KGP_PLAF7
ID KGP_PLAF7 Reviewed; 853 AA.
AC Q8I719;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=cGMP-dependent protein kinase {ECO:0000303|PubMed:12068803};
DE EC=2.7.11.12 {ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:12817987, ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:29251493, ECO:0000269|PubMed:30315162, ECO:0000269|PubMed:31239348};
DE AltName: Full=PfPKG {ECO:0000303|PubMed:12068803};
GN Name=PKG {ECO:0000303|PubMed:12068803};
GN ORFNames=PF3D7_1436600 {ECO:0000312|EMBL:CZU00064.1};
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|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 [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, DEVELOPMENTAL STAGE, PHOSPHORYLATION, AND MUTAGENESIS OF
RP 2-GLU--THR-114 AND 2-GLU--PHE-434.
RX PubMed=12068803; DOI=10.1046/j.1365-2958.2002.02948.x;
RA Deng W., Baker D.A.;
RT "A novel cyclic GMP-dependent protein kinase is expressed in the ring stage
RT of the Plasmodium falciparum life cycle.";
RL Mol. Microbiol. 44:1141-1151(2002).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, DOMAIN, PHOSPHORYLATION,
RP AND MUTAGENESIS OF SER-133; SER-251; GLY-360 AND THR-493.
RX PubMed=12817987; DOI=10.1042/bj20030474;
RA Deng W., Parbhu-Patel A., Meyer D.J., Baker D.A.;
RT "The role of two novel regulatory sites in the activation of the cGMP-
RT dependent protein kinase from Plasmodium falciparum.";
RL Biochem. J. 374:559-565(2003).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=18532880; DOI=10.1371/journal.pbio.0060139;
RA McRobert L., Taylor C.J., Deng W., Fivelman Q.L., Cummings R.M.,
RA Polley S.D., Billker O., Baker D.A.;
RT "Gametogenesis in malaria parasites is mediated by the cGMP-dependent
RT protein kinase.";
RL PLoS Biol. 6:e139-e139(2008).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP THR-618.
RX PubMed=19915077; DOI=10.1128/ec.00186-09;
RA Taylor H.M., McRobert L., Grainger M., Sicard A., Dluzewski A.R.,
RA Hopp C.S., Holder A.A., Baker D.A.;
RT "The malaria parasite cyclic GMP-dependent protein kinase plays a central
RT role in blood-stage schizogony.";
RL Eukaryot. Cell 9:37-45(2010).
RN [6] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=23139764; DOI=10.1371/journal.pone.0048206;
RA Hopp C.S., Flueck C., Solyakov L., Tobin A., Baker D.A.;
RT "Spatiotemporal and functional characterisation of the Plasmodium
RT falciparum cGMP-dependent protein kinase.";
RL PLoS ONE 7:e48206-e48206(2012).
RN [7] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF THR-618.
RX PubMed=23675297; DOI=10.1371/journal.ppat.1003344;
RA Collins C.R., Hackett F., Strath M., Penzo M., Withers-Martinez C.,
RA Baker D.A., Blackman M.J.;
RT "Malaria parasite cGMP-dependent protein kinase regulates blood stage
RT merozoite secretory organelle discharge and egress.";
RL PLoS Pathog. 9:e1003344-e1003344(2013).
RN [8] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF THR-618.
RX PubMed=24594931; DOI=10.1371/journal.pbio.1001806;
RA Brochet M., Collins M.O., Smith T.K., Thompson E., Sebastian S.,
RA Volkmann K., Schwach F., Chappell L., Gomes A.R., Berriman M., Rayner J.C.,
RA Baker D.A., Choudhary J., Billker O.;
RT "Phosphoinositide metabolism links cGMP-dependent protein kinase G to
RT essential Ca(2+) signals at key decision points in the life cycle of
RT malaria parasites.";
RL PLoS Biol. 12:e1001806-e1001806(2014).
RN [9] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=26149123; DOI=10.1038/ncomms8285;
RA Alam M.M., Solyakov L., Bottrill A.R., Flueck C., Siddiqui F.A., Singh S.,
RA Mistry S., Viskaduraki M., Lee K., Hopp C.S., Chitnis C.E., Doerig C.,
RA Moon R.W., Green J.L., Holder A.A., Baker D.A., Tobin A.B.;
RT "Phosphoproteomics reveals malaria parasite Protein Kinase G as a
RT signalling hub regulating egress and invasion.";
RL Nat. Commun. 6:7285-7285(2015).
