GCYA_PLAF7
ID GCYA_PLAF7 Reviewed; 4226 AA.
AC Q8IHY1; Q9N9H5;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Guanylate cyclase alpha {ECO:0000305};
DE Short=PfGCalpha {ECO:0000303|PubMed:10747978};
DE EC=4.6.1.2 {ECO:0000305|PubMed:33500341};
DE AltName: Full=Guanylyl cyclase {ECO:0000303|PubMed:10747978};
GN Name=GCalpha {ECO:0000303|PubMed:10747978};
GN ORFNames=PF3D7_1138400 {ECO:0000312|EMBL:CZT99049.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|EMBL:CAC00546.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=10747978; DOI=10.1074/jbc.m001021200;
RA Carucci D.J., Witney A.A., Muhia D.K., Warhurst D.C., Schaap P., Meima M.,
RA Li J.L., Taylor M.C., Kelly J.M., Baker D.A.;
RT "Guanylyl cyclase activity associated with putative bifunctional integral
RT membrane proteins in Plasmodium falciparum.";
RL J. Biol. Chem. 275:22147-22156(2000).
RN [2] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP DOMAIN, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-756.
RX PubMed=33500341; DOI=10.1128/mbio.02694-20;
RA Nofal S.D., Patel A., Blackman M.J., Flueck C., Baker D.A.;
RT "Plasmodium falciparum Guanylyl Cyclase-Alpha and the Activity of Its
RT Appended P4-ATPase Domain Are Essential for cGMP Synthesis and Blood-Stage
RT Egress.";
RL MBio 12:0-0(2021).
CC -!- FUNCTION: Catalyzes the synthesis of the second messenger cGMP from GTP
CC (Probable). In asexual blood stage schizonts, required for cGMP
CC production which is essential for PKG activation, PKG-dependent Ca(2+)
CC release, and ultimately merozoite egress from host erythrocytes
CC (PubMed:33500341). {ECO:0000269|PubMed:33500341,
CC ECO:0000305|PubMed:33500341}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=4.6.1.2;
CC Evidence={ECO:0000305|PubMed:33500341};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8IDA0};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q8IDA0};
CC Note=Binds 2 magnesium ions per subunit (By similarity). Is also active
CC with manganese (in vitro) (By similarity).
CC {ECO:0000250|UniProtKB:P30803, ECO:0000250|UniProtKB:Q8IDA0};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10747978};
CC Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:33500341}; Multi-pass membrane protein
CC {ECO:0000255}. Note=In gametocytes, localizes to the cell membrane
CC and/or the parasitophorous vacuole membrane.
CC {ECO:0000269|PubMed:10747978}.
CC -!- DEVELOPMENTAL STAGE: During the parasite blood stage, highly expressed
CC in mature schizonts and in gametocytes. {ECO:0000269|PubMed:10747978,
CC ECO:0000269|PubMed:33500341}.
CC -!- DOMAIN: The N-terminus contains a P-type ATPase-like domain which may
CC be important for guanylate cyclase activity.
CC {ECO:0000305|PubMed:33500341}.
CC -!- DISRUPTION PHENOTYPE: Knockout at the asexual blood stage causes growth
CC arrest (PubMed:33500341). Mature schizonts accumulate in host
CC erythrocytes due to a defect in merozoite egress (PubMed:33500341).
CC Lack of swelling or rupture of the parasitophorous vacuole membrane
CC and, no Ca(2+) release from intracellular stores and no secretion of
CC protease SERA5 (PubMed:33500341). Mature schizonts fail to synthesize
CC cGMP; no defect in cAMP levels (PubMed:33500341).
CC {ECO:0000269|PubMed:33500341}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the cation transport
CC ATPase (P-type) (TC 3.A.3) family. Type IV subfamily. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the adenylyl cyclase
CC class-4/guanylyl cyclase family. {ECO:0000305}.
