UniProtKB - P17612 (KAPCA_HUMAN)
cAMP-dependent protein kinase catalytic subunit alpha
PRKACA
Functioni
Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984).
Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984).
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 (PubMed:21423175).
RORA is activated by phosphorylation (PubMed:21514275).
Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837).
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 (PubMed:15642694, PubMed:20356841).
Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334).
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+ (PubMed:17693412).
PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987).
Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176).
NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694).
Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. 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) (By similarity).
Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454).
Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490).
By similarity13 PublicationsPhosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation.
By similarityCatalytic 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 | ATP | 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: UniProtKB-KW
- cAMP-dependent protein kinase activity Source: BHF-UCL
- magnesium ion binding Source: Ensembl
- manganese ion binding Source: Ensembl
- protein domain specific binding Source: Ensembl
- protein kinase activity Source: UniProtKB
- protein kinase A regulatory subunit binding Source: BHF-UCL
- protein kinase binding Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: MGI
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- calcium-mediated signaling using intracellular calcium source Source: BHF-UCL
- cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
- cellular response to cold Source: Ensembl
- cellular response to epinephrine stimulus Source: BHF-UCL
- cellular response to glucose stimulus Source: UniProtKB
- cellular response to heat Source: UniProtKB
- cellular response to parathyroid hormone stimulus Source: Ensembl
- cytokine-mediated signaling pathway Source: Reactome
- high-density lipoprotein particle assembly Source: Reactome
- mesoderm formation Source: Ensembl
- modulation of chemical synaptic transmission Source: Ensembl
- mRNA processing Source: UniProtKB
- negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: Ensembl
- neural tube closure Source: Ensembl
- peptidyl-serine phosphorylation Source: BHF-UCL
- peptidyl-threonine phosphorylation Source: Ensembl
- positive regulation of protein export from nucleus Source: Ensembl
- protein autophosphorylation Source: Ensembl
- protein kinase A signaling Source: GO_Central
- protein localization to lipid droplet Source: Ensembl
- protein phosphorylation Source: UniProtKB
- regulation of bicellular tight junction assembly Source: UniProtKB
- regulation of cardiac conduction Source: Reactome
- regulation of cardiac muscle contraction Source: BHF-UCL
- regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
- regulation of cell cycle Source: UniProtKB
- regulation of cytosolic calcium ion concentration Source: BHF-UCL
- regulation of heart rate Source: BHF-UCL
- regulation of macroautophagy Source: ParkinsonsUK-UCL
- regulation of osteoblast differentiation Source: UniProtKB
- regulation of proteasomal protein catabolic process Source: UniProtKB