RN [10] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, DOMAIN, AND MUTAGENESIS
RP OF 2-GLU--LEU-31; 2-GLU--LYS-157; 2-GLU--LEU-274; 2-GLU--ILE-400 AND
RP 2-GLU--GLN-518.
RX PubMed=29251493; DOI=10.1021/acsinfecdis.7b00222;
RA Franz E., Knape M.J., Herberg F.W.;
RT "cGMP Binding Domain D Mediates a Unique Activation Mechanism in Plasmodium
RT falciparum PKG.";
RL ACS Infect. Dis. 4:415-423(2018).
RN [11] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF THR-618.
RX PubMed=30315162; DOI=10.1038/s41467-018-06733-w;
RA Fang H., Gomes A.R., Klages N., Pino P., Maco B., Walker E.M.,
RA Zenonos Z.A., Angrisano F., Baum J., Doerig C., Baker D.A., Billker O.,
RA Brochet M.;
RT "Epistasis studies reveal redundancy among calcium-dependent protein
RT kinases in motility and invasion of malaria parasites.";
RL Nat. Commun. 9:4248-4248(2018).
RN [12] {ECO:0007744|PDB:4OFF, ECO:0007744|PDB:4OFG}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 401-542 IN COMPLEX WITH CGMP,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, DOMAIN, AND
RP MUTAGENESIS OF ARG-484; GLN-532 AND ASP-533.
RX PubMed=25646845; DOI=10.1371/journal.ppat.1004639;
RA Kim J.J., Flueck C., Franz E., Sanabria-Figueroa E., Thompson E.,
RA Lorenz R., Bertinetti D., Baker D.A., Herberg F.W., Kim C.;
RT "Crystal structures of the carboxyl cGMP binding domain of the Plasmodium
RT falciparum cGMP-dependent protein kinase reveal a novel capping triad
RT crucial for merozoite egress.";
RL PLoS Pathog. 11:e1004639-e1004639(2015).
RN [13] {ECO:0007744|PDB:5DYK, ECO:0007744|PDB:5E16}
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS), X-RAY CRYSTALLOGRAPHY (1.65
RP ANGSTROMS) OF 21-162 IN COMPLEX WITH CGMP, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, SUBUNIT, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DOMAIN, AND
RP MUTAGENESIS OF 2-GLU--ASP-29.
RX PubMed=31239348; DOI=10.1073/pnas.1905558116;
RA El Bakkouri M., Kouidmi I., Wernimont A., Amani M., Hutchinson A.,
RA Loppnau P., Kim J.J., Flueck C., Walker J.R., Seitova A., Senisterra G.,
RA Kakihara Y., Kim C., Blackman M.J., Calmettes C., Baker D.A., Hui R.;
RT "Structures of the cGMP-dependent protein kinase in malaria parasites
RT reveal a unique structural relay mechanism for activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:14164-14173(2019).
CC -!- FUNCTION: Serine/threonine protein kinase which acts as a downstream
CC effector of the second messenger cGMP (PubMed:12068803,
CC PubMed:12817987, PubMed:26149123). Controls the release of Ca(2+) from
CC intracellular stores by regulating phosphoinositide biosynthesis
CC (PubMed:24594931). Ca(2+) signals are essential for merozoite and
CC sporozoite invasion and egress from host hepatocytes and erythrocytes,
CC and, in the mosquito vector, for gametocyte activation, and ookinete
CC and sporozoite motility (PubMed:24594931). During the host liver stage,
CC regulates the initial invasion of host hepatocytes by sporozoites by
CC regulating sporozoite motility and microneme exocytosis (By
CC similarity). Following parasite development in the hepatocytes,
CC required for the release of merosomes, a vesicle containing the mature
CC merozoites (By similarity). During the asexual blood stage, required
CC for the progression from schizont to the ring stage following merozoite
CC invasion of host erythrocytes and for merozoite egress
CC (PubMed:19915077, PubMed:26149123, PubMed:25646845). Regulates
CC merozoite egress by promoting the release of exonemes and micronemes
CC which contain proteins essential for egress (PubMed:23675297).
CC Phosphorylates CDPK1 predominantly at the late schizont stage;
CC phosphorylation at 'Ser-64' regulates CDPK1 protein-protein interaction
CC and phosphorylation at 'Thr-231' may regulate CDPK1 kinase activity
CC (PubMed:26149123). Phosphorylates MyoA at 'Ser-19' (PubMed:26149123).
