KGP2_RAT
ID KGP2_RAT Reviewed; 762 AA.
AC Q64595;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=cGMP-dependent protein kinase 2;
DE Short=cGK 2;
DE Short=cGK2;
DE EC=2.7.11.12 {ECO:0000269|PubMed:18031684};
DE AltName: Full=cGMP-dependent protein kinase II;
DE Short=cGKII;
GN Name=Prkg2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Intestine;
RX PubMed=7937783; DOI=10.1073/pnas.91.20.9426;
RA Jarchau T., Haeusler C., Markert T., Poehler D., Vandekerckhove J.,
RA de Jonge H.R., Lohmann S.M., Walter U.;
RT "Cloning, expression, and in situ localization of rat intestinal cGMP-
RT dependent protein kinase II.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9426-9430(1994).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-2.
RX PubMed=9465038; DOI=10.1073/pnas.95.4.1466;
RA Vaandrager A.B., Smolenski A., Tilly B.C., Houtsmuller A.B., Ehlert E.M.,
RA Bot A.G., Edixhoven M., Boomaars W.E., Lohmann S.M., de Jonge H.R.;
RT "Membrane targeting of cGMP-dependent protein kinase is required for cystic
RT fibrosis transmembrane conductance regulator Cl- channel activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:1466-1471(1998).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=15872007; DOI=10.1152/ajpcell.00544.2004;
RA Golin-Bisello F., Bradbury N., Ameen N.;
RT "STa and cGMP stimulate CFTR translocation to the surface of villus
RT enterocytes in rat jejunum and is regulated by protein kinase G.";
RL Am. J. Physiol. 289:C708-C716(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH GRIA1/GLUR1.
RX PubMed=18031684; DOI=10.1016/j.neuron.2007.09.016;
RA Serulle Y., Zhang S., Ninan I., Puzzo D., McCarthy M., Khatri L.,
RA Arancio O., Ziff E.B.;
RT "A GluR1-cGKII interaction regulates AMPA receptor trafficking.";
RL Neuron 56:670-688(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110; SER-117 AND SER-431, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) OF 40-83.
RX PubMed=25070890; DOI=10.1074/jbc.m114.575894;
RA Reger A.S., Yang M.P., Koide-Yoshida S., Guo E., Mehta S., Yuasa K.,
RA Liu A., Casteel D.E., Kim C.;
RT "Crystal structure of the cGMP-dependent protein kinase II leucine zipper
RT and Rab11b protein complex reveals molecular details of G-kinase-specific
RT interactions.";
RL J. Biol. Chem. 289:25393-25403(2014).
CC -!- FUNCTION: Crucial regulator of intestinal secretion and bone growth (By
CC similarity). Phosphorylates and activates CFTR on the plasma membrane
CC (PubMed:9465038). Plays a key role in intestinal secretion by
CC regulating cGMP-dependent translocation of CFTR in jejunum (Probable).
CC Acts downstream of NMDAR to activate the plasma membrane accumulation
CC of GRIA1/GLUR1 in synapse and increase synaptic plasticity.
CC Phosphorylates GRIA1/GLUR1 at Ser-863 (PubMed:18031684). Acts as
CC regulator of gene expression and activator of the extracellular signal-
CC regulated kinases MAPK3/ERK1 AND MAPK1/ERK2 in mechanically stimulated
CC osteoblasts. Under fluid shear stress, mediates ERK activation and
CC subsequent induction of FOS, FOSL1/FRA1, FOSL2/FRA2 and FOSB that play
CC a key role in the osteoblast anabolic response to mechanical
CC stimulation (By similarity). {ECO:0000250|UniProtKB:Q61410,
CC ECO:0000269|PubMed:18031684, ECO:0000269|PubMed:9465038,
CC ECO:0000305|PubMed:15872007}.
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:18031684};
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:18031684};
CC -!- ACTIVITY REGULATION: Binding of cGMP results in enzyme activation.
CC {ECO:0000305|PubMed:15872007}.
CC -!- SUBUNIT: Interacts with GRIA1/GLUR1. {ECO:0000269|PubMed:18031684}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q13237}; Lipid-anchor {ECO:0000255}. Cell
CC membrane {ECO:0000269|PubMed:9465038}; Lipid-anchor
CC {ECO:0000305|PubMed:9465038}. Note=Plasma membrane localization is
CC required for its function in the activation of CFTR.
CC {ECO:0000269|PubMed:9465038}.
CC -!- TISSUE SPECIFICITY: Highly expressed in intestinal mucosa and is 20
CC times less abundant in brain and kidney (PubMed:7937783). Expressed in
CC jejunum, in the apical domain of the villus epithelium
CC (PubMed:15872007). {ECO:0000269|PubMed:15872007,
CC ECO:0000269|PubMed:7937783}.
CC -!- PTM: Myristoylation mediates membrane localization. {ECO:0000250}.
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; Z36276; CAA85284.1; -; mRNA.
DR PIR; I59329; I59329.
DR RefSeq; NP_037144.1; NM_013012.1.
DR PDB; 4OJK; X-ray; 2.66 A; C/D=40-83.
DR PDBsum; 4OJK; -.