- regulation of protein binding Source: BHF-UCL
- regulation of protein processing Source: Ensembl
- regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
- renal water homeostasis Source: Reactome
- sperm capacitation 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, 2681 |
PathwayCommonsi | P17612 |
Reactomei | R-HSA-111931, PKA-mediated phosphorylation of CREB R-HSA-163358, PKA-mediated phosphorylation of key metabolic factors R-HSA-163560, Triglyceride catabolism R-HSA-163615, PKA activation R-HSA-164378, PKA activation in glucagon signalling R-HSA-180024, DARPP-32 events R-HSA-2565942, Regulation of PLK1 Activity at G2/M Transition R-HSA-380259, Loss of Nlp from mitotic centrosomes R-HSA-380270, Recruitment of mitotic centrosome proteins and complexes R-HSA-380284, Loss of proteins required for interphase microtubule organization from the centrosome R-HSA-380320, Recruitment of NuMA to mitotic centrosomes R-HSA-381676, Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-HSA-392517, Rap1 signalling R-HSA-422356, Regulation of insulin secretion R-HSA-432040, Vasopressin regulates renal water homeostasis via Aquaporins R-HSA-4420097, VEGFA-VEGFR2 Pathway R-HSA-442720, CREB1 phosphorylation through the activation of Adenylate Cyclase R-HSA-512988, Interleukin-3, Interleukin-5 and GM-CSF signaling R-HSA-5578775, Ion homeostasis R-HSA-5610780, Degradation of GLI1 by the proteasome R-HSA-5610783, Degradation of GLI2 by the proteasome R-HSA-5610785, GLI3 is processed to GLI3R by the proteasome R-HSA-5610787, Hedgehog 'off' state R-HSA-5620912, Anchoring of the basal body to the plasma membrane R-HSA-5621575, CD209 (DC-SIGN) signaling R-HSA-5687128, MAPK6/MAPK4 signaling R-HSA-8853659, RET signaling R-HSA-8854518, AURKA Activation by TPX2 R-HSA-8963896, HDL assembly R-HSA-9010642, ROBO receptors bind AKAP5 R-HSA-9022535, Loss of phosphorylation of MECP2 at T308 R-HSA-9022692, Regulation of MECP2 expression and activity R-HSA-9634600, Regulation of glycolysis by fructose 2,6-bisphosphate metabolism R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production R-HSA-9664323, FCGR3A-mediated IL10 synthesis R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
SABIO-RKi | P17612 |
SignaLinki | P17612 |
SIGNORi | P17612 |
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 Synonyms:PKACA |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9380, PRKACA |
MIMi | 601639, gene |
neXtProti | NX_P17612 |
VEuPathDBi | HostDB:ENSG00000072062 |
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Nucleus
- Nucleus By similarity
Plasma membrane
Cytoplasm and Cytosol
Other locations
- Membrane Curated; Lipid-anchor Curated
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 (PubMed:21085490).By similarity1 Publication
Other locations
Note: Expressed in the midpiece region of the sperm flagellum (PubMed:10906071). 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).By similarity1 Publication
Cytoskeleton
- centrosome Source: UniProtKB
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Mitochondrion
- mitochondrion Source: UniProtKB-SubCell
Nucleus
- nuclear speck Source: UniProtKB
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane raft Source: UniProtKB
Other locations
- acrosomal vesicle Source: UniProtKB
- calcium channel complex Source: BHF-UCL
- cAMP-dependent protein kinase complex Source: UniProtKB
- ciliary base Source: Reactome
