KGP_EIMTE
ID KGP_EIMTE Reviewed; 1003 AA.
AC Q8MMZ8;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=cGMP-dependent protein kinase {ECO:0000303|PubMed:11834729};
DE EC=2.7.11.12 {ECO:0000269|PubMed:11834729, ECO:0000269|PubMed:11897122, ECO:0000269|PubMed:11914085};
GN Name=PKG {ECO:0000303|PubMed:11834729};
OS Eimeria tenella (Coccidian parasite).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC Eucoccidiorida; Eimeriorina; Eimeriidae; Eimeria.
OX NCBI_TaxID=5802 {ECO:0000312|EMBL:AAM20900.1};
RN [1] {ECO:0000312|EMBL:AAM20900.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, PROTEIN
RP SEQUENCE OF 59-75; 100-115; 138-153; 281-288; 328-332; 338-342 AND 664-669,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND DEVELOPMENTAL STAGE.
RX PubMed=11834729; DOI=10.1074/jbc.m108393200;
RA Gurnett A., Liberator P.A., Dulski P., Salowe S.P., Donald R.G.K.,
RA Anderson J.W., Wiltsie J., Diaz-Saldana C.A., Harris G., Chang B.,
RA Darkin-Rattray S.J., Nare B., Crumley T., Blum P., Misura A., Tamas T.,
RA Sardana M., Yuan J., Biftu T., Schmatz D.;
RT "Purification and molecular characterization of cGMP-dependent protein
RT kinase from Apicomplexan parasites. A novel chemotherapeutic target.";
RL J. Biol. Chem. 277:15913-15922(2002).
RN [2] {ECO:0000312|EMBL:AAM20900.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, FUNCTION,
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2,
RP PALMITOYLATION AT CYS-4, AND MUTAGENESIS OF MET-1; MET-48; ARG-247; ARG-366
RP AND 643-ARG--ARG-644.
RX PubMed=11897122; DOI=10.1016/s0166-6851(01)00451-0;
RA Donald R.G., Liberator P.A.;
RT "Molecular characterization of a coccidian parasite cGMP dependent protein
RT kinase.";
RL Mol. Biochem. Parasitol. 120:165-175(2002).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP ARG-247; ARG-366; GLU-635 AND 643-ARG--ARG-644.
RX PubMed=11914085; DOI=10.1021/bi0156658;
RA Salowe S.P., Wiltsie J., Liberator P.A., Donald R.G.;
RT "The role of a parasite-specific allosteric site in the distinctive
RT activation behavior of Eimeria tenella cGMP-dependent protein kinase.";
RL Biochemistry 41:4385-4391(2002).
CC -!- FUNCTION: Serine/threonine protein kinase which acts as a downstream
CC effector of the second messenger cGMP. {ECO:0000269|PubMed:11834729,
CC ECO:0000269|PubMed:11897122, ECO:0000269|PubMed:11914085}.
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:11834729, ECO:0000269|PubMed:11897122,
CC ECO:0000269|PubMed:11914085};
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:11834729,
CC ECO:0000269|PubMed:11897122, ECO:0000269|PubMed:11914085};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11834729};
CC -!- ACTIVITY REGULATION: Activated by cGMP (PubMed:11834729,
CC PubMed:11914085). The cGMP-binding domains acts cooperatively to
CC activate PKG (PubMed:11914085). Inhibited by the antiparasitic small
CC molecule 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1Hpyrrol- 3-
CC yl]pyridine (compound 1) (PubMed:11834729).
CC {ECO:0000269|PubMed:11834729, ECO:0000269|PubMed:11914085}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12 uM for ATP (at 30 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:11834729};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11834729}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000305|PubMed:11897122}; Lipid-anchor
CC {ECO:0000305|PubMed:11897122}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000305|PubMed:11897122}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=Isoform I {ECO:0000303|PubMed:11897122};
CC IsoId=Q8MMZ8-1; Sequence=Displayed;
CC Name=2; Synonyms=Isoform II {ECO:0000303|PubMed:11897122};
CC IsoId=Q8MMZ8-2; Sequence=VSP_060885;
CC -!- DEVELOPMENTAL STAGE: Expressed in unsporulated oocysts.
CC {ECO:0000269|PubMed:11834729}.
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; AF411961; AAM20900.1; -; mRNA.
DR AlphaFoldDB; Q8MMZ8; -.
DR SMR; Q8MMZ8; -.
DR BindingDB; Q8MMZ8; -.
DR ChEMBL; CHEMBL5036; -.
DR VEuPathDB; ToxoDB:ETH2_0728900; -.
DR VEuPathDB; ToxoDB:ETH2_0729000; -.
DR VEuPathDB; ToxoDB:ETH2_0742100; -.
DR VEuPathDB; ToxoDB:ETH_00017800; -.
DR VEuPathDB; ToxoDB:ETH_00027525; -.
DR BRENDA; 2.7.11.12; 2046.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030553; F:cGMP binding; IDA:UniProtKB.
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:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR CDD; cd00038; CAP_ED; 3.
DR CDD; cd05572; STKc_cGK; 1.
DR Gene3D; 2.60.120.10; -; 4.
DR InterPro; IPR000961; AGC-kinase_C.
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 SMART; SM00100; cNMP; 3.
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; 2.
