BID(BH3 interacting-domain death agonist)属于BH3-only蛋白家族,是Bcl-2蛋白家族的重要成员之一。该基因编码的蛋白是一种促凋亡蛋白,主要参与线粒体途径的细胞凋亡调控。BID的生物学功能是通过其BH3结构域(Bcl-2 homology domain 3)与其他Bcl-2家族蛋白相互作用,激活下游凋亡信号。当细胞受到凋亡刺激(如死亡受体激活)时,BID会被caspase-8剪切生成截短形式tBID(truncated BID),tBID转移到线粒体膜上,促使线粒体外膜通透性增加,导致细胞色素c释放,进而激活caspase级联反应引发细胞凋亡。BID的主要作用位点是线粒体,其功能受上游死亡受体信号(如Fas/CD95)调控。BID突变可能导致其无法被caspase-8有效剪切或丧失与Bcl-2家族蛋白相互作用的能力,从而抑制凋亡过程,这种异常与肿瘤发生发展相关。研究表明BID功能缺失可能促进肿瘤细胞存活,而其过度激活可能导致组织损伤。BID过表达会增强细胞对凋亡信号的敏感性,可能引起病理性细胞死亡;而低表达则可能导致凋亡抵抗,与癌症化疗耐药性有关。BID与多种疾病相关,包括肝癌、白血病等恶性肿瘤,以及肝衰竭等凋亡过度激活疾病。BH3-only蛋白家族的共性是通过BH3结构域与抗凋亡Bcl-2家族蛋白(如Bcl-2、Bcl-xL)结合,中和它们的抗凋亡作用或直接激活促凋亡蛋白(如BAX、BAK),在凋亡信号传递中起关键作用。这个家族的蛋白通常以非活性形式存在,需要被特定蛋白酶剪切或翻译后修饰才能发挥功能。BID的特殊性在于它是连接死亡受体通路和线粒体通路的关键分子。
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]
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BID基因(以及对应的蛋白质)的细胞分布位置:
BID基因的本体(GO)信息:
名称 |
---|
4071 Sphingolipid signaling pathway [PATH:hsa04071] |
4210 Apoptosis [PATH:hsa04210] |
4115 p53 signaling pathway [PATH:hsa04115] |
4650 Natural killer cell mediated cytotoxicity [PATH:hsa04650] |
5200 Pathways in cancer [PATH:hsa05200] |
5010 Alzheimer's disease [PATH:hsa05010] |
5014 Amyotrophic lateral sclerosis (ALS) [PATH:hsa05014] |
5416 Viral myocarditis [PATH:hsa05416] |
4932 Non-alcoholic fatty liver disease (NAFLD) [PATH:hsa04932] |
5152 Tuberculosis [PATH:hsa05152] |
名称 |
---|
Activation and oligomerization of BAK protein |
Activation of BAD and translocation to mitochondria |
Activation of BH3-only proteins |
Activation, myristolyation of BID and translocation to mitochondria |
Activation, translocation and oligomerization of BAX |
Apoptosis |
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members |
Intrinsic Pathway for Apoptosis |
Programmed Cell Death |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
Stomach Neoplasms | 0.122367032 | 2 | 0 | CTD_human_GAD |
Liver carcinoma | 0.120271442 | 2 | 0 | BeFree_CTD_human |
Myocardial Reperfusion Injury | 0.08 | 1 | 0 | RGD |
Reperfusion Injury | 0.08 | 1 | 0 | RGD |
Mammary Neoplasms | 0.008173051 | 3 | 0 | LHGDN |
Adenocarcinoma | 0.007815732 | 3 | 0 | GAD_LHGDN |
Malignant neoplasm of breast | 0.005819831 | 5 | 5 | BeFree_GAD |
melanoma | 0.002995792 | 2 | 1 | BeFree_LHGDN |
Colonic Neoplasms | 0.00272435 | 1 | 0 | LHGDN |
Lung Neoplasms | 0.00272435 | 1 | 0 | LHGDN |
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