P00515

EV
Gene name
PRKAR2A
Protein name
cAMP-dependent protein kinase type II-alpha regulatory subunit
Names
Species
Bos taurus (Bovine)
KEGG Pathway
bta:100139910
EC number
Protein Class
CAMP-DEPENDENT PROTEIN KINASE REGULATORY CHAIN (PTHR11635)

Descriptions

PKA is a major intracellular receptor of cAMP and modulates diverse cellular signalings. The N-terminal regulatory domain contains a pseudosubstrate sequence that may interact with the catalytic kinase domain.

Autoinhibitory domains (AIDs)

93-97 (Autoinhibitory segment) EV

Target domain

136-256 (Cyclic nucleotide-binding domain)

Relief mechanism

Ligand binding

Assay

Mutagenesis experiment

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for P00515

Entry ID Method Resolution Chain Position Source
AF-P00515-F1 Predicted AlphaFoldDB

35 variants for P00515

Variant ID(s) Position Change Description Diseaes Association Provenance
rs444323872 23 R>G No Ensembl
rs462751510 25 R>L No Ensembl
rs478020287 26 P>R No Ensembl
rs445255726 28 D>H No Ensembl
rs460648277 29 L>I No Ensembl
rs479249640 31 D>V No Ensembl
rs449433260 36 Y>C No Ensembl
rs468072053 37 F>L No Ensembl
rs483316007 39 R>H No Ensembl
rs443413407 54 P>T No Ensembl
rs799807465 62 D>E No Ensembl
rs135235955 73 A>G No Ensembl
rs137749375 89 G>V No Ensembl
rs455670343 115 V>G No Ensembl
rs474298595 116 I>M No Ensembl
rs444495248 121 D>V No Ensembl
rs456676728 123 Q>K No Ensembl
rs472027639 125 C>F No Ensembl
rs134219211 125 C>G No Ensembl
rs472027639 125 C>Y No Ensembl
rs439120639 127 L>I No Ensembl
rs460868872 128 Q>* No Ensembl
rs479389243 128 Q>H No Ensembl
rs439951079 129 E>V No Ensembl
rs461736655 130 A>G No Ensembl
rs480310815 131 C>F No Ensembl
rs459751606 161 E>D No Ensembl
rs481537534 162 H>Y No Ensembl
rs468390888 248 M>I No Ensembl
rs480499371 252 F>Y No Ensembl
rs454742042 278 V>G No Ensembl
rs445041884 282 G>R No Ensembl
rs475069408 304 S>N No Ensembl
rs454653392 343 P>A No Ensembl
rs210984398 353 D>N No Ensembl

No associated diseases with P00515

7 regional properties for P00515

Type Name Position InterPro Accession
domain Cyclic nucleotide-binding domain 137 - 253 IPR000595-1
domain Cyclic nucleotide-binding domain 255 - 376 IPR000595-2
domain cAMP-dependent protein kinase regulatory subunit, dimerization-anchoring domain 25 - 62 IPR003117
conserved_site Cyclic nucleotide-binding, conserved site 164 - 180 IPR018488-1
conserved_site Cyclic nucleotide-binding, conserved site 200 - 217 IPR018488-2
conserved_site Cyclic nucleotide-binding, conserved site 282 - 298 IPR018488-3
conserved_site Cyclic nucleotide-binding, conserved site 324 - 341 IPR018488-4

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Cell membrane
  • Colocalizes with PJA2 in the cytoplasm and the cell membrane
PANTHER Family PTHR11635 CAMP-DEPENDENT PROTEIN KINASE REGULATORY CHAIN
PANTHER Subfamily PTHR11635:SF153 CAMP-DEPENDENT PROTEIN KINASE TYPE II-ALPHA REGULATORY SUBUNIT
PANTHER Protein Class kinase modulator
PANTHER Pathway Category Metabotropic glutamate receptor group III pathway
PKA
Muscarinic acetylcholine receptor 2 and 4 signaling pathway
PKA
GABA-B receptor II signaling
PKA
5HT1 type receptor mediated signaling pathway
PKA
Enkephalin release
PKA
Histamine H2 receptor mediated signaling pathway
PKA
Dopamine receptor mediated signaling pathway
PKA
Transcription regulation by bZIP transcription factor
PKA
Beta2 adrenergic receptor signaling pathway
PKA
Metabotropic glutamate receptor group II pathway
PKA
Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
PKA-r
Hedgehog signaling pathway
PKA
Beta1 adrenergic receptor signaling pathway
PKA
Endothelin signaling pathway
PKA

6 GO annotations of cellular component

Name Definition
axoneme The bundle of microtubules and associated proteins that forms the core of cilia (also called flagella) in eukaryotic cells and is responsible for their movements.
cAMP-dependent protein kinase complex An enzyme complex, composed of regulatory and catalytic subunits, that catalyzes protein phosphorylation. Inactive forms of the enzyme have two regulatory chains and two catalytic chains; activation by cAMP produces two active catalytic monomers and a regulatory dimer.
centrosome A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
nucleotide-activated protein kinase complex A protein complex that possesses nucleotide-dependent protein kinase activity. The nucleotide can be AMP (in S. pombe and human) or ADP (in S. cerevisiae).
plasma membrane raft A membrane raft that is part of the plasma membrane.

