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FLASH GENE

Symbol

BID

contributors: mct/pgu - updated : 18-09-2015

HGNC name	BH3 interacting domain death agonist
HGNC id	1050

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001196 6 - 2214 NP_001187 - 195 - 2005 15899861 NM_197966 6 - 1101 NP_932070 26.6 241 predominantly in tissues hemopoietic, spleen and bone marrow, also expressed at high levels in cerebral and cerebellar cortex, as might be expected given the importance of BID in regulating neuronal cell death 2005 15899861 also called BID(EL) an additional 45 amino acids at the N terminus that do not contain any recognized conserved domains NM_197967 5 splicing 2144 NP_932071 11.3 99 lung, pancreas 2005 15899861 also called BID(ES) only the BID sequence downstream of the BH3 domain induces apoptosis but is also able to partially inhibit the pro-apoptotic effects of truncated BID NM_001244569 5 - 2006 NP_001231498 15 99 - 2013 23744079 also called BIDT truncated form formed upon cleavage of BID by protease caspase-8, and can promote the oligomerization/insertion of BAX into the outer mitochondrial membrane can induce apoptosis by promoting BAX activation interaction of MTCH2 and tBID is a potential target for therapeutic control of BID initiated cell death contains the BH3 domain and serves as the active form of BID: it translocates to the mitochondria and activates BAX/BAK1 homo-oligomerization in the outer mitochondrial membrane MTCH2 recruits tBID to the mitochondria, and consequently tBID activates the BAX protein to initiate apoptosis NM_001244567 6 - 2128 NP_001231496 - 195 - 2005 15899861 NM_001244570 6 - 1935 NP_001231499 - 99 - 2005 15899861 NM_001244572 4 - 2272 NP_001231501 - 99 - 2005 15899861

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive intestine large intestine colon     Homo sapiens   liver

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial absorptive excretory digestive epithelium (mucosa)     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Digestive epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	eight alpha helices, containing from the N terminal
	three BCL2 homology domain

mono polymer

heteromer , dimer

HOMOLOGY

interspecies

homolog to murine Bid

Homologene

FAMILY

BCL-2 family of cell death regulators

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,outer
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic
text	expressed in cytosol and translocated to mitochondria after proteolytic activation by CASP8
	truncated BID (tBID) translocates to the mitochondria, facilitates the release of cytochrome c, and activates the intrinsic pathways
	binds to the membrane, and undergoes slow structural rearrangements that result in an equilibrium between two major tBID conformations on the membrane

basic FUNCTION	death agonist (inducing apoptosis), inducing mitochondrial damage by caspase-8 cleavage
	acting downstream of MAPK8 in TNF signaling to mitochondria
	important role in activating the mitochondrial apoptosis pathway after death receptor engagement, particularly in hepatocytes
	regulates hepatocyte proliferation by positively affecting [Ca(2+)](ER) homeostasis, which could be important for liver regeneration and carcinogenesis
	having a unique role in signaling of apoptosis, because it links the death receptor signaling pathway to the mitochondrial signaling pathway mediated by BCL2 proteins
	mediator of mitochondrial damage induced by caspase-8 (CASP8)
	a pro-apoptotic BCL-2 family member playing an essential role in initiating this program
	involved in the Bak/Bax-dependent mitochondrial cell death pathway
	putative cathepsin B target in SPARC-induced apoptosis
	novel role of BID in inflammation and immunity independent of its apoptotic function
	potential proximal regulator of the NOD1 signalling complex
	involved in tumor necrosis factor death receptor I (TNFRI)-mediated destructive signal transduction pathways such as cell dysfunction or neurodegeneration in the temporal cortex of patients with Parkinson disease

CELLULAR PROCESS	cell life, cell death/apoptosis
	nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	heterodimerizing with either agonists (BAX) or antagonists (BCL2) of apoptosis
	cleaved in response to apoptotic stimuli into two fragments, p7 and tBid (p15), that are held together by strong hydrophobic interactions until the complex binds to membranes (9)

INTERACTION

DNA

RNA

small molecule

protein	MAPK8, DIABLO for TNF-mediated CASP8 cleavage and apoptosis
	GZMK directly processes BID to release cytochrome c and endonuclease G leading to mitochondria-dependent cell death
	preferentially associated with the CK2alpha (CSNK2A1) subunit
	BID, BCL2L11, and BBC3 are required to activate BAX- and BAK1-dependent mitochondrial apoptosis
	CAV1 regulates hyperoxia/ROS-induced apoptosis through interactions with FAS and BID, probably via FAS palmitoylation and CAV1 Y14 phosphorylation, respectively
	interacts with NOD1, NOD2 and the IKB kinase (IKK) complex, impacting NFKB and extracellular signal-regulated kinase (ERK) signalling
	BID associates with RPA1 and stimulates the recruitment and/or stabilization of ATR-ATRIP to the DNA damage sensor complex
	activates BAK1 to mitochondrial outer-membrane permeabilization (MOMP), which leads to apoptosis
	KAT2B and TADA3 regulate BID processing via PACS2, to modulate the mitochondrial cell death pathway in response to GZMB
	role for MOAP1 in FAS signaling in the liver by promoting MTCH2-mediated BID recruitment to mitochondria
	ANXA1 interacted with the BID (BH3-interacting-domain death agonist) promoter directly

cell & other

REGULATION

activated by

CASP8

Other

regulated in part by alternative splicing

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function loss of BID function impaired the ability of NOD2 but not TLR3 to trigger tissue repair responses upon injury

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast with its substrate CTSB were shown to be molecular links between apoptosis and autophagy in breast cancer MCF-7 cells exposed to the cytostatic drug, camptothecin

ANIMAL & CELL MODELS

Bid-/- mice are unresponsive to local or systemic exposure to NOD agonists or their protective effect in experimental colitis