PRKACA Gene (Protein Coding)

Protein Kinase CAMP-Activated Catalytic Subunit Alpha

GC19M014092
GIFtS:
51
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... See more...

Aliases for PRKACA Gene

Aliases for PRKACA Gene

  • Protein Kinase CAMP-Activated Catalytic Subunit Alpha 2 3 5
  • Protein Kinase, CAMP-Dependent, Alpha Catalytic Subunit 2 3
  • CAMP-Dependent Protein Kinase Catalytic Subunit Alpha 3 4
  • Protein Kinase, CAMP-Dependent, Catalytic, Alpha 2 3
  • EC 2.7.11.11 4 51
  • PKA C-Alpha 3 4
  • PKACA 3 4
  • Protein Kinase A Catalytic Subunit 3
  • EC 2.7.11 51
  • PPNAD4 3
  • PRKACA 5
  • PKACa 2

External Ids for PRKACA Gene

Previous GeneCards Identifiers for PRKACA Gene

  • GC19M014557
  • GC19M014047
  • GC19M014063
  • GC19M014202
  • GC19M013774

Summaries for PRKACA Gene

Entrez Gene Summary for PRKACA Gene

  • 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]

CIViC Summary for PRKACA Gene

  • PRKACA has been studied in breast cancer and has been found to mediate resistance to HER2 targeted therapies. It has also been found to contain a mutation hotspot that contributes to neoplastic behavior in neuroendocrine cancers. In hepatocellular fibrolamellar carcinoma (FL-HCC), the fusion DNAJB1 to PRKACA is suggested to be a diagnostic marker for this rare subtype of HCC. In one study, this fusion was observed in 15/15 FL-HCC cases examined and functional studies found that the fusion retained kinase activity.

GeneCards Summary for PRKACA Gene

PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha) is a Protein Coding gene. Diseases associated with PRKACA include Pigmented Nodular Adrenocortical Disease, Primary, 4 and Fibrolamellar Carcinoma. Among its related pathways are Adenylate cyclase inhibitory pathway and DAG and IP3 signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is PRKACB.

UniProtKB/Swiss-Prot Summary for PRKACA Gene

  • 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 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+) (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).
  • [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation.

Tocris Summary for PRKACA Gene

  • Protein kinase A (PKA, aka cAMP-dependent protein kinase) is involved in the regulation of lipid and glucose metabolism and is a component of the signal transduction mechanism of certain GPCRs. PKA is composed of two regulatory subunits and two catalytic subunits.

Gene Wiki entry for PRKACA Gene

Additional gene information for PRKACA Gene

No data available for PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PRKACA Gene

Genomics for PRKACA Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for PRKACA Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PRKACA on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PRKACA

Top Transcription factor binding sites by QIAGEN in the PRKACA gene promoter:
  • c-Ets-1
  • GR
  • GR-alpha

Genomic Locations for PRKACA Gene

Genomic Locations for PRKACA Gene
chr19:14,091,688-14,118,084
(GRCh38/hg38)
Size:
26,397 bases
Orientation:
Minus strand
chr19:14,202,500-14,228,896
(GRCh37/hg19)
Size:
26,397 bases
Orientation:
Minus strand

Genomic View for PRKACA Gene

Genes around PRKACA on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PRKACA Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PRKACA Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for PRKACA Gene

Proteins for PRKACA Gene

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  • Protein details for PRKACA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P17612-KAPCA_HUMAN
    Recommended name:
    cAMP-dependent protein kinase catalytic subunit alpha
    Protein Accession:
    P17612
    Secondary Accessions:
    • Q32P54
    • Q9H2Y0
    • Q9NRB4
    • Q9NRH9

    Protein attributes for PRKACA Gene

    Size:
    351 amino acids
    Molecular mass:
    40590 Da
    Quaternary structure:
    • 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. 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).