- cytoplasm Source: UniProtKB
- dendritic spine Source: Ensembl
- membrane Source: BHF-UCL
- neuromuscular junction Source: Ensembl
- nucleotide-activated protein kinase complex Source: BHF-UCL
- perinuclear region of cytoplasm Source: UniProtKB
- sperm flagellum Source: Ensembl
- sperm midpiece Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cell projection, Cilium, Cytoplasm, Cytoplasmic vesicle, Flagellum, Membrane, Mitochondrion, NucleusPathology & Biotechi
Involvement in diseasei
Primary pigmented nodular adrenocortical disease 4 (PPNAD4)4 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_071707 | 206 | L → R in PPNAD4; somatic mutation; the mutation results in cAMP-independent basal protein kinase activity and constitutive activation of protein kinase A. 4 PublicationsCorresponds to variant dbSNP:rs386352352EnsemblClinVar. | 1 |
Cardioacrofacial dysplasia 1 (CAFD1)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_085198 | 137 | G → R in CAFD1; decreased interaction with regulatory subunit PRKAR2B. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 48 | K → R: Enhanced basal kinase activity; when associated with Q-96, L-121, A-124, K-182 and A-184. 1 Publication | 1 | |
Mutagenesisi | 96 | L → Q: Enhanced basal kinase activity; when associated with R-48, L-121, A-124, K-182 and A-184. 1 Publication | 1 | |
Mutagenesisi | 121 | M → L: Enhanced basal kinase activity; when associated with R-48, Q-96, A-124, K-182 and A-184. 1 Publication | 1 | |
Mutagenesisi | 124 | V → A: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, K-182 and A-184. 1 Publication | 1 | |
Mutagenesisi | 182 | Q → K: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, A-124 and A-184. 1 Publication | 1 | |
Mutagenesisi | 184 | T → A: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, A-124 and K-182. 1 Publication | 1 | |
Mutagenesisi | 195 | R → A: No phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 201 | G → A: No phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 202 | T → A: No phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 205 | Y → A: Loss of allosteric regulation. 1 Publication | 1 |
Keywords - Diseasei
Cushing syndrome, Disease variantOrganism-specific databases
DisGeNETi | 5566 |
MalaCardsi | PRKACA |
MIMi | 615830, phenotype 619142, phenotype |
OpenTargetsi | ENSG00000072062 |
Orphaneti | 401920, Fibrolamellar hepatocellular carcinoma 189439, Primary pigmented nodular adrenocortical disease |
PharmGKBi | PA33748 |
Miscellaneous databases
Pharosi | P17612, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4101 |
DrugBanki | DB07204, (1S)-1-(1H-INDOL-3-YLMETHYL)-2-(2-PYRIDIN-4-YL-[1,7]NAPHTYRIDIN-5-YLOXY)-EHYLAMINE DB07107, (1S)-2-(1H-INDOL-3-YL)-1-[({5-[(E)-2-PYRIDIN-4-YLVINYL]PYRIDIN-3-YL}OXY)METHYL]ETHYLAMINE DB07857, (2R)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamine DB07860, (2R)-2-(4-CHLOROPHENYL)-2-PHENYLETHANAMINE DB08073, (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE DB06959, (2S)-1-(3H-Indol-3-yl)-3-{[5-(6-isoquinolinyl)-3-pyridinyl]oxy}-2-propanamine DB07124, (2S)-1-(6H-INDOL-3-YL)-3-{[5-(7H-PYRAZOLO[3,4-C]PYRIDIN-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE DB06977, (2S)-1-{[5-(1H-Indazol-5-yl)-3-pyridinyl]oxy}-3-(7aH-indol-3-yl)-2-propanamine DB07858, (2S)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamine DB07583, (4R,2S)-5'-(4-(4-CHLOROBENZYLOXY)PYRROLIDIN-2-YLMETHANESULFONYL)ISOQUINOLINE