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Protein

cGMP-dependent protein kinase 1

Gene

PRKG1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -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 similarity

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 sitei282cGMP 2By similarity1
Binding sitei336cAMP or cGMP 2By similarity1
Binding sitei390ATP1
Active sitei484Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi167 – 170cAMP or cGMP 1Combined sources1 Publication4
Nucleotide bindingi177 – 178cAMP or cGMP 1Combined sources1 Publication2
Nucleotide bindingi291 – 294cAMP or cGMP 2By similarity4
Nucleotide bindingi301 – 302cAMP or cGMP 2By similarity2
Nucleotide bindingi366 – 374ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAllosteric enzyme, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, cGMP, cGMP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.12 908
ReactomeiR-BTA-392517 Rap1 signalling
R-BTA-418457 cGMP effects

Names & Taxonomyi

Protein namesi
Recommended name:
cGMP-dependent protein kinase 1 (EC:2.7.11.12)
Short name:
cGK 1
Short name:
cGK1
Alternative name(s):
cGMP-dependent protein kinase I
Short name:
cGKI
Gene namesi
Name:PRKG1
Synonyms:PRKG1B, PRKGR1A, PRKGR1B
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 26

Organism-specific databases

VGNCiVGNC:33340 PRKG1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3183

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000861142 – 671cGMP-dependent protein kinase 1Add BLAST670

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserine1 Publication1
Disulfide bondi43Interchain
Modified residuei59Phosphothreonine; by autocatalysis1 Publication1
Modified residuei515PhosphothreonineBy similarity1

Post-translational modificationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei78 – 79Cleavage2

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

PRIDEiP00516

PTM databases

iPTMnetiP00516

Expressioni

Tissue specificityi

High concentrations are detected in various smooth muscle: lung, rumen, trachea, aorta, uterus and stomach. Isoform alpha is expressed predominantly in heart, cerebellum and lung, whereas the beta isoform is expressed in high concentrations in trachea, aorta, stomach and uterus.1 Publication

Gene expression databases

BgeeiENSBTAG00000018404
ExpressionAtlasiP00516 baseline

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

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi159293, 2 interactors
CORUMiP00516
DIPiDIP-59143N
IntActiP00516, 3 interactors

Chemistry databases

BindingDBiP00516

Structurei

Secondary structure

1671
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi88 – 99Combined sources12
Turni102 – 106Combined sources5
Helixi109 – 118Combined sources10
Beta strandi120 – 124Combined sources5
Beta strandi129 – 131Combined sources3
Beta strandi140 – 146Combined sources7
Beta strandi148 – 152Combined sources5
Beta strandi155 – 160Combined sources6
Beta strandi165 – 167Combined sources3
Helixi170 – 172Combined sources3
Turni173 – 175Combined sources3
Beta strandi179 – 185Combined sources7
Beta strandi187 – 192Combined sources6
Helixi194 – 216Combined sources23
Helixi220 – 224Combined sources5
Helixi227 – 233Combined sources7
Turni234 – 236Combined sources3
Beta strandi238 – 242Combined sources5
Beta strandi247 – 249Combined sources3
Beta strandi257 – 270Combined sources14
Beta strandi273 – 275Combined sources3
Beta strandi279 – 285Combined sources7
Helixi292 – 295Combined sources4
Beta strandi296 – 300Combined sources5
Beta strandi302 – 317Combined sources16
Helixi318 – 325Combined sources8
Helixi333 – 354Combined sources22

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3SHRX-ray2.50A/B79-356[»]
ProteinModelPortaliP00516
SMRiP00516
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 dimerizationAdd 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.
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

Keywords - Domaini

Coiled coil

Phylogenomic databases

GeneTreeiENSGT00810000125385
HOGENOMiHOG000233033
HOVERGENiHBG006211
InParanoidiP00516
KOiK07376
OMAiEPQTHQD

Family and domain databases

CDDicd00038 CAP_ED, 2 hits
cd05572 STKc_cGK, 1 hit
Gene3Di2.60.120.10, 2 hits
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR002374 cGMP_dep_kinase
IPR018490 cNMP-bd-like
IPR018488 cNMP-bd_CS
IPR000595 cNMP-bd_dom
IPR011009 Kinase-like_dom_sf
IPR031831 PKcGMP_CC
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR014710 RmlC-like_jellyroll
IPR008271 Ser/Thr_kinase_AS
IPR035014 STKc_cGK
PfamiView protein in Pfam
PF00027 cNMP_binding, 2 hits
PF16808 PKcGMP_CC, 1 hit
PF00069 Pkinase, 1 hit
PIRSFiPIRSF000559 cGMP-dep_kinase, 1 hit
PRINTSiPR00104 CGMPKINASE
SMARTiView protein in SMART
SM00100 cNMP, 2 hits
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF51206 SSF51206, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00888 CNMP_BINDING_1, 2 hits
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

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: P00516-1) [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 FRKFTKSERS KDLIKEAILD
110 120 130 140 150
NDFMKNLELS QIQEIVDCMY PVEYGKDSCI IKEGDVGSLV YVMEDGKVEV
160 170 180 190 200
TKEGVKLCTM GPGKVFGELA ILYNCTRTAT VKTLVNVKLW AIDRQCFQTI
210 220 230 240 250
MMRTGLIKHT EYMEFLKSVP TFQSLPEEIL SKLADVLEET HYENGEYIIR
260 270 280 290 300
QGARGDTFFI ISKGKVNVTR EDSPNEDPVF 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
SFPEDNDEPP PDDNSGWDID F
Length:671
Mass (Da):76,419
Last modified:January 23, 2007 - v2
Checksum:i9FE7A48422DA9CDF
GO
Isoform Beta (identifier: P00516-2) [UniParc] [UniParc]FASTAAdd to basket
Also known as: CGK1-beta

The sequence of this isoform differs from the canonical sequence as follows:
     1-89: MSELEEDFAK...AFRKFTKSER → MGTLRDLQYA...TLPFYPKSPQ

Show »
Length:686
Mass (Da):77,858
Checksum:i6E48359C35BB96EB
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0387131 – 89MSELE…TKSER → MGTLRDLQYALQEKIEELRQ RDALIDELELELDQKDELIQ KLQNELDKYRSVIRPATQQA QKQSASTLQGEPRTKRQAIS AEPTAFDIQDLSHVTLPFYP KSPQ in isoform Beta. 2 PublicationsAdd BLAST89

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16086 mRNA Translation: CAA34214.1
X54289 mRNA Translation: CAA38184.1
Y08961 mRNA Translation: CAA70155.1
PIRiA00619 OKBOG
S05035
RefSeqiNP_776861.1, NM_174436.2 [P00516-1]
UniGeneiBt.63035
Bt.9

Genome annotation databases

EnsembliENSBTAT00000024490; ENSBTAP00000024490; ENSBTAG00000018404 [P00516-1]
GeneIDi282004
KEGGibta:282004

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKGP1_BOVIN
AccessioniPrimary (citable) accession number: P00516
Secondary accession number(s): P21136
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 163 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health