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 29-OCT-2014, entry version 135. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Hansson V., Jahnsen T., Sandberg M.; RT "Molecular cloning, cDNA structure, and chromosomal localization of RT the 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 RT upon introduction of SV40 T antigen or immortalization in human RT 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA 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., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA 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., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 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., RA Sandberg M.; RT "Characterization of the gene encoding the human type II cGMP- RT dependent 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 RT cGMP-dependent protein kinase type II."; RL J. Biol. Chem. 271:7025-7029(1996). RN [7] 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., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- ENZYME REGULATION: Binding of cGMP results in enzyme activation. 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 Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Highly concentrated in brain, lung and CC intestinal 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 -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 2 cyclic nucleotide-binding domains. CC {ECO:0000255|PROSITE-ProRule:PRU00060}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. 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 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_005263126.1. [Q13237-1] DR UniGene; Hs.232044; -. DR UniGene; Hs.570833; -. DR UniGene; Hs.739943; -. DR ProteinModelPortal; Q13237; -. DR SMR; Q13237; 77-762. DR BioGrid; 111579; 6. DR IntAct; Q13237; 3. DR STRING; 9606.ENSP00000264399; -. DR BindingDB; Q13237; -. DR ChEMBL; CHEMBL2896; -. DR GuidetoPHARMACOLOGY; 1493; -. DR PhosphoSite; Q13237; -. DR DMDM; 6226833; -. DR MaxQB; Q13237; -. DR PaxDb; Q13237; -. DR PRIDE; Q13237; -. DR DNASU; 5593; -. DR Ensembl; ENST00000264399; ENSP00000264399; ENSG00000138669. [Q13237-1] DR Ensembl; ENST00000395578; ENSP00000378945; ENSG00000138669. [Q13237-1] DR GeneID; 5593; -. DR KEGG; hsa:5593; -. DR UCSC; uc003hmh.2; human. [Q13237-1] DR CTD; 5593; -. DR GeneCards; GC04M082009; -. DR HGNC; HGNC:9416; PRKG2. DR HPA; CAB018739; -. DR HPA; HPA007386; -. DR MIM; 601591; gene. DR neXtProt; NX_Q13237; -. DR PharmGKB; PA33778; -. DR eggNOG; COG0515; -. DR GeneTree; ENSGT00550000074358; -. DR HOGENOM; HOG000233033; -. DR HOVERGEN; HBG006211; -. DR InParanoid; Q13237; -. DR KO; K07376; -. DR OMA; NPPFSGI; -. DR OrthoDB; EOG75B84Q; -. DR PhylomeDB; Q13237; -. DR TreeFam; TF313261; -. DR BRENDA; 2.7.11.12; 2681. DR Reactome; REACT_111176; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation. DR Reactome; REACT_172761; Ca2+ pathway. DR Reactome; REACT_23767; cGMP effects. DR SignaLink; Q13237; -. DR GenomeRNAi; 5593; -. DR NextBio; 21704; -. DR PRO; PR:Q13237; -. DR Bgee; Q13237; -. DR CleanEx; HS_PRKG2; -. DR ExpressionAtlas; Q13237; baseline and differential. DR Genevestigator; Q13237; -. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW. 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; IEA:UniProtKB-EC. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0032922; P:circadian regulation of gene expression; IEA:Ensembl. DR GO; GO:0046209; P:nitric oxide metabolic process; TAS:Reactome. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 2.60.120.10; -; 2. DR InterPro; IPR000961; AGC-kinase_C. DR InterPro; IPR016232; cGMP-dependent_protein_kinase. 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. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR014710; RmlC-like_jellyroll. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase. DR InterPro; IPR008271; Ser/Thr_kinase_AS. 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 Alternative splicing; ATP-binding; Cell membrane; cGMP; cGMP-binding; KW Complete proteome; Kinase; Lipoprotein; Membrane; Myristate; KW Nucleotide-binding; Polymorphism; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT INIT_MET 1 1 Removed. FT CHAIN 2 762 cGMP-dependent protein kinase 2. FT /FTId=PRO_0000086123. FT DOMAIN 453 711 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT DOMAIN 712 762 AGC-kinase C-terminal. FT NP_BIND 168 285 cGMP 1. FT NP_BIND 286 417 cGMP 2. FT NP_BIND 459 467 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT ACT_SITE 576 576 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 482 482 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT LIPID 2 2 N-myristoyl glycine. FT {ECO:0000269|PubMed:8636133}. FT VAR_SEQ 441 469 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_055121. FT VARIANT 22 22 T -> S (in dbSNP:rs34956759). FT /FTId=VAR_051633. FT VARIANT 106 106 H -> R (in dbSNP:rs34616910). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040608. FT VARIANT 716 716 W -> R (in a colorectal adenocarcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040609. FT CONFLICT 57 58 QL -> HG (in Ref. 2; BAA18934). FT {ECO:0000305}. FT CONFLICT 154 154 S -> I (in Ref. 5; CAA76073). FT {ECO:0000305}. FT CONFLICT 388 388 N -> D (in Ref. 3; BAG60035). FT {ECO:0000305}. FT CONFLICT 460 460 G -> A (in Ref. 2; BAA18934). FT {ECO:0000305}. 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 //