DB07855, (S)-1-PHENYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINE DB07876, (S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE DB08149, 1-[4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine DB08148, 1-[4-(4-chlorophenyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine DB08070, 2-[4-(3-METHYL-1H-PYRAZOL-4-YL)PHENYL]ETHANAMINE DB03374, 3,5-Diiodotyrosine DB07458, 3-(1H-indol-3-yl)-4-{1-[2-(1-methylpyrrolidin-2-yl)ethyl]-1H-indol-3-yl}-1H-pyrrole-2,5-dione DB02155, 3-[(3-sec-butyl-4-hydroxybenzoyl)amino]azepan-4-yl 4-(2-hydroxy-5-methoxybenzoyl)benzoate DB08113, 3-pyridin-4-yl-1H-indazole DB08569, 3-PYRIDIN-4-YL-2,4-DIHYDRO-INDENO[1,2-.C.] PYRAZOLE DB08150, 4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-aminium DB07859, 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE DB07996, 5-(2-methylpiperazine-1-sulfonyl)isoquinoline DB08114, 5-benzyl-1,3-thiazol-2-amine DB07856, 6-{4-[4-(4-CHLOROPHENYL)PIPERIDIN-4-YL]PHENYL}-9H-PURINE DB08568, A-674563 DB04098, Balanol DB02611, Balanol Analog 1 DB01940, Balanol Analog 2 DB04522, Dexfosfoserine DB08846, Ellagic acid DB08162, Fasudil DB12010, Fostamatinib DB07995, H-89 DB04707, Hydroxyfasudil DB07947, ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE DB08231, Myristic acid DB07235, N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE DB07997, N-[2-(METHYLAMINO)ETHYL]-5-ISOQUINOLINESULFONAMIDE DB07854, N-METHYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINE DB01919, Pentanal DB02482, Phosphonothreonine DB04530, S,S-(2-Hydroxyethyl)Thiocysteine DB08756, Y-27632 |
DrugCentrali | P17612 |
GuidetoPHARMACOLOGYi | 1476 |
Genetic variation databases
BioMutai | PRKACA |
DMDMi | 125205 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed2 Publications | |||
ChainiPRO_0000086052 | 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 glycine2 Publications | 1 | |
Modified residuei | 3 | Deamidated asparagineBy similarity | 1 | |
Modified residuei | 11 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 49 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 140 | PhosphoserineBy similarity | 1 | |
Modified residuei | 196 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 198 | Phosphothreonine; by PDPK17 Publications | 1 | |
Modified residuei | 331 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 339 | PhosphoserineCombined sources6 Publications | 1 |
Post-translational modificationi
Keywords - PTMi
Lipoprotein, Myristate, PhosphoproteinProteomic databases
EPDi | P17612 |
jPOSTi | P17612 |
MassIVEi | P17612 |
MaxQBi | P17612 |
PaxDbi | P17612 |
PeptideAtlasi | P17612 |
PRIDEi | P17612 |
ProteomicsDBi | 53496 [P17612-1] 53497 [P17612-2] |
PTM databases
GlyGeni | P17612, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P17612 |
PhosphoSitePlusi | P17612 |
SwissPalmi | P17612 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000072062, Expressed in heart and 241 other tissues |
ExpressionAtlasi | P17612, baseline and differential |
Genevisiblei | P17612, HS |
Organism-specific databases
HPAi | ENSG00000072062, Tissue enhanced (skeletal) |
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 PRKAR1A and PRKAR2B (PubMed:33058759).
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.
Interacts with APOBEC3G and AICDA.
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).
Isoform 2 interacts with TCP11 (By similarity).
Interacts with HSF1 (PubMed:21085490).
By similarity9 PublicationsBinary interactionsi
