P00514

EV
Gene name
PRKAR1A
Protein name
cAMP-dependent protein kinase type I-alpha regulatory subunit
Names
Species
Bos taurus (Bovine)
KEGG Pathway
bta:615074
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 autoinhibitory sequence of the regulatory subunit may interact with the catalytic kinase domain and keeping the catalytic subunit inactive by blocking the active site in the absence of cAMP.

Autoinhibitory domains (AIDs)

96-100 (Autoinhibitory segment) EV

Target domain

136-252 (Cyclic nucleotide-binding domain)

Relief mechanism

Ligand binding

Assay

Mutagenesis experiment

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

23 structures for P00514

Entry ID Method Resolution Chain Position Source
1NE4 X-ray 240 A A 95-377 PDB
1NE6 X-ray 230 A A 95-377 PDB
1RGS X-ray 280 A A 93-380 PDB
1RL3 X-ray 270 A A/B 93-380 PDB
2EZW NMR - A/B 13-62 PDB
2QCS X-ray 220 A B 91-380 PDB
3FHI X-ray 200 A B 92-245 PDB
3IIA X-ray 270 A A 92-245 PDB
3IM3 X-ray 200 A A 13-62 PDB
3IM4 X-ray 228 A A/B 13-62 PDB
3PLQ X-ray 230 A A 92-245 PDB
3PNA X-ray 150 A A/B 92-245 PDB
3PVB X-ray 330 A B 85-244 PDB
4JV4 X-ray 295 A A 93-380 PDB
4MX3 X-ray 388 A A/B 2-380 PDB
4X6R X-ray 240 A B 91-380 PDB
5HVZ X-ray 200 A A/B 13-62 PDB
5JR7 X-ray 356 A B/D 92-366 PDB
6BYR X-ray 366 A B/D 2-380 PDB
6BYS X-ray 475 A B/D/F/H 2-380 PDB
6NO7 X-ray 355 A B/D/F/H 1-380 PDB
7LZ4 X-ray 416 A A/B/C/D/E/F/G/H 109-377 PDB
AF-P00514-F1 Predicted AlphaFoldDB

106 variants for P00514

Variant ID(s) Position Change Description Diseaes Association Provenance
rs135283999 6 T>P No Ensembl
rs481459873 7 A>D No Ensembl
rs447778005 12 R>C No Ensembl
rs477450926 14 L>I No Ensembl
rs477450926 14 L>V No Ensembl
rs483328506 16 E>D No Ensembl
rs442441595 25 N>T No Ensembl
rs472166095 28 A>E No Ensembl
rs453840374 33 S>P No Ensembl
rs438466416 39 T>P No Ensembl
rs471270757 47 A>V No Ensembl
rs456195014 48 F>C No Ensembl
rs467724166 58 K>E No Ensembl
rs440471181 60 E>K No Ensembl
rs473269570 61 A>E No Ensembl
rs451812312 64 I>L No Ensembl
rs433325930 64 I>T No Ensembl
rs469698250 65 Q>K No Ensembl
rs457630857 66 N>H No Ensembl
rs435225321 66 N>T No Ensembl
rs468196738 70 A>E No Ensembl
rs1114625527 71 G>S No Ensembl
rs446418554 72 S>R No Ensembl
rs1118113689 73 R>C No Ensembl
rs464229917 74 A>P No Ensembl
rs463663326 75 D>A No Ensembl
rs448369233 75 D>E No Ensembl
rs482002750 75 D>Y No Ensembl
rs481331472 77 R>G No Ensembl
rs440334132 78 E>V No Ensembl
rs473331171 81 I>L No Ensembl
rs458062676 81 I>T No Ensembl
rs439802417 83 P>Q No Ensembl
rs457421949 84 P>T No Ensembl
rs475274693 85 P>H No Ensembl
rs435898485 85 P>T No Ensembl
rs452951649 87 N>T No Ensembl
rs464119704 89 V>A No Ensembl
rs464119704 89 V>G No Ensembl
rs445669589 90 V>A No Ensembl
rs445669589 90 V>G No Ensembl
rs437029318 91 K>E No Ensembl
rs470091793 91 K>T No Ensembl
rs481242171 92 G>V No Ensembl
rs446865962 93 R>G No Ensembl
rs439559484 96 R>H No Ensembl
rs464047029 97 G>R No Ensembl
rs475206735 99 I>L No Ensembl
rs434423581 99 I>M No Ensembl
rs453542528 99 I>S No Ensembl
rs475206735 99 I>V No Ensembl
rs470683348 101 A>G No Ensembl
rs436775944 102 E>* No Ensembl
rs469796359 102 E>G No Ensembl
rs454792281 103 V>G No Ensembl
rs436303026 105 T>P No Ensembl
rs465760939 106 E>A No Ensembl
rs465760939 106 E>G No Ensembl
rs464483571 108 D>E No Ensembl
rs447402515 108 D>N No Ensembl
rs477055674 108 D>V No Ensembl
rs446134893 109 A>P No Ensembl
rs446134893 109 A>T No Ensembl
rs463739050 111 S>A No Ensembl
rs463739050 111 S>T No Ensembl
rs442270023 112 Y>D No Ensembl
rs481782573 112 Y>F No Ensembl
rs459887508 114 R>G No Ensembl
rs441434027 115 K>Q No Ensembl
rs382810255 152 M>T No Ensembl
rs450398153 158 I>M No Ensembl
rs440356673 230 Y>* No Ensembl
rs466136680 247 E>K No Ensembl
rs434855385 259 D>N No Ensembl
rs478148752 286 E>K No Ensembl
rs462854177 286 E>V No Ensembl
rs455003345 292 F>L No Ensembl
rs442964601 294 I>F No Ensembl
rs472539829 294 I>N No Ensembl
rs454106150 296 E>G No Ensembl
rs464338138 311 F>V No Ensembl
rs450926995 326 I>N No Ensembl
rs480388143 327 A>V No Ensembl
rs461990638 328 L>M No Ensembl
rs440643985 332 R>G No Ensembl
rs440643985 332 R>W No Ensembl
rs439776530 333 P>H No Ensembl
rs458491505 333 P>S No Ensembl
rs476033042 336 A>V No Ensembl
rs463419223 337 T>P No Ensembl
rs441754204 340 A>V No Ensembl
rs470862575 347 V>G No Ensembl
rs436936450 353 R>G No Ensembl
rs469825552 354 F>I No Ensembl
rs435656843 359 G>C No Ensembl
rs468746689 361 C>G No Ensembl
rs446799399 362 S>P No Ensembl
rs479891350 363 D>A No Ensembl
rs458356259 364 I>N No Ensembl
rs458356259 364 I>T No Ensembl
rs446352431 365 L>I No Ensembl
rs482380598 369 I>L No Ensembl
rs463960825 372 Y>C No Ensembl
rs441690812 376 V>G No Ensembl
rs474692989 380 V>F No Ensembl
rs459489001 381 V>C No Ensembl