    Three dimensional structures from OCA and Proteopedia for PRKACA Gene

    Alternative splice isoforms for PRKACA Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PRKACA Gene

Protein Expression for PRKACA Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for PRKACA Gene

P17612:
  • GDTSNFDDYEEE
  • EKCGKEF
  • GRFSEPHA
  • TLGTGSFGRV
  • EHTLNEKRILQA
  • GTPEYLAPE
  • HKWFATTDWIAIYQRKVEAPFIPKF
  • RDLKPENLLIDQQGY
  • ESVKEFLAKAKE
  • LGVLIYEM
  • YLAPEII
  • YLHSLDLI
  • SDLKDLLRNLLQVDLTKR
  • VDWWALGVL
  • GVNDIKN
  • LKPENLL
  • RDLKPEN
  • TDFGFAK
  • ADQPIQIYEKIVSG
  • DIKNHKWF

Post-translational modifications for PRKACA Gene

  • Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively.
  • Autophosphorylated. Phosphorylation is enhanced by vitamin K(2). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity.
  • Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PRKACA Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for PRKACA Gene

Gene Families for PRKACA Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for PRKACA Gene

InterPro:
Blocks:
  • Protein kinase C-terminal domain
ProtoNet:

Suggested Antigen Peptide Sequences for PRKACA Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58698, highly similar to cAMP-dependent protein kinase, alpha-catalytic subunit (EC 2.7.11.11) (B7Z708_HUMAN)
  • cAMP-dependent protein kinase catalytic subunit alpha (KAPCA_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P17612

UniProtKB/Swiss-Prot:

KAPCA_HUMAN :
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.
Family:
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.
genes like me logo Genes that share domains with PRKACA: view

Function for PRKACA Gene

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Molecular function for PRKACA Gene

UniProtKB/Swiss-Prot Function:
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 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+) (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).
UniProtKB/Swiss-Prot Function:
[Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.11;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.11;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. Inhibited by H89 (N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-amino-aminomethylbenzamide analogs, ARC-1032 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-carbamoylbutyl]hexanamide), ARC-1034 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]hexanamide), ARC-582, ARC-902 (Adc-6-aminohexanoic acid-(D-Arg)(6)-NH(2)), ARC-1012 ((2R)-6-amino-2-(6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}hexanamido)-N-(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)hexanamide) and ARC-1039 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-1-[(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)carbamoyl]ethyl]he xanamide).
GENATLAS Biochemistry:
protein kinase,cAMP-dependent,catalytic,alpha subunit

Enzyme Numbers (IUBMB) for PRKACA Gene

Phenotypes From GWAS Catalog for PRKACA Gene

Gene Ontology (GO) - Molecular Function for PRKACA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding IEA --
GO:0004672 protein kinase activity IEA,IDA 12475942
GO:0004674 protein serine/threonine kinase activity IEA,IMP 26537248
GO:0004679 AMP-activated protein kinase activity IEA --
genes like me logo Genes that share ontologies with PRKACA: view
genes like me logo Genes that share phenotypes with PRKACA: view

Human Phenotype Ontology for PRKACA Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PRKACA Gene

MGI Knock Outs for PRKACA:

Animal Model Products

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Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PRKACA

No data available for Transcription Factor Targets and HOMER Transcription for PRKACA Gene

Localization for PRKACA Gene

Subcellular locations from UniProtKB/Swiss-Prot for PRKACA Gene

Cytoplasm. Cell membrane. Nucleus. Mitochondrion. Membrane. Lipid-anchor. 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). {ECO:0000250, ECO:0000269 PubMed:21085490}.
[Isoform 2]: Cell projection, cilium, flagellum. Cytoplasmic vesicle, secretory vesicle, acrosome. 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). {ECO:0000250 UniProtKB:P05132, ECO:0000269 PubMed:10906071}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PRKACA gene
Compartment Confidence
plasma membrane 5
cytoskeleton 5
nucleus 5
cytosol 5
extracellular 4
mitochondrion 4
endoplasmic reticulum 2
peroxisome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PRKACA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001669 acrosomal vesicle ISS --
GO:0005623 cell IEA --
GO:0005634 nucleus IBA,IDA 21085490
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA,IDA 21085490
genes like me logo Genes that share ontologies with PRKACA: view