DR AlphaFoldDB; Q64595; -.
DR SMR; Q64595; -.
DR STRING; 10116.ENSRNOP00000003237; -.
DR iPTMnet; Q64595; -.
DR PhosphoSitePlus; Q64595; -.
DR PaxDb; Q64595; -.
DR Ensembl; ENSRNOT00000003237; ENSRNOP00000003237; ENSRNOG00000002361.
DR GeneID; 25523; -.
DR KEGG; rno:25523; -.
DR UCSC; RGD:3401; rat.
DR CTD; 5593; -.
DR RGD; 3401; Prkg2.
DR eggNOG; KOG0614; Eukaryota.
DR GeneTree; ENSGT00940000159393; -.
DR HOGENOM; CLU_000288_73_2_1; -.
DR InParanoid; Q64595; -.
DR OMA; SKNPDGH; -.
DR OrthoDB; 401933at2759; -.
DR PhylomeDB; Q64595; -.
DR TreeFam; TF313261; -.
DR BRENDA; 2.7.11.12; 5301.
DR Reactome; R-RNO-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-RNO-418457; cGMP effects.
DR Reactome; R-RNO-9648002; RAS processing.
DR PRO; PR:Q64595; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000002361; Expressed in jejunum and 8 other tissues.
DR Genevisible; Q64595; RN.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0031965; C:nuclear membrane; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR GO; GO:0004692; F:cGMP-dependent protein kinase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0071476; P:cellular hypotonic response; ISO:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0045794; P:negative regulation of cell volume; ISO:RGD.
DR GO; GO:2001226; P:negative regulation of chloride transport; IDA:CAFA.
DR GO; GO:1902731; P:negative regulation of chondrocyte proliferation; IGI:RGD.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; IDA:RGD.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; IGI:RGD.
DR CDD; cd00038; CAP_ED; 2.
DR CDD; cd05572; STKc_cGK; 1.
DR Gene3D; 2.60.120.10; -; 2.
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; 2.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF000559; cGMP-dep_kinase; 1.
DR PRINTS; PR00104; CGMPKINASE.
DR SMART; SM00100; cNMP; 2.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF51206; SSF51206; 2.
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; 2.
DR PROSITE; PS50042; CNMP_BINDING_3; 2.
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; Cell membrane; cGMP; cGMP-binding; Kinase;
KW Lipoprotein; Membrane; Myristate; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..762
FT /note="cGMP-dependent protein kinase 2"
FT /id="PRO_0000086125"
FT DOMAIN 453..711
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 712..762
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 112..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 168..283
FT /note="cGMP-binding, high affinity; cAMP-binding, moderate
FT affinity"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT REGION 286..416
FT /note="cGMP-binding, high affinity; cAMP-binding, low
FT affinity"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT REGION 740..762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 576
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 232..235
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT BINDING 242..243
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT BINDING 347
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT BINDING 356..359
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT BINDING 366..367
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT BINDING 412
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT BINDING 415
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT BINDING 459..467
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 482
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 609
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q61410"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
FT MUTAGEN 2
FT /note="G->A: Cytosolic localization."
FT /evidence="ECO:0000269|PubMed:9465038"
FT HELIX 48..80
FT /evidence="ECO:0007829|PDB:4OJK"
SQ SEQUENCE 762 AA; 87182 MW; F0DF4F7684675B38 CRC64;
MGNGSVKPKH SKHPDGQSGN LSNEALRSKV AELEREVKRK DAELQEREYH LKELREQLAK
QTVAIAELTE ELQSKCIQLN KLQDVIHVQG GSPLQASPDK VPLDVHRKTS GLVSLHSRRG
AKAGVSAEPT SRTYDLNKPP EFSFEKARVR KDSSEKKLIT DALNKNQFLK RLDPQQIKDM
VECMYGRNYQ QGSYIVKQGE PGNHIFVLAE GRLEVFQGEK LLSSIPMWTT FGELAILYNC
TRTASVKAIT NVKTWALDRE VFQNIMRRTA QARDEEYRNF LRSVSLLKNL PEDKLTKIID
CLEVEYYDKG DYIIREGEEG STFFILAKGK VKVTQSTEGH DQPQLIKTLQ KGEYFGEKAL
ISDDVRSANI IAEENDVACL VIDRETFNQT VGTFDELQKY LEGYVATLNR DDEKRHAKRS
MSSWKLSKAL SLEMIQLKEK VARFSSTSPF QNLEIIATLG VGGFGRVELV KVKNENIAFA
MKCIRKKHIV DTKQQEHVYS EKRILEELCS PFIVKLYRTF KDNKYVYMLL EACLGGELWS
ILRDRGSFDE PTSKFCVACV TEAFDYLHRL GIIYRDLKPE NLILDADGYL KLVDFGFAKK
IGSGQKTWTF CGTPEYVAPE VILNKGHDFS VDFWSLGILV YELLTGNPPF SGIDQMMTYN
LILKGIEKMD FPRKITRRPE DLIRRLCRQN PTERLGNLKN GINDIKKHRW LNGFNWEGLK
ARSLPSPLRR ELSGPIDHSY FDKYPPEKGV PPDEMSGWDK DF
