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O77676 (KGP1_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
cGMP-dependent protein kinase 1
Short name=cGK 1
Short name=cGK1
EC=2.7.11.12
Gene names
Name:PRKG1
OrganismOryctolagus cuniculus (Rabbit) [Complete proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length671 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine protein kinasethat 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. Smoth 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. Ref.2

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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

Subunit structure

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.

Subcellular location

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

Domain

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.

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.

Post-translational modification

Autophosphorylation increases kinase activity By similarity.

65 kDa monomer is produced by proteolytic cleavage By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 2 cyclic nucleotide-binding domains.

Contains 1 protein kinase domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]
Isoform Alpha (identifier: O77676-1)

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.
Isoform Beta (identifier: O77676-2)

Also known as: CGK1-beta;

The sequence of this isoform is not available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 671670cGMP-dependent protein kinase 1
PRO_0000086116

Regions

Domain9 – 4436Leucine-zipper
Domain360 – 619260Protein kinase
Domain620 – 67152AGC-kinase C-terminal
Nucleotide binding167 – 1704cAMP or cGMP By similarity
Nucleotide binding177 – 1782cAMP or cGMP By similarity
Nucleotide binding366 – 3749ATP By similarity
Region2 – 102101Required for dimerization By similarity
Region50 – 7526Autoinhibitory domain By similarity
Region103 – 220118cGMP-binding, high affinity By similarity
Region221 – 341121cGMP-binding, low affinity By similarity

Sites

Active site4841Proton acceptor By similarity
Binding site3901ATP By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue591Phosphothreonine; by autocatalysis By similarity
Modified residue5151Phosphothreonine By similarity
Disulfide bond43Interchain By similarity

Natural variations

Natural variant5581F → S.

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha (CGK1-alpha) [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: F8E50992F39C0D81

FASTA67176,454
        10         20         30         40         50         60 
MSELEEDFAK ILMLKEERIK ELEKRLSEKE EEIQELKRKL HKCQSVLPVP STHIGPRTTR 

        70         80         90        100        110        120 
AQGISAEPQT YRSFHDLRQA FRKFTKFERS KDLIKEAILD NDFMKNLELS QIQEIVDCMY 

       130        140        150        160        170        180 
PVEYGKDSCI IKEGDVGSLA YVMEDGKVEV TKEGVKLCTM GPGKVFGELA ILYNCTRTAT 

       190        200        210        220        230        240 
VKTLVNVKLW AIDRQCFQTI MMRTGLIKHT EYMEFLKSVP TFQSLPEEIL SKLADVLEET 

       250        260        270        280        290        300 
HYENEEYSIR QGARGDTFFI ISKGKVNVTR EDSPSEDPIF LRTLGKGDWF GEKALQGEDV 

       310        320        330        340        350        360 
RTANVIAAEA VTCLVIDRDS FKHLIGGLDD VSNKAYEDAE AKAKYEAEAA FFANLKLSDF 

       370        380        390        400        410        420 
NIIDTLGVGG FGRVELVQLK SEESKTFAMK ILKKRHIVDT RQQEHIRSEK QIMQGAHSDF 

       430        440        450        460        470        480 
IVRLYRTFKD SKYLYMLMEA CLGGELWTIL RDRGSFEDST TRFYTACVVE AFAYLHSKGI 

       490        500        510        520        530        540 
IYRDLKPENL ILDHRGYAKL VDFGFAKKIG FGKKTWTFCG TPEYVAPEII LNKGHDISAD 

       550        560        570        580        590        600 
YWSLGILMYE LLTGSPPFSG PDPMKTYNII LRGIDMIEFP KKIAKNAANL IKKLCRDNPS 

       610        620        630        640        650        660 
ERLGNLKNGV KDIQKHKWFE GFNWEGLRKG TLTPPIIPSV ASPTDTSNFD GFPEDNDEPP 

       670 
PDDNSGWDID F

« Hide

Isoform Beta (CGK1-beta) (Sequence not available). ––

References

[1]"Analysis of expression of cGMP-dependent protein kinase in rabbit heart cells."
Kumar R., Joyner R.W., Komalavilas P., Lincoln T.M.
J. Pharmacol. Exp. Ther. 291:967-975(1999) [PubMed: 10565812] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: New Zealand white.
Tissue: Heart.
[2]"Inhibition of Galphaq-dependent PLC-beta1 activity by PKG and PKA is mediated by phosphorylation of RGS4 and GRK2."
Huang J., Zhou H., Mahavadi S., Sriwai W., Murthy K.S.
Am. J. Physiol. 292:C200-C208(2007) [PubMed: 16885398] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RGS4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF076969 mRNA. Translation: AAC31192.1.
RefSeqNP_001075511.1. NM_001082042.1.
UniGeneOcu.2417.

3D structure databases

ProteinModelPortalO77676.
SMRO77676. Positions 9-44.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100008694.

Organism-specific databases

CTD5592.

Phylogenomic databases

eggNOGmaNOG19158.
GeneTreeENSGT00550000074358.
HOVERGENHBG006211.
OrthoDBEOG4V9TQ7.

Enzyme and pathway databases

BRENDA2.7.11.12. 1749.

Family and domain databases

InterProIPR000961. 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.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]
Gene3DG3DSA:2.60.120.10. RmlC-like_jellyroll. 2 hits.
PfamPF00027. cNMP_binding. 2 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF000559. cGMP-dep_kinase. 1 hit.
PRINTSPR00104. CGMPKINASE.
SMARTSM00100. cNMP. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF51206. cNMP_binding. 2 hits.
SSF56112. Kinase_like. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00888. CNMP_BINDING_1. False negative.
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]
ProtoNetSearch...

Entry information

Entry nameKGP1_RABIT
AccessionPrimary (citable) accession number: O77676
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: January 25, 2012
This is version 90 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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