cAMP-dependent protein kinase catalytic subunit alpha

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P36887 (KAPCA_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 114. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
cAMP-dependent protein kinase catalytic subunit alpha
Short name=PKA C-alpha
EC=2.7.11.11

Gene names

Name:

PRKACA

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

Protein attributes

Sequence length	351 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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, 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.
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. 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.
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. Ref.3
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-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.
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 component	Cell membrane Cytoplasm Membrane Mitochondrion Nucleus
Ligand	ATP-binding Nucleotide-binding cAMP
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cAMP-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

Molecule processing

Initiator methionine

Removed Ref.2

Chain

2 – 351

350

cAMP-dependent protein kinase catalytic subunit alpha

PRO_0000086054

Regions

Domain

44 – 298

255

Protein kinase

Domain

299 – 351

AGC-kinase C-terminal

Nucleotide binding

50 – 58

ATP

Nucleotide binding

122 – 128

ATP By similarity

Nucleotide binding

169 – 172

ATP By similarity

Sites

Active site

167

Proton acceptor By similarity

Binding site

ATP

Amino acid modifications

Modified residue

Deamidated asparagine; partial Ref.2 Ref.3

Modified residue

Phosphoserine; by autocatalysis By similarity

Modified residue

Phosphothreonine By similarity

Modified residue

140

Phosphoserine By similarity

Modified residue

196

Phosphothreonine By similarity

Modified residue

198

Phosphothreonine; by PDPK1 By similarity

Modified residue

202

Phosphothreonine By similarity

Modified residue

339

Phosphoserine By similarity

Lipidation

N-myristoyl glycine Ref.2

Secondary structure

351

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P36887 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: B65EC7C42DD56DE5
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FASTA

351

40,617

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

        70         80         90        100        110        120 
VKHKETGNHF AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEYS 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

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References

[1]	"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.
[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, MYRISTOYLATION AT GLY-2, DEAMIDATION AT ASN-3.
[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.
[4]	"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X07617 mRNA. Translation: CAA30470.1.

PIR

S00086.

UniGene

Ssc.13872.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CDK	X-ray	2.00	A/B	2-351	[»]
1CMK	X-ray	2.90	E	2-351	[»]
1CTP	X-ray	2.90	E	2-351	[»]

ProteinModelPortal

P36887.

SMR

P36887. Positions 2-351.

ModBase

Search...

Protein-protein interaction databases

IntAct

P36887. 1 interaction.

Proteomic databases

PaxDb

P36887.

PRIDE

P36887.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233033.

HOVERGEN

HBG108317.

OrthoDB

EOG4RXZ0C.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

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.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P36887.

Entry information

Entry name

KAPCA_PIG

Accession

Primary (citable) accession number: P36887

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 114 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Phylogenomic databases

Family and domain databases

Other

Entry information

Relevant documents