UniProtKB - P36887 (KAPCA_PIG)
cAMP-dependent protein kinase catalytic subunit alpha
PRKACA
Functioni
Phosphorylates a large number of substrates in the cytoplasm and the nucleus (By similarity).
Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (By similarity).
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. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (By similarity).
Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity).
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. 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 (By similarity).
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) (By similarity).
Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (By similarity).
By similarityCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 73 | ATP | 1 | |
Active sitei | 167 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 50 – 58 | ATP | 9 | |
Nucleotide bindingi | 122 – 128 | ATPPROSITE-ProRule annotation | 7 | |
Nucleotide bindingi | 169 – 172 | ATPPROSITE-ProRule annotation | 4 |
GO - Molecular functioni
- AMP-activated protein kinase activity Source: UniProtKB-EC
- ATP binding Source: UniProtKB-KW
- cAMP-dependent protein kinase activity Source: AgBase
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
GO - Biological processi
- cellular response to heat Source: UniProtKB
- negative regulation of meiotic cell cycle process involved in oocyte maturation Source: AgBase
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, cAMP, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | Recommended name: cAMP-dependent protein kinase catalytic subunit alpha (EC:2.7.11.11)Short name: PKA C-alpha |
Gene namesi | Name:PRKACA |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Plasma membrane
- Cell membrane By similarity
Nucleus
- Nucleus By similarity
Other locations
- Membrane By similarity; Lipid-anchor By similarity
- flagellum By similarity
- acrosome 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). Expressed in the midpiece region of the sperm flagellum (By similarity). Colocalizes with MROH2B and TCP11 on the acrosome and tail regions in round spermatids and spermatozoa regardless of the capacitation status of the sperm (By similarity). Colocalizes with HSF1 in nuclear stress bodies (nSBs) upon heat shock (By similarity).By similarity
Mitochondrion
- mitochondrion Source: UniProtKB-SubCell
Nucleus
- germinal vesicle Source: AgBase
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- acrosomal vesicle Source: UniProtKB
- cytoplasm Source: AgBase
- perinuclear region of cytoplasm Source: UniProtKB
- sperm flagellum Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cell projection, Cilium, Cytoplasm, Cytoplasmic vesicle, Flagellum, Membrane, Mitochondrion, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000086054 | 2 – 351 | cAMP-dependent protein kinase catalytic subunit alphaAdd BLAST | 350 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycine1 Publication | 1 | |
Modified residuei | 3 | Deamidated asparagine; partial2 Publications | 1 | |
Modified residuei | 11 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 49 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 140 | PhosphoserineBy similarity | 1 | |
Modified residuei | 196 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 198 | Phosphothreonine; by PDPK1By similarity | 1 | |
Modified residuei | 331 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 339 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Lipoprotein, Myristate, PhosphoproteinProteomic databases
PaxDbi | P36887 |
PeptideAtlasi | P36887 |
PRIDEi | P36887 |
PTM databases
iPTMneti | P36887 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
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).
Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly (By similarity).
Found in a complex at least composed of MROH2B, PRKACA and TCP11 (By similarity).
Interacts with MROH2B (By similarity).
Interacts with TCP11 (By similarity).
Interacts with HSF1 (By similarity).
By similarityProtein-protein interaction databases
IntActi | P36887, 1 interactor |
STRINGi | 9823.ENSSSCP00000014641 |
Structurei
Secondary structure
3D structure databases
SMRi | P36887 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P36887 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 44 – 298 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 255 | |
Domaini | 299 – 351 | AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST | 53 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0616, Eukaryota |
InParanoidi | P36887 |
Family and domain databases
CDDi | cd14209, STKc_PKA, 1 hit |
IDEALi | IID50158 |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR044109, STKc_PKA |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in 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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WENPAQNTAH LDQFERIKTL
60 70 80 90 100
GTGSFGRVML VKHKETGNHF AMKILDKQKV VKLKQIEHTL NEKRILQAVN
110 120 130 140 150
FPFLVKLEYS FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ
160 170 180 190 200
IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY IQVTDFGFAK RVKGRTWTLC
210 220 230 240 250
GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK
260 270 280 290 300
IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT
310 320 330 340 350
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFSE
F
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X07617 mRNA Translation: CAA30470.1 |
PIRi | S00086 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X07617 mRNA Translation: CAA30470.1 |
PIRi | S00086 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
SMRi | P36887 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | P36887, 1 interactor |
STRINGi | 9823.ENSSSCP00000014641 |
PTM databases
iPTMneti | P36887 |
Proteomic databases
PaxDbi | P36887 |
PeptideAtlasi | P36887 |
PRIDEi | P36887 |
Phylogenomic databases
eggNOGi | KOG0616, Eukaryota |
InParanoidi | P36887 |
Miscellaneous databases
EvolutionaryTracei | P36887 |
Family and domain databases
CDDi | cd14209, STKc_PKA, 1 hit |
IDEALi | IID50158 |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR044109, STKc_PKA |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | KAPCA_PIG | |
Accessioni | P36887Primary (citable) accession number: P36887 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 23, 2022 | |
This is version 161 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families