Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  cAMP-dependent protein kinase catalytic subunit alpha  

UniProtKB / Swiss-Prot ID :  KAPCA_BOVIN

Gene Name (Synonyms) : 
PRKACA  

Species :  Bos taurus (Bovine). 

Subcellular Localization :  Cytoplasm. Nucleus. Cell membrane (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 inc 

Protein 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, 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 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+). TRPC1 activation by phosphorylation promotes Ca(2+) 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 redumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). 

Protein Sequence MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWENPAQNTAHLDQFERIKTLGTGSFGRVMLVKHMETGNHY...
Predicted Secondary Structure CCCCCCCCCCCCCCCCCHHHCCCCCHHHHHCCCCCCCCCCCCCEEEEEEEEECCCEEEEEEEECCCCCEE...
Protein Variant -
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
2N-myristoyl glycine.---MGNAAA
---CCCCCC
32.27UniProtKB
Link-
3Deamidated asparagine; partial.--MGNAAAA
--CCCCCCC
25.71UniProtKB
Link-
11PhosphoserineAKKGSEQES
CCCCCCCCC
45.01PhosphoELM
Link
11PhosphoserineAKKGSEQES
CCCCCCCCC
45.01Phosphositeplus
Link
15PhosphoserineSEQESVKEF
CCCCCCCHH
37.88Phosphositeplus
Link
49PhosphothreonineERIKTLGTG
EEEEEEEEC
28.22Phosphositeplus
Link
54PhosphoserineLGTGSFGRV
EEECCCEEE
25.10Phosphositeplus
Link
140PhosphoserineIGRFSEPHA
CCCCCHHHH
49.19PhosphoELM
Link
140PhosphoserineIGRFSEPHA
CCCCCHHHH
49.19Phosphositeplus
Link
198PhosphothreonineGRTWTLCGT
CCCEEEEEC
16.14Phosphositeplus
Link
198Phosphothreonine (PKA_group)GRTWTLCGT
CCCEEEEEC
16.14PhosphoELM
Link
198Phosphothreonine; by PDPK1.GRTWTLCGT
CCCEEEEEC
16.14UniProtKB
Link
213PhosphoserineEIILSKGYN
HHHCCCCCC
17.39Phosphositeplus
Link
260PhosphoserineVRFPSHFSS
CCCCCCCCH
34.16Phosphositeplus
Link
326PhosphoserinePGDTSNFDD
CCCCCCCCC
39.99Phosphositeplus
Link
339PhosphoserineEIRVSINEK
CCCCCCCCC
15.17Phosphositeplus
Link
339Phosphoserine (PKA_group)EIRVSINEK
CCCCCCCCC
15.17PhosphoELM
Link
339Phosphoserine.EIRVSINEK
CCCCCCCCC
15.17UniProtKB
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
There are no Protein-Protein Interactions.
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Disease Reference
Drug Reference
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Related Literatures of Post-Translational Modification
Deamidation
ReferencePubMed
"A conserved deamidation site at Asn 2 in the catalytic subunit ofmammalian cAMP-dependent protein kinase detected by capillary LC-MSand tandem mass spectrometry.";
Jedrzejewski P.T., Girod A., Tholey A., Koenig N., Thullner S.,Kinzel V., Bossemeyer D.;
Protein Sci. 7:457-469(1998).
Cited for: PROTEIN SEQUENCE OF 2-8, MUTAGENESIS OF ASN-3, AND DEAMIDATION ATASN-3.
"Intracellular distribution of mammalian protein kinase A catalyticsubunit 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).
Cited for: DEAMIDATION AT ASN-3, AND SUBCELLULAR LOCATION.
"The amino terminus of PKA catalytic subunit- a site for introductionof posttranslational heterogeneities by deamidation: D-Asp2 and D-isoAsp2 containing isozymes.";
Kinzel V., Koenig N., Pipkorn R., Bossemeyer D., Lehmann W.D.;
Protein Sci. 9:2269-2277(2000).
Cited for: DEAMIDATION AT ASN-3, AND CHARACTERIZATION OF ASP-3 ISOMERS.
Myristoylation
ReferencePubMed
"Complete amino acid sequence of the catalytic subunit of bovinecardiac muscle cyclic AMP-dependent protein kinase.";
Shoji S., Parmelee D.C., Wade R.D., Kumar S., Ericsson L.H.,Walsh K.A., Neurath H., Lonh G.L., Demaille J.G., Fischer E.H.,Titani K.;
Proc. Natl. Acad. Sci. U.S.A. 78:848-851(1981).
Cited for: PROTEIN SEQUENCE OF 2-351, MYRISTOYLATION AT GLY-2, ANDPHOSPHORYLATION AT THR-198 AND SER-339.
Phosphorylation
ReferencePubMed
"Complete amino acid sequence of the catalytic subunit of bovinecardiac muscle cyclic AMP-dependent protein kinase.";
Shoji S., Parmelee D.C., Wade R.D., Kumar S., Ericsson L.H.,Walsh K.A., Neurath H., Lonh G.L., Demaille J.G., Fischer E.H.,Titani K.;
Proc. Natl. Acad. Sci. U.S.A. 78:848-851(1981).
Cited for: PROTEIN SEQUENCE OF 2-351, MYRISTOYLATION AT GLY-2, ANDPHOSPHORYLATION AT THR-198 AND SER-339.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures