UniProt Accession

 KGP1_MOUSE; P0C605; Q14DK6; Q9Z0Z0 

Genbank Protein ID

 AF084547; AC102751; AC103405; AC108399; AC116507; AC119158; AC122548; BC113162 

Genbank Nucleotide ID

 AAD16044.1; AAI13163.1 

Protein Name

 cGMP-dependent protein kinase 1 

Protein Synonyms/Alias

 cGK 1; cGK1; cGMP-dependent protein kinase I; cGKI 

Gene Name

 Prkg1 

Gene Synonyms/Alias

 Prkg1b; Prkgr1a; Prkgr1b 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
322	VIDRDSFKHLIGGLD	acetylation	[1]

Reference

 [1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405] 

Functional Description

 Serine/threonine protein kinase that acts as key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates MRVI1/IRAG and inhibits IP3- induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling alters also gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle. 

Sequence Annotation

 DOMAIN 360 619 Protein kinase.
 DOMAIN 620 671 AGC-kinase C-terminal.
 NP_BIND 167 170 cAMP or cGMP (By similarity).
 NP_BIND 177 178 cAMP or cGMP (By similarity).
 NP_BIND 366 374 ATP (By similarity).
 REGION 2 102 Required for dimerization (By
 REGION 9 44 Leucine-zipper.
 REGION 50 75 Autoinhibitory domain (By similarity).
 REGION 103 220 cGMP-binding, high affinity (By
 REGION 221 341 cGMP-binding, low affinity (By
 ACT_SITE 484 484 Proton acceptor (By similarity).
 BINDING 390 390 ATP (By similarity).
 MOD_RES 2 2 N-acetylserine (By similarity).
 MOD_RES 59 59 Phosphothreonine; by autocatalysis (By
 DISULFID 43 43 Interchain (By similarity).  

Keyword

 Acetylation; Allosteric enzyme; Alternative splicing; ATP-binding; cGMP; cGMP-binding; Coiled coil; Complete proteome; Cytoplasm; Disulfide bond; Kinase; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 671 AA 

Protein Sequence

Gene Ontology

 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005246; F:calcium channel regulator activity; ISS:UniProtKB.
 GO:0030553; F:cGMP binding; IDA:UniProtKB.
 GO:0004692; F:cGMP-dependent protein kinase activity; IDA:UniProtKB.
 GO:0016358; P:dendrite development; IMP:MGI.
 GO:0030900; P:forebrain development; IMP:MGI.
 GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB.
 GO:0001764; P:neuron migration; IMP:MGI.
 GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
 GO:0007165; P:signal transduction; IDA:UniProtKB. 

Interpro

 IPR000961; AGC-kinase_C.
 IPR016232; cGMP-dependent_protein_kinase.
 IPR002374; cGMP_dep_kinase.
 IPR018490; cNMP-bd-like.
 IPR018488; cNMP-bd_CS.
 IPR000595; cNMP-bd_dom.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR014710; RmlC-like_jellyroll.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00027; cNMP_binding
 PF00069; Pkinase 

SMART

 SM00100; cNMP
 SM00133; S_TK_X
 SM00220; S_TKc 

PROSITE

 PS51285; AGC_KINASE_CTER
 PS00888; CNMP_BINDING_1
 PS00889; CNMP_BINDING_2
 PS50042; CNMP_BINDING_3
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS

 PR00104; CGMPKINASE.