KGP2_HUMAN
ID KGP2_HUMAN Reviewed; 762 AA.
AC Q13237; B4DMX3; E7EPE6; O00125; O60916;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 192.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8607838; DOI=10.1006/bbrc.1996.0477;
RA Orstavik S., Solberg R., Taskn K., Nordahl M., Altherr M.R., Hansson V.,
RA Jahnsen T., Sandberg M.;
RT "Molecular cloning, cDNA structure, and chromosomal localization of the
RT human type II cGMP-dependent protein kinase.";
RL Biochem. Biophys. Res. Commun. 220:759-765(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7498513; DOI=10.1016/0014-5793(95)01223-2;
RA Fujii M., Ogata T., Takahashi E., Yamada K., Nakabayashi K., Oishi M.,
RA Ayusawa D.;
RT "Expression of the human cGMP-dependent protein kinase II gene is lost upon
RT introduction of SV40 T antigen or immortalization in human cells.";
RL FEBS Lett. 375:263-267(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Heart;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-734.
RX PubMed=9535793; DOI=10.1006/bbrc.1998.8399;
RA Witczak O., Orstavik S., Natarajan V., Frengen E., Jahnsen T., Sandberg M.;
RT "Characterization of the gene encoding the human type II cGMP-dependent
RT protein kinase.";
RL Biochem. Biophys. Res. Commun. 245:113-119(1998).
RN [6]
RP MYRISTOYLATION AT GLY-2, AND SUBCELLULAR LOCATION.
RX PubMed=8636133; DOI=10.1074/jbc.271.12.7025;
RA Vaandrager A.B., Ehlert E.M., Jarchau T., Lohmann S.M., de Jonge H.R.;
RT "N-terminal myristoylation is required for membrane localization of cGMP-
RT dependent protein kinase type II.";
RL J. Biol. Chem. 271:7025-7029(1996).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-106 AND ARG-716.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [9]
RP INVOLVEMENT IN SMDP, INVOLVEMENT IN AMD4, VARIANT AMD4 569-ARG--PHE-762
RP DEL, AND CHARACTERIZATION OF VARIANT AMD4 569-ARG--PHE-762 DEL.
RX PubMed=34782440; DOI=10.1136/jmedgenet-2021-108027;
RG Genomics England Research Consortium;
RA Pagnamenta A.T., Diaz-Gonzalez F., Banos-Pinero B., Ferla M.P., Toosi M.B.,
RA Calder A.D., Karimiani E.G., Doosti M., Wainwright A., Wordsworth P.,
RA Bailey K., Ejeskaer K., Lester T., Maroofian R., Heath K.E., Tajsharghi H.,
RA Shears D., Taylor J.C.;
RT "Variable skeletal phenotypes associated with biallelic variants in
RT PRKG2.";
RL J. Med. Genet. 0:0-0(2021).
RN [10]
RP VARIANT AMD4 569-ARG--PHE-762 DEL, CHARACTERIZATION OF VARIANT AMD4
RP 569-ARG--PHE-762 DEL, AND FUNCTION.
RX PubMed=33106379; DOI=10.1136/jmedgenet-2020-107177;
RA Diaz-Gonzalez F., Wadhwa S., Rodriguez-Zabala M., Kumar S., Aza-Carmona M.,
RA Sentchordi-Montane L., Alonso M., Ahmad I., Zahra S., Kumar D., Kushwah N.,
RA Shamim U., Sait H., Kapoor S., Roldan B., Nishimura G., Offiah A.C.,
RA Faruq M., Heath K.E.;
RT "Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants
RT cause a novel acromesomelic dysplasia.";
RL J. Med. Genet. 59:28-38(2022).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 137-418 IN COMPLEX WITH CAMP AND
RP CGMP, ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-412 AND ARG-415.
RX PubMed=26769964; DOI=10.1074/jbc.m115.691303;
RA Campbell J.C., Kim J.J., Li K.Y., Huang G.Y., Reger A.S., Matsuda S.,
RA Sankaran B., Link T.M., Yuasa K., Ladbury J.E., Casteel D.E., Kim C.;
RT "Structural basis of cyclic nucleotide selectivity in cGMP-dependent
RT protein kinase II.";
RL J. Biol. Chem. 291:5623-5633(2016).
CC -!- FUNCTION: Crucial regulator of intestinal secretion and bone growth.
