LipidDB ID

LipidDB-10090-00844

Entry Name

UniProt Accession

P05132; Q9JID0;

Theoretical PI

8.84

Molecular Weight

40570.62

Genbank Protein ID

AAA39937.1; AAA39937.1; AAA39937.1; AAA39937.1; AAA39937.1; AAA39937.1; AAA39937.1; AAA39937.1; AAA39937.1; AAA39937.1; AAA39936.1; AAH03238.1; AAH54834.1; AAF76425.1;

Genbank Nucleotide ID

M19960; M18240; M18241; M19953; M19954; M19955; M19956; M19957; M19958; M19959; M12303; BC003238; BC054834; AF239743;

Protein Name

cAMP-dependent protein kinase catalytic subunit alpha

Protein Synonyms/Alias

PKA C-alpha; 2.7.11.11;

Gene Name

Prkaca

Gene Synonyms/Alias

Pkaca;

Created Date

13-AUG-1987

Organism

Mus musculus (Mouse)

NCBI Taxa ID

10090

Reference

[1] Tholey A, Pipkorn R, Bossemeyer D, Kinzel V, Reed J. Influence ofmyristoylation, phosphorylation, and deamidation on the structural behavior ofthe N-terminus of the catalytic subunit of cAMP-dependent protein kinase.Biochemistry. 2001 Jan 9;40(1):225-31.[PMID:11141074]

Functional Description

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 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+). 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). Phosphorylates APOBEC3G and AICDA. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation (By similarity).

Sequence Annotation

Domain: 44 298 Protein kinase.
Domain: 299 351 AGC-kinase C-terminal.
Nucleotide-binding: 50 58 ATP.
Nucleotide-binding: 122 128 ATP.
Nucleotide-binding: 169 172 ATP.
Active site: 167 167 Proton acceptor.
Binding site: 73 73 ATP.
Modified residue: 3 3 Deamidated asparagine; partial.
Modified residue: 11 11 Phosphoserine; by autocatalysis.
Modified residue: 49 49 Phosphothreonine.
Modified residue: 140 140 Phosphoserine.
Modified residue: 196 196 Phosphothreonine.
Modified residue: 198 198 Phosphothreonine; by PDPK1.
Modified residue: 202 202 Phosphothreonine.
Modified residue: 331 331 Phosphotyrosine.
Modified residue: 339 339 Phosphoserine.

Protein Length

351 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0031588; C:AMP-activated protein kinase complex; IEA:Ensembl
GO:0005813; C:centrosome; IEA:Ensembl
GO:0097546; C:ciliary base; IDA:MGI
GO:0005737; C:cytoplasm; IDA:MGI
GO:0005829; C:cytosol; TAS:Reactome
GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl
GO:0005739; C:mitochondrion; IDA:MGI
GO:0031594; C:neuromuscular junction; IDA:MGI
GO:0005654; C:nucleoplasm; TAS:Reactome
GO:0005634; C:nucleus; IDA:MGI
GO:0005886; C:plasma membrane; IDA:MGI
GO:0097225; C:sperm midpiece; IEA:Ensembl
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0004691; F:cAMP-dependent protein kinase activity; IDA:UniProtKB
GO:0004672; F:protein kinase activity; IDA:MGI
GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI
GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:MGI
GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl
GO:0071374; P:cellular response to parathyroid hormone stimulus; IMP:MGI
GO:0001707; P:mesoderm formation; IGI:MGI
GO:1901621; P:negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IGI:MGI
GO:0001843; P:neural tube closure; IGI:MGI
GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI
GO:0018107; P:peptidyl-threonine phosphorylation; IDA:MGI
GO:0071158; P:positive regulation of cell cycle arrest; IDA:UniProtKB
GO:0046827; P:positive regulation of protein export from nucleus; IMP:MGI
GO:0046777; P:protein autophosphorylation; IDA:MGI
GO:0006468; P:protein phosphorylation; IDA:MGI
GO:0045667; P:regulation of osteoblast differentiation; IEA:Ensembl
GO:0061136; P:regulation of proteasomal protein catabolic process; IEA:Ensembl
GO:0070613; P:regulation of protein processing; IGI:MGI
GO:0050804; P:regulation of synaptic transmission; IMP:MGI
GO:2000810; P:regulation of tight junction assembly; IEA:Ensembl
GO:0048240; P:sperm capacitation; IDA:UniProtKB

Interpro

InterPro; IPR000961; AGC-kinase_C
InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR002290; Ser/Thr_dual-sp_kinase
InterPro; IPR008271; Ser/Thr_kinase_AS

Pfam

Pfam; PF00069; Pkinase;

SMART

SMART; SM00133; S_TK_X;
SMART; SM00220; S_TKc;

PROSITE

PROSITE; PS51285; AGC_KINASE_CTER;
PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00108; PROTEIN_KINASE_ST;

PRINTS