Protein:PRKACA |
Protein Summary |
 Gene summary |
| Gene name: PRKACA | ASpdb.0 ID: 5566 | Gene | Gene symbol | PRKACA | Gene ID | 5566 |
| Gene name | protein kinase cAMP-activated catalytic subunit alpha |
| Synonyms | CAFD1|PKACA|PPNAD4 |
| Cytomap | 19p13.12 |
| Type of gene | protein-coding |
| Description | cAMP-dependent protein kinase catalytic subunit alphaPKA C-alphaprotein kinase A catalytic subunitprotein kinase, cAMP-dependent, alpha catalytic subunitprotein kinase, cAMP-dependent, catalytic, alpha |
| Modification date | 20240411 |
| UniProtAcc | P17612 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | PRKACA | GO:0004672 | protein kinase activity | 12475942 |
| Gene | PRKACA | GO:0004674 | protein serine/threonine kinase activity | 21085490 |
| Gene | PRKACA | GO:0004691 | cAMP-dependent protein kinase activity | 11029056|31112131 |
| Gene | PRKACA | GO:0004712 | protein serine/threonine/tyrosine kinase activity | 22797923 |
| Gene | PRKACA | GO:0005634 | nucleus | 21085490 |
| Gene | PRKACA | GO:0005737 | cytoplasm | 21085490 |
| Gene | PRKACA | GO:0005813 | centrosome | 21399614 |
| Gene | PRKACA | GO:0005886 | plasma membrane | 15569306 |
| Gene | PRKACA | GO:0005930 | axoneme | 12475942 |
| Gene | PRKACA | GO:0005952 | cAMP-dependent protein kinase complex | 12475942 |
| Gene | PRKACA | GO:0006397 | mRNA processing | 17594903 |
| Gene | PRKACA | GO:0006468 | protein phosphorylation | 12475942 |
| Gene | PRKACA | GO:0016607 | nuclear speck | 17594903 |
| Gene | PRKACA | GO:0018105 | peptidyl-serine phosphorylation | 10805756|11029056 |
| Gene | PRKACA | GO:0031625 | ubiquitin protein ligase binding | 21423175 |
| Gene | PRKACA | GO:0034605 | cellular response to heat | 21085490 |
| Gene | PRKACA | GO:0044853 | plasma membrane raft | 17911601 |
| Gene | PRKACA | GO:0045667 | regulation of osteoblast differentiation | 19949837 |
| Gene | PRKACA | GO:0048471 | perinuclear region of cytoplasm | 21085490 |
| Gene | PRKACA | GO:0061136 | regulation of proteasomal protein catabolic process | 17565987 |
| Gene | PRKACA | GO:0071333 | cellular response to glucose stimulus | 19949837 |
| Gene | PRKACA | GO:0106310 | protein serine kinase activity | 22797923 |
| Gene | PRKACA | GO:1904262 | negative regulation of TORC1 signaling | 31112131 |
| Gene | PRKACA | GO:2000810 | regulation of bicellular tight junction assembly | 15905176 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P17612-1 | P17612-1_3ama_A.pdb | 3AMA | X-ray | 1.75 | A | 2 | 351 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P17612 | PRKACA | P17612-1 | P17612-2 | 351 | 343 | 1 | 15 | Substitution | MGNAAAAKKGSEQES | MASNSSD | 1 | 7 |
| Multiple sequence alignment of our canonical and alternatively spliced PRKACA |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of PRKACA |
| UniProt-id | ENSG | ENST | ENSP |
| P17612-1 | ENSG00000072062.16 | ENST00000308677.9 | ENSP00000309591.3 |
| P17612-1 | ENSG00000288516.1 | ENST00000673550.1 | ENSP00000499940.1 |
| P17612-2 | ENSG00000072062.16 | ENST00000589994.6 | ENSP00000466651.1 |
| P17612-2 | ENSG00000288516.1 | ENST00000672938.1 | ENSP00000500293.1 |
| UniProt-id | NM ID | NP ID |
| P17612-1 | NM_002730.3 | NP_002721.1 |
| P17612-2 | NM_207518.2 | NP_997401.1 |
| Amino acid sequences of our canonical and alternatively spliced PRKACA |
| accession_id | Protein sequence |
| P17612-1 | MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWESPAQNTAHLDQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTL NEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGY IQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLL |
| P17612-2 | MASNSSDVKEFLAKAKEDFLKKWESPAQNTAHLDQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQA VNFPFLVKLEFSFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGYIQVTDFGF AKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| PRKACA (go to UniProt):P17612 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
Gene Isoform Structures and Expression Levels for PRKACA |
| Gene structures of our canonical and alternative spliced genes of PRKACA * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P17612-1 |
| 3D view using mol* of P17612-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P17612-1 |
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| pLDDT distribution across the protein length of P17612-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P17612-1 |
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| Ramachandran plot of P17612-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P17612-1 | 1.071 | 143 | 1.037 | 422.919 | 0.478 | 0.804 | 1.016 | 0.95 | 1.182 | 0.804 | 1.072 | 50,51,52,53,54,55,56,57,58,71,73,75,85,88,89,92,10 5,121,122,123,124,127,128,131,167,169,171,172,174, 184,185,187,188,327,328,329,331 |
| P17612-2 | 1.066 | 117 | 1.038 | 427.378 | 0.581 | 0.797 | 1.017 | 0.693 | 1.166 | 0.594 | 0.852 | 42,43,44,45,46,47,48,49,50,63,65,67,77,80,84,88,97 ,113,114,115,116,119,120,123,159,161,163,164,166,1 76,177,178,179,180,319,320,321,323 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P17612-1_P17612-1_3ama_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P17612-1_3ama_A_P17612-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P17612-1_P17612-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P17612-1_vs_P17612-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P17612-1_vs_P17612-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to PRKACA |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P17612 | PRKACA | DB08568 | A-674563 | experimental | |
| P17612 | PRKACA | DB08569 | 3-PYRIDIN-4-YL-2,4-DIHYDRO-INDENO[1,2-.C.] PYRAZOLE | experimental | |
| P17612 | PRKACA | DB08162 | Fasudil | investigational | |
| P17612 | PRKACA | DB07124 | (2S)-1-(6H-INDOL-3-YL)-3-{[5-(7H-PYRAZOLO[3,4-C]PYRIDIN-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE | experimental | |
| P17612 | PRKACA | DB04098 | Balanol | experimental | |
| P17612 | PRKACA | DB07997 | N-[2-(METHYLAMINO)ETHYL]-5-ISOQUINOLINESULFONAMIDE | experimental | |
| P17612 | PRKACA | DB02611 | Balanol Analog 1 | experimental | |
| P17612 | PRKACA | DB07583 | (4R,2S)-5'-(4-(4-CHLOROBENZYLOXY)PYRROLIDIN-2-YLMETHANESULFONYL)ISOQUINOLINE | experimental | |
| P17612 | PRKACA | DB07947 | ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE | experimental | |
| P17612 | PRKACA | DB07204 | (1S)-1-(1H-INDOL-3-YLMETHYL)-2-(2-PYRIDIN-4-YL-[1,7]NAPHTYRIDIN-5-YLOXY)-EHYLAMINE | experimental | |
| P17612 | PRKACA | DB07859 | 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE | experimental | |
| P17612 | PRKACA | DB01919 | Pentanal | experimental | |
| P17612 | PRKACA | DB08846 | Ellagic acid | investigational | inhibitor |
| P17612 | PRKACA | DB01940 | Balanol Analog 2 | experimental | |
| P17612 | PRKACA | DB04530 | S,S-(2-Hydroxyethyl)Thiocysteine | experimental | |
| P17612 | PRKACA | DB03374 | 3,5-Diiodotyrosine | experimental | |
| P17612 | PRKACA | DB08231 | Myristic acid | experimental | |
| P17612 | PRKACA | DB08114 | 5-benzyl-1,3-thiazol-2-amine | experimental | |
| P17612 | PRKACA | DB07458 | 3-(1H-indol-3-yl)-4-{1-[2-(1-methylpyrrolidin-2-yl)ethyl]-1H-indol-3-yl}-1H-pyrrole-2,5-dione | experimental | |
| P17612 | PRKACA | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P17612 | PRKACA | DB07860 | (2R)-2-(4-CHLOROPHENYL)-2-PHENYLETHANAMINE | experimental | |
| P17612 | PRKACA | DB08113 | 3-pyridin-4-yl-1H-indazole | experimental | |
| P17612 | PRKACA | DB07876 | (S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE | experimental | |
| P17612 | PRKACA | DB02155 | 3-[(3-sec-butyl-4-hydroxybenzoyl)amino]azepan-4-yl 4-(2-hydroxy-5-methoxybenzoyl)benzoate | experimental | |
| P17612 | PRKACA | DB06959 | (2S)-1-(3H-Indol-3-yl)-3-{[5-(6-isoquinolinyl)-3-pyridinyl]oxy}-2-propanamine | experimental | |
| P17612 | PRKACA | DB07996 | 5-(2-methylpiperazine-1-sulfonyl)isoquinoline | experimental | |
| P17612 | PRKACA | DB04522 | Dexfosfoserine | experimental | |
| P17612 | PRKACA | DB07854 | N-METHYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINE | experimental | |
| P17612 | PRKACA | DB07857 | (2R)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamine | experimental | |
| P17612 | PRKACA | DB08070 | 2-[4-(3-METHYL-1H-PYRAZOL-4-YL)PHENYL]ETHANAMINE | experimental | |
| P17612 | PRKACA | DB08756 | Y-27632 | experimental | |
| P17612 | PRKACA | DB07107 | (1S)-2-(1H-INDOL-3-YL)-1-[({5-[(E)-2-PYRIDIN-4-YLVINYL]PYRIDIN-3-YL}OXY)METHYL]ETHYLAMINE | experimental | |
| P17612 | PRKACA | DB08073 | (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE | experimental | |
| P17612 | PRKACA | DB07995 | H-89 | experimental | |
| P17612 | PRKACA | DB08148 | 1-[4-(4-chlorophenyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine | experimental | |
| P17612 | PRKACA | DB08149 | 1-[4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine | experimental | |