CC -!- CAUTION: Unlike the two guanylate cyclase domains of GCbeta, the
CC guanylate cyclase domains 1 and 2 of GCalpha lack catalytic activity
CC when expressed on their own or in combination.
CC {ECO:0000269|PubMed:10747978}.
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DR EMBL; AJ245435; CAC00546.1; -; Genomic_DNA.
DR EMBL; LN999945; CZT99049.1; -; Genomic_DNA.
DR RefSeq; XP_001348065.1; XM_001348029.1.
DR SMR; Q8IHY1; -.
DR STRING; 5833.PF11_0395; -.
DR PRIDE; Q8IHY1; -.
DR EnsemblProtists; CZT99049; CZT99049; PF3D7_1138400.
DR GeneID; 810941; -.
DR KEGG; pfa:PF3D7_1138400; -.
DR VEuPathDB; PlasmoDB:PF3D7_1138400; -.
DR VEuPathDB; PlasmoDB:Pf7G8_110042200; -.
DR VEuPathDB; PlasmoDB:PfCD01_110043800; -.
DR VEuPathDB; PlasmoDB:PfDd2_110041600; -.
DR VEuPathDB; PlasmoDB:PfGA01_110042600; -.
DR VEuPathDB; PlasmoDB:PfGB4_110044900; -.
DR VEuPathDB; PlasmoDB:PfGN01_110042900; -.
DR VEuPathDB; PlasmoDB:PfHB3_110041800; -.
DR VEuPathDB; PlasmoDB:PfIT_110042900; -.
DR VEuPathDB; PlasmoDB:PfKE01_110042900; -.
DR VEuPathDB; PlasmoDB:PfKH01_110042700; -.
DR VEuPathDB; PlasmoDB:PfKH02_110043600; -.
DR VEuPathDB; PlasmoDB:PfML01_110043200; -.
DR VEuPathDB; PlasmoDB:PfSD01_110041000; -.
DR VEuPathDB; PlasmoDB:PfSN01_110041500; -.
DR VEuPathDB; PlasmoDB:PfTG01_110042800; -.
DR HOGENOM; CLU_224277_0_0_1; -.
DR InParanoid; Q8IHY1; -.
DR OMA; NTMCVEI; -.
DR PhylomeDB; Q8IHY1; -.
DR Reactome; R-PFA-6798695; Neutrophil degranulation.
DR Reactome; R-PFA-936837; Ion transport by P-type ATPases.
DR Proteomes; UP000001450; Chromosome 11.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:GeneDB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0140326; F:ATPase-coupled intramembrane lipid transporter activity; IBA:GO_Central.
DR GO; GO:0004383; F:guanylate cyclase activity; TAS:GeneDB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006182; P:cGMP biosynthetic process; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:GeneDB.
DR CDD; cd07302; CHD; 2.
DR Gene3D; 3.30.70.1230; -; 2.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR InterPro; IPR032630; P_typ_ATPase_c.
DR Pfam; PF00211; Guanylate_cyc; 3.
DR Pfam; PF16212; PhoLip_ATPase_C; 1.
DR SMART; SM00044; CYCc; 2.
DR SUPFAM; SSF55073; SSF55073; 2.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE 1: Evidence at protein level;
KW Cell membrane; cGMP biosynthesis; Cytoplasmic vesicle; Glycoprotein; Lyase;
KW Magnesium; Membrane; Metal-binding; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..4226
FT /note="Guanylate cyclase alpha"
FT /id="PRO_0000452805"
FT TOPO_DOM 1..104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..131
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..392
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 393..413
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 414..2083
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 2084..2104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2105..2119
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 2120..2140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2141..2169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 2170..2190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2191..2202
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 2203..2223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2224..2235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 2236..2256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2257..2275
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 2276..2296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2297..2787
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 2788..2808
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2809..2828
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 2829..2849
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2850..2860
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 2861..2881
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2882..2900
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 2901..2921
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2922..2930
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 2931..2951
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2952..3008
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 3009..3029
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3030..3738
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 3739..3759
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3760..3773
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 3774..3794
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3795..3811
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 3812..3832
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3833..3840
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 3841..3861
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3862..3871
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 3872..3892
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3893
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 3894..3914
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3915..4226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 3013..3270
FT /note="Guanylate cyclase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT DOMAIN 3970..4104
FT /note="Guanylate cyclase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 552..572
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 832..904
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 968..989
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1740..1765
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2477..2505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3077..3150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3201..3230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 850..871
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 872..904
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2477..2500
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3109..3141
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3215..3230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 3975
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 3975
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 3976
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 4019
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 4019
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 756
FT /note="D->N: Lethal in the asexual blood stage."
