BID

This gene encodes a death agonist that heterodimerizes with either agonist BAX or antagonist BCL2. The encoded protein is a member of the BCL-2 family of cell death regulators. It is a mediator of mitochondrial damage induced by caspase-8 (CASP8); CASP8 cleaves this encoded protein, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. Multiple alternatively spliced transcript variants have been found, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

Full Name

BH3 Interacting Domain Death Agonist

Function

The major proteolytic product p15 BID allows the release of cytochrome c (By similarity).
Isoform 1, isoform 2 and isoform 4 induce ICE-like proteases and apoptosis. Isoform 3 does not induce apoptosis. Counters the protective effect of Bcl-2.

Biological Process

Activation of cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
Apoptotic mitochondrial changes Source: GO_Central
Establishment of protein localization to membrane Source: BHF-UCL
Extrinsic apoptotic signaling pathway via death domain receptors Source: ProtInc
Hepatocyte apoptotic process Source: Ensembl
Mitochondrial ATP synthesis coupled electron transport Source: Ensembl
Mitochondrial outer membrane permeabilization Source: Ensembl
Negative regulation of apoptotic process Source: Reactome
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
Neuron apoptotic process Source: HGNC-UCL
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
Positive regulation of fibroblast apoptotic process Source: Ensembl
Positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
Positive regulation of mitochondrial membrane potential Source: Ensembl
Positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: Reactome
Positive regulation of protein-containing complex assembly Source: UniProtKB
Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
Positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
Protein-containing complex assembly Source: Ensembl
Protein targeting to mitochondrion Source: Ensembl
Regulation of apoptotic process Source: Reactome
Regulation of cell population proliferation Source: Ensembl
Regulation of G1/S transition of mitotic cell cycle Source: Ensembl
Release of cytochrome c from mitochondria Source: HGNC-UCL
Signal transduction in response to DNA damage Source: UniProtKB

Cellular Location

Mitochondrion membrane; Mitochondrion outer membrane; Cytoplasm. When uncleaved, it is predominantly cytoplasmic.
BH3-interacting domain death agonist p15: Mitochondrion membrane. Translocates to mitochondria as an integral membrane protein.
BH3-interacting domain death agonist p13: Mitochondrion membrane. Associated with the mitochondrial membrane.
Isoform 1: Cytoplasm
Isoform 2: Mitochondrion membrane. A significant proportion of isoform 2 localizes to mitochondria, it may be cleaved constitutively.
Isoform 3: Cytoplasm

PTM

TNF-alpha induces a caspase-mediated cleavage of p22 BID into a major p15 and minor p13 and p11 products.
p15 BID is ubiquitinated by ITCH; ubiquitination results in proteasome-dependent degradation.