P17612
GO - Molecular functioni
- protein domain specific binding Source: Ensembl
- protein kinase A regulatory subunit binding Source: BHF-UCL
- protein kinase binding Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 111553, 284 interactors |
CORUMi | P17612 |
DIPi | DIP-33878N |
ELMi | P17612 |
IntActi | P17612, 154 interactors |
MINTi | P17612 |
STRINGi | 9606.ENSP00000309591 |
Chemistry databases
BindingDBi | P17612 |
Miscellaneous databases
RNActi | P17612, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P17612 |
BMRBi | P17612 |
SMRi | P17612 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P17612 |
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 |
GeneTreei | ENSGT00940000162186 |
InParanoidi | P17612 |
OMAi | WQDSRNL |
OrthoDBi | 963519at2759 |
PhylomeDBi | P17612 |
TreeFami | TF313399 |
Family and domain databases
CDDi | cd14209, STKc_PKA, 1 hit |
IDEALi | IID00366 |
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 7 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 WESPAQNTAH LDQFERIKTL
60 70 80 90 100
GTGSFGRVML VKHKETGNHY 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 NEKCGKEFSE
F
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A7I2V5J4 | A0A7I2V5J4_HUMAN | cAMP-dependent protein kinase | PRKACA | 293 | Annotation score: | ||
Q15136 | Q15136_HUMAN | Protein kinase A-alpha | PRKACA KIN27 | 207 | Annotation score: | ||
K7ERP6 | K7ERP6_HUMAN | cAMP-dependent protein kinase catal... | PRKACA | 251 | Annotation score: | ||
B7Z708 | B7Z708_HUMAN | cAMP-dependent protein kinase catal... | PRKACA | 230 | Annotation score: | ||
A0A7I2YQ82 | A0A7I2YQ82_HUMAN | cAMP-dependent protein kinase catal... | PRKACA | 134 | Annotation score: | ||
K7ENJ5 | K7ENJ5_HUMAN | cAMP-dependent protein kinase catal... | PRKACA | 124 | Annotation score: | ||
K7EMV1 | K7EMV1_HUMAN | cAMP-dependent protein kinase catal... | PRKACA | 25 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040591 | 41 | L → V1 PublicationCorresponds to variant dbSNP:rs56029020Ensembl. | 1 | |
Natural variantiVAR_040592 | 46 | R → Q1 PublicationCorresponds to variant dbSNP:rs56085217Ensembl. | 1 | |
Natural variantiVAR_085198 | 137 | G → R in CAFD1; decreased interaction with regulatory subunit PRKAR2B. 1 Publication | 1 | |
Natural variantiVAR_071707 | 206 | L → R in PPNAD4; somatic mutation; the mutation results in cAMP-independent basal protein kinase activity and constitutive activation of protein kinase A. 4 PublicationsCorresponds to variant dbSNP:rs386352352EnsemblClinVar. | 1 | |
Natural variantiVAR_040593 | 264 | S → C1 PublicationCorresponds to variant dbSNP:rs35635531Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_004759 | 1 – 15 | MGNAA…SEQES → MASNSSD in isoform 2. 3 PublicationsAdd BLAST | 15 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X07767 mRNA Translation: CAA30597.1 AK290147 mRNA Translation: BAF82836.1 DQ667173 Genomic DNA Translation: ABG25918.1 CH471106 Genomic DNA Translation: EAW84399.1 BC039846 mRNA Translation: AAH39846.1 BC108259 mRNA Translation: AAI08260.1 AF208004 mRNA Translation: AAG35720.1 AF239744 mRNA Translation: AAF76426.1 AF224718 mRNA Translation: AAF75622.1 |
CCDSi | CCDS12304.1 [P17612-1] CCDS12305.1 [P17612-2] |
PIRi | S01404, OKHU2C |
RefSeqi | NP_001291278.1, NM_001304349.1 NP_002721.1, NM_002730.3 [P17612-1] NP_997401.1, NM_207518.2 [P17612-2] |
Genome annotation databases
Ensembli | ENST00000308677.9; ENSP00000309591.3; ENSG00000072062.15 ENST00000589994.6; ENSP00000466651.1; ENSG00000072062.15 [P17612-2] ENST00000672938.1; ENSP00000500293.1; ENSG00000288516.1 [P17612-2] ENST00000673550.1; ENSP00000499940.1; ENSG00000288516.1 |
GeneIDi | 5566 |
KEGGi | hsa:5566 |
MANE-Selecti | ENST00000308677.9; ENSP00000309591.3; NM_002730.4; NP_002721.1 |
UCSCi | uc002myb.4, human [P17612-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
SeattleSNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X07767 mRNA Translation: CAA30597.1 AK290147 mRNA Translation: BAF82836.1 DQ667173 Genomic DNA Translation: ABG25918.1 CH471106 Genomic DNA Translation: EAW84399.1 BC039846 mRNA Translation: AAH39846.1 BC108259 mRNA Translation: AAI08260.1 AF208004 mRNA Translation: AAG35720.1 AF239744 mRNA Translation: AAF76426.1 AF224718 mRNA Translation: AAF75622.1 |
CCDSi | CCDS12304.1 [P17612-1] CCDS12305.1 [P17612-2] |
PIRi | S01404, OKHU2C |
RefSeqi | NP_001291278.1, NM_001304349.1 NP_002721.1, NM_002730.3 [P17612-1] NP_997401.1, NM_207518.2 [P17612-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2GU8 | X-ray | 2.20 | A | 15-351 | [»] | |
3AGL | X-ray | 2.10 | A/B | 1-351 | [»] | |
3AGM | X-ray | 2.00 | A | 1-351 | [»] | |
3AMA | X-ray | 1.75 | A | 1-351 | [»] | |
3AMB | X-ray | 2.25 | A | 1-351 | [»] | |
3L9L | X-ray | 2.00 | A/B | 1-351 | [»] | |
3L9M | X-ray | 1.90 | A/B | 1-351 | [»] | |
3L9N | X-ray | 2.00 | A | 1-351 | [»] | |
3MVJ | X-ray | 2.49 | A/B/E | 1-351 | [»] | |
3NX8 | X-ray | 2.00 | A | 1-351 | [»] | |
3OOG | X-ray | 2.00 | A | 1-351 | [»] | |
3OVV | X-ray | 1.58 | A | 1-351 | [»] | |
3OWP | X-ray | 1.88 | A | 1-351 | [»] | |
3OXT | X-ray | 2.20 | A | 1-351 | [»] | |
3P0M | X-ray | 2.03 | A | 1-351 | [»] | |
3POO | X-ray | 1.60 | A | 1-351 | [»] | |
3VQH | X-ray | 1.95 | A | 1-351 | [»] | |
4AE6 | X-ray | 2.10 | A/B | 16-351 | [»] | |
4AE9 | X-ray | 2.30 | A/B | 16-351 | [»] | |
4UJ1 | X-ray | 1.77 | A | 1-351 | [»] | |
4UJ2 | X-ray | 2.02 | A | 1-351 | [»] | |
4UJ9 | X-ray | 1.87 | A | 1-351 | [»] | |
4UJA | X-ray | 1.93 | A | 1-351 | [»] | |
4UJB | X-ray | 1.95 | A | 1-351 | [»] | |
4WB5 | X-ray | 1.64 | A | 2-351 | [»] | |
4WB6 | X-ray | 2.10 | A/B | 2-351 | [»] | |
4WB7 | X-ray | 1.90 | A/B | 16-351 | [»] | |
4WB8 | X-ray | 1.55 | A | 16-351 | [»] | |
5BX6 | X-ray | 1.89 | A | 1-351 | [»] | |
5BX7 | X-ray | 1.89 | A | 1-350 | [»] | |
5IZF | X-ray | 2.10 | A | 1-351 | [»] | |
5IZJ | X-ray | 1.85 | A/B | 1-351 | [»] | |
5J5X | X-ray | 2.60 | A | 1-351 | [»] | |
5N23 | X-ray | 2.09 | A | 1-351 | [»] | |
5UZK | X-ray | 2.30 | A | 1-351 | [»] | |
6BYR | X-ray | 3.66 | A/C | 16-351 | [»] | |
6BYS | X-ray | 4.75 | A/C/E/G | 2-351 | [»] | |
6C0U | X-ray | 2.65 | A | 1-351 | [»] | |
6FRX | X-ray | 1.88 | A | 1-351 | [»] | |
6NO7 | X-ray | 3.55 | A/C/E/G | 2-351 | [»] | |
6QJ7 | X-ray | 1.69 | A | 1-351 | [»] | |
6WJF | electron microscopy | 7.50 | A/B | 16-351 | [»] | |
6WJG | electron microscopy | 6.20 | A/B | 16-351 | [»] | |
AlphaFoldDBi | P17612 | |||||
BMRBi | P17612 | |||||
SMRi | P17612 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111553, 284 interactors |
CORUMi | P17612 |
DIPi | DIP-33878N |
ELMi | P17612 |
IntActi | P17612, 154 interactors |
MINTi | P17612 |
STRINGi | 9606.ENSP00000309591 |
Chemistry databases
BindingDBi | P17612 |
ChEMBLi | CHEMBL4101 |