Pathways & Interactions for PRKACA Gene

PathCards logo

SuperPathways for PRKACA Gene

SuperPathway Contained pathways
1 DAG and IP3 signaling
DAG and IP3 signaling
.94
EGFR interacts with phospholipase C-gamma
.94
PLC-gamma1 signalling
.94
Ca-dependent events
.93
Calmodulin induced events
.93
CaM pathway
.93
PLC beta mediated events
.65
G-protein mediated events
.64
Opioid Signalling
.56
Beta-2 adrenergic-dependent CFTR expression
.50
G Protein Signaling Pathways
.44
Neurophysiological process PGE2-induced pain processing
.38
Signal transduction Calcium signaling
.35
Inhibitory action of Lipoxin A4 on PDGF, EGF and LTD4 signaling
.33
Development Beta-adrenergic receptors signaling via cAMP
.32
Development Role of Activin A in cell differentiation and proliferation
.32
CREB phosphorylation through the activation of Adenylate Cyclase
.01
PKA activation
.01
PKA activation in glucagon signalling
.01
PKA-mediated phosphorylation of CREB
.01
2 RET signaling
Interleukin-3, 5 and GM-CSF signaling
.94
Downstream signal transduction
.94
Signaling by PDGF
.94
DAP12 signaling
.92
RET signaling
.92
Signaling by EGFR
.90
DAP12 interactions
.89
NGF signalling via TRKA from the plasma membrane
.87
MAPK family signaling cascades
.87
Signalling by NGF
.81
VEGFA-VEGFR2 Pathway
.78
Signaling by VEGF
.76
3 Regulation of PLK1 Activity at G2/M Transition
Centrosome maturation
.88
Loss of Nlp from mitotic centrosomes
.88
Loss of proteins required for interphase microtubule organization from the centrosome
.88
Recruitment of mitotic centrosome proteins and complexes
.88
AURKA Activation by TPX2
.85
Regulation of PLK1 Activity at G2/M Transition
.80
Anchoring of the basal body to the plasma membrane
.72
G2/M Transition
.50
Mitotic G2-G2/M phases
.49
4 Aldosterone synthesis and secretion
Aldosterone synthesis and secretion
.48
Cortisol synthesis and secretion
.48
Cushing syndrome
.41
Melanogenesis
.41
Insulin secretion
.36
Thyroid hormone synthesis
.34
5 G-Beta Gamma Signaling
G-Beta Gamma Signaling
.46
GHRH Signaling
.46
CRHR Pathway
.44
Relaxin Pathway
.37
Hedgehog Signaling in Mammals
.32
Signaling in Gap Junctions
.30
genes like me logo Genes that share pathways with PRKACA: view

Pathways by source for PRKACA Gene

40 GeneGo (Thomson Reuters) pathways for PRKACA Gene
  • Apoptosis and survival BAD phosphorylation
  • Beta-2 adrenergic-dependent CFTR expression
  • Cell cycle_Role of APC in cell cycle regulation
  • Cytoskeleton remodeling Role of PKA in cytoskeleton reorganisation
  • Development A1 receptor signaling
52 Qiagen pathways for PRKACA Gene
  • 14-3-3 and Regulation of BAD Activity
  • 14-3-3 Induced Apoptosis
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • AMPK Enzyme Complex Pathway
2 Cell Signaling Technology pathways for PRKACA Gene
1 GeneTex pathway for PRKACA Gene

SIGNOR curated interactions for PRKACA Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for PRKACA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000086 G2/M transition of mitotic cell cycle TAS --
GO:0001707 mesoderm formation IEA --
GO:0001843 neural tube closure IEA --
GO:0002027 regulation of heart rate TAS 23507255
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with PRKACA: view

Drugs & Compounds for PRKACA Gene

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  1. Drug

(58) Drugs for PRKACA Gene - From: DrugBank, ApexBio, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
H-89 Experimental Pharma Target 0
Pentanal Experimental Pharma Target 0
A-674563 Experimental Pharma Target Akt1/PKA/CDK2 inhibitor,potent and selective 0
cyclic amp Experimental Pharma 0

(3) Additional Compounds for PRKACA Gene - From: HMDB, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
H 89 dihydrochloride
130964-39-5

(5) Tocris Compounds for PRKACA Gene

Compound Action Cas Number
cGMP Dependent Kinase Inhibitor Peptide Inhibitor of protein kinases G and A 82801-73-8
H 89 dihydrochloride Protein kinase A inhibitor 130964-39-5
KT 5720 Selective protein kinase A inhibitor 108068-98-0
PKA inhibitor fragment (6-22) amide Potent protein kinase A inhibitor 121932-06-7
PKI 14-22 amide, myristoylated Cell-permeable protein kinase A inhibitor 201422-03-9