FT /evidence="ECO:0000269|PubMed:33500341"
FT CONFLICT 206
FT /note="P -> H (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="N -> T (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="I -> S (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="T -> S (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="N -> T (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 823
FT /note="F -> N (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 2265
FT /note="I -> L (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 3014
FT /note="I -> T (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 3581
FT /note="E -> K (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 3591
FT /note="S -> P (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
FT CONFLICT 3756
FT /note="S -> Y (in Ref. 1; CAC00546)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 4226 AA; 496021 MW; 04B292AC3FD6356D CRC64;
MSDSKKHYNE SNVRYKVKYS GKIFGNNMKK LNENNNHDFT TAEAAWMEKK KKLYKDTNNQ
PLWDFRKIQI NPTETDELIS FPSNKICSKN YGKYSFIFKG LYEQFLRLPN IWFLLISLLE
FIPQYQNLSN YMYYSKHSSF FLLLFFICVS IIKNIYEDSR RSNIDYQINN RLCHMLDGPN
SQLKAVRWME LSVGSIIRLI ENEQVPADIL LLSCNNSEGV VYIETSLLNG ETNLNKKYCV
NETRNETSIY AISNIRGRIV CEKPNSNMES FNGSLKLDAH PRATSLSINN VIFKGSHIKN
TEYIFGVILY TGNDTKIMKN ISNNKHKLGY VNKELNSYTI IGLIFTFICV FISVLFKWTE
DDKFRNGSHF FLITVKDNIC ESIVKYTLLY SNIIPISILI SVDLISILQS ILIENDNHIS
TFENYETSEP STIDDMDNEL GDFKMDKSHT FFKKYTYFLN NRSKNFTNNR YSSTNTERAS
DFRKSFFGTF DKLKTIKRYF YSIKSKIKSI SQSNTLYNKS SAGGSIIRSD KNKQTTFSKS
FIDIFQRTNN NEHSQTLDNN NNNDNNNNNN ICKEKYQNVN NSKNVYVSED SSNNKYKQND
YLQKSQEQNE IHSINNNNYN NKNDNNLQTE FSNHNFRINA YKTNRTTKDD TYNNKHISLN
SRSKSNQKGI LINSNEINRK KKKNLLQKIF PFFKKKRTNI SEDLSKYVFR RSKQLNINHN
NSEKYNLNDY DEYGWGLCLN SNMHGDLGNV DFIFTDKTGT LTNNNMTFNM CSIAGKTYGS
KCKNKKKIYN NPKSNNDNKL NSYDKNIFKN KFSSEASIKK ISFVRDFSNN VSSKNDLTLD
DPTELISDEG NNYLRDKYEH TSDKKNDTNK NRDGANNSNN NNNKDVSNNK NKNNNNYNYN
SNNDYIKQNG ECNIYNNQNN TNNTHNNNIY YDEYNNTNEG NMKNTNVNKD TNSKCNKKDF
IINTSDIINN NNNNNNDQKT NNLKYKSSSS WNSKAKKSSY INLNSYNKYQ SFQNSSMLSS
SLSSTCSSET EDENGSQLMY YSSSNYDNLD INNDMDSTKT YSHYTEQNYY NSVKDDKDIN
SEHQRYQQKK TNKQTKNIQQ NQCDQWEDNR YTQESIKNQY FFDRNYQTFL MKQNFPRPKS
FRLNMNSSSV KGRCDFNDTK IYNDLNSQSW RGYYIDEFFK CMTLCHAVTP FIQFDYIRNK
HLTYTNSRSS KGISNNMDRY NINPTTTTTN NNNNNNNINN INNINNNNNN NNNNNNNKQF
SCDYMKNRND IIFETSTDYY ANQDNAKRKR EKTLFDNVSH CGEIQEYRDN KKYRMKRSQT
CSNNRKIFSN QRTLYDYRNM NNNLKNKNSY LRNKLKSKIF LDKSYRKRKK SSGTYKGSDI
CKGIEKKETR RWKRFLHMKG SNNRNIFSRI KDFKSNSIIY NNQDKTNDYK NGYSNNINNN
NSNNYTNEKI NRSFNKRHSA VSFKQMSKEK LIPINNVLSN RCDVESYPNE ELSFSKKKKK
NSEIVSFASG KSDIGFEERT DAGIAGKNME LSYNELEKYK YVKHIDSNNK YINNNNNSIH
MSHMSSNNNT FESHIYFDAI KYQSSSLDEE CLIYSSSFLG YRLVLRNKNT MCIEIDGSFN
KWTIIGVNEF TNRRGKMSIV VKPDSMESGS ILYVKGSDSS ILSLLNLKYS KFLDKKYSRK
RRNKNIQKYK QKREEYNELK SKDINIEEFQ KSKSLSLKNF KNNTPKVLFG ECTLDNNNNN
INKNYKYDKN DKHNNNNNNN NNNSNYSYNY LHDSNNLDAM QNQKYSYAYE DKEDYYYTNN
GECNKYKERY RRLEKQLRKF SVKGLRSMIF AFRYLSEEET IKYKRMYDDA CSSIYNKEQR
LEKVAEEFER DLIYLGITGV KNGLQEKVPK TIDILNQSGI RIWMLTGDNV EYSLHVSFLC
KFLNKHTKIF HAALENSNAK KLKREGMALY ELFQLEKEEK KPYENLCLLV NGRNLQTFLN
YTDLQTHFLN MACTCDVVIA CRITAKQKAF LVQLIKNRLY PTPNTLAIGD GANDIAMIQE
ANIGVSIMTS DCIISAGYSD YCIKKFCYLR KLLFIYGSKH LYTISIILYW NFFKNILLIL
PIFFYQAYAS WSCVKIYPEL LYTFFSIFWV FIPIIYYMFL QHNLNYDILY NIPLFYALSR
RRYNMNCFKF LPWIFEAIFY SMIIYFFAYA ALKENSHLNN GEVITINTFG NICFIGCLLI
SILRLFLEGS LWSPSILITC FGCFLFVFFP SLLFICFAYL SNEYIREVFR QTFLWAPLYV
LLILWFSTCI ISYIFINFTK SILFPNIYNV VNHWLFEQYQ EKHNKNKYIF SLSGKNKFLK
LRKLGKKIKF KFKRNYSKKY DTNVIREHPL LHHTFKSEQD QNKCNEQFSK DPFISNSLLK
SKNCKFKKDS SYSKSNIHVD EEQTYKGLKV VLSEQVVHAK ENLVSFKNEK KNKNNKNTSM
NVNDNIIIKN NNINIKNNDN NNDDNDNDNN NNNNNNDNYN NNDHNKKEFK QKHIQNNYEN