CC In the mosquito vector, required for the initiation of gametogenesis
CC induced by xanthurenic acid, specifically the gametocyte
CC differentiation from the crescent-shaped form to the spherical form
CC (PubMed:18532880). Required for the gliding motility of ookinetes to
CC reach and penetrate the midgut epithelium by promoting Ca(2+)-mediated
CC activation of CDPK1 and CDPK4 (By similarity). Also required for
CC microneme secretion in ookinete by promoting Ca(2+)-mediated activation
CC of CDPK3 (By similarity). {ECO:0000250|UniProtKB:A0A509AKL0,
CC ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:12817987,
CC ECO:0000269|PubMed:18532880, ECO:0000269|PubMed:19915077,
CC ECO:0000269|PubMed:23675297, ECO:0000269|PubMed:24594931,
CC ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:26149123}.
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=2.7.11.12;
CC Evidence={ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:12817987,
CC ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:26149123,
CC ECO:0000269|PubMed:29251493, ECO:0000269|PubMed:30315162,
CC ECO:0000269|PubMed:31239348};
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=2.7.11.12; Evidence={ECO:0000269|PubMed:12068803,
CC ECO:0000269|PubMed:12817987, ECO:0000269|PubMed:25646845,
CC ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:29251493,
CC ECO:0000269|PubMed:30315162, ECO:0000269|PubMed:31239348};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:25646845};
CC -!- ACTIVITY REGULATION: Activated by cGMP (PubMed:12068803,
CC PubMed:12817987, PubMed:26149123, PubMed:29251493, PubMed:25646845,
CC PubMed:31239348). Not activated by cAMP (PubMed:12068803,
CC PubMed:12817987). cGMP binding allosterically triggers a conformational
CC change at the alpha C-helix of cGMP-binding domain 4, which bridges the
CC regulatory and catalytic domains, causing the capping triad, composed
CC of Arg-484, Gln-532 and Asp-533, to form and stabilize the active
CC conformation (PubMed:29251493, PubMed:25646845). The cGMP-binding
CC domains acts cooperatively to activate PKG (PubMed:29251493,
CC PubMed:12817987). {ECO:0000269|PubMed:12068803,
CC ECO:0000269|PubMed:12817987, ECO:0000269|PubMed:25646845,
CC ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:29251493,
CC ECO:0000269|PubMed:31239348}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:12068803};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:26149123,
CC ECO:0000269|PubMed:31239348}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19915077,
CC ECO:0000269|PubMed:23139764, ECO:0000269|PubMed:31239348}. Endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:23139764}; Peripheral membrane
CC protein {ECO:0000269|PubMed:23139764}; Cytoplasmic side
CC {ECO:0000269|PubMed:23139764}. Note=Predominantly localizes to the
CC cytoplasm during schizogony. {ECO:0000269|PubMed:23139764}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite blood stage,
CC expression is low at the ring stage and in early trophozoites, then
CC increases during the parasite maturation to peak at the late schizont
CC stage (at protein level) (PubMed:31239348, PubMed:19915077,
CC PubMed:23139764, PubMed:12068803). Expression is low in gametocytes (at
CC protein level) (PubMed:23139764). {ECO:0000269|PubMed:12068803,
CC ECO:0000269|PubMed:19915077, ECO:0000269|PubMed:23139764,
CC ECO:0000269|PubMed:31239348}.
CC -!- DOMAIN: The cNMP-binding domains 1, 2 and 4 bind preferentially cGMP
CC (PubMed:25646845). The cNMP-binding domain 4 binds cGMP with the
CC highest affinity and is highly selective for cGMP (PubMed:29251493,
CC PubMed:25646845, PubMed:31239348). The cNMP-binding domain 3 does not
CC bind cGMP but is required for cGMP-dependent catalytic activity
CC (PubMed:12817987). The cNMP-binding domains 1, 2 and 4 can bind cAMP
CC but with less affinity (PubMed:25646845). {ECO:0000269|PubMed:12817987,
CC ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:29251493,
CC ECO:0000269|PubMed:31239348}.
CC -!- DOMAIN: The autoinhibitory segment (AIS) interacts with the active site
CC and inhibits catalytic activity. {ECO:0000269|PubMed:31239348}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:12068803,
CC ECO:0000269|PubMed:12817987}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. cGMP subfamily. {ECO:0000305}.
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DR EMBL; LN999946; CZU00064.1; -; Genomic_DNA.
DR RefSeq; XP_001348520.1; XM_001348484.1.
DR PDB; 4OFF; X-ray; 1.89 A; A=401-542.
DR PDB; 4OFG; X-ray; 2.00 A; A=401-542.
DR PDB; 5DYK; X-ray; 2.45 A; A=1-853.
DR PDB; 5E16; X-ray; 1.65 A; A=21-162.
DR PDBsum; 4OFF; -.
DR PDBsum; 4OFG; -.
DR PDBsum; 5DYK; -.
DR PDBsum; 5E16; -.
DR AlphaFoldDB; Q8I719; -.
DR SMR; Q8I719; -.
DR STRING; 5833.PF14_0346; -.
DR GuidetoPHARMACOLOGY; 3013; -.
DR PRIDE; Q8I719; -.
DR EnsemblProtists; CZU00064; CZU00064; PF3D7_1436600.
DR GeneID; 811928; -.
DR KEGG; pfa:PF3D7_1436600; -.
DR VEuPathDB; PlasmoDB:PF3D7_1436600; -.
DR HOGENOM; CLU_000288_73_2_1; -.
DR InParanoid; Q8I719; -.
DR OMA; SKNPDGH; -.
DR PhylomeDB; Q8I719; -.
DR BRENDA; 2.7.11.12; 4889.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:GeneDB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:GeneDB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR GO; GO:0004692; F:cGMP-dependent protein kinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0007276; P:gamete generation; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00038; CAP_ED; 4.
DR CDD; cd05572; STKc_cGK; 1.
DR Gene3D; 2.60.120.10; -; 4.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR002374; cGMP_dep_kinase.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR035014; STKc_cGK.
DR Pfam; PF00027; cNMP_binding; 3.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF000559; cGMP-dep_kinase; 1.
DR SMART; SM00100; cNMP; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF51206; SSF51206; 4.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00888; CNMP_BINDING_1; 3.
DR PROSITE; PS00889; CNMP_BINDING_2; 3.
DR PROSITE; PS50042; CNMP_BINDING_3; 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 3D-structure; ATP-binding; cGMP; cGMP-binding; Cytoplasm;
KW Endoplasmic reticulum; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..853
FT /note="cGMP-dependent protein kinase"
FT /id="PRO_0000451908"
FT DOMAIN 541..798
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 799..853
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..29
FT /note="Autoinhibitory segment"
FT /evidence="ECO:0000269|PubMed:31239348"
FT REGION 58..173
FT /note="cNMP-binding domain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
FT REGION 176..275
FT /note="cNMP-binding domain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
FT REGION 295..398
FT /note="cNMP-binding domain 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
FT REGION 418..517
FT /note="cNMP-binding domain 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
FT REGION 827..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 664
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 113
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:31239348,
FT ECO:0007744|PDB:5E16"
FT BINDING 122
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:31239348,
FT ECO:0007744|PDB:5E16"
FT BINDING 123
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:31239348,
FT ECO:0007744|PDB:5E16"
FT BINDING 125
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:31239348,
FT ECO:0007744|PDB:5E16"
FT BINDING 132
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:31239348,
FT ECO:0007744|PDB:5E16"
FT BINDING 133
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:31239348,
FT ECO:0007744|PDB:5E16"
FT BINDING 473
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:25646845,
FT ECO:0007744|PDB:4OFG"
FT BINDING 482
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:25646845,
FT ECO:0007744|PDB:4OFG"
FT BINDING 483
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:25646845,
FT ECO:0007744|PDB:4OFG"
FT BINDING 485
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:25646845,
FT ECO:0007744|PDB:4OFG"
FT BINDING 492
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:25646845,
FT ECO:0007744|PDB:4OFG"
FT BINDING 493
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:25646845,
FT ECO:0007744|PDB:4OFG"
FT BINDING 547..555
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 570
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 484
FT /note="Part of a catalytic triad required for cGMP binding
FT and cGMP-dependent kinase activity"
FT /evidence="ECO:0000269|PubMed:25646845"
FT SITE 532
FT /note="Part of a catalytic triad required for cGMP binding
FT and cGMP-dependent kinase activity"
FT /evidence="ECO:0000269|PubMed:25646845"
FT SITE 533
FT /note="Part of a catalytic triad required for cGMP binding
FT and cGMP-dependent kinase activity"
FT /evidence="ECO:0000269|PubMed:25646845"
FT MUTAGEN 2..518
FT /note="Missing: Loss of catalytic activity and irresponsive
FT to cGMP, with peptides as substrates."
