tribbles homolog 3; TRB-3; neuronal cell death-inducible putative kinase; SINK; p65-interacting inhibitor of NF-kappa-B (TRIB3, C20orf97, NIPK, SKIP3, TRB3)
Jump to navigation
Jump to search
Function
- disrupts insulin signaling by binding directly to Akt kinases & blocking their activation
- may bind directly to & mask the Thr-308 phosphorylation site in AKT1
- binds to ATF4 & inhibits its transcriptional activation activity
- interacts with the NF-kappa-B transactivator p65 RELA & inhibits its phosphorylation & thus its transcriptional activation activity
- interacts with MAPK kinases & regulates activation of MAP kinases
- may play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells
- does not display kinase activity
- interacts with AKT1, AKT2, ATF4, MAP2K1 & MAP2K7
Structure
- belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family, tribbles subfamily
- contains 1 protein kinase domain
Compartment
nucleus (probable)
Expression
- highest expression in liver, pancreas, peripheral blood leukocytes & bone marrow
- highly expressed in a number of primary lung, colon & breast tumors
- expressed in spleen, thymus, & prostate & is undetectable in other examined tissues, including testis, ovary, small intestine, colon, leukocyte, heart, brain, placenta, lung, skeletal muscle, & kidney
- induced by hypoxia, TNF & by nutrient starvation
- expression is PI 3-kinase &/or NF-kappa-B-dependent