UniProtKB - P27791 (KAPCA_RAT)
cAMP-dependent protein kinase catalytic subunit alpha
Prkaca
Functioni
Phosphorylates a large number of substrates in the cytoplasm and the nucleus (By similarity).
Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (By similarity).
Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (By similarity).
Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity).
Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca2+, leading to reduced amplitude and increased frequency of store overload-induced Ca2+ release (SOICR) characterized by an increased rate of Ca2+ release and propagation velocity of spontaneous Ca2+ waves, despite reduced wave amplitude and resting cytosolic Ca2+. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis (By similarity).
Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity).
May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (PubMed:20844122).
Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (By similarity).
By similarity1 PublicationCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 73 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 167 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 50 – 58 | ATPPROSITE-ProRule annotation | 9 | |
Nucleotide bindingi | 122 – 128 | ATPPROSITE-ProRule annotation | 7 | |
Nucleotide bindingi | 169 – 172 | ATPPROSITE-ProRule annotation | 4 |
GO - Molecular functioni
- AMP-activated protein kinase activity Source: UniProtKB-EC
- ATP binding Source: RGD
- cAMP-dependent protein kinase activity Source: RGD
- magnesium ion binding Source: RGD
- manganese ion binding Source: RGD
- protein-containing complex binding Source: RGD
- protein domain specific binding Source: RGD
- protein kinase activity Source: RGD
- protein kinase A regulatory subunit binding Source: RGD
- protein kinase binding Source: BHF-UCL
- protein serine/threonine/tyrosine kinase activity Source: RGD
- protein serine/threonine kinase activity Source: RGD
- protein serine kinase activity Source: RHEA
- small GTPase binding Source: UniProtKB
- ubiquitin protein ligase binding Source: RGD
GO - Biological processi
- cellular response to cold Source: RGD
- cellular response to glucose stimulus Source: RGD
- cellular response to heat Source: UniProtKB
- cellular response to parathyroid hormone stimulus Source: RGD
- circadian sleep/wake cycle, REM sleep Source: RGD
- mesoderm formation Source: RGD
- modulation of chemical synaptic transmission Source: RGD
- mRNA processing Source: RGD
- negative regulation of meiotic cell cycle Source: RGD
- negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: RGD
- neural tube closure Source: RGD
- peptidyl-serine phosphorylation Source: RGD
- peptidyl-threonine phosphorylation Source: RGD
- positive regulation of cell population proliferation Source: RGD
- positive regulation of protein export from nucleus Source: RGD
- protein autophosphorylation Source: RGD
- protein kinase A signaling Source: GO_Central
- protein localization to lipid droplet Source: RGD
- protein phosphorylation Source: RGD
- regulation of bicellular tight junction assembly Source: RGD
- regulation of cell cycle Source: RGD
- regulation of cellular respiration Source: RGD
- regulation of osteoblast differentiation Source: RGD
- regulation of proteasomal protein catabolic process Source: RGD
- regulation of protein processing Source: RGD
- regulation of synaptic transmission, glutamatergic Source: RGD
- sperm capacitation Source: RGD
- spontaneous exocytosis of neurotransmitter Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, cAMP, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.11, 5301 |
