| Structural highlights
1apm is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| NonStd Res: | , |
| Activity: | Transferase, with EC number 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[KAPCA_MOUSE] 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).[1] [2] [3] [IPKA_MOUSE] Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
. A mutant (Serl39Ala) of the mouse recombinant catalytic (C) subunit of cAMP-dependent protein kinase was co-crystallized with a peptide inhibitor, PKI(5-24), and MEGA-8 (octanoyl-N-methylglucamide) detergent. This structure was refined using all observed data (30 248 reflections) between 30 and 1.95 A resolution to an R factor of 0.186. R.m.s. deviations of bond lengths and bond angles are 0.013 A and 2.3 degrees, respectively. The final model has 3075 atoms (207 solvent) with a mean B factor of 31.9 A(2). The placement of invariant protein-kinase residues and most C:PKI(5-24) interactions were confirmed, but register errors affecting residues 55-64 and 309-339 were corrected during refinement by shifting the affected sequences toward the C terminus along the previously determined backbone path. New details of C:PKI(5-24) interactions and the Ser338 autophosphorylation site are described, and the acyl group binding site near the catalytic subunit NH(2) terminus is identified.
2.0 A refined crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with a peptide inhibitor and detergent.,Knighton DR, Bell SM, Zheng J, Ten Eyck LF, Xuong NH, Taylor SS, Sowadski JM Acta Crystallogr D Biol Crystallogr. 1993 May 1;49(Pt 3):357-61. PMID:15299526[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nolan MA, Babcock DF, Wennemuth G, Brown W, Burton KA, McKnight GS. Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility. Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13483-8. Epub 2004 Aug 31. PMID:15340140 doi:10.1073/pnas.0405580101
- ↑ Pirino G, Wescott MP, Donovan PJ. Protein kinase A regulates resumption of meiosis by phosphorylation of Cdc25B in mammalian oocytes. Cell Cycle. 2009 Feb 15;8(4):665-70. Epub 2009 Feb 14. PMID:19223768
- ↑ Baker MA, Hetherington L, Curry B, Aitken RJ. Phosphorylation and consequent stimulation of the tyrosine kinase c-Abl by PKA in mouse spermatozoa; its implications during capacitation. Dev Biol. 2009 Sep 1;333(1):57-66. doi: 10.1016/j.ydbio.2009.06.022. Epub 2009, Jun 26. PMID:19560455 doi:10.1016/j.ydbio.2009.06.022
- ↑ Knighton DR, Bell SM, Zheng J, Ten Eyck LF, Xuong NH, Taylor SS, Sowadski JM. 2.0 A refined crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with a peptide inhibitor and detergent. Acta Crystallogr D Biol Crystallogr. 1993 May 1;49(Pt 3):357-61. PMID:15299526 doi:10.1107/S0907444993000502
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