catalytic activity:ATP + a protein = ADP + a phosphoprotein. , cofactor:Magnesium. , enzyme regulation:Appears to be activated by multiple phosphorylations on threonine and serine residues. ERK1/2 and MAPK14/p38-alpha may play a role in this process. , function:Serine/threonine kinase required for the mitogen or stress-induced phosphorylation of the transcription factors CREB (cAMP response element-binding protein) and ATF1 (activating transcription factor-1) . Essential role in the control of RELA transcriptional activity in response to TNF. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and epidemal growth-factor (EGF) , which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen-and stress-induced phosphorylation of high mobility group protein 14 (HMG-14) . , miscellaneous:Enzyme activity requires the presence of both kinase domains. , PTM:Ser-376 and Thr-581 phosphorylation is required for kinase activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. , similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. , similarity:Contains 1 AGC-kinase C-terminal domain. , similarity:Contains 2 protein kinase domains. , subcellular location:Predominantly nuclear. Partially cytoplasmic. , subunit:Forms a complex with either ERK1 or ERK2 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA. , tissue specificity:Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver. ,