BID (Homo sapiens)
- Synonyms: BID,
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: BH3-interacting domain death agonist (p22 BID)(BID) [Contains BH3-interacting domain death agonist p15(p15 BID);BH3-interacting domain death agonist p13(p13 BID);BH3-interacting domain death agonist p11(p11 BID)] [Source:UniProtKB/Swiss-Prot;Acc:P55957]
- Family: Bcl-2 family : BH3-only
- Process: apoptosis,
- Pathways: extrinsic pathway, pre-mitochondrial signaling events,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Bid
- WIKI: BID-H_sapiens
- BID: a novel BH3 domain-only death agonist.
- Wang K, Yin XM, Chao DT, Milliman CL, Korsmeyer SJ
- The BCL-2 family of proteins consists of both antagonists (e.g., BCL-2) and agonists (e.g., BAX) that regulate apoptosis and compete through dimerization. The BH1 and BH2 domains of BCL-2 are required to heterodimerize with BAX and to repress cell death; conversely, the BH3 domain of BAX is required to heterodimerize with BCL-2 and to promote cell death. To extend this pathway, we used interactive cloning to identify Bid, which encodes a novel death agonist that heterodimerizes with either agonists (BAX) or antagonists (BCL-2). BID possesses only the BH3 domain, lacks a carboxy-terminal signal-anchor segment, and is found in both cytosolic and membrane locations. BID counters the protective effect of BCL-2. Moreover, expression of BID, without another death stimulus, induces ICE-like proteases and apoptosis. Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. A BH3 mutant of BID that still heterodimerized with BCL-2 failed to promote apoptosis, dissociating these activities. In contrast, the only BID BH3 mutant that retained death promoting activity interacted with BAX, but not BCL-2. This BH3-only molecule supports BH3 as a death domain and favors a model in which BID represents a death ligand for the membrane-bound receptor BAX. Genes Dev. 1996 Nov 15;10(22):2859-69.
- References from Mouse ortholog(s):
- Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis.
- Yin XM, Wang K, Gross A, Zhao Y, Zinkel S, Klocke B, Roth KA, Korsmeyer SJ
- The protein Bid is a participant in the pathway that leads to cell death (apoptosis), mediating the release of cytochrome c from mitochondria in response to signals from 'death' receptors known as TNFR1/Fas on the cell surface. It is a member of the proapoptotic Bcd-2 family and is activated as a result of its cleavage by caspase 8, one of a family of proteolytic cell-death proteins. To investigate the role of Bid in vivo, we have generated mice deficient for Bid. We find that when these mice are injected with an antibody directed against Fas, they nearly all survive, whereas wild-type mice die from hepatocellular apoptosis and haemorrhagic necrosis. About half of the Bid-deficient animals had no apparent liver injury and showed no evidence of activation of the effector caspases 3 and 7, although the initiator caspase 8 had been activated. Other Bid-deficient mice survived with only moderate damage: all three caspases (8 and 37) were activated but their cell nuclei were intact and no mitochondrial cytochrome c was released. We also investigated the effects of Bid deficiency in cultured cells treated with anti-Fas antibody (hepatocytes and thymocytes) or with TNFalpha. (fibroblasts). In these Bid-/- cells, mitochondrial dysfunction was delayed, cytochrome c was not released, effector caspase activity was reduced and the cleavage of apoptosis substrates was altered. This loss-of-function model indicates that Bid is a critical substrate in vivo for signalling by death-receptor agonists, which mediates a mitochondrial amplification loop that is essential for the apoptosis of selected cells. Nature. 1999 Aug 26;400(6747):886-91.
Structure & Sequence [+]
Pfam domains: (Pfam is a large collection of protein families.)
Protein sequence [+]
BID | Homo sapiens | 9606 | length:253
View protein alignment and tree with Jalview:
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Homologs list [+]
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Gene Ontology [+]
|GO id||Name||Ontology type||Evidence|
|GO:0043065||positive regulation of apoptosis||biological_proccess||IEA|
|GO:0042981||regulation of apoptosis||biological_proccess||IEA|
|GO:0046902||regulation of mitochondrial membrane permeability||biological_proccess||IEA|
|GO:0001836||release of cytochrome c from mitochondria||biological_proccess||IDA|
|GO:0008625||induction of apoptosis via death domain receptors||biological_proccess||TAS|
|GO:0008633||activation of pro-apoptotic gene products||biological_proccess||EXP|
|GO:0006626||protein targeting to mitochondrion||biological_proccess||IEA|
|GO:0001836||release of cytochrome c from mitochondria||biological_proccess||IEA|
|GO:0005123||death receptor binding||mollecular_function||TAS|
|GO:0005741||mitochondrial outer membrane||cell_component||EXP|
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
|OTTHUMT00000316179 *||OTTHUMP00000196195 *|
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- OMIM gene information: 601997
- OMIM disease information:
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