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 17-JUN-2020, entry version 182. 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 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 (By CC similarity). Phosphorylates and activates CFTR on the plasma membrane. CC Plays a key role in intestinal secretion by regulating cGMP-dependent CC translocation of CFTR in jejunum (By similarity). Acts downstream of CC NMDAR to activate the plasma membrane accumulation of GRIA1/GLUR1 in CC synapse and increase synaptic plasticity. Phosphorylates GRIA1/GLUR1 at CC Ser-863 (By similarity). Acts as regulator of gene expression and CC activator of the extracellular signal-regulated kinases MAPK3/ERK1 and CC MAPK1/ERK2 in mechanically stimulated osteoblasts. Under fluid shear CC stress, mediates ERK activation and subsequent induction of FOS, CC FOSL1/FRA1, FOSL2/FRA2 and FOSB that play a key role in the osteoblast CC anabolic response to mechanical stimulation (By similarity). CC {ECO:0000250|UniProtKB:Q61410, ECO:0000250|UniProtKB:Q64595}. 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 -!- 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 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; 229 antibodies. DR DNASU; 5593; -. DR Ensembl; ENST00000264399; ENSP00000264399; ENSG00000138669. [Q13237-1] DR Ensembl; ENST00000395578; ENSP00000378945; ENSG00000138669. [Q13237-1] DR Ensembl; ENST00000628926; ENSP00000486129; ENSG00000138669. [Q13237-2] DR GeneID; 5593; -. DR KEGG; hsa:5593; -. DR UCSC; uc003hmh.3; human. [Q13237-1] DR CTD; 5593; -. DR DisGeNET; 5593; -. DR EuPathDB; HostDB:ENSG00000138669.9; -. DR GeneCards; PRKG2; -. DR HGNC; HGNC:9416; PRKG2. DR HPA; ENSG00000138669; Tissue enhanced (intestine). DR MIM; 601591; gene. DR neXtProt; NX_Q13237; -. DR OpenTargets; ENSG00000138669; -. DR PharmGKB; PA33778; -. DR eggNOG; KOG0616; Eukaryota. DR eggNOG; ENOG410XPQQ; LUCA. DR GeneTree; ENSGT00940000159393; -. DR HOGENOM; CLU_000288_73_2_1; -. DR InParanoid; Q13237; -. DR KO; K19477; -. DR OMA; PTDYSYF; -. DR OrthoDB; 401933at2759; -. DR PhylomeDB; Q13237; -. DR TreeFam; TF313261; -. DR BRENDA; 2.7.11.12; 2681. 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 SignaLink; Q13237; -. DR SIGNOR; Q13237; -. DR BioGRID-ORCS; 5593; 6 hits in 816 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 intestine and 100 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:0051186; P:cofactor metabolic process; TAS:Reactome. DR GO; GO:2001226; P:negative regulation of chloride transport; 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:CAFA. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. 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; Kinase; Lipoprotein; Membrane; Myristate; KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; KW 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 NP_BIND 232..235 FT /note="cAMP or cGMP 1" FT /evidence="ECO:0000244|PDB:5C6C, ECO:0000244|PDB:5C8W, FT ECO:0000269|PubMed:26769964" FT NP_BIND 242..243 FT /note="cAMP or cGMP 1" FT /evidence="ECO:0000244|PDB:5C6C, ECO:0000244|PDB:5C8W, FT ECO:0000269|PubMed:26769964" FT NP_BIND 357..359 FT /note="cAMP or cGMP 2" FT /evidence="ECO:0000244|PDB:5BV6, FT ECO:0000269|PubMed:26769964" FT NP_BIND 366..367 FT /note="cAMP or cGMP 2" FT /evidence="ECO:0000244|PDB:5BV6, FT ECO:0000269|PubMed:26769964" FT NP_BIND 459..467 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" 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 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 347 FT /note="cAMP or cGMP 2" FT /evidence="ECO:0000269|PubMed:26769964, FT ECO:0000312|PDB:5BV6" FT BINDING 412 FT /note="cAMP or cGMP 2" FT /evidence="ECO:0000269|PubMed:26769964, FT ECO:0000312|PDB:5BV6" FT BINDING 415 FT /note="cAMP or cGMP 2" FT /evidence="ECO:0000269|PubMed:26769964, FT ECO:0000312|PDB:5BV6" FT BINDING 482 FT /note="ATP" 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 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:0000244|PDB:5C8W" FT HELIX 169..171 FT /evidence="ECO:0000244|PDB:5C8W" FT HELIX 174..183 FT /evidence="ECO:0000244|PDB:5C8W" FT STRAND 185..189 FT /evidence="ECO:0000244|PDB:5C8W" FT STRAND 194..196 FT /evidence="ECO:0000244|PDB:5C8W" FT STRAND 204..211 FT /evidence="ECO:0000244|PDB:5C8W" FT STRAND 213..217 FT /evidence="ECO:0000244|PDB:5C8W" FT STRAND 220..224 FT /evidence="ECO:0000244|PDB:5C8W" FT STRAND 230..232 FT /evidence="ECO:0000244|PDB:5C8W" FT HELIX 233..238 FT /evidence="ECO:0000244|PDB:5C8W" FT STRAND 243..250 FT /evidence="ECO:0000244|PDB:5C8W" FT STRAND 252..258 FT /evidence="ECO:0000244|PDB:5C8W" FT HELIX 259..266 FT /evidence="ECO:0000244|PDB:5C8W" FT HELIX 270..282 FT /evidence="ECO:0000244|PDB:5JIX" FT HELIX 285..287 FT /evidence="ECO:0000244|PDB:5JIX" FT HELIX 292..301 FT /evidence="ECO:0000244|PDB:5JIX" FT STRAND 303..307 FT /evidence="ECO:0000244|PDB:5JIX" FT STRAND 312..314 FT /evidence="ECO:0000244|PDB:5JIX" FT STRAND 323..335 FT /evidence="ECO:0000244|PDB:5JIX" FT STRAND 344..350 FT /evidence="ECO:0000244|PDB:5JIX" FT HELIX 357..362 FT /evidence="ECO:0000244|PDB:5JIX" FT STRAND 368..372 FT /evidence="ECO:0000244|PDB:5JIX" FT STRAND 377..382 FT /evidence="ECO:0000244|PDB:5JIX" FT HELIX 384..389 FT /evidence="ECO:0000244|PDB:5JIX" FT HELIX 391..393 FT /evidence="ECO:0000244|PDB:5JIX" FT HELIX 395..414 FT /evidence="ECO:0000244|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 //