P00516

SS
Gene name
PRKG1 (PRKG1B, PRKGR1A, PRKGR1B)
Protein name
cGMP-dependent protein kinase 1
Names
cGK 1, cGK1, cGMP-dependent protein kinase I, cGKI
Species
Bos taurus (Bovine)
KEGG Pathway
bta:282004
EC number
2.7.11.12: Protein-serine/threonine kinases
Protein Class

Descriptions

(Annotation from UniProt)
PKG is a major intracellular receptor of cGMP and modulates diverse cellular signalings. The N-terminal regulatory domain contains a pseudosubstrate sequence that may interact with the catalytic kinase domain. 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.

Autoinhibitory domains (AIDs)

50-57 (Autoinhibitory region) SS

Target domain

360-619 (Protein kinase domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

501-523 (Activation loop from InterPro)

Target domain

360-619 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

2 structures for P00516

Entry ID Method Resolution Chain Position Source
3SHR X-ray 250 A A/B 79-356 PDB
AF-P00516-F1 Predicted AlphaFoldDB

119 variants for P00516

Variant ID(s) Position Change Description Diseaes Association Provenance
rs462169068 7 D>G No Ensembl
rs440392165 14 L>I No Ensembl
rs460470011 18 R>M No Ensembl
rs137206006 27 S>* No Ensembl
rs136191661 27 S>A No Ensembl
rs437695154 29 K>M No Ensembl
rs437695154 29 K>T No Ensembl
rs433576103 30 E>D No Ensembl
rs473823027 30 E>K No Ensembl
rs455195531 30 E>V No Ensembl
rs467213887 31 E>* No Ensembl
rs133549056 31 E>G No Ensembl
rs433342403 34 Q>L No Ensembl
rs469620455 36 L>R No Ensembl
rs451016793 37 K>Q No Ensembl
rs480669269 39 K>N No Ensembl
rs468708013 40 L>P No Ensembl
rs479876812 42 K>T No Ensembl
rs438694897 43 C>* No Ensembl
rs460380673 43 C>Y No Ensembl
rs477795854 44 Q>K No Ensembl
rs462628746 44 Q>P No Ensembl
rs444199228 45 S>* No Ensembl
rs473859083 46 V>A No Ensembl
rs439973864 49 V>G No Ensembl
rs455446758 49 V>M No Ensembl
rs452015396 50 P>A No Ensembl
rs433508356 50 P>R No Ensembl
rs452015396 50 P>S No Ensembl
rs469679371 51 S>A No Ensembl
rs469679371 51 S>P No Ensembl
rs435802413 52 T>P No Ensembl
rs468621211 53 H>P No Ensembl
rs446968369 53 H>Q No Ensembl
rs479844807 54 I>F No Ensembl
rs464605065 54 I>S No Ensembl
rs464605065 54 I>T No Ensembl
rs445093991 55 G>A No Ensembl
rs477858869 57 R>G No Ensembl
rs444160793 58 T>P No Ensembl
rs461805863 59 T>P No Ensembl
rs451270152 61 A>P No Ensembl
rs476069887 62 Q>L No Ensembl
rs476069887 62 Q>R No Ensembl
rs435758858 63 G>A No Ensembl
rs435758858 63 G>D No Ensembl
rs453326556 64 I>F No Ensembl
rs453326556 64 I>L No Ensembl
rs434922449 64 I>S No Ensembl
rs434922449 64 I>T No Ensembl
rs453326556 64 I>V No Ensembl
rs445962710 65 S>P No Ensembl
rs437172283 65 S>W No Ensembl
rs469088707 66 A>P No Ensembl
rs480468966 67 E>* No Ensembl
rs137644000 70 T>A No Ensembl
rs446610791 73 S>A No Ensembl
rs479519274 74 F>C No Ensembl
rs457848627 75 H>D No Ensembl
rs439198392 75 H>P No Ensembl
rs464037787 76 D>A No Ensembl
rs475426552 76 D>H No Ensembl
rs442347536 77 L>P No Ensembl
rs475205193 80 A>T No Ensembl
rs434985896 81 F>S No Ensembl
rs470870945 82 R>G No Ensembl
rs437145491 83 K>N No Ensembl
rs437145491 83 K>N No Ensembl
rs470052437 84 F>S No Ensembl
rs435431123 85 T>P No Ensembl
rs468454596 86 K>N No Ensembl
rs479630711 87 S>C No Ensembl
rs446601947 87 S>P No Ensembl
rs445796249 89 R>G No Ensembl
rs481804143 89 R>K No Ensembl
rs449461415 170 A>V No Ensembl
rs434186040 171 I>F No Ensembl
rs467145758 173 Y>* No Ensembl
rs445379684 175 C>F No Ensembl
rs478383176 176 T>P No Ensembl
rs478383176 176 T>S No Ensembl
rs473488417 177 R>L No Ensembl
rs462988676 178 T>A No Ensembl
rs450939077 178 T>R No Ensembl
rs480579413 179 A>G No Ensembl
rs461253158 180 T>A No Ensembl
rs461253158 180 T>P No Ensembl
rs472478008 181 V>A No Ensembl
rs442697178 181 V>L No Ensembl
rs453342745 184 L>R No Ensembl
rs456248572 289 W>* No Ensembl
rs439376418 377 V>I No Ensembl
rs441644925 445 E>G No Ensembl
rs456879473 445 E>K No Ensembl
rs462983882 455 S>* No Ensembl
rs478214764 455 S>T No Ensembl
rs444533965 462 R>G No Ensembl
rs474312902 462 R>K No Ensembl
rs455684825 462 R>S No Ensembl
rs469535159 501 V>G No Ensembl
rs451062932 504 G>C No Ensembl
rs480863937 529 I>L No Ensembl
rs462319576 530 I>F No Ensembl
rs446979389 532 N>I No Ensembl
rs479892081 533 K>* No Ensembl
rs439653049 544 L>M No Ensembl
rs462865955 546 I>S No Ensembl
rs464306326 558 F>V No Ensembl
rs445881490 559 S>T No Ensembl
rs481144276 596 R>S No Ensembl
rs467717726 615 K>R No Ensembl
rs444146623 645 D>E No Ensembl
rs473926098 646 T>A No Ensembl
rs455238935 647 S>I No Ensembl
rs433562780 652 F>L No Ensembl
rs451939263 656 N>K No Ensembl
rs450974839 659 P>Q No Ensembl
rs469638220 659 P>T No Ensembl
rs468676645 661 P>T No Ensembl

