Function: Li et al. (1998) reported that BID is a specific proximal substrate of CASP8 in the Fas apoptotic signaling pathway. While full-length BID is localized in cytosol, truncated BID translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria. Truncated BID induces first the clustering of mitochondria around the nuclei and release of cytochrome c independent of caspase activity, and then the loss of mitochondrial membrane potential, cell shrinkage, and nuclear condensation in a caspase-dependent fashion. The results of Li et al. (1998) indicated that BID is a mediator of mitochondrial damage induced by CASP8.

Function: Zha et al. (2000) found that BID underwent posttranslational (rather than classic cotranslocational) N-myristoylation when cleavage by CASP8 caused exposure of a glycine residue at position 60. N-myristoylation enabled the targeting of a complex of p7 and myristoylated p15 fragments of BID to artificial membranes bearing the lipid composition of mitochondria, as well as to intact mitochondria. Zha et al. (2000) found that this post-proteolytic N-myristoylation serves as an activating switch, enhancing BID-induced release of cytochrome c and cell death.

Function: The caspase-activated form of BID, tBID, triggers the homooligomerization of multidomain conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. Wei et al. (2001) found that cells lacking both BAK and BAX, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, Wei et al. (2001) concluded that activation of a 'multidomain' proapoptotic member, BAK or BAX, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli.

Function: Sax et al. (2002) presented evidence that BID is 1 of a subset of p53 (OMIM:191170)-upregulated targets whose induction and subsequent processing mediates p53-induced apoptosis.

Function: A central issue in the regulation of apoptosis by the BCL2 family is whether its BH3-only members initiate apoptosis by directly binding to the essential cell death mediators BAX (OMIM:600040) and BAK (OMIM:600516), or whether they can act indirectly, by engaging their prosurvival BCL2-like relatives. Contrary to the direct-activation model, Willis et al. (2007) showed that BAX and BAK can mediate apoptosis without discernable association with the putative BH3-only activators (BIM, OMIM:603827; BID; and PUMA, OMIM:605854), even in cells with no BIM or BID and reduced PUMA. Willis et al. (2007) concluded that BH3-only proteins induce apoptosis at least primarily by engaging with multiple prosurvival relatives guarding BAX and BAK.

Summary

Top-ranked sequences

Query    87 GHELPVLAPQWEGYDELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMDRS  146
            ||||||||||||||||||||||||||||||#||||||||||||||||||||||||||||||
Query    87 GHELPVLAPQWEGYDELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMDRS  146

Query    87 GHELPVLAPQWEGYDELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMDRS  146
            ||||||||||||||||||||||||||||||#||||||||||||||||||||||||||||||
Query    87 GHELPVLAPQWEGYDELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMDRS  146

Query    87 GHELPVLAPQWEGYDELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMDRS  146
            ||||||||||||||||||||||||||||||#||||||||||||||||||||||||||||||
Query    87 GHELPVLAPQWEGYDELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMDRS  146

Query    87 GHELPVLAPQWEG--YDELQTDGNRSSHS-RLG#RIEADSESQEDIIRNIARHLAQVGDSM  143
            | |||| |  ||    |||||||+++| |   |#||| ||||||+|| ||||||||+|| |
Sbjct    39 GRELPVQA-YWEADLEDELQTDGSQASRSFNQG#RIEPDSESQEEIIHNIARHLAQIGDEM   97

Query   144 DRS  146
            | +
Sbjct    98 DHN  100

Query    87 GHELPVLAPQWEGYDELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMD  144
            ||||||      | ||||||||| |+    #  | |||||| +||+||||||++|| |+
Sbjct    41 GHELPV---HTSGSDELQTDGNRCSYFMED#AAETDSESQEAVIRDIARHLARIGDRME   95

Query    87 GHELPV-LAPQWEGYDELQTDGNRSSHSRL-G#RIEADSESQEDIIRNIARHLAQVGDSMD  144
            | |||| +  + +  |||||||+|+| |   |#||| |||||+++| |||||||| || +|
Sbjct    40 GQELPVQVYLEGDREDELQTDGSRASRSFYHG#RIEPDSESQDEVIHNIARHLAQAGDELD   99

Query   145 RS  146
             |
Sbjct   100 HS  101

Query    87 GHELPVLAPQWEGYD-ELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMDR  145
            |||||| |   | +| |||||||| |+   |# +  ||||||+||++||| |||+|| || 
Sbjct   121 GHELPVPAYLKEDHDNELQTDGNRCSYFLDG#GVR-DSESQEEIIQDIARQLAQIGDRMDH  179

Query   146 S  146
            |
Query   146 S  146

Query    87 GHELPVLAPQWEGY----DELQTDGNRSSHSRLG-#RIEADSESQEDIIRNIARHLAQVGD  141
            |||||       |+    ||||||||| ||  |  #  | ||| ||+ +| +|| |||+||
Sbjct    41 GHELP-------GHLFHDDELQTDGNRCSHFPLAA#EAETDSERQEEAVREVARQLAQIGD   93

Query   142 SMDRS  146
             ++ |
Sbjct    94 RLEGS   98

Query   102 ELQTDGNRSSH--SRLG#RIEADSESQEDIIRNIARHLAQVGDSMDRS  146
            ||||||||| |     |#++ +||||||+||+ ||  ||++||+++ |
Sbjct    69 ELQTDGNRSCHFEEEEG#KLLSDSESQEEIIQRIAMQLAKIGDNIENS  115

Query   102 ELQTDGNRSSHSRLG#RIEADSESQEDIIRNIARHLAQVGDSMDR  145
            ||||||||| | + |# +  | |  | |+| ||  ||++|| +|+
Sbjct    57 ELQTDGNRSGHLQNG#ELVPDPEVNEAIVRTIAAQLAEIGDQLDK  100