Atividade catalítica: ATP + a protein = ADP + a phosphoprotein.
Regulação de enzima: Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser- 474), need to be phosphorylated for its full activation. Aminofurazans are potent AKT2 inhibitors.
Estrutura da subunidade: Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CLK2, PBH2 and TRAF6.
Domínio: Binding of the PH domain to phosphatidylinositol 3,4,5- trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3- kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane.
Localização subcelular: Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Note=Localizes within both nucleus and cytoplasm of proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts. By virtue of the N-terminal PH domain, is recruited to sites of the plasma membrane containing increased PI(3,4,5)P3 or PI(3,4)P2.
Especificidade do tecido: Expressed in all cell types so far analyzed.
Pós-translacional: Phosphorylation on Thr-309 and Ser-474 is required for full activity. Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT2 ubiquitination. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. O-GlcNAcylation at Thr-306 and Thr-313 inhibits activating phosphorylation at Thr-309 via disrupting the interaction between AKT and PDK1 (By similarity).
Envolvimento na doença: Note=Defects in AKT2 are a cause of susceptibility to breast cancer (BC). AKT2 promotes metastasis of tumor cells without affecting the latency of tumor development. With AKT3, plays also a pivotal role in the biology of glioblastoma. Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note=The disease is caused by mutations affecting the gene represented in this entry. Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) [MIM:240900]: A disorder characterized by hypoglycemia, low insulin levels, low serum levels of ketone bodies and branched-chain amino acids, left-sided hemihypertrophy, neonatal macrosomia, reduced consciousness and hypoglycemic seizures. Note=The disease is caused by mutations affecting the gene represented in this entry.
Semelhança da sequência: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 PH domain. Contains 1 protein kinase domain.