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P00517 (KAPCA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. 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·Interactions·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
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

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. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) By similarity. Phosphorylates APOBEC3G and AICDA By similarity.

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. 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. Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly. Ref.8

Subcellular location

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 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.6

Tissue specificity

Ubiquitously expressed in mammalian tissues.

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-3' (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.2

Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficienncy By similarity. Ref.2

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
Cytoplasm
Membrane
Mitochondrion
Nucleus
   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_processcellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to parathyroid hormone stimulus

Inferred from electronic annotation. Source: Ensembl

mesoderm formation

Inferred from sequence or structural similarity. Source: AgBase

peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein export from nucleus

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from sequence or structural similarity. Source: AgBase

regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of proteasomal protein catabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic transmission

Inferred from electronic annotation. Source: Ensembl

regulation of tight junction assembly

Inferred from electronic annotation. Source: Ensembl

sperm capacitation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentAMP-activated protein kinase complex

Inferred from electronic annotation. Source: Ensembl

centrosome

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from sequence or structural similarity. Source: AgBase

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuromuscular junction

Inferred from sequence or structural similarity. Source: AgBase

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

sperm midpiece

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cAMP-dependent protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 19765080. Source: IntAct

protein kinase activity

Inferred from sequence or structural similarity. Source: AgBase

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Kcnj3P632516EBI-7251007,EBI-7250981From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2 Ref.3 Ref.5
Chain2 – 351350cAMP-dependent protein kinase catalytic subunit alpha
PRO_0000086049

Regions

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

Sites

Active site1671Proton acceptor Ref.4
Binding site731ATP

Amino acid modifications

Modified residue31Deamidated asparagine; partial Ref.5 Ref.6 Ref.7
Modified residue111Phosphoserine; by autocatalysis By similarity
Modified residue491Phosphothreonine By similarity
Modified residue1401Phosphoserine By similarity
Modified residue1961Phosphothreonine By similarity
Modified residue1981Phosphothreonine; by PDPK1 Ref.2
Modified residue2021Phosphothreonine By similarity
Modified residue3311Phosphotyrosine By similarity
Modified residue3391Phosphoserine Ref.2
Lipidation21N-myristoyl glycine Ref.2

Experimental info

Mutagenesis31N → D: No myristoylation. Ref.5
Sequence conflict2021T → N AA sequence Ref.4
Sequence conflict2041E → Q AA sequence Ref.4
Sequence conflict2061L → S AA sequence Ref.4
Sequence conflict2871N → D AA sequence Ref.2
Sequence conflict2871N → D AA sequence Ref.3

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P00517 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 59DDD227D2DEEE5D

FASTA35140,620
        10         20         30         40         50         60 
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WENPAQNTAH LDQFERIKTL GTGSFGRVML 

        70         80         90        100        110        120 
VKHMETGNHY 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 NEKCGKEFSE F 

