tribbles homolog 3; TRB-3; neuronal cell death-inducible putative kinase; SINK; p65-interacting inhibitor of NF-kappa-B (TRIB3, C20orf97, NIPK, SKIP3, TRB3)

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

General

nuclear protein protein kinase

Properties

SIZE: entity length = 358 aa MW = 40 kD COMPARTMENT: cell nucleus MOTIF: kinase domain SITE: 68-316 MOTIF: ATP-binding site NAME: ATP-binding site STATE: active state

Database Correlations

OMIM 607898 UniProt Q96RU7 Pfam PF00069 Entrez Gene 57761 Kegg hsa:57761

References

UniProt :accession Q96RU7