASFDGSEK QYDILPDFSP AEVAELWPAF
SGEHDNMDAQ SLVKCTFQGG RCSNEEKPVD RLLITLMSEC IESDVQAQSV VKSPFQQDCG
DLNPFTRHLA VVHLRCVCRL IMVCKELVQL PNMLDEKTVD QAVLDKLSFC LRILKLLGSL
SKDVQSIEND GSLLQAVASF TDAFPKLFRV FFEFTNHTAT EGNIESLSLA LVEGFLNLVQ
LIFGKSSVFQ NVQACVAASI VSNLDSSVWR YDGSSCNLTP PLAYFPRSVI YTLKLIQDLK
RQPYHIHDLR VLESEVTYED VSSTVDSVYF HLRQEKIPLL KCFTVEDIMR VIFPSSSQWM
DNFFHLVYFL HREGVKLRPK VERTYSSLRS NSFAEVESQI SHDDEALFGN LFSEGSRSLC
SIEPNDQPPV SVSSNLLLQA AKELLNFLRA CILCQEWVPS IYEDGCKKLD TGHIDILLNI
VGCSIEDKAS DGGCMLQDEG RPGHVAFELL LNLLRSRALS DFLESYLFQQ ILVVENSDFN
YNDKTLALLA HTLLCRPGLA GAQLRAKIYD GFVSFVTERA RGICAEALSL KELTACLPSA
FHIEILLMAF HLSNEAEKAK FSNLIASCLH KVDTPAGICD GPQLSSWAML ISRLLVLLHH
MLLHPNTCPT SLMLDLRSKL REVRSCGSNL HVTVGDHLSS WASLVARGIT DSWAEDESVS
HLMSQMIDFS PHPPTFQNDV STAKTLNLDY GDLSASLCRV LGLWKGKKAG KVEDLLVERY
IFMLSSDIAR INCALDSQPS LHVNYQNVDI SNSVDLISTS HLLVGDINVV GRNIELRNIL
IGVLNQLQAA PEQVVEDLGW DYIREGAWLS LLLYFLDGGV WDYCNKNSCS EIDPFWKECT
SVDAKYVAAA EGVVSYLMKT GDIAELLRML SSLVGKYLRV YKKAFLATFS DWNHHGHSSP
SLLLLKHTQF GKSLQGEYAK IGDNSLHLQC IFYLSKLDSL GDGRGSGVLW KVFWEFMVHG
FPTSLQTSSA ILLSCILSIR CIVLTINGLL KLGNSKEKFG VDTSVLHQLL DSIMIIKFDQ
VFESFHGKCE EIHQNICAVL QLPDLTELFL MKDMEGFVRD ISAEQIDRSQ VLEGVITKIV
DVMDSLSKDS SKSDIFKFYL GVDAVSEHTR EFYELQRGDL SVFIDSLDYC SLEPVNIKVL
NFLVDLLSVA QSPDLRRRVQ QKFIDMDLIS LSGWLERRLL GSFVEEIDGK KTAKGNSLPF
REAAMNFINC LVSSTNDLQT RELQNHLFEA LLISLDTAFL SFDIHMSMSY FHFVLQLARE
DNLMKMVLKR TIMLMEKLAA EEKLLPGLKF IFGVIGTLLS NRSPSHGESL CGKSLASYKN
TATGPLVPKL SGTTKKSDTL ALPVDQEGSS ISLECDVTSV DEDEDDGTSD GEVASLDKED
EEDANSERYL ASKVCTFTSS GSNFMEQHWY FCYTCDLTVS KGCCSVCAKV CHRGHRVVYS
RSSRFFCDCG AGGVRGSSCQ CLKPRKYNGN GSAPARGTNN FQSFLPLSED ADQLGESDSD
VEEDGFGEEN HVVLYIPKET QYKMSLLLEE LGIEDRVLEL FSSLLPSITS KRDSGLSKEK
QVNLGKDKVL SFDTDLLQLK KAYKSGSLDL KIKADYTNSK DLKSLLANGS LVKSLLSVSV