DrugBanki | DB07204, (1S)-1-(1H-INDOL-3-YLMETHYL)-2-(2-PYRIDIN-4-YL-[1,7]NAPHTYRIDIN-5-YLOXY)-EHYLAMINE DB07107, (1S)-2-(1H-INDOL-3-YL)-1-[({5-[(E)-2-PYRIDIN-4-YLVINYL]PYRIDIN-3-YL}OXY)METHYL]ETHYLAMINE DB07857, (2R)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamine DB07860, (2R)-2-(4-CHLOROPHENYL)-2-PHENYLETHANAMINE DB08073, (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE DB06959, (2S)-1-(3H-Indol-3-yl)-3-{[5-(6-isoquinolinyl)-3-pyridinyl]oxy}-2-propanamine DB07124, (2S)-1-(6H-INDOL-3-YL)-3-{[5-(7H-PYRAZOLO[3,4-C]PYRIDIN-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE DB06977, (2S)-1-{[5-(1H-Indazol-5-yl)-3-pyridinyl]oxy}-3-(7aH-indol-3-yl)-2-propanamine DB07858, (2S)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamine DB07583, (4R,2S)-5'-(4-(4-CHLOROBENZYLOXY)PYRROLIDIN-2-YLMETHANESULFONYL)ISOQUINOLINE DB07855, (S)-1-PHENYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINE DB07876, (S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE DB08149, 1-[4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine DB08148, 1-[4-(4-chlorophenyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine DB08070, 2-[4-(3-METHYL-1H-PYRAZOL-4-YL)PHENYL]ETHANAMINE DB03374, 3,5-Diiodotyrosine DB07458, 3-(1H-indol-3-yl)-4-{1-[2-(1-methylpyrrolidin-2-yl)ethyl]-1H-indol-3-yl}-1H-pyrrole-2,5-dione DB02155, 3-[(3-sec-butyl-4-hydroxybenzoyl)amino]azepan-4-yl 4-(2-hydroxy-5-methoxybenzoyl)benzoate DB08113, 3-pyridin-4-yl-1H-indazole DB08569, 3-PYRIDIN-4-YL-2,4-DIHYDRO-INDENO[1,2-.C.] PYRAZOLE DB08150, 4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-aminium DB07859, 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE DB07996, 5-(2-methylpiperazine-1-sulfonyl)isoquinoline DB08114, 5-benzyl-1,3-thiazol-2-amine DB07856, 6-{4-[4-(4-CHLOROPHENYL)PIPERIDIN-4-YL]PHENYL}-9H-PURINE DB08568, A-674563 DB04098, Balanol DB02611, Balanol Analog 1 DB01940, Balanol Analog 2 DB04522, Dexfosfoserine DB08846, Ellagic acid DB08162, Fasudil DB12010, Fostamatinib DB07995, H-89 DB04707, Hydroxyfasudil DB07947, ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE DB08231, Myristic acid DB07235, N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE DB07997, N-[2-(METHYLAMINO)ETHYL]-5-ISOQUINOLINESULFONAMIDE DB07854, N-METHYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINE DB01919, Pentanal DB02482, Phosphonothreonine DB04530, S,S-(2-Hydroxyethyl)Thiocysteine DB08756, Y-27632 |
DrugCentrali | P17612 |
GuidetoPHARMACOLOGYi | 1476 |
PTM databases
GlyGeni | P17612, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P17612 |
PhosphoSitePlusi | P17612 |
SwissPalmi | P17612 |
Genetic variation databases
BioMutai | PRKACA |
DMDMi | 125205 |
Proteomic databases
EPDi | P17612 |
jPOSTi | P17612 |
MassIVEi | P17612 |
MaxQBi | P17612 |
PaxDbi | P17612 |
PeptideAtlasi | P17612 |
PRIDEi | P17612 |
ProteomicsDBi | 53496 [P17612-1] 53497 [P17612-2] |
Protocols and materials databases
Antibodypediai | 4159, 522 antibodies from 41 providers |
DNASUi | 5566 |
Genome annotation databases
Ensembli | ENST00000308677.9; ENSP00000309591.3; ENSG00000072062.15 ENST00000589994.6; ENSP00000466651.1; ENSG00000072062.15 [P17612-2] ENST00000672938.1; ENSP00000500293.1; ENSG00000288516.1 [P17612-2] ENST00000673550.1; ENSP00000499940.1; ENSG00000288516.1 |
GeneIDi | 5566 |
KEGGi | hsa:5566 |
MANE-Selecti | ENST00000308677.9; ENSP00000309591.3; NM_002730.4; NP_002721.1 |
UCSCi | uc002myb.4, human [P17612-1] |
Organism-specific databases
CTDi | 5566 |
DisGeNETi | 5566 |
GeneCardsi | PRKACA |
