LipidDB ID

LipidDB-9823-01259

Entry Name

UniProt Accession

P36887;

Theoretical PI

8.84

Molecular Weight

40616.69

Genbank Protein ID

CAA30470.1;

Genbank Nucleotide ID

X07617;

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

Created Date

01-JUN-1994

Organism

Sus scrofa (Pig)

NCBI Taxa ID

9823

Reference

[1] Jedrzejewski PT, Girod A, Tholey A, König N, Thullner S, Kinzel V, Bossemeyer D. A conserved deamidation site at Asn 2 in the catalytic subunit of mammaliancAMP-dependent protein kinase detected by capillary LC-MS and tandem massspectrometry. Protein Sci. 1998 Feb;7(2):457-69.[PMID:9521123]

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) (By similarity). Phosphorylates APOBEC3G and AICDA (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:0005739; C:mitochondrion; IEA:UniProtKB-KW
GO:0005634; C:nucleus; IEA:UniProtKB-KW
GO:0005886; C:plasma membrane; IEA:UniProtKB-KW
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0004691; F:cAMP-dependent protein kinase activity; IEA:UniProtKB-EC

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