Reactomei | R-RNO-163615, PKA activation R-RNO-164378, PKA activation in glucagon signalling R-RNO-180024, DARPP-32 events R-RNO-2565942, Regulation of PLK1 Activity at G2/M Transition R-RNO-380259, Loss of Nlp from mitotic centrosomes R-RNO-380270, Recruitment of mitotic centrosome proteins and complexes R-RNO-380284, Loss of proteins required for interphase microtubule organization from the centrosome R-RNO-380320, Recruitment of NuMA to mitotic centrosomes R-RNO-381676, Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-RNO-392517, Rap1 signalling R-RNO-422356, Regulation of insulin secretion R-RNO-432040, Vasopressin regulates renal water homeostasis via Aquaporins R-RNO-4420097, VEGFA-VEGFR2 Pathway R-RNO-442720, CREB1 phosphorylation through the activation of Adenylate Cyclase R-RNO-512988, Interleukin-3, Interleukin-5 and GM-CSF signaling R-RNO-5578775, Ion homeostasis R-RNO-5610785, GLI3 is processed to GLI3R by the proteasome R-RNO-5610787, Hedgehog 'off' state R-RNO-5620912, Anchoring of the basal body to the plasma membrane R-RNO-5687128, MAPK6/MAPK4 signaling R-RNO-8853659, RET signaling R-RNO-8854518, AURKA Activation by TPX2 R-RNO-8963896, HDL assembly R-RNO-983231, Factors involved in megakaryocyte development and platelet production |
Names & Taxonomyi
Protein namesi | Recommended name: cAMP-dependent protein kinase catalytic subunit alpha (EC:2.7.11.11)Short name: PKA C-alpha |
Gene namesi | Name:Prkaca |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 3389, Prkaca |
Subcellular locationi
Nucleus
- Nucleus By similarity
Plasma membrane
- Cell membrane By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Mitochondrion
- Mitochondrion By similarity
Other locations
- Membrane By similarity; Lipid-anchor By similarity
Note: Translocates into the nucleus (monomeric catalytic subunit). The inactive holoenzyme is found in the cytoplasm. Distributed throughout the cytoplasm in meiotically incompetent oocytes. Associated to mitochondrion as meiotic competence is acquired. Aggregates around the germinal vesicles (GV) at the immature GV stage oocytes (By similarity). Colocalizes with HSF1 in nuclear stress bodies (nSBs) upon heat shock (By similarity).By similarity
Other locations
Note: Expressed in the midpiece region of the sperm flagellum. Expressed in the midpiece region of the sperm flagellum. Colocalizes with MROH2B and TCP11 on the acrosome and tail regions in round spermatids and spermatozoa regardless of the capacitation status of the sperm.By similarity
Cytoskeleton
- centrosome Source: RGD
Cytosol
- cytosol Source: Reactome
Golgi apparatus
- Golgi apparatus Source: RGD
Mitochondrion
- mitochondrion Source: RGD
Nucleus
- nuclear speck Source: RGD
- nucleoplasm Source: Reactome
- nucleus Source: RGD
Plasma Membrane
- plasma membrane Source: RGD
- plasma membrane raft Source: RGD
Other locations
- acrosomal vesicle Source: UniProtKB
- cAMP-dependent protein kinase complex Source: RGD
- ciliary base Source: RGD
- cytoplasm Source: RGD
- dendritic spine Source: RGD
- membrane Source: RGD
- neuromuscular junction Source: RGD
- neuron projection Source: RGD
- perinuclear region of cytoplasm Source: RGD
- presynapse Source: UniProtKB
- protein-containing complex Source: RGD
- sperm flagellum Source: UniProtKB
- sperm midpiece Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cell projection, Cilium, Cytoplasm, Cytoplasmic vesicle, Flagellum, Membrane, Mitochondrion, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000086055 | 2 – 351 | cAMP-dependent protein kinase catalytic subunit alphaAdd BLAST | 350 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycine1 Publication | 1 | |
Modified residuei | 3 | Deamidated asparagine; partial1 Publication | 1 | |
Modified residuei | 11 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 49 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 140 | PhosphoserineBy similarity | 1 | |
Modified residuei | 196 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 198 | Phosphothreonine; by PDPK1By similarity | 1 | |
Modified residuei | 331 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 339 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Lipoprotein, Myristate, PhosphoproteinProteomic databases
jPOSTi | P27791 |
PaxDbi | P27791 |
PRIDEi | P27791 |
PTM databases
iPTMneti | P27791 |
PhosphoSitePlusi | P27791 |
Expressioni
Tissue specificityi
Developmental stagei
Interactioni
Subunit structurei
A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively.
Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes (By similarity).
Interacts with APOBEC3G and AICDA (By similarity).
Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly.
Found in a complex at least composed of MROH2B, PRKACA isoform 2 and TCP11 (By similarity).
Interacts with MROH2B (By similarity).
Interacts with HSF1 (By similarity).
Isoform 2 interacts with TCP11 (By similarity).
