BID Gene: Function, Mutations, and Role in Apoptosis

BID (BH3 Interacting Domain Death Agonist) is a pro-apoptotic member of the BCL-2 family. It contains only a BH3 domain and acts as a death agonist. Upon cleavage by caspase-8 (or other proteases), the truncated form (tBID) translocates to mitochondria, where it promotes the oligomerization of BAX and BAK, leading to mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release. BID is a key mediator of the extrinsic apoptotic pathway and is involved in various cellular processes including development, immune response, and tumor suppression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Apoptosis (KEGG hsa04210)

• p53 signaling pathway (KEGG hsa04115)

• Fas signaling pathway (BioCarta)

• Intrinsic Pathway for Apoptosis (Reactome R-HSA-109606)

BID is a 195-amino acid pro-apoptotic protein (UniProt P55957) that is predominantly cytosolic in its full-length form. Upon death receptor activation, caspase-8 cleaves BID at Asp59, generating a truncated C-terminal fragment (tBID, p15) that translocates to mitochondria. tBID induces BAX/BAK oligomerization, leading to MOMP and cytochrome c release. BID also has non-apoptotic roles in cell cycle regulation and DNA damage response. Its expression is regulated by p53 and is frequently lost or reduced in various cancers.