P05132

Background

Protein Name
cAMP-dependent protein kinase catalytic subunit alpha
Gene Name
Prkaca
Organism
Mus musculus

Annotations

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 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).

Mapping Statistics

Site
Maximum Consensus Site Population
Minimum Consensus Site Population
Median Consensus Site Population
EDI 15 2 6.0
MT3 22 3 6.5
PIF 22 1 10.0
ATP 27 1 8.0
DRS 35 4 14.0
AAS 5 4 4.5
DFG 13 2 6.0
PDIG 6 4 5.0
PMP 26 1 10.0

Mapping Results

PDB ID
Maximum Consensus Site Population
EDI site
MT3 site
PIF site
ATP site
DEF site
DRS site
AAS site
MPP site
DFG site
LBP site
CMP site
PDIG site
PMP site
Total Druggable Structures per Site 0 4 3 32 0 35 0 0 0 0 0 0 17
1APM 0 0 0 10 0 9 0 0 11 0 0 0 14
1ATP 9 11 0 15 0 9 0 0 0 0 0 0 8
1BKX 0 0 4 16 0 16 0 0 0 0 0 0 0
1BX6 0 0 13 14 0 16 0 0 0 0 0 0 9
1FMO 0 0 11 15 0 11 0 0 2 0 0 0 16
1J3H 0 0 15 14 0 20 0 0 2 0 0 6 13
1JBP 0 0 14 17 0 20 0 0 5 0 0 0 18
1JLU 0 0 14 6 0 4 0 0 8 0 0 0 22
1L3R 0 15 8 12 0 28 0 0 0 0 0 0 26
1RDQ 0 0 12 11 0 32 0 0 6 0 0 0 15
1RE8 0 6 13 14 0 26 0 0 3 0 0 0 15
1REJ 6 0 6 21 0 14 0 0 7 0 0 0 13
1REK 4 22 12 13 0 0 0 0 0 0 0 0 8
1SYK 0 17 12 13 0 10 0 0 0 0 0 0 20
2CPK 0 0 0 8 0 0 0 0 11 0 0 0 13
2ERZ 8 0 0 13 0 25 0 0 8 0 0 0 10
2QCS 0 13 0 17 0 0 0 0 5 0 0 0 12
2QUR 0 0 0 16 0 20 0 0 0 0 0 0 15
2QVS 0 0 0 0 0 13 0 0 0 0 0 0 13
3FHI 0 7 0 8 0 0 0 0 9 0 0 0 15
3FJQ 0 9 0 10 0 13 0 0 0 0 0 0 11
3IDB 6 6 15 14 0 29 0 0 9 0 0 0 16
3IDC 12 10 2 12 0 4 0 0 0 0 0 0 5
3J4Q 0 0 0 0 0 0 0 0 0 0 0 0 15
3J4R 0 0 0 0 0 8 0 0 0 0 0 0 9
3O7L 15 0 13 19 0 14 4 0 5 0 0 0 15
3OW3 0 0 12 12 0 25 0 0 4 0 0 0 8
3PVB 0 16 10 13 0 0 0 0 7 0 0 0 10
3QAL 0 0 8 17 0 24 0 0 6 0 0 0 16
3QAM 3 6 7 13 0 14 0 0 13 0 0 0 10
3TNP 0 0 22 20 0 14 0 0 0 0 0 0 14
3X2U 3 0 14 19 0 27 0 0 0 0 0 0 10
3X2V 0 0 7 20 0 13 0 0 5 0 0 0 22
3X2W 0 3 15 21 0 27 0 0 4 0 0 0 15
4DFX 0 0 8 7 0 26 0 0 7 0 0 0 11
4DFY 0 12 0 19 0 16 5 0 0 0 0 0 0
4DFZ 0 0 13 15 0 21 0 0 5 0 0 0 10
4DG0 4 0 11 11 0 29 0 0 9 0 0 0 9
4DG2 0 0 9 11 0 30 0 0 0 0 0 0 17
4DG3 9 0 16 19 0 0 0 0 8 0 0 0 15
4DH1 6 0 11 10 0 35 0 0 0 0 0 0 15
4DH3 6 4 11 10 0 35 0 0 2 0 0 0 10
4DH5 0 0 10 4 0 31 0 0 8 0 0 0 11
4DH7 10 4 15 9 0 13 0 0 2 0 0 0 10
4DH8 3 0 14 6 0 28 0 0 4 0 0 0 12
4DIN 0 0 7 15 0 18 0 0 0 0 0 0 13
4HPT 0 0 0 22 0 25 0 0 10 0 0 0 17
4HPU 0 0 0 22 0 0 0 0 13 0 0 0 14
4IAC 0 0 14 12 0 0 0 0 6 0 0 0 17
4IAD 5 0 12 15 0 29 0 0 5 0 0 0 12
4IAF 0 0 12 20 0 27 0 0 6 0 0 0 17
4IAI 0 0 14 23 0 0 0 0 7 0 0 0 10
4IAK 6 0 10 21 0 12 0 0 6 0 0 0 12
4IAY 0 0 12 19 0 29 0 0 7 0 0 0 16
4IAZ 0 0 13 23 0 28 0 0 8 0 0 0 13
4IB0 0 0 14 27 0 7 0 0 9 0 0 0 19
4IB1 0 0 17 26 0 26 0 0 6 0 0 0 12
4IB3 0 6 12 27 0 27 0 0 7 0 0 0 11
4NTS 0 0 13 18 0 13 0 0 0 0 0 4 12
4NTT 0 0 15 18 0 11 0 0 0 0 0 0 10
4O21 0 0 12 20 0 27 0 0 0 0 0 0 9
4O22 5 0 14 19 0 13 0 0 0 0 0 0 13
4WBB 2 16 10 21 0 8 0 0 0 0 0 0 16
4X6Q 0 0 11 21 0 14 0 0 0 0 0 0 12
4X6R 0 0 13 15 0 22 0 0 8 0 0 0 8
4XW4 0 0 8 20 0 23 0 0 8 0 0 0 9
4XW5 0 0 8 24 0 31 0 0 4 0 0 0 17
4XW6 0 0 12 18 0 0 0 0 9 0 0 0 16
AFP05132 0 0 0 0 0 0 0 0 0 0 0 0 10