KGP2_MOUSE
ID KGP2_MOUSE Reviewed; 762 AA.
AC Q61410;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=cGMP-dependent protein kinase 2;
DE Short=cGK 2;
DE Short=cGK2;
DE EC=2.7.11.12;
DE AltName: Full=cGMP-dependent protein kinase II;
DE Short=cGKII;
GN Name=Prkg2; Synonyms=Prkgr2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=8514791; DOI=10.1016/s0021-9258(19)38689-2;
RA Uhler M.D.;
RT "Cloning and expression of a novel cyclic GMP-dependent protein kinase from
RT mouse brain.";
RL J. Biol. Chem. 268:13586-13591(1993).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8953039; DOI=10.1126/science.274.5295.2082;
RA Pfeifer A., Aszodi A., Seidler U., Ruth P., Hofmann F., Faessler R.;
RT "Intestinal secretory defects and dwarfism in mice lacking cGMP-dependent
RT protein kinase II.";
RL Science 274:2082-2086(1996).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=19282289; DOI=10.1074/jbc.m806486200;
RA Rangaswami H., Marathe N., Zhuang S., Chen Y., Yeh J.C., Frangos J.A.,
RA Boss G.R., Pilz R.B.;
RT "Type II cGMP-dependent protein kinase mediates osteoblast
RT mechanotransduction.";
RL J. Biol. Chem. 284:14796-14808(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-609, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Crucial regulator of intestinal secretion and bone growth
CC (PubMed:8953039). Phosphorylates and activates CFTR on the plasma
CC membrane. Plays a key role in intestinal secretion by regulating cGMP-
CC dependent translocation of CFTR in jejunum (By similarity). Acts
CC downstream of NMDAR to activate the plasma membrane accumulation of
CC GRIA1/GLUR1 in synapse and increase synaptic plasticity. Phosphorylates
CC GRIA1/GLUR1 at Ser-863 (By similarity). Acts as regulator of gene
CC expression and activator of the extracellular signal-regulated kinases
CC MAPK3/ERK1 AND MAPK1/ERK2 in mechanically stimulated osteoblasts. Under
CC fluid shear stress, mediates ERK activation and subsequent induction of
CC FOS, FOSL1/FRA1, FOSL2/FRA2 and FOSB that play a key role in the
CC osteoblast anabolic response to mechanical stimulation
CC (PubMed:19282289). {ECO:0000250|UniProtKB:Q64595,
CC ECO:0000269|PubMed:19282289, ECO:0000269|PubMed:8953039}.
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 -!- 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;
CC -!- ACTIVITY REGULATION: Binding of cGMP results in enzyme activation.
CC {ECO:0000305|PubMed:19282289}.
CC -!- SUBUNIT: Interacts with GRIA1/GLUR1. {ECO:0000250|UniProtKB:Q64595}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q13237}; Lipid-anchor {ECO:0000255}. Cell
CC membrane {ECO:0000269|PubMed:19282289}; Lipid-anchor {ECO:0000255}.
CC -!- PTM: Myristoylation mediates membrane localization. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Dwarfism, caused by a severe defect in
CC endochondral ossification at the growth plates.
CC {ECO:0000269|PubMed:8953039}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. cGMP subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L12460; AAA02572.1; -; mRNA.
DR CCDS; CCDS19459.1; -.
DR PIR; A46590; A46590.
DR AlphaFoldDB; Q61410; -.
DR SMR; Q61410; -.
DR STRING; 10090.ENSMUSP00000124963; -.
DR iPTMnet; Q61410; -.
DR PhosphoSitePlus; Q61410; -.
DR jPOST; Q61410; -.
DR MaxQB; Q61410; -.
DR PaxDb; Q61410; -.
DR PRIDE; Q61410; -.
DR ProteomicsDB; 263596; -.
DR MGI; MGI:108173; Prkg2.
DR eggNOG; KOG0614; Eukaryota.
DR InParanoid; Q61410; -.
DR BRENDA; 2.7.11.12; 3474.
DR Reactome; R-MMU-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-MMU-418457; cGMP effects.
DR Reactome; R-MMU-9648002; RAS processing.
DR ChiTaRS; Prkg2; mouse.
DR PRO; PR:Q61410; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q61410; protein.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0071476; P:cellular hypotonic response; IDA:CAFA.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:MGI.
DR GO; GO:0007623; P:circadian rhythm; IMP:MGI.
DR GO; GO:0045794; P:negative regulation of cell volume; IGI:CAFA.
DR GO; GO:2001226; P:negative regulation of chloride transport; ISO:MGI.
DR GO; GO:1902731; P:negative regulation of chondrocyte proliferation; ISO:MGI.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; ISO:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; ISO:MGI.
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 ATP-binding; Cell membrane; cGMP; cGMP-binding; Kinase; Lipoprotein;
KW 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_0000086124"
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..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..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:0000250|UniProtKB:Q64595"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64595"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64595"
FT MOD_RES 609
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:Q13237"
SQ SEQUENCE 762 AA; 87085 MW; 74F9D9A6835711A5 CRC64;
MGNGSVKPKH AKHPDGHSGN LSNEALRSKV LELERELRRK DAELQEREYH LKELREQLAK
QTVAIAELTE ELQSKCIQLN KLQDVIHVQG GSPLQASPDK VPLDVHRKTS GLVSLHSRRG
AKAGVSAEPT TRTYDLNKPP EFSFEKARVR KDSSEKKLIT DALNKNQFLK RLDPQQIKDM
VECMYGEKLS TGSYVIKQGE 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 KVKNENVAFA
MKCIRKKHIV DTKQQEHVYS EKRILEELCS PFIVKLYRTF KDNKYVYMLL EACLGGELWS
ILRDRGSFDE PTSKFCVACV TEAFDYLHLL GIIYRDLKPE NLILDADGYL KLVDFGFAKK
IGSGQKTWTF CGTPEYVAPE VILNKGHDFS VDFWSLGILV YELLTGNPPF SGIDQMMTYN
LILKGIEKMD FPRKITRRPE DLIRRLCRQN PTERLGNLKN GINDIKKHRW LNGFNWEGLK
ARSLPSPLRR ELSGPIDHSY FDKYPPEKGV PPDEMSGWDK DF