No associated diseases with P00516

4 regional properties for P00516

Type Name Position InterPro Accession
domain Protein kinase domain 525 - 791 IPR000719
active_site Serine/threonine-protein kinase, active site 643 - 655 IPR008271
binding_site Protein kinase, ATP binding site 531 - 553 IPR017441
domain Protein kinase Mps1 family, catalytic domain 523 - 791 IPR027084

Functions

Description
EC Number 2.7.11.12 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Colocalized with TRPC7 in the plasma membrane
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

7 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
calcium channel regulator activity Modulates the activity of a calcium channel.
cGMP binding Binding to cGMP, the nucleotide cyclic GMP (guanosine 3',5'-cyclophosphate).
cGMP-dependent protein kinase activity cGMP dependent catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein.
identical protein binding Binding to an identical protein or proteins.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

9 GO annotations of biological process

Name Definition
cGMP-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell via cyclic GMP (cGMP). Includes production of cGMP, and downstream effectors that further transmit the signal within the cell.
dendrite development The process whose specific outcome is the progression of the dendrite over time, from its formation to the mature structure.
forebrain development The process whose specific outcome is the progression of the forebrain over time, from its formation to the mature structure. The forebrain is the anterior of the three primary divisions of the developing chordate brain or the corresponding part of the adult brain (in vertebrates, includes especially the cerebral hemispheres, the thalamus, and the hypothalamus and especially in higher vertebrates is the main control center for sensory and associative information processing, visceral functions, and voluntary motor functions).
negative regulation of platelet aggregation Any process that decreases the rate, frequency or extent of platelet aggregation. Platelet aggregation is the adhesion of one platelet to one or more other platelets via adhesion molecules.
negative regulation of vascular associated smooth muscle cell migration Any process that stops, prevents or reduces the frequency, rate or extent of vascular associated smooth muscle cell migration.
negative regulation of vascular associated smooth muscle cell proliferation Any process that stops, prevents or reduces the frequency, rate or extent of vascular smooth muscle cell proliferation.
neuron migration The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature.
regulation of GTPase activity Any process that modulates the rate of GTP hydrolysis by a GTPase.
relaxation of vascular associated smooth muscle A negative regulation of smooth muscle contraction resulting in relaxation of vascular smooth muscle. The relaxation is mediated by a decrease in the phosphorylation state of myosin light chain. This can be achieved by removal of calcium from the cytoplasm to the sarcoplasmic reticulum lumen through the action of Ca2+ ATPases leading to a decrease myosin light chain kinase activity, and through calcium-independent pathways leading to a increase in myosin light chain phosphatase activity.

8 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P00517 PRKACA cAMP-dependent protein kinase catalytic subunit alpha Bos taurus (Bovine) PR
Q03043 for cGMP-dependent protein kinase, isozyme 2 forms cD4/T1/T3A/T3B Drosophila melanogaster (Fruit fly) SS
Q13237 PRKG2 cGMP-dependent protein kinase 2 Homo sapiens (Human) PR
Q13976 PRKG1 cGMP-dependent protein kinase 1 Homo sapiens (Human) EV
Q61410 Prkg2 cGMP-dependent protein kinase 2 Mus musculus (Mouse) PR
P0C605 Prkg1 cGMP-dependent protein kinase 1 Mus musculus (Mouse) SS
Q64595 Prkg2 cGMP-dependent protein kinase 2 Rattus norvegicus (Rat) PR
O76360 egl-4 cGMP-dependent protein kinase egl-4 Caenorhabditis elegans PR
10 20 30 40 50 60
MSELEEDFAK ILMLKEERIK ELEKRLSEKE EEIQELKRKL HKCQSVLPVP STHIGPRTTR
70 80 90 100 110 120
AQGISAEPQT YRSFHDLRQA FRKFTKSERS KDLIKEAILD NDFMKNLELS QIQEIVDCMY
130 140 150 160 170 180
PVEYGKDSCI IKEGDVGSLV YVMEDGKVEV TKEGVKLCTM GPGKVFGELA ILYNCTRTAT
190 200 210 220 230 240
VKTLVNVKLW AIDRQCFQTI MMRTGLIKHT EYMEFLKSVP TFQSLPEEIL SKLADVLEET
250 260 270 280 290 300
HYENGEYIIR QGARGDTFFI ISKGKVNVTR EDSPNEDPVF 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 SFPEDNDEPP
670
PDDNSGWDID F