TRIB1TRIB3

TRIB1TRIB3 is a putative protein identified in mammalian genomes that appears to arise from a gene fusion event combining the Tribbles homolog 1 (TRIB1) and Tribbles homolog 3 (TRIB3) domains. The Tribbles family belongs to a class of pseudokinases that regulate signaling pathways through scaffold interactions rather than enzymatic activity. Each segment of TRIB1TRIB3 retains conserved motifs such as the phospho‑binding loop and the C‑terminal TRIB sequence, suggesting that the fusion protein could simultaneously engage binding partners of both parent proteins.

The gene encoding TRIB1TRIB3 is located on chromosome 15 in humans, within a cluster that includes TRIB1, TRIB2, and TRIB3. Transcripts have been detected primarily in liver, adipose tissue, and certain immune cell subsets, but expression levels are significantly lower than those of the individual TRIB members. Alternative splicing gives rise to at least two isoforms differing in the length of the linker region that connects the TRIB1 and TRIB3 domains.

Functional assays in cultured cells indicate that TRIB1TRIB3 modulates MAPK/ERK signaling, similar to TRIB1, while also influencing AMPK activation pathways reminiscent of TRIB3. Knockdown experiments reduce cellular proliferation in hepatocellular carcinoma lines, pointing to a potential tumor suppressor role. Conversely, overexpression in adipocytes increases lipid accumulation, implicating the protein in metabolic regulation.

Although no direct disease associations have been conclusively established, genome‑wide association studies hint at a modest link between polymorphisms in the TRIB1TRIB3 locus and lipid‐profile variation in human populations. Continued investigation into its structural dynamics and interaction networks is expected to clarify the biological significance of this fusion protein.