CDPK1_PLAFO
ID CDPK1_PLAFO Reviewed; 524 AA.
AC A0A2I0BVG8;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Calcium-dependent protein kinase 1 {ECO:0000303|PubMed:27923926};
DE EC=2.7.11.1 {ECO:0000269|PubMed:27923926};
DE AltName: Full=PfCDPK1 {ECO:0000303|PubMed:27923926};
GN Name=PDCK1 {ECO:0000303|PubMed:27923926};
GN ORFNames=CK202_3261 {ECO:0000312|EMBL:PKC46465.1};
OS Plasmodium falciparum (isolate NF54).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5843 {ECO:0000312|Proteomes:UP000232684};
RN [1] {ECO:0000312|Proteomes:UP000232684}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NF54 {ECO:0000312|Proteomes:UP000232684};
RA Bryant J.M., Baumgarten S., Scheidig-Benatar C., Scherf A.;
RT "Plasmodium falciparum NF54 genome assembly.";
RL Submitted (NOV-2017) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP PHOSPHORYLATION, AND MUTAGENESIS OF THR-145.
RX PubMed=27923926; DOI=10.1128/mbio.02011-16;
RA Bansal A., Ojo K.K., Mu J., Maly D.J., Van Voorhis W.C., Miller L.H.;
RT "Reduced Activity of Mutant Calcium-Dependent Protein Kinase 1 Is
RT Compensated in Plasmodium falciparum through the Action of Protein Kinase
RT G.";
RL MBio 7:0-0(2016).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF THR-145.
RX PubMed=29311293; DOI=10.1073/pnas.1715443115;
RA Bansal A., Molina-Cruz A., Brzostowski J., Liu P., Luo Y., Gunalan K.,
RA Li Y., Ribeiro J.M.C., Miller L.H.;
RT "PfCDPK1 is critical for malaria parasite gametogenesis and mosquito
RT infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:774-779(2018).
CC -!- FUNCTION: Calcium-dependent protein kinase which acts as a sensor and
CC effector of intracellular Ca(2+) levels probably in part downstream of
CC cGMP-activated PKG kinase (PubMed:27923926). By phosphorylating various
CC proteins, required for microneme secretion and thus merozoite egress
CC from and invasion of host erythrocytes (By similarity). During
CC gametogenesis, essential for the development of both male and female
CC gametes (PubMed:29311293). Phosphorylates SERA5 p50 which enhances
CC SERA5 p50 protease activity; however, SERA5 p50 protease activity has
CC been shown in other studies to be controversial. Probably by
CC phosphorylating SERA5 p50, plays a role in merozoite egress from host
CC erythrocytes. Probably prior or during merozoite invasion of host
CC erythrocytes, phosphorylates rhoptry protein RhopH3 which is required
CC for RhopH3 localization to rhoptries and for its secretion. Probably in
CC late schizonts, phosphorylates myosin A tail domain-interacting protein
CC MTIP and glideosome-associated protein 45 GAP45, both of which are
CC components of the motor complex that generates the force required by
CC the parasite to invade host cells. In late schizonts, phosphorylates
CC inner membrane complex protein IMC1g. In late schizonts, phosphorylates
CC PKA regulatory subunit PKAr in a calcium-dependent manner, which may
CC contribute to the dissociation of regulatory PKAr and catalytic PKAc
CC subunits and promote the activation of PKAc. May phosphorylate raf
CC kinase inhibitory protein RKIP which in turn may regulate CDPK1
CC catalytic activity (By similarity). May phosphorylate proteins of the
CC host erythrocyte membranes (By similarity).
CC {ECO:0000250|UniProtKB:P62343, ECO:0000250|UniProtKB:P62344,
CC ECO:0000269|PubMed:27923926, ECO:0000269|PubMed:29311293}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:27923926};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:27923926};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:27923926};
CC -!- ACTIVITY REGULATION: Activated by calcium (PubMed:27923926). Upon
CC calcium binding to the EF-hand domains, the C-terminus of the junction
CC domain (J domain) undergoes a conformational change which results in
CC the dissociation of the pseudo-substrate inhibitory motif from the
CC catalytic domain. This, in turn may facilitate the autophosphorylation
CC of the activation loop at Thr-231, which leads to the kinase activation
CC (By similarity). {ECO:0000250|UniProtKB:P62344,
CC ECO:0000269|PubMed:27923926}.