5 GO annotations of molecular function

Name Definition
cAMP binding Binding to cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate).
cAMP-dependent protein kinase inhibitor activity Binds to and stops, prevents or reduces the activity of a cAMP-dependent protein kinase.
protein domain specific binding Binding to a specific domain of a protein.
protein kinase A catalytic subunit binding Binding to one or both of the catalytic subunits of protein kinase A.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.

1 GO annotations of biological process

Name Definition
negative regulation of cAMP-dependent protein kinase activity Any process that stops, prevents or reduces the frequency, rate or extent of cAMP-dependent protein kinase activity.

23 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P07278 BCY1 cAMP-dependent protein kinase regulatory subunit Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P00514 PRKAR1A cAMP-dependent protein kinase type I-alpha regulatory subunit Bos taurus (Bovine) EV
P31322 PRKAR2B cAMP-dependent protein kinase type II-beta regulatory subunit Bos taurus (Bovine) EV
Q5ZM91 PRKAR1A cAMP-dependent protein kinase type I-alpha regulatory subunit Gallus gallus (Chicken) SS
P16905 Pka-R1 cAMP-dependent protein kinase type I regulatory subunit Drosophila melanogaster (Fruit fly) PR
P81900 Pka-R2 cAMP-dependent protein kinase type II regulatory subunit Drosophila melanogaster (Fruit fly) PR
Q96M20 CNBD2 Cyclic nucleotide-binding domain-containing protein 2 Homo sapiens (Human) PR
P10644 PRKAR1A cAMP-dependent protein kinase type I-alpha regulatory subunit Homo sapiens (Human) EV
P31321 PRKAR1B cAMP-dependent protein kinase type I-beta regulatory subunit Homo sapiens (Human) EV
P31323 PRKAR2B cAMP-dependent protein kinase type II-beta regulatory subunit Homo sapiens (Human) PR
P13861 PRKAR2A cAMP-dependent protein kinase type II-alpha regulatory subunit Homo sapiens (Human) PR
Q9D5U8 Cnbd2 Cyclic nucleotide-binding domain-containing protein 2 Mus musculus (Mouse) PR
P12849 Prkar1b cAMP-dependent protein kinase type I-beta regulatory subunit Mus musculus (Mouse) PR
P31324 Prkar2b cAMP-dependent protein kinase type II-beta regulatory subunit Mus musculus (Mouse) PR
Q9DBC7 Prkar1a cAMP-dependent protein kinase type I-alpha regulatory subunit [Cleaved into: cAMP-dependent protein kinase type I-alpha regulatory subunit, N-terminally processed] Mus musculus (Mouse) SS
P12367 Prkar2a cAMP-dependent protein kinase type II-alpha regulatory subunit Mus musculus (Mouse) PR
P05207 PRKAR2A cAMP-dependent protein kinase type II-alpha regulatory subunit Sus scrofa (Pig) SS
P07802 PRKAR1A cAMP-dependent protein kinase type I-alpha regulatory subunit Sus scrofa (Pig) SS
P81377 Prkar1b cAMP-dependent protein kinase type I-beta regulatory subunit Rattus norvegicus (Rat) PR
P09456 Prkar1a cAMP-dependent protein kinase type I-alpha regulatory subunit Rattus norvegicus (Rat) SS
P12368 Prkar2a cAMP-dependent protein kinase type II-alpha regulatory subunit Rattus norvegicus (Rat) PR
P12369 Prkar2b cAMP-dependent protein kinase type II-beta regulatory subunit Rattus norvegicus (Rat) PR
P30625 kin-2 cAMP-dependent protein kinase regulatory subunit Caenorhabditis elegans SS
10 20 30 40 50 60
MSHIQIPPGL TELLQGYTVE VLRQRPPDLV DFAVDYFTRL REARSRASTP PAAPPSGSQD
70 80 90 100 110 120
FDPGAGLVAD AVADSESEDE EDLDVPIPGR FDRRVSVCAE TYNPDEEEED TDPRVIHPKT
130 140 150 160 170 180
DQQRCRLQEA CKDILLFKNL DPEQLSQVLD AMFERTVKVD EHVIDQGDDG DNFYVIERGT
190 200 210 220 230 240
YDILVTKDNQ TRSVGQYDNH GSFGELALMY NTPRAATIVA TSEGSLWGLD RVTFRRIIVK
250 260 270 280 290 300
NNAKKRKMFE SFIESVPLLK SLEVSERMKI VDVIGEKVYK DGERIITQGE KADSFYIIES
310 320 330 340 350 360
GEVSILIKSK TKVNKDGENQ EVEIARCHKG QYFGELALVT NKPRAASAYA VGDVKCLVMD
370 380 390 400
VQAFERLLGP CMDIMKRNIS HYEEQLVKMF GSSMDLIDPG Q