CC Phosphorylates and activates CFTR on the plasma membrane. Plays a key
CC role in intestinal secretion by regulating cGMP-dependent translocation
CC of CFTR in jejunum (PubMed:33106379). Acts downstream of NMDAR to
CC activate the plasma membrane accumulation of GRIA1/GLUR1 in synapse and
CC increase synaptic plasticity. Phosphorylates GRIA1/GLUR1 at Ser-863 (By
CC similarity). Acts as regulator of gene expression and activator of the
CC extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2 in
CC mechanically stimulated osteoblasts. Under fluid shear stress, mediates
CC ERK activation and subsequent induction of FOS, FOSL1/FRA1, FOSL2/FRA2
CC and FOSB that play a key role in the osteoblast anabolic response to
CC mechanical stimulation (By similarity). {ECO:0000250|UniProtKB:Q61410,
CC ECO:0000250|UniProtKB:Q64595, ECO:0000269|PubMed:33106379}.
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:0000269|PubMed:26769964}.
CC -!- SUBUNIT: Interacts with GRIA1/GLUR1. {ECO:0000250|UniProtKB:Q64595}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:8636133}; Lipid-anchor
CC {ECO:0000269|PubMed:8636133}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13237-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13237-2; Sequence=VSP_055121;
CC -!- TISSUE SPECIFICITY: Highly concentrated in brain, lung and intestinal
CC mucosa.
CC -!- PTM: Myristoylation mediates membrane localization.
CC {ECO:0000269|PubMed:8636133}.
CC -!- DISEASE: Spondylometaphyseal dysplasia, Pagnamenta type (SMDP)
CC [MIM:619638]: A form of spondylometaphyseal dysplasia, a group of short
CC stature disorders distinguished by abnormalities in the vertebrae and
CC the metaphyses of the tubular bones. SMDP is an autosomal recessive
CC form characterized by short stature and mild platyspondyly with no
CC disproportion between the limbs. Mild metaphyseal changes are present.
CC {ECO:0000269|PubMed:34782440}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Acromesomelic dysplasia 4 (AMD4) [MIM:619636]: A form of
CC acromesomelic dysplasia, a skeletal disorder characterized by short
CC stature, very short limbs and hand/foot malformations. The severity of
CC limb abnormalities increases from proximal to distal with profoundly
CC affected hands and feet showing brachydactyly and/or rudimentary
CC fingers (knob-like fingers). AMD4 radiographic hallmarks include mild
CC to moderate platyspondyly, moderate brachydactyly, iliac flaring, and
CC metaphyseal alterations of the long bones that progressively increase
CC with age. AMD4 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:33106379, ECO:0000269|PubMed:34782440}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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; X94612; CAA64318.1; -; mRNA.
DR EMBL; D70899; BAA18934.1; -; mRNA.
DR EMBL; AK297673; BAG60035.1; -; mRNA.
DR EMBL; AC098819; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC139722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y16106; CAA76073.1; -; Genomic_DNA.
DR EMBL; Y16107; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16108; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16109; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16110; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16111; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16112; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16113; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16114; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16115; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16116; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16117; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16118; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16119; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16120; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16121; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16122; CAA76073.1; JOINED; Genomic_DNA.
DR EMBL; Y16123; CAA76073.1; JOINED; Genomic_DNA.
DR CCDS; CCDS3589.1; -. [Q13237-1]
DR CCDS; CCDS64005.1; -. [Q13237-2]
DR PIR; S68217; S68217.
DR RefSeq; NP_001269409.1; NM_001282480.1.
DR RefSeq; NP_001269410.1; NM_001282481.1.
DR RefSeq; NP_001269411.1; NM_001282482.1.
DR RefSeq; NP_001269412.1; NM_001282483.1.
DR RefSeq; NP_001269414.1; NM_001282485.1. [Q13237-2]
DR RefSeq; NP_006250.1; NM_006259.2. [Q13237-1]
DR RefSeq; XP_005263183.1; XM_005263126.3.
DR PDB; 5BV6; X-ray; 1.94 A; A=269-418.
DR PDB; 5C6C; X-ray; 2.05 A; A/B=137-277.
DR PDB; 5C8W; X-ray; 1.80 A; A/B/C/D/E/F=137-277.
DR PDB; 5JIX; X-ray; 1.47 A; A=269-418.
DR PDB; 5JIZ; X-ray; 1.50 A; A=269-418.
DR PDB; 6BQ8; Other; 2.00 A; A=269-418.
DR PDBsum; 5BV6; -.
DR PDBsum; 5C6C; -.
DR PDBsum; 5C8W; -.
DR PDBsum; 5JIX; -.
DR PDBsum; 5JIZ; -.
DR PDBsum; 6BQ8; -.
DR AlphaFoldDB; Q13237; -.
DR SMR; Q13237; -.
DR BioGRID; 111579; 9.
DR IntAct; Q13237; 4.
DR STRING; 9606.ENSP00000264399; -.
DR BindingDB; Q13237; -.
DR ChEMBL; CHEMBL2896; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q13237; -.
DR GuidetoPHARMACOLOGY; 1493; -.
DR iPTMnet; Q13237; -.
DR PhosphoSitePlus; Q13237; -.
DR BioMuta; PRKG2; -.
