RBCC Red Blood Cell Collection

BID [Confidence: low (only semi-automatic identification from reviews)]
BH3-interacting domain death agonist (p22 BID; BID; BH3-interacting domain death agonist p15; p15 BID; BH3-interacting domain death agonist p13; p13 BID; BH3-interacting domain death agonist p11; p11 BID)

UniProt P55957
ID BID_HUMAN Reviewed; 195 AA.
AC P55957; Q549M7; Q71T04; Q7Z4M9; Q8IY86;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 1.
DT 22-JAN-2014, entry version 140.
DE RecName: Full=BH3-interacting domain death agonist;
DE AltName: Full=p22 BID;
DE Short=BID;
DE Contains:
DE RecName: Full=BH3-interacting domain death agonist p15;
DE AltName: Full=p15 BID;
DE Contains:
DE RecName: Full=BH3-interacting domain death agonist p13;
DE AltName: Full=p13 BID;
DE Contains:
DE RecName: Full=BH3-interacting domain death agonist p11;
DE AltName: Full=p11 BID;
GN Name=BID;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RX PubMed=8918887;
RA Wang K., Yin X.-M., Chao D.T., Milliman C.L., Korsmeyer S.J.;
RT "BID: a novel BH3 domain-only death agonist.";
RL Genes Dev. 10:2859-2869(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9721221; DOI=10.1006/geno.1998.5392;
RA Footz T.K., Birren B., Minoshima S., Asakawa S., Shimizu N.,
RA Riazi M.A., McDermid H.E.;
RT "The gene for death agonist BID maps to the region of human 22q11.2
RT duplicated in cat eye syndrome chromosomes and to mouse chromosome
RT 6.";
RL Genomics 51:472-475(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=14583606; DOI=10.1074/jbc.M309769200;
RA Renshaw S.A., Dempsey C.E., Barnes F.A., Bagstaff S.M., Dower S.K.,
RA Bingle C.D., Whyte M.K.;
RT "Three novel Bid proteins generated by alternative splicing of the
RT human Bid gene.";
RL J. Biol. Chem. 279:2846-2855(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Dai F.Y., Yu L., Huang H.B., Jiang C.L., Cui Y.Y., Zhao S.Y.;
RT "Cloning and expression of a new human cDNA homology to murine apoptic
RT death agonist (BID) mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-10.
RG NIEHS SNPs program;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP GLN-162.
RC TISSUE=Brain, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-54, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [11]
RP INTERACTION WITH ITCH, AND UBIQUITINATION BY ITCH.
RX PubMed=20392206; DOI=10.1111/j.1742-4658.2010.07562.x;
RA Azakir B.A., Desrochers G., Angers A.;
RT "The ubiquitin ligase Itch mediates the antiapoptotic activity of
RT epidermal growth factor by promoting the ubiquitylation and
RT degradation of the truncated C-terminal portion of Bid.";
RL FEBS J. 277:1319-1330(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP STRUCTURE BY NMR.
RX PubMed=10089877; DOI=10.1016/S0092-8674(00)80572-3;
RA Chou J.J., Li H., Salvesen G.S., Yuan J., Wagner G.;
RT "Solution structure of BID, an intracellular amplifier of apoptotic
RT signaling.";
RL Cell 96:615-624(1999).
CC -!- FUNCTION: The major proteolytic product p15 BID allows the release
CC of cytochrome c (By similarity). Isoform 1, isoform 2 and isoform
CC 4 induce ICE-like proteases and apoptosis. Isoform 3 does not
CC induce apoptosis. Counters the protective effect of Bcl-2.
CC -!- SUBUNIT: Forms heterodimers either with the pro-apoptotic protein
CC BAX or the anti-apoptotic protein Bcl-2 (By similarity). p15 BID
CC interacts with ITCH.
CC -!- INTERACTION:
CC Q07812:BAX; NbExp=15; IntAct=EBI-519672, EBI-516580;
CC P10415:BCL2; NbExp=8; IntAct=EBI-519672, EBI-77694;
CC Q07440:Bcl2a1 (xeno); NbExp=3; IntAct=EBI-519672, EBI-707754;
CC Q07817-1:BCL2L1; NbExp=6; IntAct=EBI-519672, EBI-287195;
CC Q92843:BCL2L2; NbExp=5; IntAct=EBI-519672, EBI-707714;
CC Q03135:CAV1; NbExp=3; IntAct=EBI-519672, EBI-603614;
CC P17361:VACWR028 (xeno); NbExp=2; IntAct=EBI-519672, EBI-7115640;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Mitochondrion
CC membrane (By similarity). Note=When uncleaved, it is predominantly
CC cytoplasmic.
CC -!- SUBCELLULAR LOCATION: BH3-interacting domain death agonist p15:
CC Mitochondrion membrane (By similarity). Note=Translocates to
CC mitochondria as an integral membrane protein (By similarity).
