Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

cGMP-dependent protein kinase 1

Gene

PRKG1

Organism
Bos taurus (Bovine)
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 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei390 – 3901ATP
Active sitei484 – 4841Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi167 – 1704cAMP or cGMPBy similarity
Nucleotide bindingi177 – 1782cAMP or cGMPBy similarity
Nucleotide bindingi366 – 3749ATPPROSITE-ProRule annotation

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. 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

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

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL3183.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 671670cGMP-dependent protein kinase 1PRO_0000086114Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Disulfide bondi43 – 43Interchain
Modified residuei59 – 591Phosphothreonine; by autocatalysis1 Publication
Modified residuei515 – 5151PhosphothreonineBy similarity

Post-translational modificationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei78 – 792Cleavage

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

Protein-protein interaction databases

BioGridi159293. 2 interactions.
DIPiDIP-59143N.
IntActiP00516. 3 interactions.

Chemistry

BindingDBiP00516.

Structurei

Secondary structure

1
671
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi88 – 9912Combined sources
Turni102 – 1065Combined sources
Helixi109 – 11810Combined sources
Beta strandi120 – 1245Combined sources
Beta strandi129 – 1313Combined sources
Beta strandi140 – 1467Combined sources
Beta strandi148 – 1525Combined sources
Beta strandi155 – 1606Combined sources
Beta strandi165 – 1673Combined sources
Helixi170 – 1723Combined sources
Turni173 – 1753Combined sources
Beta strandi179 – 1857Combined sources
Beta strandi187 – 1926Combined sources
Helixi194 – 21623Combined sources
Helixi220 – 2245Combined sources
Helixi227 – 2337Combined sources
Turni234 – 2363Combined sources
Beta strandi238 – 2425Combined sources
Beta strandi247 – 2493Combined sources
Beta strandi257 – 27014Combined sources
Beta strandi273 – 2753Combined sources
Beta strandi279 – 2857Combined sources
Helixi292 – 2954Combined sources
Beta strandi296 – 3005Combined sources
Beta strandi302 – 31716Combined sources
Helixi318 – 3258Combined sources
Helixi333 – 35422Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3SHRX-ray2.50A/B79-356[»]
ProteinModelPortaliP00516.
SMRiP00516. Positions 9-44.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini360 – 619260Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini620 – 67152AGC-kinase C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 102101Required for dimerizationAdd
BLAST
Regioni9 – 4436Leucine-zipperAdd
BLAST
Regioni50 – 7526Autoinhibitory domainBy similarityAdd
BLAST
Regioni103 – 220118cGMP-binding, high affinityBy similarityAdd
BLAST
Regioni221 – 341121cGMP-binding, low affinityBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili2 – 5958By similarityAdd
BLAST

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

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

GeneTreeiENSGT00810000125385.
HOGENOMiHOG000233033.
HOVERGENiHBG006211.
InParanoidiP00516.
KOiK07376.
OMAiYAKSDWS.

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.
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.
[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: 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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8989MSELE…TKSER → MGTLRDLQYALQEKIEELRQ RDALIDELELELDQKDELIQ KLQNELDKYRSVIRPATQQA QKQSASTLQGEPRTKRQAIS AEPTAFDIQDLSHVTLPFYP KSPQ in isoform Beta. 3 PublicationsVSP_038713Add
BLAST

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3SHRX-ray2.50A/B79-356[»]
ProteinModelPortaliP00516.
SMRiP00516. Positions 9-44.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi159293. 2 interactions.
DIPiDIP-59143N.
IntActiP00516. 3 interactions.

Chemistry

BindingDBiP00516.
ChEMBLiCHEMBL3183.

PTM databases

iPTMnetiP00516.

Proteomic databases

PRIDEiP00516.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5592.

Phylogenomic databases

GeneTreeiENSGT00810000125385.
HOGENOMiHOG000233033.
HOVERGENiHBG006211.
InParanoidiP00516.
KOiK07376.
OMAiYAKSDWS.

Enzyme and pathway databases

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

Gene expression databases

BgeeiENSBTAG00000018404.
ExpressionAtlasiP00516. baseline.

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.
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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKGP1_BOVIN
AccessioniPrimary (citable) accession number: P00516
Secondary accession number(s): P21136
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.