InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKACA

Summary

InnateDB Protein

IDBP-32931.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKACA

Protein Name

protein kinase, cAMP-dependent, catalytic, alpha

Synonyms

PKACA;

Species

Homo sapiens

Ensembl Protein

ENSP00000309591

InnateDB Gene

IDBG-32929 (PRKACA)

Protein Structure

UniProt Annotation

Function

Phosphorylates a large number of substrates in the cytoplasm and the nucleus. 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. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. 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. Prevents the antiproliferative and anti-invasive effects of alpha- difluoromethylornithine in breast cancer cells when activated. 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+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT). Phosphorylates APOBEC3G and AICDA. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000269PubMed:15642694, ECO:0000269PubMed:15905176, ECO:0000269PubMed:16387847, ECO:0000269PubMed:17333334, ECO:0000269PubMed:17565987, ECO:0000269PubMed:17693412, ECO:0000269PubMed:18836454, ECO:0000269PubMed:19949837, ECO:0000269PubMed:20356841, ECO:0000269PubMed:21423175, ECO:0000269PubMed:21514275, ECO:0000269PubMed:21812984}.

Subcellular Localization

Cytoplasm. Cell membrane. Nucleus {ECO:0000250}. Mitochondrion {ECO:0000250}. 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). {ECO:0000250}.Isoform 2: Cell projection, cilium, flagellum. Note=Expressed in the midpiece region of the sperm flagellum.

Disease Associations

Tissue Specificity

Isoform 1 is ubiquitous. Isoform 2 is sperm- specific and is enriched in pachytene spermatocytes but is not detected in round spermatids. {ECO:0000269PubMed:10906071, ECO:0000269PubMed:21812984}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 162 experimentally validated interaction(s) in this database.
They are also associated with 28 interaction(s) predicted by orthology.

Experimentally validated
Total	162 [view]
Protein-Protein	160 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	28 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004691	cAMP-dependent protein kinase activity
GO:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0034237	protein kinase A regulatory subunit binding

Biological Process

GO:0000086	G2/M transition of mitotic cell cycle
GO:0000278	mitotic cell cycle
GO:0001707	mesoderm formation
GO:0001843	neural tube closure
GO:0002027	regulation of heart rate
GO:0005975	carbohydrate metabolic process
GO:0006006	glucose metabolic process
GO:0006094	gluconeogenesis
GO:0006112	energy reserve metabolic process
GO:0006468	protein phosphorylation
GO:0006833	water transport
GO:0007165	signal transduction
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007202	activation of phospholipase C activity
GO:0007596	blood coagulation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010881	regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0019433	triglyceride catabolic process
GO:0034199	activation of protein kinase A activity
GO:0035556	intracellular signal transduction
GO:0035584	calcium-mediated signaling using intracellular calcium source
GO:0043393	regulation of protein binding
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response (InnateDB)
GO:0045667	regulation of osteoblast differentiation
GO:0046777	protein autophosphorylation
GO:0046827	positive regulation of protein export from nucleus
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048240	sperm capacitation
GO:0050796	regulation of insulin secretion
GO:0050804	regulation of synaptic transmission
GO:0051480	cytosolic calcium ion homeostasis
GO:0055085	transmembrane transport
GO:0055117	regulation of cardiac muscle contraction
GO:0060314	regulation of ryanodine-sensitive calcium-release channel activity
GO:0061136	regulation of proteasomal protein catabolic process
GO:0070613	regulation of protein processing
GO:0071158	positive regulation of cell cycle arrest
GO:0071333	cellular response to glucose stimulus
GO:0071374	cellular response to parathyroid hormone stimulus
GO:0071377	cellular response to glucagon stimulus
GO:0071872	cellular response to epinephrine stimulus
GO:0086064	cell communication by electrical coupling involved in cardiac conduction
GO:1901621	negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning
GO:2000810	regulation of tight junction assembly

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005813	centrosome
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005929	cilium
GO:0005952	cAMP-dependent protein kinase complex
GO:0016020	membrane
GO:0031588	AMP-activated protein kinase complex
GO:0031594	neuromuscular junction
GO:0034704	calcium channel complex
GO:0070062	extracellular vesicular exosome
GO:0097225	sperm midpiece
GO:0097546	ciliary base

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00133
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt