CPLM-002225

Genbank Nucleotide ID

cAMP-dependent protein kinase catalytic subunit alpha

Protein Synonyms/Alias

Mus musculus (Mouse)

Position	Peptide	Type	References
48	LDQFDRIKTLGTGSF	ubiquitination	[1]
267	SHFSSDLKDLLRNLL	acetylation	[2]
280	LLQVDLTKRFGNLKN	ubiquitination	[1]
286	TKRFGNLKNGVNDIK	ubiquitination	[1]

[1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
[2] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
PLoS One. 2012;7(12):e50545. [PMID: 23236377]

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, 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 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+). TRPC1 activation by phosphorylation promotes Ca(2+) 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). Phosphorylates APOBEC3G and AICDA (By similarity).

DOMAIN 44 298 Protein kinase.
DOMAIN 299 351 AGC-kinase C-terminal.
NP_BIND 50 58 ATP.
NP_BIND 122 128 ATP.
NP_BIND 169 172 ATP.
ACT_SITE 167 167 Proton acceptor.
BINDING 73 73 ATP.
MOD_RES 3 3 Deamidated asparagine; partial.
MOD_RES 11 11 Phosphoserine; by autocatalysis.
MOD_RES 35 35 Phosphoserine.
MOD_RES 49 49 Phosphothreonine (By similarity).
MOD_RES 140 140 Phosphoserine.
MOD_RES 196 196 Phosphothreonine.
MOD_RES 198 198 Phosphothreonine; by PDPK1.
MOD_RES 202 202 Phosphothreonine (By similarity).
MOD_RES 331 331 Phosphotyrosine.
MOD_RES 339 339 Phosphoserine.
LIPID 2 2 N-myristoyl glycine.

3D-structure; Alternative splicing; ATP-binding; cAMP; Cell membrane; Complete proteome; Cytoplasm; Kinase; Lipoprotein; Membrane; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005813; C:centrosome; IEA:Compara.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0005739; C:mitochondrion; IDA:MGI.
GO:0031594; C:neuromuscular junction; IDA:MGI.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0005886; C:plasma membrane; IDA:MGI.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0004691; F:cAMP-dependent protein kinase activity; IDA:UniProtKB.
GO:0071333; P:cellular response to glucose stimulus; IEA:Compara.
GO:0071374; P:cellular response to parathyroid hormone stimulus; IMP:MGI.
GO:0001707; P:mesoderm formation; IGI:MGI.
GO:0018105; P:peptidyl-serine phosphorylation; IEA:Compara.
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:0045667; P:regulation of osteoblast differentiation; IEA:Compara.
GO:0061136; P:regulation of proteasomal protein catabolic process; IEA:Compara.
GO:0050804; P:regulation of synaptic transmission; IMP:MGI.
GO:2000810; P:regulation of tight junction assembly; IEA:Compara.
GO:0048240; P:sperm capacitation; IDA:UniProtKB.

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.

SM00133; S_TK_X
SM00220; S_TKc

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