CC -!- SUBUNIT: Monomer. Forms a high molecular weight (250 and 400 kDa)
CC complex. Forms a complex composed of CDPK1, PKA regulatory subunit PKAr
CC and 14-3-3I; the complex is formed in merozoites in response to low
CC extracellular level of K(+) and may play a role in microneme secretion.
CC Interacts (when phosphorylated) with 14-3-3I in a Ca(2+)-independent
CC manner; the interaction does not regulate CDPK1 catalytic activity but
CC is required for merozoite invasion of host erythrocytes. Interacts with
CC PKA regulatory subunit PKAr; in a Ca(2+)-dependent manner. Interacts
CC with SERA5 p50 in the late schizont stage. Interacts with inner
CC membrane complex protein IMC1g in late schizonts. Interacts with
CC rhoptry protein RhopH3 in merozoites. {ECO:0000250|UniProtKB:P62344}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P62344}; Lipid-
CC anchor {ECO:0000250|UniProtKB:P62344}. Cell membrane
CC {ECO:0000269|PubMed:29311293}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62344}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P62344}. Parasitophorous vacuole membrane
CC {ECO:0000250|UniProtKB:P62344}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62344}. Cytoplasm
CC {ECO:0000269|PubMed:29311293}. Cell projection, cilium, flagellum
CC {ECO:0000269|PubMed:29311293}. Host cell membrane
CC {ECO:0000250|UniProtKB:P62344}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P62344}. Note=Localizes to the host erythrocytic
CC membrane at low level (By similarity). Localizes to the cell membrane
CC in the nascent merozoites contained within the late-stage schizonts and
CC in free merozoites. Colocalizes with MTIP around developing merozoites
CC in segmented schizonts, also localizes in membranes around the mature
CC food vacuole/residual body of the schizonts. Ser-64 phosphorylated form
CC localizes at the apical pole in punctate structures in merozoites
CC within late schizonts in free merozoites. In trophozoites and
CC schizonts, localizes to the parasitophorous vacuole (PV) and in
CC membranous systems derived from the PV including intraparasitic
CC vacuoles and the tubovesicular system, an extension of the
CC parasitophorous vacuole membrane into the host cell cytoplasm.
CC Localization to the cytoplasm in trophozoite or schizonts is minimal
CC (By similarity). In female stage V gametocytes and gametes, localizes
CC to the cell membrane. In stage V male gametocytes, localizes to the
CC cell membrane and in the cytoplasm. In male gametes, localizes to the
CC residual body, cell membrane and in the flagella (PubMed:29311293).
CC Calcium and/or autophosphorylation does not affect membrane
CC localization (By similarity). {ECO:0000250|UniProtKB:P62343,
CC ECO:0000250|UniProtKB:P62344, ECO:0000269|PubMed:29311293}.
CC -!- DEVELOPMENTAL STAGE: Expressed during parasite asexual blood stages in
CC schizonts and free merozoites (at protein level) (PubMed:29311293).
CC Expressed in female and male mature gametocytes and gametes (at protein
CC level) (PubMed:29311293). {ECO:0000269|PubMed:29311293}.
CC -!- DOMAIN: The junction domain (J domain) is composed of 2 motifs that
CC maintain the kinase inactive. The N-terminal autoinhibitory motif acts
CC as a pseudosubstrate inhibiting the catalytic domain while the C-
CC terminal motif binds the EF-hand domains.
CC {ECO:0000250|UniProtKB:P62344}.
CC -!- PTM: Myristoylated. Myristoylation, palmitoylation and the basic
CC cluster motif are required for the localization to the parasitophorous
CC vacuole membrane. {ECO:0000250|UniProtKB:P62344}.
CC -!- PTM: Palmitoylated. Palmitoylation increases in merozoites in response
CC to low level of extracellular K(+) in the host blood. Myristoylation,
CC palmitoylation and the basic cluster motif are required for the
CC localization to the parasitophorous vacuole membrane.
CC {ECO:0000250|UniProtKB:P62344}.
CC -!- PTM: Phosphorylation at Ser-64 occurs at late schizont stage and
CC regulates CDPK1 protein-protein interaction. Phosphorylated at Ser-28,
CC Ser-34 and Ser-64 in merozoites in response to low extracellular level
CC of K(+). Phosphorylation at Thr-231 may regulate CDPK1 kinase activity.
CC Phosphorylation increases in response to an increase in intracellular
CC Ca(2+) levels (By similarity). Autophosphorylated in vitro
CC (PubMed:27923926). Autophosphorylation does not affect membrane
CC localization in vitro (By similarity). {ECO:0000250|UniProtKB:P62344,
CC ECO:0000269|PubMed:27923926}.
CC -!- DISRUPTION PHENOTYPE: Knockout in a CDPK1 T145M mutant background
CC causes a reduced asexual growth due to a defect in invasion of host
CC erythrocytes (PubMed:29311293). During gametogenesis, female
CC gametocytes fail to round up upon induction and fail to exit host
CC erythrocytes (PubMed:29311293). Male gametocytes round up normally
CC after induction but fail to exflagellate, to form flagella and to exit
CC host erythrocytes (PubMed:29311293). In mature schizonts, raf kinase
CC inhibitor RKIP mRNA is up-regulated as well as several mRNAs involved
CC in parasite sexual development (PubMed:29311293).
CC {ECO:0000269|PubMed:29311293}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDPK subfamily. {ECO:0000305}.
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DR EMBL; NYMT01000009; PKC46465.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2I0BVG8; -.
DR SMR; A0A2I0BVG8; -.
DR VEuPathDB; PlasmoDB:PfNF54_020022100; -.
DR Proteomes; UP000232684; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0036126; C:sperm flagellum; IMP:UniProtKB.
DR GO; GO:0020005; C:symbiont-containing vacuole membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007292; P:female gamete generation; IMP:UniProtKB.
DR GO; GO:0048232; P:male gamete generation; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF13499; EF-hand_7; 2.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00054; EFh; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00018; EF_HAND_1; 4.
DR PROSITE; PS50222; EF_HAND_2; 4.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Calcium; Cell membrane; Cell projection; Cilium; Cytoplasm;
KW Flagellum; Host cell membrane; Host membrane; Kinase; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Myristate; Nucleotide-binding;
KW Palmitate; Phosphoprotein; Repeat; Serine/threonine-protein kinase;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT CHAIN 2..524
FT /note="Calcium-dependent protein kinase 1"
FT /id="PRO_0000453003"
FT DOMAIN 56..325
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 372..407
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 416..451
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 452..487
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 488..521
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 346..364
FT /note="J domain"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOTIF 10..20
FT /note="Basic cluster involved in membrane binding"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOTIF 346..353
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOTIF 354..364
FT /note="J domain interacts with the EF-hand domains"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT COMPBIAS 18..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 191
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 62..70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10141"
FT BINDING 385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 389
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 391
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 396
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 429
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 431
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 440
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 465
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 467
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 476
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 499
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 501
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 503
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 505
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 510
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 100
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 231
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P62344"
FT MUTAGEN 145
FT /note="T->A,G,Y,S: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:27923926"
FT MUTAGEN 145
FT /note="T->M: 47% reduction in catalytic activity. Asexual
FT blood stage growth is normal. CDPK5 and CDPK6 mRNA are
FT moderately up-regulated while CDPK2, CDPK7 and PKA mRNAs
FT are slightly down-regulated."
FT /evidence="ECO:0000269|PubMed:27923926,
FT ECO:0000269|PubMed:29311293"
SQ SEQUENCE 524 AA; 60800 MW; D2A45E1579D2C951 CRC64;
MGCSQSSNVK DFKTRRSKFT NGNNYGKSGN NKNSEDLAIN PGMYVRKKEG KIGESYFKVR
KLGSGAYGEV LLCREKHGHG EKAIKVIKKS QFDKMKYSIT NKIECDDKIH EEIYNEISLL
KSLDHPNIIK LFDVFEDKKY FYLVTEFYEG GELFEQIINR HKFDECDAAN IMKQILSGIC
YLHKHNIVHR DIKPENILLE NKHSLLNIKI VDFGLSSFFS KDNKLRDRLG TAYYIAPEVL
RKKYNEKCDV WSCGVILYIL LCGYPPFGGQ NDQDIIKKVE KGKYYFDFND WKNISEEAKE
LIKLMLTYDY NKRITAKEAL NSKWIKKYAN NINKSDQKTL CGALSNMRKF EGSQKLAQAA
ILFIGSKLTT LEERKELTDI FKKLDKNGDG QLDKKELIEG YNILRSFKNE LGELKNVEEE
VDNILKEVDF DKNGYIEYSE FISVCMDKQI LFSEERLRDA FNLFDTDKSG KITKEELANL
FGLTSISEQM WNEVLGEADK NKDNMIDFDE FVNMMHKICD NKSS
