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}. 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; 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 //