Resumen de gen: The protein encoded by this gene is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF),and IGF1. Alternatively splice transcript variants encoding distinct isoforms have been describedGeneral information above from NCBI
Actividad catalítica: ATP + a protein = ADP + a phosphoprotein.
Regulación de enzima: Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser- 472), need to be phosphorylated for its full activation (By similarity). IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival.
Estructura de subunidad: Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6.
Dominio: Binding of the PH domain to the phosphatidylinositol 3- kinase alpha (PI(3)K) results in its targeting to the plasma membrane.
Localización subcelular: Nucleus. Cytoplasm. Membrane; Peripheral membrane protein. Note=Membrane-associated after cell stimulation leading to its translocation.
Especificidad del tejido: In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.
Postranslacional: Phosphorylation on Thr-305 and Ser-472 is required for full activity (By similarity).
Ubiquitinated. 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-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1 (By similarity).
Implicación en la enfermedad: Note=AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) [MIM:603387]: A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry.
Similitud de la secuencia: 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.
General information above from UniProt