(9) ApexBio Compounds for PRKACA Gene

Compound Action Cas Number
A-674563 Akt1/PKA/CDK2 inhibitor,potent and selective 552325-73-2
AT7867 Akt1/2/3 and p70S6K/PKA inhibitor 857531-00-1
cGMP Dependent Kinase Inhibitor Peptide 82801-73-8
Daphnetin Protein kinases inhibitor for EGFR/PKA/PKC 486-35-1
GF 109203X Protein kinase C,MLCK,PKG and PKA inhibitor 133052-90-1
H 89 2HCl Potent PKA inhibitor 130964-39-5
K-252c Protein kinase inhibitor 85753-43-1
PKA inhibitor fragment (6-22) amide 121932-06-7
PKI 14-22 amide, myristoylated PKA inhibitor 201422-03-9
genes like me logo Genes that share compounds with PRKACA: view

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Transcripts for PRKACA Gene

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mRNA/cDNA for PRKACA Gene

3 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PRKACA

Alternative Splicing Database (ASD) splice patterns (SP) for PRKACA Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11 ^ 12
SP1: - -
SP2: - - - -
SP3: -
SP4: - -
SP5:

Relevant External Links for PRKACA Gene

GeneLoc Exon Structure for
PRKACA

Expression for PRKACA Gene

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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PRKACA Gene

mRNA expression in normal human tissues for PRKACA Gene
mRNA expression by GTEx for PRKACA GenemRNA expression by BioGPS for PRKACA Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PRKACA Gene



Protein tissue co-expression partners for PRKACA Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PRKACA

SOURCE GeneReport for Unigene cluster for PRKACA Gene:

Hs.631630

mRNA Expression by UniProt/SwissProt for PRKACA Gene:

P17612-KAPCA_HUMAN
Tissue specificity: Isoform 1 is ubiquitous. Isoform 2 is sperm-specific and is enriched in pachytene spermatocytes but is not detected in round spermatids.

Evidence on tissue expression from TISSUES for PRKACA Gene

  • Nervous system(4.6)
  • Liver(4.5)
  • Eye(4.4)
  • Heart(2.8)
  • Muscle(2.8)
  • Adrenal gland(2.5)
  • Skin(2.3)
  • Kidney(2.2)
  • Spleen(2.1)
  • Blood(2.1)
  • Intestine(2.1)
  • Lung(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PRKACA Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cheek
  • chin
  • ear
  • eye
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • pituitary gland
  • skull
Thorax:
  • chest wall
  • clavicle
  • heart
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • adrenal gland
  • kidney
  • pancreas
Pelvis:
  • pelvis
  • uterus
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with PRKACA: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein differential expression in normal tissues for PRKACA Gene

Orthologs for PRKACA Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PRKACA Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia PRKACA 30 31
  • 99.8 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia PRKACA 30 31
  • 93.16 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia PRKACA 30 31
  • 92.76 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Prkaca 30 17 31
  • 91.26 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia -- 31
  • 91 (a)
 OneToMany
Rat
(Rattus norvegicus)
 Mammalia Prkaca 30
  • 90.98 (n)
Platypus
(Ornithorhynchus anatinus)
 Mammalia -- 31
  • 88 (a)
 OneToMany
Chicken
(Gallus gallus)
 Aves -- 31
  • 30 (a)
 ManyToMany
Lizard
(Anolis carolinensis)
 Reptilia -- 31
  • 74 (a)
 OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia prkaca 30
  • 77.97 (n)
Zebrafish
(Danio rerio)
 Actinopterygii prkacaa 31
  • 94 (a)
 ManyToMany
prkacab 30 31
  • 78.44 (n)
 ManyToMany
CABZ01071153.1 31
  • 10 (a)
 ManyToMany
Rainbow Trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.1053 30
Fruit Fly
(Drosophila melanogaster)
 Insecta Pka-C1 32
  • 82 (a)
Pka-C3 32
  • 56 (a)
CG12069 32
  • 50 (a)
Pka-C2 31 32
  • 44 (a)
 ManyToMany
Worm
(Caenorhabditis elegans)
 Secernentea F47F2.1a 32
  • 52 (a)
F47F2.1b 32
  • 51 (a)
kin-1 31
  • 46 (a)
 OneToMany
A. gosspyii yeast
(Eremothecium gossypii)
 Saccharomycetes AGOS_AFL090W 30
  • 55.8 (n)
Baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes TPK2 30 31
  • 53.38 (n)
 ManyToMany
TPK1 31 33
  • 41 (a)
 ManyToMany
TPK3 31
  • 39 (a)
 ManyToMany
K. Lactis Yeast
(Kluyveromyces lactis)
 Saccharomycetes KLLA0D03190g 30
  • 51.59 (n)
Fission Yeast
(Schizosaccharomyces pombe)
 Schizosaccharomycetes pka1 30
  • 52.31 (n)
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 22 (a)
 ManyToMany
Species where no ortholog for PRKACA was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PRKACA Gene