« Hide

References

[1]"Cloning of the C alpha catalytic subunit of the bovine cAMP-dependent protein kinase."
Wiemann S., Kinzel V., Pyerin W.
Biochim. Biophys. Acta 1171:93-96(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[2]"Complete amino acid sequence of the catalytic subunit of bovine cardiac 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) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-351, MYRISTOYLATION AT GLY-2, PHOSPHORYLATION AT THR-198 AND SER-339.
[3]"Amino acid sequence of the catalytic subunit of bovine type II adenosine cyclic 3',5'-phosphate dependent protein kinase."
Shoji S., Ericsson L.H., Walsh K.A., Fischer E.H., Titani K.
Biochemistry 22:3702-3709(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-351.
[4]"Modification of the catalytic subunit of bovine heart cAMP-dependent protein kinase with affinity labels related to peptide substrates."
Bramson H.N., Thomas N., Matsueda R., Nelson N.C., Taylor S.S., Kaiser E.T.
J. Biol. Chem. 257:10575-10581(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 196-214, ACTIVE SITE.
[5]"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, MUTAGENESIS OF ASN-3, DEAMIDATION AT ASN-3.
[6]"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.
[7]"The amino terminus of PKA catalytic subunit- a site for introduction of 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) [PubMed] [Europe PMC] [Abstract]
Cited for: DEAMIDATION AT ASN-3, CHARACTERIZATION OF ASP-3 ISOMERS.
[8]"Rab13 regulates PKA signaling during tight junction assembly."
Koehler K., Louvard D., Zahraoui A.
J. Cell Biol. 165:175-180(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB13.
[9]"Crystal structures of catalytic subunit of cAMP-dependent protein kinase in complex with isoquinolinesulfonyl protein kinase inhibitors H7, H8, and H89. Structural implications for selectivity."
Engh R.A., Girod A., Kinzel V., Huber R., Bossemeyer D.
J. Biol. Chem. 271:26157-26164(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[10]"Staurosporine-induced conformational changes of cAMP-dependent protein kinase catalytic subunit explain inhibitory potential."
Prade L., Engh R.A., Girod A., Kinzel V., Huber R., Bossemeyer D.
Structure 5:1627-1637(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X67154 mRNA. Translation: CAA47627.1.
PIROKBO2C. S27159.
RefSeqNP_777009.1. NM_174584.2.
UniGeneBt.4420.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KMUmodel-C9-351[»]
1KMWmodel-C9-351[»]
1Q24X-ray2.60A2-351[»]
1Q61X-ray2.10A2-351[»]
1Q62X-ray2.30A2-351[»]
1Q8TX-ray2.00A2-351[»]
1Q8UX-ray1.90A2-351[»]
1Q8WX-ray2.20A2-351[»]
1SMHX-ray2.04A2-351[»]
1STCX-ray2.30E2-351[»]
1SVEX-ray2.49A2-351[»]
1SVGX-ray2.02A2-351[»]
1SVHX-ray2.30A2-351[»]
1SZMX-ray2.50A/B2-351[»]
1VEBX-ray2.89A2-351[»]
1XH4X-ray2.45A2-351[»]
1XH5X-ray2.05A2-351[»]
1XH6X-ray1.90A2-351[»]
1XH7X-ray2.47A2-351[»]
1XH8X-ray1.60A2-351[»]
1XH9X-ray1.64A2-351[»]
1XHAX-ray2.46A2-351[»]
1YDRX-ray2.20E2-351[»]
1YDSX-ray2.20E2-351[»]
1YDTX-ray2.30E2-351[»]
2C1AX-ray1.95A2-351[»]
2C1BX-ray2.00A2-351[»]
2F7EX-ray2.00E1-351[»]
2F7XX-ray1.90E1-351[»]
2F7ZX-ray3.00E1-351[»]
2GFCX-ray1.87A2-351[»]
2GNFX-ray2.28A2-351[»]
2GNGX-ray1.87A2-351[»]
2GNHX-ray2.05A2-351[»]
2GNIX-ray2.27A2-351[»]
2GNJX-ray2.28A2-351[»]
2GNLX-ray2.60A2-351[»]
2JDSX-ray2.00A2-351[»]
2JDTX-ray2.15A2-351[»]
2JDVX-ray2.08A2-351[»]
2OH0X-ray2.20E1-351[»]
2OJFX-ray2.10E1-351[»]
2UVXX-ray2.00A2-351[»]
2UVYX-ray1.95A2-351[»]
2UVZX-ray1.94A2-351[»]
2UW0X-ray2.00A2-351[»]
2UW3X-ray2.19A2-351[»]
2UW4X-ray2.00A2-351[»]
2UW5X-ray2.14A2-351[»]
2UW6X-ray2.23A2-351[»]
2UW7X-ray2.10A2-351[»]
2UW8X-ray2.00A2-351[»]
2UZTX-ray2.10A16-351[»]
2UZUX-ray2.40E16-351[»]
2UZVX-ray2.50A16-351[»]
2UZWX-ray2.20E16-351[»]
2VNWX-ray2.09A1-351[»]
2VNYX-ray1.96A1-351[»]
2VO0X-ray1.94A1-351[»]
2VO3X-ray1.98A1-351[»]
2VO6X-ray1.97A1-351[»]
2VO7X-ray1.98A1-351[»]
3AG9X-ray2.00A/B1-351[»]
3BWJX-ray2.30A2-351[»]
3DNDX-ray2.26A2-351[»]
3DNEX-ray2.00A2-351[»]
3E8CX-ray2.20A/B/C/D/E/F2-351[»]
3E8EX-ray2.00A/B/E/I/L/P2-351[»]
3KKVX-ray1.80A2-351[»]
3ZO1X-ray2.00A1-351[»]
3ZO2X-ray1.98A1-351[»]
3ZO3X-ray2.10A1-351[»]
3ZO4X-ray1.65A1-351[»]
4AXAX-ray1.90A1-351[»]
4C33X-ray1.70A1-351[»]
4C34X-ray1.78A1-351[»]
4C35X-ray2.19A1-351[»]
4C36X-ray1.98A1-351[»]
4C37X-ray1.70A1-351[»]
4C38X-ray1.58A1-351[»]
4IE9X-ray1.92A1-351[»]
4IJ9X-ray2.55A2-351[»]
ProteinModelPortalP00517.
SMRP00517. Positions 8-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid159584. 7 interactions.
IntActP00517. 4 interactions.
STRING9913.ENSBTAP00000008727.

Chemistry

BindingDBP00517.
ChEMBLCHEMBL2111446.

Proteomic databases

PaxDbP00517.
PRIDEP00517.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000008727; ENSBTAP00000008727; ENSBTAG00000006642.
GeneID282322.
KEGGbta:282322.

Organism-specific databases

CTD5566.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074358.
HOVERGENHBG108317.
InParanoidP00517.
KOK04345.
OMAGQHFAMK.
OrthoDBEOG7VX8WD.
TreeFamTF313399.

Enzyme and pathway databases

BRENDA2.7.11.11. 908.

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...

Other

EvolutionaryTraceP00517.
NextBio20806119.
PMAP-CutDBP00517.
PROP00517.

Entry information

Entry nameKAPCA_BOVIN
AccessionPrimary (citable) accession number: P00517
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 150 of the entry and version 3 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