FT /evidence="ECO:0000269|PubMed:29251493"
FT MUTAGEN 2..434
FT /note="Missing: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:12068803"
FT MUTAGEN 2..400
FT /note="Missing: Low basal catalytic activity. Normal
FT increase in catalytic activity in presence of cGMP."
FT /evidence="ECO:0000269|PubMed:29251493"
FT MUTAGEN 2..274
FT /note="Missing: Low basal catalytic activity. Normal
FT increase in catalytic activity in presence of cGMP."
FT /evidence="ECO:0000269|PubMed:29251493"
FT MUTAGEN 2..157
FT /note="Missing: Low basal catalytic activity. Normal
FT increase in catalytic activity in presence of cGMP."
FT /evidence="ECO:0000269|PubMed:29251493"
FT MUTAGEN 2..114
FT /note="Missing: Has low catalytic activity in absence of
FT cGMP. Normal increase in catalytic activity in presence of
FT cGMP."
FT /evidence="ECO:0000269|PubMed:12068803"
FT MUTAGEN 2..31
FT /note="Missing: Has low catalytic activity in absence of
FT cGMP. cGMP binding is still required for full activation."
FT /evidence="ECO:0000269|PubMed:29251493"
FT MUTAGEN 2..29
FT /note="Missing: Has low catalytic activity in absence of
FT cGMP."
FT /evidence="ECO:0000269|PubMed:31239348"
FT MUTAGEN 133
FT /note="S->A: No effect on cGMP-mediated catalytic activity.
FT Slight reduction in cGMP-mediated catalytic activity; when
FT associated with A-251. Severe loss of cGMP-mediated
FT catalytic activity; when associated with A-493 or A-251 and
FT A-493."
FT /evidence="ECO:0000269|PubMed:12817987"
FT MUTAGEN 251
FT /note="S->A: 12% reduction in cGMP-mediated catalytic
FT activity. Slight reduction in cGMP-mediated catalytic
FT activity; when associated with A-133. Severe loss of cGMP-
FT mediated catalytic activity; when associated with A-493 or
FT A-133 and A-493."
FT /evidence="ECO:0000269|PubMed:12817987"
FT MUTAGEN 360
FT /note="G->E: 55% loss in cGMP-mediated catalytic activity."
FT /evidence="ECO:0000269|PubMed:12817987"
FT MUTAGEN 484
FT /note="R->A: Reduces affinity for cGMP and severe loss of
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:25646845"
FT MUTAGEN 493
FT /note="T->A: 42% reduction in cGMP-mediated catalytic
FT activity. Severe loss of cGMP-mediated catalytic activity;
FT when associated with A-133, A-251 or A-133 and A-251."
FT /evidence="ECO:0000269|PubMed:12817987"
FT MUTAGEN 532
FT /note="Q->A: Reduces affinity for cGMP and severe loss of
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:25646845"
FT MUTAGEN 533
FT /note="D->A: Reduces affinity for cGMP and severe loss of
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:25646845"
FT MUTAGEN 618
FT /note="T->Q: 4.5-fold reduction in affinity for ATP. No
FT defect in schizogony during host erythrocyte invasion.
FT However, Ca(2+) increase in response to cGMP is reduced in
FT schizonts. Does not affect merozoite egress from host
FT erythrocytes. Resistant to trisubstituted pyrrole compound
FT 1 (C1) and imidazopyridine-based compound 2 (C2)
FT inhibitors."