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 Alternative initiation; ATP-binding; Cell membrane; cGMP; cGMP-binding;
KW Cytoplasm; Direct protein sequencing; Kinase; Lipoprotein; Magnesium;
KW Membrane; Metal-binding; Myristate; Nucleotide-binding; Palmitate;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305|PubMed:11897122"
FT CHAIN 2..1003
FT /note="cGMP-dependent protein kinase"
FT /id="PRO_0000451912"
FT DOMAIN 693..950
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 951..1003
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..289
FT /note="cNMP-binding domain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
FT REGION 292..391
FT /note="cNMP-binding domain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
FT REGION 411..548
FT /note="cNMP-binding domain 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
FT REGION 570..669
FT /note="cNMP-binding domain 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
FT COMPBIAS 55..87
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 120..141
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 816
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 237
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 238
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 247
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 248
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 625
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 634
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 635
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 637
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 644
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 645
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:Q8I719"
FT BINDING 699..707
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 722
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000305|PubMed:11897122"
FT LIPID 4
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:11897122"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_060885"
FT MUTAGEN 1
FT /note="M->A: Loss of isoform 1 expression."
FT /evidence="ECO:0000269|PubMed:11897122"
FT MUTAGEN 48
FT /note="M->A: Loss of isoform 2 expression."
FT /evidence="ECO:0000269|PubMed:11897122"
FT MUTAGEN 247
FT /note="R->A: Loss of cooperativity between the cGMP-binding
FT sites, however, addition of higher levels of cGMP restores
FT normal catalytic activity; when associated with A-366. Loss
FT of cooperativity between the cGMP-binding sites and partial
FT loss of catalytic activity which cannot be rescued by the
FT addition of higher levels of cGMP; when associated with A-
FT 366 and 643-A-A-644."
FT /evidence="ECO:0000269|PubMed:11897122,
FT ECO:0000269|PubMed:11914085"
FT MUTAGEN 366
FT /note="R->A: Loss of cooperativity between the cGMP-binding
FT sites, however, addition of higher levels of cGMP restores
FT normal catalytic activity; when associated with A-247. Loss
FT of cooperativity between the cGMP-binding sites and partial
FT loss of catalytic activity which cannot be rescued by the
FT addition of higher levels of cGMP; when associated with A-
FT 247 and 643-A-A-644."
FT /evidence="ECO:0000269|PubMed:11897122,
FT ECO:0000269|PubMed:11914085"
FT MUTAGEN 635
FT /note="E->A: Partial loss of catalytic activity. Severe
FT loss of catalytic activity; when associated with A-635."
FT /evidence="ECO:0000269|PubMed:11914085"
FT MUTAGEN 643..644
FT /note="RR->AA: Loss of cooperativity between the cGMP-
FT binding sites, however, addition of higher levels of cGMP
FT restores normal catalytic activity. Loss of cooperativity
FT between the cGMP-binding sites and partial loss of
FT catalytic activity which cannot be rescued by the addition
FT of higher levels of cGMP; when associated with A-247 and A-
FT 366. Severe loss of catalytic activity; when associated
FT with A-635."
FT /evidence="ECO:0000269|PubMed:11897122,
FT ECO:0000269|PubMed:11914085"
SQ SEQUENCE 1003 AA; 112923 MW; 8CD954FB2EB768F0 CRC64;
MGACSSKAQH QTRDPEPREQ QAAQEQKSTG PSGAPNDAPA PAEAERKMSG SSATAPKGEM
PTASTGTPEQ QQQQQQQQQQ QQEQQQHPEH QQSEKQQQHG EEQQQERKPS QQQQNEEAAA
PHKHGGERKV QKAIKQQEDT QAEDARLLGH LEKREKTPSD LSLIRDSLST NLVCSSLNDA
EVEALANAVE FFTFKKGDVV TKQGESGSYF FIVHSGEFEV IVNDKVVNKI LTGQAFGEIS
LIHNSARTAT IKTLSEDAAL WGVQRQVFRE TLKQLSSRNF AENRQFLASV KFFEMLTEAQ
KNVITNALVV QSFQPGQAIV KEGEKGDVLY ILKSGKALVS IKNKEVRVLQ RGEYFGERAL
LYDEPRSATI TAEEPTVCVS IGRDLLDRVL GNLQHVLFRN IMLEALQQSK VFASFPTEQL
SRLIGSVVVK DYPENYIILD RENRTRASAS ALFSAQGVRF FFVLEGEVSV FAYKDKSSSS
SSSSSSSSSS SSAEGEMELH LIDTLKRGQA FGDEYVLSPN KPFAHCVKSN GPTKLALLTA
SALTATLGGQ DIDETLDYNN KLAITKKMYI FRYLSEQQTQ TLIKAFKTVR YTQGESIIRE
GEIGSRFFII KLGEVVILKG EKRVRTLGRH DYFGERALLH DERRSATVAA NSPEVDLWVV
DKDVFLQIVK GPMLTHLEER IRMQDTKVEF KDLNVVRVVG RGTFGTVKLV QHIPTQMRYA
LKCVSRKSVV ALNQQDHIRL EREIMAENDH PFIIRLVRTF RDKEFLYFLT ELVTGGELYD
AIRKLGLLGR YQAQFYLASI VLAIEYLHER NIAYRDLKPE NILLDSQGYV KLIDFGCAKK
MQGRAYTLVG TPHYMAPEVI LGKGYTLTAD TWAFGVCLYE FMCGPLPFGN DAEDQLEIFR
DILAGKLIFP HYVTDQDAIN LMKRLLCRLP EVRIGCSING YKDIKEHAFF SDFDWDRLAG
RDLSPPLLPK GEIYAEDAEE GGLDIEEDEG IELEDEYEWD KDF