DR DMDM; 6226833; -.
DR jPOST; Q13237; -.
DR MassIVE; Q13237; -.
DR PaxDb; Q13237; -.
DR PeptideAtlas; Q13237; -.
DR PRIDE; Q13237; -.
DR ProteomicsDB; 17341; -.
DR ProteomicsDB; 59241; -. [Q13237-1]
DR Antibodypedia; 1102; 260 antibodies from 31 providers.
DR DNASU; 5593; -.
DR Ensembl; ENST00000264399.6; ENSP00000264399.1; ENSG00000138669.10. [Q13237-1]
DR Ensembl; ENST00000395578.3; ENSP00000378945.1; ENSG00000138669.10. [Q13237-1]
DR Ensembl; ENST00000628926.1; ENSP00000486129.1; ENSG00000138669.10. [Q13237-2]
DR GeneID; 5593; -.
DR KEGG; hsa:5593; -.
DR MANE-Select; ENST00000264399.6; ENSP00000264399.1; NM_006259.3; NP_006250.1.
DR UCSC; uc003hmh.3; human. [Q13237-1]
DR CTD; 5593; -.
DR DisGeNET; 5593; -.
DR GeneCards; PRKG2; -.
DR HGNC; HGNC:9416; PRKG2.
DR HPA; ENSG00000138669; Tissue enhanced (intestine, prostate).
DR MIM; 601591; gene.
DR MIM; 619636; phenotype.
DR MIM; 619638; phenotype.
DR neXtProt; NX_Q13237; -.
DR OpenTargets; ENSG00000138669; -.
DR PharmGKB; PA33778; -.
DR VEuPathDB; HostDB:ENSG00000138669; -.
DR eggNOG; KOG0614; Eukaryota.
DR GeneTree; ENSGT00940000159393; -.
DR HOGENOM; CLU_000288_73_2_1; -.
DR InParanoid; Q13237; -.
DR OMA; SKNPDGH; -.
DR OrthoDB; 401933at2759; -.
DR PhylomeDB; Q13237; -.
DR TreeFam; TF313261; -.
DR BRENDA; 2.7.11.12; 2681.
DR PathwayCommons; Q13237; -.
DR Reactome; R-HSA-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-418457; cGMP effects.
DR Reactome; R-HSA-9648002; RAS processing.
DR SignaLink; Q13237; -.
DR SIGNOR; Q13237; -.
DR BioGRID-ORCS; 5593; 14 hits in 1100 CRISPR screens.
DR ChiTaRS; PRKG2; human.
DR GenomeRNAi; 5593; -.
DR Pharos; Q13237; Tchem.
DR PRO; PR:Q13237; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q13237; protein.
DR Bgee; ENSG00000138669; Expressed in jejunal mucosa and 110 other tissues.
DR ExpressionAtlas; Q13237; baseline and differential.
DR Genevisible; Q13237; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
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; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IMP:UniProtKB.
DR GO; GO:2001226; P:negative regulation of chloride transport; IEA:Ensembl.
DR GO; GO:1902731; P:negative regulation of chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; IEA:Ensembl.
DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR GO; GO:0046146; P:tetrahydrobiopterin metabolic process; TAS:Reactome.
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; Alternative splicing; ATP-binding; Cell membrane; cGMP;
KW cGMP-binding; Coiled coil; Disease variant; Dwarfism; Kinase; Lipoprotein;
KW Membrane; Myristate; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8636133"
FT CHAIN 2..762
FT /note="cGMP-dependent protein kinase 2"
FT /id="PRO_0000086123"
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 117..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:0000305|PubMed:26769964"
FT REGION 286..416
FT /note="cGMP-binding, high affinity; cAMP-binding, low
FT affinity"
FT /evidence="ECO:0000305|PubMed:26769964"
FT REGION 740..762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 23..85
FT /evidence="ECO:0000255"
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 AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0007744|PDB:5C6C"
FT BINDING 232..235
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0007744|PDB:5C8W"
FT BINDING 242..243
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0007744|PDB:5C6C"
FT BINDING 242..243
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0007744|PDB:5C8W"
FT BINDING 347
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0000312|PDB:5BV6"
FT BINDING 356..359
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0007744|PDB:5BV6"
FT BINDING 366..367
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0007744|PDB:5BV6"
FT BINDING 412
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0000312|PDB:5BV6"
FT BINDING 415
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26769964,
FT ECO:0000312|PDB:5BV6"
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:0000250|UniProtKB:Q61410"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:8636133"
FT VAR_SEQ 441..469
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055121"
FT VARIANT 22
FT /note="T -> S (in dbSNP:rs34956759)"
FT /id="VAR_051633"
FT VARIANT 106
FT /note="H -> R (in dbSNP:rs34616910)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040608"
FT VARIANT 569..762
FT /note="Missing (in AMD4; decreased protein abundance;
FT unable to phosphorylate RAF1 in response to FGF2 and to
FT inhibit FGF2-induced MAPK signaling; unable to suppress
FT SOX9-induced COL2A1 expression; unable to upregulate
FT COL10A1)"
FT /id="VAR_086537"
FT VARIANT 716
FT /note="W -> R (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040609"
FT MUTAGEN 412
FT /note="D->A: Reduces cGMP binding affinity; when associated
FT with A-415."
