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Protein

cGMP-dependent protein kinase 1

Gene

PRKG1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 Ca2+ release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca2+ 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 (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei390ATPPROSITE-ProRule annotation1
Active sitei484Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi167 – 170cAMP or cGMPBy similarity4
Nucleotide bindingi177 – 178cAMP or cGMPBy similarity2
Nucleotide bindingi366 – 374ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, cGMP, cGMP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.12. 1749.

Names & Taxonomyi

Protein namesi
Recommended name:
cGMP-dependent protein kinase 1 (EC:2.7.11.12)
Short name:
cGK 1
Short name:
cGK1
Gene namesi
Name:PRKG1
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm By similarity

  • Note: Colocalized with TRPC7 in the plasma membrane.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000861162 – 671cGMP-dependent protein kinase 1Add BLAST670

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Disulfide bondi43InterchainBy similarity
Modified residuei59Phosphothreonine; by autocatalysisBy similarity1
Modified residuei515PhosphothreonineBy similarity1

Post-translational modificationi

Autophosphorylation increases kinase activity.By similarity
65 kDa monomer is produced by proteolytic cleavage.By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Interactioni

Subunit structurei

Isoform alpha: parallel homodimer or heterodimer and also heterotetramer. Interacts directly with PPP1R12A. Non-covalent dimer of dimer of PRKG1-PRKG1 and PPP1R12A-PPP1R12A. This interaction targets PRKG1 to stress fibers to mediate smooth muscle cell relaxation and vasodilation in responses to rises in cGMP (By similarity). Isoform beta: antiparallel homodimer. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with MRVI1 (By similarity). Forms a stable complex with ITPR1, MRVI1, and isoform beta of PRKG1 (By similarity). Interacts with TRPC7 (via ankyrin repeat domain) (By similarity). Isoform alpha interacts with RGS2 (By similarity). Interacts with GTF2I (By similarity).By similarity

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000009871.

Structurei

3D structure databases

ProteinModelPortaliO77676.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini360 – 619Protein kinasePROSITE-ProRule annotationAdd BLAST260
Domaini620 – 671AGC-kinase C-terminalAdd BLAST52

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 102Required for dimerizationBy similarityAdd BLAST101
Regioni9 – 44Leucine-zipperAdd BLAST36
Regioni50 – 75Autoinhibitory domainBy similarityAdd BLAST26
Regioni103 – 220cGMP-binding, high affinityBy similarityAdd BLAST118
Regioni221 – 341cGMP-binding, low affinityBy similarityAdd BLAST121

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili2 – 59By similarityAdd BLAST58

Domaini

Composed of an N-terminal leucine-zipper domain followed by an autoinhibitory domain, which mediate homodimer formation and inhibit kinase activity, respectively. Next, two cGMP-binding domains are followed by the catalytic domain at the C-terminus. Binding of cGMP to cGMP-binding domains results in a conformational change that activates kinase activity by removing the autoinhibitory domain from the catalytic cleft leaving the catalytic domain free to phosphorylate downstream substrates. Isoforms alpha and beta have identical cGMP-binding and catalytic domains but differ in their leucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity (By similarity).By similarity
Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase.By similarity

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 2 cyclic nucleotide-binding domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0616. Eukaryota.
ENOG410XPQQ. LUCA.
HOGENOMiHOG000233033.
HOVERGENiHBG006211.
InParanoidiO77676.
KOiK07376.

Family and domain databases

Gene3Di2.60.120.10. 2 hits.
InterProiIPR000961. AGC-kinase_C.
IPR002374. cGMP_dep_kinase.
IPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR011009. Kinase-like_dom.
IPR031831. PKcGMP_CC.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014710. RmlC-like_jellyroll.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00027. cNMP_binding. 2 hits.
PF16808. PKcGMP_CC. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF000559. cGMP-dep_kinase. 1 hit.
PRINTSiPR00104. CGMPKINASE.
SMARTiSM00100. cNMP. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00889. CNMP_BINDING_2. 2 hits.
PS50042. CNMP_BINDING_3. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha (identifier: O77676-1) [UniParc]FASTAAdd to basket
Also known as: CGK1-alpha

