P36887 (KAPCA_PIG) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 114. History...
Names and origin
|Protein names||Recommended name:|
cAMP-dependent protein kinase catalytic subunit alpha
Short name=PKA C-alpha
|Organism||Sus scrofa (Pig) [Reference proteome]|
|Taxonomic identifier||9823 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus|
|Sequence length||351 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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, TRPC1 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 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+. TRPC1 activation by phosphorylation promotes Ca2+ influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (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. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. 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) By similarity. Phosphorylates APOBEC3G and AICDA By similarity.
ATP + a protein = ADP + a phosphoprotein.
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.
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. Activates 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 By similarity. Interacts with APOBEC3G and AICDA By similarity.
Cytoplasm By similarity. Cell membrane By similarity. Nucleus By similarity. Mitochondrion By similarity. 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. Ref.3
Ubiquitously expressed in mammalian tissues.
Asn-3 is deaminated to Asp in more than 25% of the proteins, giving rise to 2 major isoelectric variants, called CB and CA respectively (0.4 pH unit change). Deamidation proceeds via the so-called beta-aspartyl shift mechanism and yields either 'D-Asp-2' (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation occurs after the addition of myristate. The Asn-3 form reaches a significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form.
Autophosphorylated. Phosphorylation is enhanced by vitamin K2. Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity By similarity.
Contains 1 AGC-kinase C-terminal domain.
Contains 1 protein kinase domain.
|Cellular component||Cell membrane|
Direct protein sequencing
|Gene Ontology (GO)|
Inferred from electronic annotation. Source: UniProtKB-SubCellnucleus
Inferred from electronic annotation. Source: UniProtKB-SubCellplasma membrane
Inferred from electronic annotation. Source: UniProtKB-SubCell
Inferred from electronic annotation. Source: UniProtKB-KWcAMP-dependent protein kinase activity
Inferred from electronic annotation. Source: EC
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed Ref.2|
|Chain||2 – 351||350||cAMP-dependent protein kinase catalytic subunit alpha||PRO_0000086054|
|Domain||44 – 298||255||Protein kinase|
|Domain||299 – 351||53||AGC-kinase C-terminal|
|Nucleotide binding||50 – 58||9||ATP|
|Nucleotide binding||122 – 128||7||ATP By similarity|
|Nucleotide binding||169 – 172||4||ATP By similarity|
|Active site||167||1||Proton acceptor By similarity|
Amino acid modifications
|Modified residue||3||1||Deamidated asparagine; partial Ref.2 Ref.3|
|Modified residue||11||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||49||1||Phosphothreonine By similarity|
|Modified residue||140||1||Phosphoserine By similarity|
|Modified residue||196||1||Phosphothreonine By similarity|
|Modified residue||198||1||Phosphothreonine; by PDPK1 By similarity|
|Modified residue||202||1||Phosphothreonine By similarity|
|Modified residue||339||1||Phosphoserine By similarity|
|Lipidation||2||1||N-myristoyl glycine Ref.2|
Helix Strand Turn
|Beta strand||4 – 6||3|
|Helix||11 – 32||22|
|Helix||41 – 43||3|
|Beta strand||44 – 52||9|
|Beta strand||57 – 63||7|
|Turn||64 – 66||3|
|Beta strand||69 – 76||8|
|Helix||77 – 82||6|
|Helix||86 – 98||13|
|Beta strand||107 – 112||6|
|Beta strand||114 – 121||8|
|Helix||129 – 136||8|
|Helix||141 – 160||20|
|Helix||170 – 172||3|
|Beta strand||173 – 175||3|
|Beta strand||181 – 183||3|
|Helix||203 – 205||3|
|Helix||208 – 211||4|
|Helix||220 – 234||15|
|Helix||244 – 253||10|
|Helix||264 – 273||10|
|Turn||278 – 280||3|
|Turn||282 – 284||3|
|Turn||286 – 289||4|
|Helix||290 – 293||4|
|Helix||296 – 298||3|
|Helix||303 – 307||5|
|Turn||322 – 328||7|
|Helix||346 – 348||3|
|||"Multiple mRNA species code for the catalytic subunit of the cAMP-dependent protein kinase from LLC-PK1 cells. Evidence for two forms of the catalytic subunit."|
Adavani S.R., Schwarz M., Showers M.O., Maurer R.A., Hemmings B.A.
Eur. J. Biochem. 167:221-226(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 195-351.
|||"A conserved deamidation site at Asn 2 in the catalytic subunit of mammalian cAMP-dependent protein kinase detected by capillary LC-MS and tandem mass spectrometry."|
Jedrzejewski P.T., Girod A., Tholey A., Koenig N., Thullner S., Kinzel V., Bossemeyer D.
Protein Sci. 7:457-469(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-8, MYRISTOYLATION AT GLY-2, DEAMIDATION AT ASN-3.
|||"Intracellular distribution of mammalian protein kinase A catalytic subunit altered by conserved Asn2 deamidation."|
Pepperkok R., Hotz-Wagenblatt A., Koenig N., Girod A., Bossemeyer D., Kinzel V.
J. Cell Biol. 148:715-726(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DEAMIDATION AT ASN-3, SUBCELLULAR LOCATION.
|||"Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor."|
Zheng J., Knighton D.R., ten Eyck L.F., Karlsson R., Xuong N.-H., Taylor S.S., Sowadski J.M.
Biochemistry 32:2154-2161(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH PKIA.
|+||Additional computationally mapped references.|
|X07617 mRNA. Translation: CAA30470.1.|
3D structure databases
|SMR||P36887. Positions 2-351. |
Protein-protein interaction databases
|IntAct||P36887. 1 interaction.|
Protocols and materials databases
Family and domain databases
|InterPro||IPR000961. AGC-kinase_C. |
|Pfam||PF00069. Pkinase. 1 hit. |
|SMART||SM00133. S_TK_X. 1 hit. |
SM00220. S_TKc. 1 hit.
|SUPFAM||SSF56112. Kinase_like. 1 hit. |
|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.
|Accession||Primary (citable) accession number: P36887|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|