TRIB1
Description
The TRIB1 (tribbles pseudokinase 1) is a protein-coding gene located on chromosome 8.
Tribbles homolog 1 (TRIB1) is a protein kinase encoded by the TRIB1 gene in humans. Found throughout the animal kingdom, it functions as a pseudokinase, lacking catalytic activity. TRIB1 interacts with MAPKK signaling proteins, influencing the MAPK pathway, which regulates cell proliferation, apoptosis, and differentiation. TRIB1's structure includes a broken C-helix region, a binding site for ubiquitinated substrates like C/EBPalpha, and a regulatory C-tail region. Its expression is highly variable, suggesting extensive regulation within the cell. Notably, TRIB1 contains a PEST region, characteristic of proteins susceptible to degradation. Interestingly, TRIB1 regulates its own expression by binding to its substrate, not only affecting the MAPK pathway but also protecting itself from degradation while bound.
TRIB1, also known as Tribbles homolog 1, G-protein-coupled receptor-induced gene 2 protein, or SKIP1, acts as an adapter protein in protein degradation by interacting with the COP1 ubiquitin ligase. Its COP1-binding motif is masked by autoinhibitory interactions with the protein kinase domain. TRIB1 alters COP1 substrate specificity by directing its activity toward CEBPA, binding selectively to its recognition sequence. This regulation of CEBPA expression, dependent on COP1, affects myeloid cell differentiation, controlling the differentiation of macrophages, eosinophils, and neutrophils through the COP1-binding domain. Despite interacting with MAPK kinases and regulating their activation, TRIB1 lacks kinase activity. {ECO:0000250|UniProtKB:Q8K4K4, ECO:0000269|PubMed:15299019, ECO:0000269|PubMed:26455797, ECO:0000305|PubMed:27041596}
TRIB1 is also known as C8FW, GIG-2, GIG2, SKIP1, TRB-1, TRB1.