No associated diseases with P00514

3 regional properties for P00514

Type Name Position InterPro Accession
domain GGDEF domain 224 - 409 IPR000160
domain EAL domain 419 - 658 IPR001633
domain LapD/MoxY, periplasmic domain 24 - 144 IPR032244

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane
PANTHER Family PTHR11635 CAMP-DEPENDENT PROTEIN KINASE REGULATORY CHAIN
PANTHER Subfamily PTHR11635:SF129 CAMP-DEPENDENT PROTEIN KINASE TYPE I-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
Transcription regulation by bZIP transcription factor
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
Endothelin signaling pathway
PKA
Metabotropic glutamate receptor group I pathway
PKA

11 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.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
immunological synapse An area of close contact between a lymphocyte (T-, B-, or natural killer cell) and a target cell formed through the clustering of particular signaling and adhesion molecules and their associated membrane rafts on both the lymphocyte and the target cell and facilitating activation of the lymphocyte, transfer of membrane from the target cell to the lymphocyte, and in some situations killing of the target cell through release of secretory granules and/or death-pathway ligand-receptor interaction.
multivesicular body A type of endosome in which regions of the limiting endosomal membrane invaginate to form internal vesicles; membrane proteins that enter the internal vesicles are sequestered from the cytoplasm.
neuromuscular junction The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
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.
sperm connecting piece The segment of the sperm flagellum that attaches to the implantation fossa of the nucleus in the sperm head; from the remnant of the centriole at this point, the axoneme extends throughout the length of the flagellum.

6 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.
identical protein binding Binding to an identical protein or proteins.
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.

6 GO annotations of biological process

Name Definition
cardiac muscle cell proliferation The expansion of a cardiac muscle cell population by cell division.
mesoderm formation The process that gives rise to the mesoderm. This process pertains to the initial formation of the structure from unspecified parts.
negative regulation of activated T cell proliferation Any process that stops, prevents or reduces the rate or extent of activated T cell proliferation.
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.
negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
sarcomere organization The myofibril assembly process that results in the organization of muscle actomyosin into sarcomeres. The sarcomere is the repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs.

22 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P31322 PRKAR2B cAMP-dependent protein kinase type II-beta regulatory subunit Bos taurus (Bovine) EV
P00515 PRKAR2A cAMP-dependent protein kinase type II-alpha regulatory subunit Bos taurus (Bovine) EV
Q5ZM91 PRKAR1A cAMP-dependent protein kinase type I-alpha regulatory subunit Gallus gallus (Chicken) SS
P81900 Pka-R2 cAMP-dependent protein kinase type II regulatory subunit Drosophila melanogaster (Fruit fly) PR
P16905 Pka-R1 cAMP-dependent protein kinase type I regulatory subunit Drosophila melanogaster (Fruit fly) PR
Q96M20 CNBD2 Cyclic nucleotide-binding domain-containing protein 2 Homo sapiens (Human) PR
P13861 PRKAR2A cAMP-dependent protein kinase type II-alpha regulatory subunit Homo sapiens (Human) PR
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
P10644 PRKAR1A cAMP-dependent protein kinase type I-alpha regulatory subunit Homo sapiens (Human) EV
P12367 Prkar2a cAMP-dependent protein kinase type II-alpha regulatory subunit Mus musculus (Mouse) 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
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
MASGTTASEE ERSLRECELY VQKHNIQALL KDSIVQLCTA RPERPMAFLR EYFEKLEKEE
70 80 90 100 110 120
AKQIQNLQKA GSRADSREDE ISPPPPNPVV KGRRRRGAIS AEVYTEEDAA SYVRKVIPKD
130 140 150 160 170 180
YKTMAALAKA IEKNVLFSHL DDNERSDIFD AMFPVSFIAG ETVIQQGDEG DNFYVIDQGE
190 200 210 220 230 240
MDVYVNNEWA TSVGEGGSFG ELALIYGTPR AATVKAKTNV KLWGIDRDSY RRILMGSTLR
250 260 270 280 290 300
KRKMYEEFLS KVSILESLDK WERLTVADAL EPVQFEDGQK IVVQGEPGDE FFIILEGSAA
310 320 330 340 350 360
VLQRRSENEE FVEVGRLGPS DYFGEIALLM NRPRAATVVA RGPLKCVKLD RPRFERVLGP
370
CSDILKRNIQ QYNSFVSLSV