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P27791 (KAPCA_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-dependent protein kinase catalytic subunit alpha

Short name=PKA C-alpha
EC=2.7.11.11
Gene names
Name:Prkaca
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length351 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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+. 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 By similarity. 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 By similarity. Ref.4

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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.

Subunit 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 By similarity. Interacts with APOBEC3G and AICDA By similarity. Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly. Ref.5 Ref.6

Subcellular location

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.

Isoform 2: Cell projectionciliumflagellum By similarity. Note: Expressed in the midpiece region of the sperm flagellum By similarity.

Tissue specificity

Ubiquitously expressed. Isoform 2 is round spermatid specific. Ref.1 Ref.3

Developmental stage

In spermatids, isoform 1 is expressed until spermatids become elutriated, whereafter isoform 2 is expressed. Ref.3

Post-translational modification

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. Ref.6

Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficienncy By similarity. Ref.6

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Cilium
Cytoplasm
Flagellum
Membrane
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
cAMP
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMLipoprotein
Myristate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of meiotic cell cycle

Inferred from direct assay PubMed 16816331. Source: RGD

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 15546918. Source: RGD

protein phosphorylation

Inferred from direct assay PubMed 11907174PubMed 16816331. Source: RGD

regulation of cellular respiration

Inferred from direct assay PubMed 12562968. Source: RGD

regulation of synaptic transmission, glutamatergic

Inferred from direct assay PubMed 12562968. Source: RGD

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 12086672. Source: RGD

cAMP-dependent protein kinase complex

Inferred from direct assay PubMed 11907174PubMed 16816331. Source: RGD

cilium

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from direct assay PubMed 12086672PubMed 14605213PubMed 18550536. Source: RGD

cytosol

Traceable author statement. Source: Reactome

membrane

Inferred from direct assay PubMed 12086672. Source: RGD

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuron projection

Inferred from direct assay PubMed 14605213. Source: RGD

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 12086672PubMed 14605213. Source: RGD

perinuclear region of cytoplasm

Inferred from direct assay PubMed 18550536. Source: RGD

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

protein complex

Inferred from direct assay PubMed 12672265. Source: RGD

sperm midpiece

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Rab GTPase binding

Inferred from physical interaction Ref.5. Source: UniProtKB

cAMP-dependent protein kinase activity

Inferred from direct assay PubMed 11907174PubMed 15546918PubMed 16816331. Source: RGD

protein binding

Inferred from physical interaction PubMed 18381233. Source: RGD

protein complex binding

Inferred from physical interaction PubMed 12672265. Source: RGD

protein kinase A regulatory subunit binding

Inferred by curator PubMed 16816331. Source: RGD

protein kinase binding

Inferred from physical interaction PubMed 11035810. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P27791-1)

Also known as: C-alpha-1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P27791-2)

Also known as: Cs;

The sequence of this isoform differs from the canonical sequence as follows:
     2-15: GNAAAAKKGSEQES → MASNSND

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 351350cAMP-dependent protein kinase catalytic subunit alpha
PRO_0000086055

Regions

Domain44 – 298255Protein kinase
Domain299 – 35153AGC-kinase C-terminal
Nucleotide binding50 – 589ATP By similarity
Nucleotide binding122 – 1287ATP By similarity
Nucleotide binding169 – 1724ATP By similarity

Sites

Active site1671Proton acceptor By similarity
Binding site731ATP By similarity

Amino acid modifications

Modified residue31Deamidated asparagine; partial Ref.2
Modified residue111Phosphoserine; by autocatalysis By similarity
Modified residue491Phosphothreonine By similarity
Modified residue1401Phosphoserine Ref.6
Modified residue1961Phosphothreonine By similarity
Modified residue1981Phosphothreonine; by PDPK1 Ref.6
Modified residue2021Phosphothreonine By similarity
Modified residue3311Phosphotyrosine By similarity
Modified residue3391Phosphoserine By similarity
Lipidation21N-myristoyl glycine Ref.2

Natural variations

Alternative sequence2 – 1514GNAAA…SEQES → MASNSND in isoform 2.
VSP_013277

Secondary structure

................................................ 351
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (C-alpha-1) [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 4763ACD074AB2384

FASTA35140,620
        10         20         30         40         50         60 
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WEDPSQNTAQ LDHFDRIKTL GTGSFGRVML 

        70         80         90        100        110        120 
VKHKESGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV 

       130        140        150        160        170        180 
MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY 

       190        200        210        220        230        240 
IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF 

       250        260        270        280        290        300 
ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT 

       310        320        330        340        350 
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFTE F 

« Hide

Isoform 2 (Cs) [UniParc].

Checksum: 2FCD274075C7C08B
Show »

FASTA34440,010

References

[1]"Rat C alpha catalytic subunit of the cAMP-dependent protein kinase: cDNA sequence and evidence that it is the only isoform expressed in myoblasts."
Wiemann S., Voss H., Kinzel V., Pyerin W.
Biochim. Biophys. Acta 1089:254-256(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"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 (ISOFORM 1), MYRISTOYLATION AT GLY-2, DEAMIDATION AT ASN-3.
[3]"Phosphorylation of rat spermatidal protein TP2 by sperm-specific protein kinase A and modulation of its transport into the haploid nucleus."
Ullas K.S., Rao M.R.S.
J. Biol. Chem. 278:52673-52680(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-313 (ISOFORM 2), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: Wistar.
[4]"Protein kinase A in the pedunculopontine tegmental nucleus of rat contributes to regulation of rapid eye movement sleep."
Datta S., Desarnaud F.
J. Neurosci. 30:12263-12273(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RAPID EYE MOVEMENT SLEEP.
[5]"RAB13 regulates Sertoli cell permeability barrier dynamics through protein kinase A."
Su W., Liu X.
J. Mol. Endocrinol. 50:305-318(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB13.
[6]"Structure and allostery of the PKA RIIbeta tetrameric holoenzyme."
Zhang P., Smith-Nguyen E.V., Keshwani M.M., Deal M.S., Kornev A.P., Taylor S.S.
Science 335:712-716(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-351 IN COMPLEX WITH MOUSE PRKAR2B, SUBUNIT, PHOSPHORYLATION AT SER-140 AND THR-198.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X57986 mRNA. Translation: CAA41052.1.
AY375243 mRNA. Translation: AAQ81631.1.
PIROKRT2C. S16240.
UniGeneRn.20.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3TNPX-ray2.30C/F2-351[»]
3TNQX-ray3.10B2-351[»]
ProteinModelPortalP27791.
SMRP27791. Positions 13-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP27791. 3 interactions.
MINTMINT-4564372.

Chemistry

BindingDBP27791.
ChEMBLCHEMBL3390.

PTM databases

PhosphoSiteP27791.

Proteomic databases

PaxDbP27791.
PRIDEP27791.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

RGD3389. Prkaca.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
PhylomeDBP27791.

Enzyme and pathway databases

BRENDA2.7.11.11. 5301.
ReactomeREACT_205051. Metabolism.
REACT_206767. Disease.
REACT_212996. Signal Transduction.
REACT_227097. Immune System.

Gene expression databases

GenevestigatorP27791.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameKAPCA_RAT
AccessionPrimary (citable) accession number: P27791
Secondary accession number(s): Q6UA68
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references