| P17612 | PRKACA | DB07858 | (2S)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamine | experimental | |
| P17612 | PRKACA | DB08150 | 4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-aminium | experimental | |
| P17612 | PRKACA | DB04707 | Hydroxyfasudil | experimental | |
| P17612 | PRKACA | DB02482 | Phosphonothreonine | experimental | |
| P17612 | PRKACA | DB07855 | (S)-1-PHENYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINE | experimental | |
| P17612 | PRKACA | DB07856 | 6-{4-[4-(4-CHLOROPHENYL)PIPERIDIN-4-YL]PHENYL}-9H-PURINE | experimental | |
| P17612 | PRKACA | DB07235 | N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE | experimental | |
| P17612 | PRKACA | DB06977 | (2S)-1-{[5-(1H-Indazol-5-yl)-3-pyridinyl]oxy}-3-(7aH-indol-3-yl)-2-propanamine | experimental |
Related Diseases to PRKACA |
| Previous studies relating to the alternative splicing of PRKACA and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| PRKACA | 21367856 | Cyclic AMP-dependent protein kinase regulates the alternative splicing of tau exon 10: a mechanism involved in tau pathology of Alzheimer disease. | Hyperphosphorylation and deposition of tau into neurofibrillary tangles is a hallmark of Alzheimer disease (AD). Alternative splicing of tau exon 10 generates tau isoforms containing three or four microtubule binding repeats (3R-tau and 4R-tau), which are equally expressed in adult human brain. Dysregulation of exon 10 causes neurofibrillary degeneration. Here, we report that cyclic AMP-dependent protein kinase, PKA, phosphorylates splicing factor SRSF1, modulates its binding to tau pre-mRNA, and promotes tau exon 10 inclusion in cultured cells and in vivo in rat brain. PKA-Cα, but not PKA-Cβ, interacts with SRSF1 and elevates SRSF1-mediated tau exon 10 inclusion. In AD brain, the decreased level of PKA-Cα correlates with the increased level of 3R-tau. These findings suggest that a down-regulation of PKA dysregulates the alternative splicing of tau exon 10 and contributes to neurofibrillary degeneration in AD by causing an imbalance in 3R-tau and 4R-tau expression. | D000544 | Alzheimer Disease |
| PRKACA | 21957496 | Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation. | Regulation between protein kinases is critical for the establishment of signaling pathways/networks to 'orchestrate' cellular processes. Besides posttranslational phosphorylation, alternative pre-mRNA splicing is another way to control kinase properties, but splicing regulation between two kinases and the effect of resulting variants on cells has barely been explored. Here we examined the effect of the protein kinase A (PKA) pathway on the alternative splicing and variant properties of the Ca²âº/calmodulin-dependent protein kinase kinase 2 (CaMKK2) gene in B35 neuroblastoma cells. Inclusion of the exon 16 of CaMKK2 was significantly reduced by H89, a PKA selective inhibitor. Consistently, overexpressed PKA strongly promoted the exon inclusion in a CaMKK2 sequence-dependent way in splicing reporter assays. In vitro, purified CaMKKβ1 variant proteins were found to be kinase-active. In cells, they were differentially phosphorylated by PKA. In RNA interference assays, CaMKKβ1 was found to be essential for forskolin-induced neurite growth. Interestingly, overexpression of the variant without exon 16 (-E16) promoted neurite elongation while the other one (+E16) promoted neurite branching; in contrast, reduction of the latter one enhanced neurite elongation. Moreover, the variants are differentially expressed and the exon 16-containing transcripts highly enriched in the brain, particularly the cerebellum and hippocampus. Thus, PKA regulates the alternative splicing of CaMKK2 to produce variants that differentially modulate neuronal differentiation. Taken together with the many distinct variants of kinases, alternative splicing regulation likely adds another layer of modulation between protein kinases in cellular signaling networks. | D009447 | Neuroblastoma |
Clinically important variants in PRKACA |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
| P17612 | P17612-1 | PRKACA | single nucleotide variant | p.Leu206Arg | Pathogenic/Likely pathogenic |
| P17612 | P17612-1 | PRKACA | single nucleotide variant | p.Leu206Arg | Pathogenic/Likely pathogenic |
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