PRKACA protein expression summary - The Human Protein Atlas

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PRKACA

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STRUCT & INT

PRKACA

PRKACA INFORMATION
Proteinⁱ Full gene name according to HGNC.	Protein kinase cAMP-activated catalytic subunit alpha
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	PRKACA (PKACa)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s).	Cancer-related genes Disease related genes Enzymes Human disease related genes Metabolic proteins Potential drug targets RAS pathway related proteins
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	9
Protein interactions	Interacting with 25 proteins

PROTEIN EXPRESSION AND LOCALIZATION
Tissue profileⁱ A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource. "Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.	Ubiquitous cytoplasmic expression.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	Localized to the Cytosol In addition localized to the Microtubules, Cytokinetic bridge, Primary cilium, Basal body
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.	Intracellular

TISSUE RNA EXPRESSION
Tissue specificityⁱ The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.	Tissue enhanced (Skeletal muscle)
Tissue expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Heart muscle - Cardiac muscle contraction (mainly)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category	Low human brain regional specificity
Brain expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Neurons - Mixed function (mainly)

CELL TYPE RNA EXPRESSION
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Cell type enhanced (monocytes, Cardiomyocytes)
Single cell type expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Monocytes - Innate immune response (mainly)
Tissue cell type classificationⁱ Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.	Cell type enriched (Minor Salivary Gland - Endothelial cells)
Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Low immune cell specificity
Immune cell expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Monocytes & Neutrophils - Degranulation (mainly)

CANCER & CELL LINES
Prognostic summary	PRKACA is a prognostic marker in Lung squamous cell carcinoma, Pancreatic adenocarcinoma
Cancer specificityⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.	Low cancer specificity
Cell line expression clusterⁱ The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Transcription (mainly)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Low cancer specificity

PROTEINS IN BLOOD
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.	Yes
Proximity extension assayⁱ Detectibility in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with six visits during two years. Read more	Not available

PROTEIN FUNCTION
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	Phosphorylates a large number of substrates in the cytoplasm and the nucleus 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25. 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 26. RORA is activated by phosphorylation 27. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts 28. 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 29, 30. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated 31. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+) 32. PSMC5/RPT6 activation by phosphorylation stimulates proteasome 33. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation 34. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding 35. Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (By similarity). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis 36. 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 37, 38. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock 39. Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR 40.... show less
Molecular function (UniProt)ⁱ Keywords assigned by UniProt to proteins due to their particular molecular function.	Kinase, Serine/threonine-protein kinase, Transferase
Ligand (UniProt)ⁱ Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.	ATP-binding, cAMP, Nucleotide-binding
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	This gene encodes one of the catalytic subunits of protein kinase A, which exists as a tetrameric holoenzyme with two regulatory subunits and two catalytic subunits, in its inactive form. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. cAMP-dependent phosphorylation of proteins by protein kinase A is important to many cellular processes, including differentiation, proliferation, and apoptosis. Constitutive activation of this gene caused either by somatic mutations, or genomic duplications of regions that include this gene, have been associated with hyperplasias and adenomas of the adrenal cortex and are linked to corticotropin-independent Cushing's syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. Tissue-specific isoforms that differ at the N-terminus have been described, and these isoforms may differ in the post-translational modifications that occur at the N-terminus of some isoforms. [provided by RefSeq, Jan 2015]... show less

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