ID 2.7.11.11 DE cAMP-dependent protein kinase. AN PKA. AN PKA C. AN protein kinase A. CA (1) ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]. CA (2) ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl- CA [protein]. CC -!- This eukaryotic enzyme recognizes the sequence -Arg-Arg-X- CC Ser*/Thr*-Hpo, where * indicates the phosphorylated residue and Hpo CC indicates a hydrophobic residue. CC -!- The inactive holoenzyme is a heterotetramer composed of two CC regulatory (R) subunits and two catalytic (C) subunits. CC -!- Each R subunit occludes the active site of a C subunit and contains CC two binding sites for 3',5'-cyclic-AMP (cAMP). CC -!- Binding of cAMP activates the enzyme by causing conformational CC changes that release two free monomeric C subunits from a dimer of CC the R subunits, i.e. R2C2 + 4 cAMP = R2(cAMP)4 + 2 C. CC -!- Activity requires phosphorylation of a conserved Thr in the CC activation loop (T-loop) sequence (Thr(198) in human Calpha; Thr(224) CC in budding yeast Tpk2), installed by auto-phosphorylation or by the CC 3-phosphoinositide-dependent protein kinase-1 (PDPK1). CC -!- Certain R2C2 combinations can be localized to particular subcellular CC regions by their association with diverse species of 'A Kinase- CC Anchoring Proteins' (AKAPs). CC -!- The enzyme has been characterized from many organisms. Humans have CC three C units (Calpha, Cbeta, and Cgamma) encoded by the paralogous CC genes PRKACA, PRKACB and PRKACG, respectively, and four R subunits CC (R1alpha, RIbeta, RIIalpha and RIIbeta), encoded by PKRAR1A, PKRAR1B, CC PKRAR2A and PKRAR2B, respectively. Yeast (Saccharomyces cerevisiae) CC has three C subunits (Tpk1, Tpk2, and Tpk3) encoded by the paralogous CC genes TPK1, TPK2 and TPK3, respectively, and a single R subunit CC (Bcy1) encoded by the BCY1 gene. CC -!- Some validated substrates of the enzyme include cAMP-response CC element-binding protein (CREB), phosphorylase kinase alpha subunit CC (PHKA), and tyrosine 3-monooxygenase (TH) in mammals; Adr1, Whi3, CC Nej1, and Pyk1 in yeast. CC -!- Formerly EC 2.7.1.37. DR P06244, KAPA_YEAST ; P40376, KAPB_SCHPO ; P06245, KAPB_YEAST ; DR A8XW88, KAPC1_CAEBR; P21137, KAPC1_CAEEL; P12370, KAPC1_DROME; DR A8XJQ6, KAPC2_CAEBR; Q7JP68, KAPC2_CAEEL; P00517, KAPCA_BOVIN; DR Q8MJ44, KAPCA_CANLF; P25321, KAPCA_CRIGR; P17612, KAPCA_HUMAN; DR P05132, KAPCA_MOUSE; P36887, KAPCA_PIG ; P27791, KAPCA_RAT ; DR Q9MZD9, KAPCA_SHEEP; P05131, KAPCB_BOVIN; P68180, KAPCB_CRIGR; DR P22694, KAPCB_HUMAN; P68181, KAPCB_MOUSE; P05383, KAPCB_PIG ; DR P68182, KAPCB_RAT ; P22612, KAPCG_HUMAN; O62846, KAPCG_MACMU; DR P49673, KAPC_ASCSU ; P34099, KAPC_DICDI ; Q8SRK8, KAPC_ENCCU ; DR P05986, KAPC_YEAST ; //