RGRLAVGEGD KVAIFDVGQL IGQATIAPIN ADKANVKPLS RNIVRFEIVH LSFNPVVENY
LAVAGLEDCQ ILTLNHRGEV IDRLAVELAL QGAFIRRIDW VPGSQVQLMV VTNKFVKIYD
LSQDSISPTQ YFTLPNDMIV DATLFVASRG RVFLLVLSEQ GNLYRFELSW GGNAGATPLK
EIVQIMGKDV TGKGSSVYFS PTYRLLFISY HDGSSFMGRL SSDATSLTDT SGMFEEESDC
KQRVAGLHRW KELLAGSGLF ICFSSVKSNA VLAVSLRGDG VCAQNLRHPT GSSSPMVGIT
AYKPLSKDNV HCLVLHDDGS LQIYSHVRSG VDTDSNFTAE KVKKLGSKIL NNKTYAGAKP
EFPLDFFERA FCITADVRLG SDAIRNGDSE GAKQSLASED GFIESPSPVG FKISVSNPNP
DIVMVGIRMH VGTTSASSIP SEVTIFQRSI KMDEGMRCWY DIPFTVAESL LADEDVVISV
GPTTSGTALP RIDSLEVYGR AKDEFGWKEK MDAVLDMEAR VLGHGLLLPG SSKKRALAQS
ASMEEQVIAD GLKLLSIYYS VCRPRQEVVL SELKCKQLLE TIFESDRETL LQTTACRVLQ
SVFPRKEIYY QVMFLPNSVK DTMRLLGVVK VTSILSSRLG ILGTGGSIVE EFNAQMRAVS
KVALTRKSNF SVFLEMNGSE VVDNLMQVLW GILESEPLDT PTMNNVVMSS VELIYSYAEC
LASQGKDTGV HSVAPAVQLL KALMLFPNES VQTSSRCVLV LAISSRLLQV PFPKQTMLTT
DDLVDNVTTP SVPIRTAGGN THVMIEEDSI TSSVQYCCDG CSTVPILRRR WHCTVCPDFD
LCEACYEVLD ADRLPPPHTR DHPMTAIPIE VESLGADTNE IQFSADEVGI SNMLPVVTSS
IPQASTPSIH VLEPGESAEF SASLTDPISI SASKRAVNSL ILSEFLQELS GWMETVSGVQ
AIPVMQLFYR LSSAIGGAFM DSSKPEEISL DKLIKWLLGE INLSKPFAAS TRSSLGEIVI
LVFMFFTLML RSWHQPGSDG SSSKLGGSTD VHDRRIVQSS TVVATQSSLH VQERDDFASQ
LVRACSCLRN QEFVNYLMNI LQQLVHVFKS RAANVEARGS SSGSGCGAML TVRRDLPAGN
YSPFFSDSYA KAHRADIFVD YHRLLLENVF RLVYTLVRPE KQEKMGEKEK VYRNASSKDL
KLDGFQDVLC SYINNPHTAF VRRYARRLFL HLCGSKTQYY SVRDSWQFSN EVKNLYKHVE
KSGGFENNVS YERSVKIVKS LSTIAEVAVA RPRNWQKYCL RHGDFLSFLL NGVFHFAEES
VIQTLKLLNL AFYQGKDVSS SVQKAEATEV VTGSNRSGSQ SVDSKKKKKG EDGHDSGLEK
LYVDMEGVVD IFSANCGDLL RQFIDFFLLE WNSSSVRTEA KSVIYGLWHH GRHSFKESLL
AALLQKVRYL PAYGQNIVEY TELVSLLLDK APENNSKQAI NELVDRCLNP DVIRCFFETL
HSQNELIANH PNSRIYSTLG NLVEFDGYYL ESEPCVACSS PDVPYSKMKL ESLKSETKFT
DNRIIVKCTG SYTIQSVTMN VHDARKSKSV KVLNLYYNNR PVSDLSELKN NWSLWKRAKS