ENSEMBL:
Gene Tree for PRKACA (if available)
TreeFam:
Gene Tree for PRKACA (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PRKACA: view image

Paralogs for PRKACA Gene

Paralogs for PRKACA Gene

(127) SIMAP similar genes for PRKACA Gene using alignment to 4 proteins:

  • KAPCA_HUMAN
  • K7EMV1_HUMAN
  • K7ENJ5_HUMAN
  • K7ERP6_HUMAN
genes like me logo Genes that share paralogs with PRKACA: view

Variants for PRKACA Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PRKACA Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
708471 Benign: not provided 14,107,354(-) G/A SYNONYMOUS_VARIANT
731258 Benign: not provided 14,100,864(-) C/T SYNONYMOUS_VARIANT
733752 Likely Benign: not provided 14,106,894(-) G/A INTRON_VARIANT
737730 Likely Benign: not provided 14,097,597(-) A/C SYNONYMOUS_VARIANT
739600 Likely Benign: not provided 14,100,917(-) A/G INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for PRKACA Gene

Structural Variations from Database of Genomic Variants (DGV) for PRKACA Gene

Variant ID Type Subtype PubMed ID
dgv49n68 CNV loss 17160897
dgv6274n54 CNV loss 21841781
dgv6276n54 CNV gain 21841781
dgv6279n54 CNV loss 21841781
esv22154 CNV gain 19812545
esv2677290 CNV deletion 23128226
nsv1071913 CNV deletion 25765185
nsv1143911 CNV deletion 24896259
nsv578642 CNV gain 21841781
nsv578645 CNV loss 21841781
nsv578658 CNV loss 21841781
nsv578661 CNV loss 21841781
nsv578663 CNV loss 21841781
nsv828452 CNV loss 20364138
nsv828454 CNV gain 20364138
nsv828455 CNV gain 20364138
nsv833761 CNV loss 17160897
nsv953980 CNV deletion 24416366

Variation tolerance for PRKACA Gene

Residual Variation Intolerance Score: 17% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.24; 5.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PRKACA Gene

Human Gene Mutation Database (HGMD)
PRKACA
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PRKACA

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PRKACA Gene

Disorders for PRKACA Gene

MalaCards: The human disease database

(10) MalaCards diseases for PRKACA Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
pigmented nodular adrenocortical disease, primary, 4
  • ppnad4
fibrolamellar carcinoma
  • fibrolamellar hepatocellular carcinoma
primary pigmented nodular adrenocortical disease
  • pigmented nodular adrenocortical disease, primary, 2
mixed fibrolamellar hepatocellular carcinoma
acth-independent cushing syndrome
  • adrenal cushing syndrome
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

KAPCA_HUMAN
  • Primary pigmented nodular adrenocortical disease 4 (PPNAD4) [MIM:615830]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. {ECO:0000269 PubMed:24571724, ECO:0000269 PubMed:24700472, ECO:0000269 PubMed:24747643, ECO:0000269 PubMed:24855271}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for PRKACA

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PRKACA: view

No data available for Genatlas for PRKACA Gene

Publications for PRKACA Gene

  1. DNA binding of repressor nuclear factor-kappaB p50/p50 depends on phosphorylation of Ser337 by the protein kinase A catalytic subunit. (PMID: 15642694) Guan H … Ricciardi RP (The Journal of biological chemistry 2005) 3 4 23
  2. Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome. (PMID: 24855271) Sato Y … Ogawa S (Science (New York, N.Y.) 2014) 3 4
  3. Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors. (PMID: 24747643) Goh G … Lifton RP (Nature genetics 2014) 3 4
  4. Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome. (PMID: 24700472) Cao Y … Ning G (Science (New York, N.Y.) 2014) 3 4
  5. Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. (PMID: 24571724) Beuschlein F … Allolio B (The New England journal of medicine 2014) 3 4

ExternalLinks

View latest publications for PRKACA gene in Mastermind

Products for PRKACA Gene