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSELEEDFAK ILMLKEERIK ELEKRLSEKE EEIQELKRKL HKCQSVLPVP
60 70 80 90 100
STHIGPRTTR AQGISAEPQT YRSFHDLRQA FRKFTKFERS KDLIKEAILD
110 120 130 140 150
NDFMKNLELS QIQEIVDCMY PVEYGKDSCI IKEGDVGSLA YVMEDGKVEV
160 170 180 190 200
TKEGVKLCTM GPGKVFGELA ILYNCTRTAT VKTLVNVKLW AIDRQCFQTI
210 220 230 240 250
MMRTGLIKHT EYMEFLKSVP TFQSLPEEIL SKLADVLEET HYENEEYSIR
260 270 280 290 300
QGARGDTFFI ISKGKVNVTR EDSPSEDPIF LRTLGKGDWF GEKALQGEDV
310 320 330 340 350
RTANVIAAEA VTCLVIDRDS FKHLIGGLDD VSNKAYEDAE AKAKYEAEAA
360 370 380 390 400
FFANLKLSDF NIIDTLGVGG FGRVELVQLK SEESKTFAMK ILKKRHIVDT
410 420 430 440 450
RQQEHIRSEK QIMQGAHSDF IVRLYRTFKD SKYLYMLMEA CLGGELWTIL
460 470 480 490 500
RDRGSFEDST TRFYTACVVE AFAYLHSKGI IYRDLKPENL ILDHRGYAKL
510 520 530 540 550
VDFGFAKKIG FGKKTWTFCG TPEYVAPEII LNKGHDISAD YWSLGILMYE
560 570 580 590 600
LLTGSPPFSG PDPMKTYNII LRGIDMIEFP KKIAKNAANL IKKLCRDNPS
610 620 630 640 650
ERLGNLKNGV KDIQKHKWFE GFNWEGLRKG TLTPPIIPSV ASPTDTSNFD
660 670
GFPEDNDEPP PDDNSGWDID F
Length:671
Mass (Da):76,454
Last modified:January 23, 2007 - v3
Checksum:iF8E50992F39C0D81
GO
Isoform Beta (identifier: O77676-2)
Also known as: CGK1-beta
Sequence is not available
Length:
Mass (Da):

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti558F → S.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076969 mRNA. Translation: AAC31192.1.
RefSeqiNP_001075511.1. NM_001082042.2. [O77676-1]
UniGeneiOcu.2417.

Genome annotation databases

GeneIDi100008694.
KEGGiocu:100008694.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076969 mRNA. Translation: AAC31192.1.
RefSeqiNP_001075511.1. NM_001082042.2. [O77676-1]
UniGeneiOcu.2417.

3D structure databases

ProteinModelPortaliO77676.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000009871.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100008694.
KEGGiocu:100008694.

Organism-specific databases

CTDi5592.

Phylogenomic databases

eggNOGiKOG0616. Eukaryota.
ENOG410XPQQ. LUCA.
HOGENOMiHOG000233033.
HOVERGENiHBG006211.
InParanoidiO77676.
KOiK07376.

Enzyme and pathway databases

BRENDAi2.7.11.12. 1749.

Family and domain databases

Gene3Di2.60.120.10. 2 hits.
InterProiIPR000961. AGC-kinase_C.
IPR002374. cGMP_dep_kinase.
IPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR011009. Kinase-like_dom.
IPR031831. PKcGMP_CC.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014710. RmlC-like_jellyroll.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00027. cNMP_binding. 2 hits.
PF16808. PKcGMP_CC. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF000559. cGMP-dep_kinase. 1 hit.
PRINTSiPR00104. CGMPKINASE.
SMARTiSM00100. cNMP. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00889. CNMP_BINDING_2. 2 hits.
PS50042. CNMP_BINDING_3. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKGP1_RABIT
AccessioniPrimary (citable) accession number: O77676
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: October 5, 2016
This is version 119 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.