HGNCi | HGNC:9380, PRKACA |
HPAi | ENSG00000072062, Tissue enhanced (skeletal) |
MalaCardsi | PRKACA |
MIMi | 601639, gene 615830, phenotype 619142, phenotype |
neXtProti | NX_P17612 |
OpenTargetsi | ENSG00000072062 |
Orphaneti | 401920, Fibrolamellar hepatocellular carcinoma 189439, Primary pigmented nodular adrenocortical disease |
PharmGKBi | PA33748 |
VEuPathDBi | HostDB:ENSG00000072062 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0616, Eukaryota |
GeneTreei | ENSGT00940000162186 |
InParanoidi | P17612 |
OMAi | WQDSRNL |
OrthoDBi | 963519at2759 |
PhylomeDBi | P17612 |
TreeFami | TF313399 |
Enzyme and pathway databases
BRENDAi | 2.7.11.11, 2681 |
PathwayCommonsi | P17612 |
Reactomei | R-HSA-111931, PKA-mediated phosphorylation of CREB R-HSA-163358, PKA-mediated phosphorylation of key metabolic factors R-HSA-163560, Triglyceride catabolism R-HSA-163615, PKA activation R-HSA-164378, PKA activation in glucagon signalling R-HSA-180024, DARPP-32 events R-HSA-2565942, Regulation of PLK1 Activity at G2/M Transition R-HSA-380259, Loss of Nlp from mitotic centrosomes R-HSA-380270, Recruitment of mitotic centrosome proteins and complexes R-HSA-380284, Loss of proteins required for interphase microtubule organization from the centrosome R-HSA-380320, Recruitment of NuMA to mitotic centrosomes R-HSA-381676, Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-HSA-392517, Rap1 signalling R-HSA-422356, Regulation of insulin secretion R-HSA-432040, Vasopressin regulates renal water homeostasis via Aquaporins R-HSA-4420097, VEGFA-VEGFR2 Pathway R-HSA-442720, CREB1 phosphorylation through the activation of Adenylate Cyclase R-HSA-512988, Interleukin-3, Interleukin-5 and GM-CSF signaling R-HSA-5578775, Ion homeostasis R-HSA-5610780, Degradation of GLI1 by the proteasome R-HSA-5610783, Degradation of GLI2 by the proteasome R-HSA-5610785, GLI3 is processed to GLI3R by the proteasome R-HSA-5610787, Hedgehog 'off' state R-HSA-5620912, Anchoring of the basal body to the plasma membrane R-HSA-5621575, CD209 (DC-SIGN) signaling R-HSA-5687128, MAPK6/MAPK4 signaling R-HSA-8853659, RET signaling R-HSA-8854518, AURKA Activation by TPX2 R-HSA-8963896, HDL assembly R-HSA-9010642, ROBO receptors bind AKAP5 R-HSA-9022535, Loss of phosphorylation of MECP2 at T308 R-HSA-9022692, Regulation of MECP2 expression and activity R-HSA-9634600, Regulation of glycolysis by fructose 2,6-bisphosphate metabolism R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production R-HSA-9664323, FCGR3A-mediated IL10 synthesis R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
SABIO-RKi | P17612 |
SignaLinki | P17612 |
SIGNORi | P17612 |
Miscellaneous databases
BioGRID-ORCSi | 5566, 45 hits in 1122 CRISPR screens |
ChiTaRSi | PRKACA, human |
EvolutionaryTracei | P17612 |
GeneWikii | PRKACA |
GenomeRNAii | 5566 |
Pharosi | P17612, Tchem |
PROi | PR:P17612 |
RNActi | P17612, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000072062, Expressed in heart and 241 other tissues |
ExpressionAtlasi | P17612, baseline and differential |
Genevisiblei | P17612, HS |
Family and domain databases
CDDi | cd14209, STKc_PKA, 1 hit |
IDEALi | IID00366 |
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_HUMAN | |
Accessioni | P17612Primary (citable) accession number: P17612 Secondary accession number(s): Q32P54 Q9NRH9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 240 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families