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Overview

Uniprot IDP36887
Protein NamecAMP-dependent protein kinase catalytic subunit alpha
Gene NamePRKACA
OrganismSus scrofa

Kla Sites from experimental identification

Position Flanking peptide
24 KEFLAKAKEDFLKKW
310 WIAIYQRKVEAPFIP
93 IEHTLNEKRILQAVN

Function

Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, histone H1.4 (H1-4), PSMC5/RPT6, PJA2, RYR2, RORA, SLC6A6, SOX9, UHRF1 and VASP. 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. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (By similarity). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). 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 (By similarity). Acts as a key inhibitor of smoothened signaling pathway by mediating phosphorylation of GLI (GLI1, GLI2 and GLI3) transcription factors in absence of hedgehog (DHH, IHH or SHH) morphogens: GLI phosphorylation promotes their processing and prevents transcriptional activation of smoothened target genes (By similarity). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity). Also inhibits the smoothened signaling pathway in embryonic development by catalyzing phosphorylation of OFD1 in ciliogenesis (By similarity). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock. Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR. Phosphorylates AKAP19 (By similarity)

Protein Sequence

10 MGNAAAAKKG 20 SEQESVKEFL 30 AKAKEDFLKK 40 WENPAQNTAH 50 LDQFERIKTL 60 GTGSFGRVML 70 VKHKETGNHF 80 AMKILDKQKV 90 VKLKQIEHTL 100 NEKRILQAVN 110 FPFLVKLEYS 120 FKDNSNLYMV 130 MEYVPGGEMF 140 SHLRRIGRFS 150 EPHARFYAAQ 160 IVLTFEYLHS 170 LDLIYRDLKP 180 ENLLIDQQGY 190 IQVTDFGFAK 200 RVKGRTWTLC 210 GTPEYLAPEI 220 ILSKGYNKAV 230 DWWALGVLIY 240 EMAAGYPPFF 250 ADQPIQIYEK 260 IVSGKVRFPS 270 HFSSDLKDLL 280 RNLLQVDLTK 290 RFGNLKNGVN 300 DIKNHKWFAT 310 TDWIAIYQRK 320 VEAPFIPKFK 330 GPGDTSNFDD 340 YEEEEIRVSI 350 NEKCGKEFSE F

Gene Ontology

Classification GO ID Description
Cellular Component GO:0001669 acrosomal vesicle
Cellular Component GO:0005952 cAMP-dependent protein kinase complex
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0042585 germinal vesicle
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0036126 sperm flagellum
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0004691 cAMP-dependent protein kinase activity
Molecular Function GO:0140198 histone H1-4S35 kinase activity
Molecular Function GO:0034237 protein kinase A regulatory subunit binding
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Biological Process GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
Biological Process GO:0034605 cellular response to heat
Biological Process GO:1904145 negative regulation of meiotic cell cycle process involved in oocyte maturation
Biological Process GO:1904262 negative regulation of TORC1 signaling

Reference

[1] Fan S, Zhou R, Wen H, Ye H, Ma S et al.. Global profiling of protein lactylome in porcine granulosa cells.. J Ovarian Res 18(1):177. 2025 Aug 8. PMID: 40781717.