FT /evidence="ECO:0000269|PubMed:26769964"
FT MUTAGEN 415
FT /note="R->A: Reduces cGMP binding affinity; when associated
FT with A-412."
FT /evidence="ECO:0000269|PubMed:26769964"
FT CONFLICT 57..58
FT /note="QL -> HG (in Ref. 2; BAA18934)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="S -> I (in Ref. 5; CAA76073)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="N -> D (in Ref. 3; BAG60035)"
FT /evidence="ECO:0000305"
FT CONFLICT 460
FT /note="G -> A (in Ref. 2; BAA18934)"
FT /evidence="ECO:0000305"
FT HELIX 153..164
FT /evidence="ECO:0007829|PDB:5C8W"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:5C8W"
FT HELIX 174..183
FT /evidence="ECO:0007829|PDB:5C8W"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:5C8W"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:5C8W"
FT STRAND 204..211
FT /evidence="ECO:0007829|PDB:5C8W"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:5C8W"
FT STRAND 220..224
FT /evidence="ECO:0007829|PDB:5C8W"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:5C8W"
FT HELIX 233..238
FT /evidence="ECO:0007829|PDB:5C8W"
FT STRAND 243..250
FT /evidence="ECO:0007829|PDB:5C8W"
FT STRAND 252..258
FT /evidence="ECO:0007829|PDB:5C8W"
FT HELIX 259..266
FT /evidence="ECO:0007829|PDB:5C8W"
FT HELIX 270..282
FT /evidence="ECO:0007829|PDB:5JIX"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:5JIX"
FT HELIX 292..301
FT /evidence="ECO:0007829|PDB:5JIX"
FT STRAND 303..307
FT /evidence="ECO:0007829|PDB:5JIX"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:5JIX"
FT STRAND 323..335
FT /evidence="ECO:0007829|PDB:5JIX"
FT STRAND 344..350
FT /evidence="ECO:0007829|PDB:5JIX"
FT HELIX 357..362
FT /evidence="ECO:0007829|PDB:5JIX"
FT STRAND 368..372
FT /evidence="ECO:0007829|PDB:5JIX"
FT STRAND 377..382
FT /evidence="ECO:0007829|PDB:5JIX"
FT HELIX 384..389
FT /evidence="ECO:0007829|PDB:5JIX"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:5JIX"
FT HELIX 395..414
FT /evidence="ECO:0007829|PDB:5JIX"
SQ SEQUENCE 762 AA; 87432 MW; FA7BA149906B5996 CRC64;
MGNGSVKPKH SKHPDGHSGN LTTDALRNKV TELERELRRK DAEIQEREYH LKELREQLSK
QTVAIAELTE ELQNKCIQLN KLQDVVHMQG GSPLQASPDK VPLEVHRKTS GLVSLHSRRG
AKAGVSAEPT TRTYDLNKPP EFSFEKARVR KDSSEKKLIT DALNKNQFLK RLDPQQIKDM
VECMYGRNYQ QGSYIIKQGE PGNHIFVLAE GRLEVFQGEK LLSSIPMWTT FGELAILYNC
TRTASVKAIT NVKTWALDRE VFQNIMRRTA QARDEQYRNF LRSVSLLKNL PEDKLTKIID
CLEVEYYDKG DYIIREGEEG STFFILAKGK VKVTQSTEGH DQPQLIKTLQ KGEYFGEKAL
ISDDVRSANI IAEENDVACL VIDRETFNQT VGTFEELQKY LEGYVANLNR DDEKRHAKRS
MSNWKLSKAL SLEMIQLKEK VARFSSSSPF QNLEIIATLG VGGFGRVELV KVKNENVAFA
MKCIRKKHIV DTKQQEHVYS EKRILEELCS PFIVKLYRTF KDNKYVYMLL EACLGGELWS
ILRDRGSFDE PTSKFCVACV TEAFDYLHRL GIIYRDLKPE NLILDAEGYL KLVDFGFAKK
IGSGQKTWTF CGTPEYVAPE VILNKGHDFS VDFWSLGILV YELLTGNPPF SGVDQMMTYN
LILKGIEKMD FPRKITRRPE DLIRRLCRQN PTERLGNLKN GINDIKKHRW LNGFNWEGLK
ARSLPSPLQR ELKGPIDHSY FDKYPPEKGM PPDELSGWDK DF