FT /evidence="ECO:0000269|PubMed:19915077,
FT ECO:0000269|PubMed:23675297, ECO:0000269|PubMed:24594931,
FT ECO:0000269|PubMed:30315162"
FT TURN 22..25
FT /evidence="ECO:0007829|PDB:5E16"
FT HELIX 28..35
FT /evidence="ECO:0007829|PDB:5E16"
FT HELIX 43..55
FT /evidence="ECO:0007829|PDB:5E16"
FT TURN 57..61
FT /evidence="ECO:0007829|PDB:5E16"
FT HELIX 64..73
FT /evidence="ECO:0007829|PDB:5E16"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:5E16"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:5E16"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:5E16"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:5E16"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:5E16"
FT HELIX 123..128
FT /evidence="ECO:0007829|PDB:5E16"
FT STRAND 134..148
FT /evidence="ECO:0007829|PDB:5E16"
FT HELIX 149..157
FT /evidence="ECO:0007829|PDB:5E16"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 182..190
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 228..233
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 251..266
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 267..274
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 277..292
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 301..310
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 311..316
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 330..339
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 348..353
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 361..365
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 373..387
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 388..395
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 404..414
FT /evidence="ECO:0007829|PDB:4OFF"
FT HELIX 417..419
FT /evidence="ECO:0007829|PDB:4OFF"
FT HELIX 424..433
FT /evidence="ECO:0007829|PDB:4OFF"
FT STRAND 435..439
FT /evidence="ECO:0007829|PDB:4OFF"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:4OFF"
FT STRAND 454..461
FT /evidence="ECO:0007829|PDB:4OFF"
FT STRAND 463..467
FT /evidence="ECO:0007829|PDB:4OFF"
FT STRAND 470..475
FT /evidence="ECO:0007829|PDB:4OFF"
FT HELIX 483..486
FT /evidence="ECO:0007829|PDB:4OFF"
FT STRAND 493..498
FT /evidence="ECO:0007829|PDB:4OFF"
FT STRAND 503..509
FT /evidence="ECO:0007829|PDB:4OFF"
FT HELIX 510..517
FT /evidence="ECO:0007829|PDB:4OFF"
FT HELIX 519..521
FT /evidence="ECO:0007829|PDB:4OFF"
FT HELIX 538..540
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 541..548
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 553..560
FT /evidence="ECO:0007829|PDB:5DYK"
FT TURN 561..564
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 565..573
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 574..579
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 583..595
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 604..609
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 611..619
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 626..633
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 638..657
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 667..669
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 670..672
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 678..680
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 700..702
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 705..709
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 716..731
FT /evidence="ECO:0007829|PDB:5DYK"
FT STRAND 735..737
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 743..752
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 764..773
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 778..780
FT /evidence="ECO:0007829|PDB:5DYK"
FT TURN 786..789
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 790..793
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 796..798
FT /evidence="ECO:0007829|PDB:5DYK"
FT HELIX 803..807
FT /evidence="ECO:0007829|PDB:5DYK"
SQ SEQUENCE 853 AA; 97694 MW; DBBB189707A480E2 CRC64;
MEEDDNLKKG NERNKKKAIF SNDDFTGEDS LMEDHLELRE KLSEDIDMIK TSLKNNLVCS
TLNDNEILTL SNYMQFFVFK SGNLVIKQGE KGSYFFIINS GKFDVYVNDK KVKTMGKGSS
FGEAALIHNT QRSATIIAET DGTLWGVQRS TFRATLKQLS NRNFNENRTF IDSVSVFDML
TEAQKNMITN ACVIQNFKSG ETIVKQGDYG DVLYILKEGK ATVYINDEEI RVLEKGSYFG
ERALLYDEPR SATIIAKEPT ACASICRKLL NIVLGNLQVV LFRNIMTEAL QQSEIFKQFS
GDQLNDLADT AIVRDYPANY NILHKDKVKS VKYIIVLEGK VELFLDDTSI GILSRGMSFG
DQYVLNQKQP FKHTIKSLEV CKIALITETC LADCLGNNNI DASIDYNNKK SIIKKMYIFR
YLTDKQCNLL IEAFRTTRYE EGDYIIQEGE VGSRFYIIKN GEVEIVKNKK RLRTLGKNDY
FGERALLYDE PRTASVISKV NNVECWFVDK SVFLQIIQGP MLAHLEERIK MQDTKVEMDE
LETERIIGRG TFGTVKLVHH KPTKIRYALK CVSKRSIINL NQQNNIKLER EITAENDHPF
IIRLVRTFKD SKYFYFLTEL VTGGELYDAI RKLGLLSKSQ AQFYLGSIIL AIEYLHERNI
VYRDLKPENI LLDKQGYVKL IDFGCAKKVQ GRAYTLVGTP HYMAPEVILG KGYGCTVDIW
ALGICLYEFI CGPLPFGNDE EDQLEIFRDI LTGQLTFPDY VTDTDSINLM KRLLCRLPQG
RIGCSINGFK DIKDHPFFSN FNWDKLAGRL LDPPLVSKSE TYAEDIDIKQ IEEEDAEDDE
EPLNDEDNWD IDF
