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_MOUSE

Gene Name (Synonyms) : 
Prkaca, Pkaca  

Species :  Mus musculus (Mouse). 

Subcellular Localization :  Cytoplasm. Cell membrane (By similarity). Nucleus (By similarity). Mitochondrion. Note=Translocates into the nucleus (monomeric catalytic subunit) (By similarity). The inactive holoenzyme is found in the cytoplasm. Distributed throughout the cytoplasm in 

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). 

Protein Sequence MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWETPSQNTAQLDQFDRIKTLGTGSFGRVMLVKHKESGNHY...
Predicted Secondary Structure CCCCCCCCCCCCCCCCHHHHHHHHHHHHHHHCCCCCCCCCCCCEEEEEEEEECCCEEEEEEEECCCCCEE...
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
45.01Phosphositeplus
Link
11Phosphoserine; by autocatalysis.AKKGSEQES
CCCCCCCCC
45.01UniProtKB
Link
35PhosphoserineWETPSQNTA
HCCCCCCCC
43.41PhosphoELM
Link
35PhosphoserineWETPSQNTA
HCCCCCCCC
43.41Phosphositeplus
Link
35Phosphoserine.WETPSQNTA
HCCCCCCCC
43.41UniProtKB
Link
110PhosphoserineKLEFSFKDN
EEEEEEEEC
23.24Phosphositeplus
Link
140PhosphoserineIGRFSEPHA
CCCCCHHHH
49.19Phosphositeplus
Link
140Phosphoserine.IGRFSEPHA
CCCCCHHHH
49.19UniProtKB
Link
184PhosphothreonineYIQVTDFGF
CEEEEECCE
14.83Phosphositeplus
Link
196PhosphothreonineVKGRTWTLC
ECCCCEEEE
31.32PhosphoELM
Link
196PhosphothreonineVKGRTWTLC
ECCCCEEEE
31.32Phosphositeplus
Link
196PhosphothreonineVKGRTWTLC
ECCCCEEEE
31.32SysPTM
Link
196Phosphothreonine.VKGRTWTLC
ECCCCEEEE
31.32UniProtKB
Link
198PhosphothreonineGRTWTLCGT
CCCEEEEEC
16.14Phosphositeplus
Link
198Phosphothreonine (PDK-1;PKA_alpha)GRTWTLCGT
CCCEEEEEC
16.14PhosphoELM
Link
198Phosphothreonine; by PDPK1.GRTWTLCGT
CCCEEEEEC
16.14UniProtKB
Link
202PhosphothreonineTLCGTPEYL
EEEECHHHC
16.38Phosphositeplus
Link
331PhosphotyrosineNFDDYEEEE
CCCCCCCCC
27.38Phosphositeplus
Link
339PhosphoserineEIRVSINEK
CCCCCCCCC
15.17Phosphositeplus
Link
339Phosphoserine (PKA_alpha)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
"Influence of myristoylation, phosphorylation, and deamidation on thestructural behavior of the N-terminus of the catalytic subunit ofcAMP-dependent protein kinase.";
Tholey A., Pipkorn R., Bossemeyer D., Kinzel V., Reed J.;
Biochemistry 40:225-231(2001).
Cited for: MYRISTOYLATION AT GLY-2, PHOSPHORYLATION AT SER-11, AND DEAMIDATION ATASN-3.
Myristoylation
ReferencePubMed
"Influence of myristoylation, phosphorylation, and deamidation on thestructural behavior of the N-terminus of the catalytic subunit ofcAMP-dependent protein kinase.";
Tholey A., Pipkorn R., Bossemeyer D., Kinzel V., Reed J.;
Biochemistry 40:225-231(2001).
Cited for: MYRISTOYLATION AT GLY-2, PHOSPHORYLATION AT SER-11, AND DEAMIDATION ATASN-3.
Phosphorylation
ReferencePubMed
"Protein phosphorylation and expression profiling by Yin-yangmultidimensional liquid chromatography (Yin-yang MDLC) massspectrometry.";
Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R.;
J. Proteome Res. 6:250-262(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND MASSSPECTROMETRY.
"Phosphorylation and activation of cAMP-dependent protein kinase byphosphoinositide-dependent protein kinase.";
Cheng X., Ma Y., Moore M., Hemmings B.A., Taylor S.S.;
Proc. Natl. Acad. Sci. U.S.A. 95:9849-9854(1998).
Cited for: PHOSPHORYLATION AT THR-198 BY PDPK1.
"Influence of myristoylation, phosphorylation, and deamidation on thestructural behavior of the N-terminus of the catalytic subunit ofcAMP-dependent protein kinase.";
Tholey A., Pipkorn R., Bossemeyer D., Kinzel V., Reed J.;
Biochemistry 40:225-231(2001).
Cited for: MYRISTOYLATION AT GLY-2, PHOSPHORYLATION AT SER-11, AND DEAMIDATION ATASN-3.
"Phosphoproteomic analysis of the developing mouse brain.";
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
Mol. Cell. Proteomics 3:1093-1101(2004).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-196, AND MASSSPECTROMETRY.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures