PRKG1

Protein identityUniProt · HPA

UniProt accession

Q13976

Gene

PRKG1

Ensembl

ENSG00000185532

Chromosome

10

Canonical length

671 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. [provided by RefSeq, Sep 2011]

Canonical amino-acid sequenceUniProt

671 residues, UniProt reviewed canonical sequence.

>Q13976|PRKG1
     1  MSELEEDFAK ILMLKEERIK ELEKRLSEKE EEIQELKRKL HKCQSVLPVP STHIGPRTTR
    61  AQGISAEPQT YRSFHDLRQA FRKFTKSERS KDLIKEAILD NDFMKNLELS QIQEIVDCMY
   121  PVEYGKDSCI IKEGDVGSLV YVMEDGKVEV TKEGVKLCTM GPGKVFGELA ILYNCTRTAT
   181  VKTLVNVKLW AIDRQCFQTI MMRTGLIKHT EYMEFLKSVP TFQSLPEEIL SKLADVLEET
   241  HYENGEYIIR QGARGDTFFI ISKGTVNVTR EDSPSEDPVF LRTLGKGDWF GEKALQGEDV
   301  RTANVIAAEA VTCLVIDRDS FKHLIGGLDD VSNKAYEDAE AKAKYEAEAA FFANLKLSDF
   361  NIIDTLGVGG FGRVELVQLK SEESKTFAMK ILKKRHIVDT RQQEHIRSEK QIMQGAHSDF
   421  IVRLYRTFKD SKYLYMLMEA CLGGELWTIL RDRGSFEDST TRFYTACVVE AFAYLHSKGI
   481  IYRDLKPENL ILDHRGYAKL VDFGFAKKIG FGKKTWTFCG TPEYVAPEII LNKGHDISAD
   541  YWSLGILMYE LLTGSPPFSG PDPMKTYNII LRGIDMIEFP KKIAKNAANL IKKLCRDNPS
   601  ERLGNLKNGV KDIQKHKWFE GFNWEGLRKG TLTPPIIPSV ASPTDTSNFD SFPEDNDEPP
   661  PDDNSGWDID F

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PRKG1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

64 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PRKG1.

Disease | AllUniProt

Conditions PRKG1 is implicated in, by any mechanism.

• Aortic aneurysm, familial thoracic 8 (AAT8) MIM:615436

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 972 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Aortic aneurysm, familial thoracic 8
• Familial thoracic aortic aneurysm and aortic dissection

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.24

gnomAD pLI

1

gnomAD missense Z

2.98

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bone growth
• cell growth involved in cardiac muscle cell development
• cerebellum development
• cGMP-mediated signaling
• collateral sprouting
• dendrite development
• forebrain development
• negative regulation of glutamate secretion
• negative regulation of inositol phosphate biosynthetic process
• negative regulation of platelet aggregation
• negative regulation of vascular associated smooth muscle cell migration
• negative regulation of vascular associated smooth muscle cell proliferation
• neuron migration
• positive regulation of circadian rhythm
• positive regulation of cytosolic calcium ion concentration
• regulation of testosterone biosynthetic process
• regulation of vascular permeability
• relaxation of vascular associated smooth muscle
• signal transduction
• spermatid development

Molecular functions

• ATP binding
• calcium channel regulator activity
• cGMP binding
• cGMP-dependent protein kinase activity
• identical protein binding
• mitogen-activated protein kinase p38 binding
• protein kinase activity
• protein serine kinase activity

Cellular components

• acrosomal vesicle
• cytoplasm
• cytosol
• Golgi apparatus
• nucleoplasm
• plasma membrane
• sarcolemma

Protein domainsUniProt · Pfam · InterPro

• Cyclic nucleotide-binding domain
• Protein kinase domain
• AGC-kinase, C-terminal
• cGMP-dependent kinase
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• RmlC-like jelly roll fold
• Protein kinase, ATP binding site
• Cyclic nucleotide-binding, conserved site
• Cyclic nucleotide-binding domain superfamily
• cGMP-dependent protein kinase, catalytic domain
• Cyclic nucleotide-binding domain
• Protein kinase domain
• cGMP-dependent protein kinase, N-terminal coiled-coil domain
• Coiled-coil N-terminus of cGMP-dependent protein kinase

KeywordsUniProt

• Acetylation
• Allosteric enzyme
• Aortic aneurysm
• ATP-binding
• cGMP
• cGMP-binding
• Coiled coil
• Cytoplasm
• Disulfide bond
• Kinase
• Nucleotide-binding
• Phosphoprotein
• Serine/threonine-protein kinase
• Transferase

InteractionsUniProt · HPA

Protein binding partners of PRKG1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GTF2I
• IRAG1
• PPP1R12A
• RGS2
• TRPC7
• GKAP1