LFNHTQVENN LIKENLSIRN DNNRRDNKNE TDYIKQSDED YEMNPSITSL RKRECINDSK
YIDNKSYDNK ISNNHEEKDG FKSDDRSLIN SNMMDYKNEF TENDTTYSFN DSHMFYDFPS
NSKTTKDYKV INSRIDDSIM ADMKNCLNPL KNTFLVDLLP PGKRFRINED HIYFKNNERM
ENIPEALDVN KKYYHIIQNK AEYYDNDSLS EFSYTSSNSS INNKKKNENT QKEIVKVSHL
INRFTLAFKD MQLESGFQIH KKNKFYKTFT PWYRFIFLLL GVFFLYVWKL ESSLSQLWNM
PSDASTDVFI LFLSLLLELV LLAATVTTFF SNIFIENFNK IISAVVILII TYHVVSYSVT
HIDGVFQAVL FPLYTFVILR LPFVNAVLCN IIFLGLFIIR FNGDHFLDKK GLAHYIPLFI
GVDVFVGFVG YRLEYNQRKN FLLEYSVESS RRKQREILNT MLPPFVVDEM IYSELNEEGI
PISLKAEDIS TVTIIFCDIY DFQNIVASIE PTRLVEVLDR LFLCFDKCTE QFNCTKIETV
FETYLAACGL VKREKDEDEL ENNKYSNNNK NNNNNYYYNR KKKKKKNNNN NNNNNNNNNN
NNNNNNNLNN NNNNNNVNTS DDDGDFFEED DANNHQIYNQ MKGQEDAHDS IDFALSILHV
SSHIKYEKSK MMLKKNDSFE DANDDTHNVN DSFNNDKAEN DNTNTDNNKP TRIRVKVGIH
SGRIIAGVVG SKKPQYALFG DTVNTASRMK TTGKPDYIHI SEATYNLVKD DKTLIYEKKE
TEIKGKGIMT TYLLTSVIGL NYPFLGEHVE KKGHFISELY EDDLSNNLNY DKTQNILGYY
SNKINQNNDS NINEGIINNN MNTFNTIDGD TSNYYVNLKD LSLNDLPNEY IKDVNTHYCE
IIKLRNLKIG TAVGYQLKQK DFYNMTFLNN GLNNDTATNF NQYIESHKDF DDIKDLRIGM
NKLSISDSLY YLNENVIRNE PINEYKNKIK INSVNTNKKS YEDAHLNAGN IIYTNNEYPN
GQNIEEDDDL LLTNHYNKTN VNNNNNNNIY DVSKELIEHN EEDYKNILMC SKRCKNCNET
YCTPNDCNNN DHVYHVMYHR KLSNIKKNYL KNIRKDANIK KDIEKEELNK IHSNKKSFNF
FYLFSYIFKI FPFIGKINKE EKKNKSYKKG EQDKSSKRII ALNSEWIFLK FSDKNLEAKY
RAHFYSNKSN INSIEQALII FLVTFVMQTL ISSTVSIVFI DHKRATQTLH INYFAYWSVR
SVYTFFGFVL WLLFHYRTRP EVSSLLNIKW MIFFLNLLFI SAACVFSIAY LWAISETDQT
TSYTIWMTND TIEFFFYLVI LHHNTGMLFQ TCILVDLLFI TMSLTFIATS VVKTITTDST
VLLIPWYVAF NLISTYCKES IDRRTFYANE SAKKTENRAT ELLNDMLPKH VLEEFQQDKL
KLAYTHDRLT FLFADICGFT SWANGVDASE VLTLLQKLFA KFDNDSTKYG LYKLCTIGDA
YVAISEPVTE DNKDYDPVDG TERVLEMAYS MIRIIKEIRE KLYIPNLNMR IGLHYGSCVG
GVIGSGRLRY DLWGIDVLTG NLMESNGIPG KINVSETLKN FLLQQFKNRF IFKPHTTIRV
IYKDVKCFII TDKKEVESSN HSKLLQNKNY LLNKKFSTQN YLVKNIFAKK KHSSISSSKN
IHSYDEKKKK KNDLFYINVN DRQSNL
