BH3-interacting domain death agonist; p22 BID; BID; contains: BH3-interacting domain death agonist p15; p15 BID; contains: BH3-interacting domain death agonist p13; p13 BID; contains: BH3-interacting domain death agonist p11; p11 BID (BID)
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Function
- the major proteolytic product p15 BID allows the release of cytochrome c (putative)
- isoform 1, isoform 2 & isoform 4 induce ICE-like proteases & apoptosis
- isoform 3 does not induce apoptosis
- counters the protective effect of Bcl-2
- TNF-alpha induces a caspase-mediated cleavage of p22 BID into a major p15 & minor p13 & p11 products (putative)
- caspase-8 cleavage of cytosolic BID is followed by translocation of its C-terminal fragment to mitochondria where it induces allosteric conformation activation of BAK & BAX, including their intramembranous oligomerization
- phosphorylated upon DNA damage, probably by ATM or ATR
- sequential phosphorylation of BID at Ser-61 followed by Ser-62 inhibits cleavage by caspase-8.
- forms heterodimers either with the pro-apoptotic protein BAX or the anti-apoptotic protein Bcl-2 (putative)
Structure
- intact BH3 motif is required by BIK, BID, BAK, BAD & BAX for their pro-apoptotic activity & for their interaction with anti-apoptotic members of the Bcl-2 family
Compartment
- cytoplasm (putative), mitochondrial membrane (putative
- when uncleaved, it is predominantly cytoplasmic
- BH3-interacting domain death agonist p15:
- mitochondrial membrane (putative)
- translocates to mitochondria as an integral membrane protein (putative)
- BH3-interacting domain death agonist p13:
- mitochondrial membrane (putative)
- associated with the mitochondrial membrane (putative)
- isoform 1: cytoplasm
- isoform 3: cytoplasm
- isoform 2:
- mitochondrial membrane
- a significant proportion of isoform 2 localizes to mitochondria, it may be cleaved constitutively
Alternative splicing
named isoforms=4
Expression
- isoforms 2 & 3 are expressed in spleen, bone marrow, cerebral cortex & cerebellar cortex
- isoform 2 is expressed in spleen, pancreas & placenta (at protein level)
- isoform 3 is expressed in lung, pancreas & spleen (at protein level)
- isoform 4 is expressed in lung & pancreas (at protein level)
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P55957.html
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/bid/
- ↑ Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell. 2001 Sep;8(3):705-11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11583631
- ↑ Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci. 2001 Jan;26(1):61-6. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11165519
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=637