CHLSFNQTEL KVEFPIPITA CNFMIELDSF YENLQALSLE PLQCPRCSRP VTDKHGICSN
CHENAYQCRQ CRNINYENLD SFLCNECGYS KYGRFEFNFM AKPSFIFDNM ENDEDMKKGL
AAIESESENA HKRYQQLLGF KKPLLKIVSS IGETEMDSQH KDTVQQMMAS LPGPSCKINR
KIALLGVLYG EKCKAAFDSV SKSVQTLQGL RRVLMSYLHQ KNSNFSSGAS RCVVSKTPNN
CYGCATTFVT QCLEILQVLS KHPRSRKQLV AAGILSELFE NNIHQGPKTA RAQARAALST
FSEGDLSAVN ELNNLVQKKI MYCLEHHRSM DIALATREEM LLLSEVCSLT DEFWESRLRL
VFQLLFSSIK LGAKHPAISE HIILPCLKII SVACTPPKPD TAEKEQTMGK SAPAVQEKDE
NAAGVIKYSS ESEENNLNVS QKTRDIQLVS YLEWEKGASY LDFVRRQYKA SQSIRGASQK
SRTHRSDFLA LKYTLRWKRR SSRTSKGGLQ AFELGSWVTE LILSACSQSI RSEMCTLISL
LAAQSSPRRY RLINLLIGLL PATLAAGESS AEYFELLFKM IETQDALLFL TVRGCLTTIC
KLISQEVGNI ESLERSLQID ISQGFTLHKL LELLGKFLEV PNIRSRFMRD NLLSHVLEAL
IVIRGLIVQK TKLINDCNRR LKDLLDGLLL ESSENKRQFI RACVSGLQTH AEENKGRTCL
FILEQLCNLI CPSKPEAVYM LILNKSHTQE EFIRGSMTKN PYSSAEIGPL MRDVKNKICQ
QLDLLGLLED DYGMELLVAG NIISLDLSIA QVYELVWKKS NQSSTSLTNS ALLASNAAPS
RDCPPMTVTY RLQGLDGEAT EPMIKELEED REESQDPEIE FAIAGAVREY GGLEILLDMI
KSLQDDFKSN QEEMVAVLDL LNHCCKIREN RRALLRLGAL SLLLETARRA FSVDAMEPAE
GILLIVESLT LEANESDSIS AAQSALTVSN EETGTWEQAK KIVLMFLERL SHPSGLKKSN
KQQRNTEMVA RILPYLTYGE PAAMEALIEH FSPYLQNWSE FDQLQQRHEE DPKDDSIAQQ
AAKQRFTVEN FVRVSESLKT SSCGERLKDI VLENGIIAVA VKHIKEIFAI TGQTGFKSSK
EWLLALKLPS VPLILSMLRG LSMGHLPTQT CIDEGGILTL LHALEGVSGE NDIGARAENL
LDTLADKEGK GDGFLGEKVR ALRDATKDEM RRRALRKREE LLQGLGMRQE LSSDGGERIV
VSQPILEGFE DVEEEEDGLA CMVCREGYKL RPSDLLGVYS YSKRVNLGVG NSGSARGECV
YTTVSYFNII HFQCHQEAKR ADAALKNPKK EWEGAMLRNN ESLCNSLFPV KGPSVPLAQY
LRYVDQYWDN LNALGRADGS RLRLLTYDIV LMLARFATGA SFSADCRGGG RDSNSRFLPF
MFQMARHLLD QGGPVQRTNM ARSVSSYISS SSTSTATAPS SDSRPLTPGS QLSSTGTEET
VQFMMVNSLL SESYESWLQH RRVFLQRGIY HTFMQHAHGR VASRAAEPTS SGGKTQDAET
LTGDELLSIV KPMLVYTGMI EQLQQLFKPK KPVHIEPIKK EGTSSGVELE PWEIVMKEKL
LNVKEMIGFS KELISWLDEI NSATDLQEAF DIVGVLADVL SEGVTQCDQF VRSAIDKD