By similarity1 PublicationGO - Molecular functioni
- protein domain specific binding Source: RGD
- protein kinase A regulatory subunit binding Source: RGD
- protein kinase binding Source: BHF-UCL
- small GTPase binding Source: UniProtKB
- ubiquitin protein ligase binding Source: RGD
Protein-protein interaction databases
CORUMi | P27791 |
DIPi | DIP-37312N |
IntActi | P27791, 5 interactors |
MINTi | P27791 |
STRINGi | 10116.ENSRNOP00000044732 |
Chemistry databases
BindingDBi | P27791 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 44 – 298 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 255 | |
Domaini | 299 – 351 | AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST | 53 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0616, Eukaryota |
InParanoidi | P27791 |
PhylomeDBi | P27791 |
Family and domain databases
CDDi | cd14209, STKc_PKA, 1 hit |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR044109, STKc_PKA |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51285, AGC_KINASE_CTER, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WEDPSQNTAQ LDHFDRIKTL
60 70 80 90 100
GTGSFGRVML VKHKESGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN
110 120 130 140 150
FPFLVKLEFS FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ
160 170 180 190 200
IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY IQVTDFGFAK RVKGRTWTLC
210 220 230 240 250
GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK
260 270 280 290 300
IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT
310 320 330 340 350
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFTE
F
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA1L1M0 | A1L1M0_RAT | cAMP-dependent protein kinase | Prkaca rCG_51506 | 351 | Annotation score: | ||
A0A8I5YBQ9 | A0A8I5YBQ9_RAT | cAMP-dependent protein kinase catal... | Prkaca | 353 | Annotation score: | ||
A0A8I5ZMH0 | A0A8I5ZMH0_RAT | cAMP-dependent protein kinase catal... | Prkaca | 351 | Annotation score: | ||
A0A8I5ZTW8 | A0A8I5ZTW8_RAT | cAMP-dependent protein kinase catal... | Prkaca | 352 | Annotation score: | ||
A0A8I6AD31 | A0A8I6AD31_RAT | cAMP-dependent protein kinase catal... | Prkaca | 343 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_013277 | 1 – 15 | MGNAA…SEQES → MASNSND in isoform 2. 1 PublicationAdd BLAST | 15 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X57986 mRNA Translation: CAA41052.1 AY375243 mRNA Translation: AAQ81631.1 |
PIRi | S16240, OKRT2C |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X57986 mRNA Translation: CAA41052.1 AY375243 mRNA Translation: AAQ81631.1 |
PIRi | S16240, OKRT2C |
3D structure databases
AlphaFoldDBi | P27791 |
BMRBi | P27791 |
SMRi | P27791 |
ModBasei | Search... |
Protein-protein interaction databases
CORUMi | P27791 |
DIPi | DIP-37312N |
IntActi | P27791, 5 interactors |
MINTi | P27791 |
STRINGi | 10116.ENSRNOP00000044732 |
Chemistry databases
BindingDBi | P27791 |
ChEMBLi | CHEMBL3390 |
GuidetoPHARMACOLOGYi | 1476 |
PTM databases
iPTMneti | P27791 |
PhosphoSitePlusi | P27791 |
Proteomic databases
jPOSTi | P27791 |
PaxDbi | P27791 |
PRIDEi | P27791 |
Organism-specific databases
RGDi | 3389, Prkaca |
Phylogenomic databases
eggNOGi | KOG0616, Eukaryota |
InParanoidi | P27791 |
PhylomeDBi | P27791 |
Enzyme and pathway databases
BRENDAi | 2.7.11.11, 5301 |
Reactomei | R-RNO-163615, PKA activation R-RNO-164378, PKA activation in glucagon signalling R-RNO-180024, DARPP-32 events R-RNO-2565942, Regulation of PLK1 Activity at G2/M Transition R-RNO-380259, Loss of Nlp from mitotic centrosomes R-RNO-380270, Recruitment of mitotic centrosome proteins and complexes R-RNO-380284, Loss of proteins required for interphase microtubule organization from the centrosome R-RNO-380320, Recruitment of NuMA to mitotic centrosomes R-RNO-381676, Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-RNO-392517, Rap1 signalling R-RNO-422356, Regulation of insulin secretion R-RNO-432040, Vasopressin regulates renal water homeostasis via Aquaporins R-RNO-4420097, VEGFA-VEGFR2 Pathway R-RNO-442720, CREB1 phosphorylation through the activation of Adenylate Cyclase R-RNO-512988, Interleukin-3, Interleukin-5 and GM-CSF signaling R-RNO-5578775, Ion homeostasis R-RNO-5610785, GLI3 is processed to GLI3R by the proteasome R-RNO-5610787, Hedgehog 'off' state R-RNO-5620912, Anchoring of the basal body to the plasma membrane R-RNO-5687128, MAPK6/MAPK4 signaling R-RNO-8853659, RET signaling R-RNO-8854518, AURKA Activation by TPX2 R-RNO-8963896, HDL assembly R-RNO-983231, Factors involved in megakaryocyte development and platelet production |
Miscellaneous databases
PROi | PR:P27791 |
Family and domain databases
CDDi | cd14209, STKc_PKA, 1 hit |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR044109, STKc_PKA |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51285, AGC_KINASE_CTER, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KAPCA_RAT | |
Accessioni | P27791Primary (citable) accession number: P27791 Secondary accession number(s): Q6UA68 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1992 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 194 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families