CC -!- SUBCELLULAR LOCATION: BH3-interacting domain death agonist p13:
CC Mitochondrion membrane (By similarity). Note=Associated with the
CC mitochondrial membrane (By similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: Isoform 3: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Mitochondrion membrane. Note=A
CC significant proportion of isoform 2 localizes to mitochondria, it
CC may be cleaved constitutively.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=BID(L);
CC IsoId=P55957-1; Sequence=Displayed;
CC Name=2; Synonyms=BID(EL);
CC IsoId=P55957-2; Sequence=VSP_017267;
CC Name=3; Synonyms=BID(S);
CC IsoId=P55957-3; Sequence=VSP_017268, VSP_017269;
CC Name=4; Synonyms=BID(ES);
CC IsoId=P55957-4; Sequence=VSP_017266;
CC -!- TISSUE SPECIFICITY: Isoform 2 and isoform 3 are expressed in
CC spleen, bone marrow, cerebral and cerebellar cortex. Isoform 2 is
CC expressed in spleen, pancreas and placenta (at protein level).
CC Isoform 3 is expressed in lung, pancreas and spleen (at protein
CC level). Isoform 4 is expressed in lung and pancreas (at protein
CC level).
CC -!- DOMAIN: Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX
CC for their pro-apoptotic activity and for their interaction with
CC anti-apoptotic members of the Bcl-2 family.
CC -!- PTM: TNF-alpha induces a caspase-mediated cleavage of p22 BID into
CC a major p15 and minor p13 and p11 products (By similarity).
CC -!- PTM: p15 BID is ubiquitinated by ITCH; ubiquitination results in
CC proteasome-dependent degradation.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH22072.2; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/bid/";
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DR EMBL; AF042083; AAC34365.1; -; mRNA.
DR EMBL; AF250233; AAO32633.1; -; mRNA.
DR EMBL; AY005151; AAF89091.1; -; mRNA.
DR EMBL; AF087891; AAP97190.1; -; mRNA.
DR EMBL; CR456389; CAG30275.1; -; mRNA.
DR EMBL; CR407603; CAG28531.1; -; mRNA.
DR EMBL; AY309922; AAP50259.1; -; Genomic_DNA.
DR EMBL; BC009197; AAH09197.1; -; mRNA.
DR EMBL; BC022072; AAH22072.2; ALT_INIT; mRNA.
DR EMBL; BC033634; AAH33634.1; -; mRNA.
DR EMBL; BC036364; AAH36364.2; -; mRNA.
DR RefSeq; NP_001187.1; NM_001196.3.
DR RefSeq; NP_001231496.1; NM_001244567.1.
DR RefSeq; NP_001231498.1; NM_001244569.1.
DR RefSeq; NP_001231499.1; NM_001244570.1.
DR RefSeq; NP_001231501.1; NM_001244572.1.
DR RefSeq; NP_932070.1; NM_197966.2.
DR RefSeq; NP_932071.1; NM_197967.2.
DR UniGene; Hs.591054; -.
DR PDB; 1ZY3; NMR; -; B=82-101.
DR PDB; 2BID; NMR; -; A=1-195.
DR PDB; 2KBW; NMR; -; B=76-106.
DR PDB; 2M5B; NMR; -; B=80-101.
DR PDB; 2M5I; NMR; -; A=61-195.
DR PDB; 4BD2; X-ray; 2.21 A; C=76-109.
DR PDBsum; 1ZY3; -.
DR PDBsum; 2BID; -.
DR PDBsum; 2KBW; -.
DR PDBsum; 2M5B; -.
DR PDBsum; 2M5I; -.
DR PDBsum; 4BD2; -.
DR ProteinModelPortal; P55957; -.
DR SMR; P55957; 1-195.
DR DIP; DIP-34937N; -.
DR IntAct; P55957; 26.
DR MINT; MINT-270277; -.
DR STRING; 9606.ENSP00000318822; -.
DR BindingDB; P55957; -.
DR PhosphoSite; P55957; -.
DR DMDM; 2493285; -.
DR OGP; P55957; -.
DR PaxDb; P55957; -.
DR PRIDE; P55957; -.
DR DNASU; 637; -.
DR Ensembl; ENST00000317361; ENSP00000318822; ENSG00000015475.
DR Ensembl; ENST00000342111; ENSP00000344594; ENSG00000015475.
DR Ensembl; ENST00000399765; ENSP00000382667; ENSG00000015475.
DR Ensembl; ENST00000399767; ENSP00000382669; ENSG00000015475.
DR Ensembl; ENST00000399774; ENSP00000382674; ENSG00000015475.
DR Ensembl; ENST00000551952; ENSP00000449236; ENSG00000015475.
DR GeneID; 637; -.
DR KEGG; hsa:637; -.
DR UCSC; uc002znd.2; human.
DR CTD; 637; -.
DR GeneCards; GC22M018216; -.
DR HGNC; HGNC:1050; BID.
DR HPA; CAB003771; -.
DR HPA; HPA000722; -.
DR MIM; 601997; gene.
DR neXtProt; NX_P55957; -.
DR PharmGKB; PA25353; -.
DR eggNOG; NOG78659; -.
DR HOGENOM; HOG000010016; -.
DR HOVERGEN; HBG001703; -.
DR InParanoid; P55957; -.
DR KO; K04726; -.
DR OMA; KVADHTP; -.
DR OrthoDB; EOG73V6MW; -.
DR Reactome; REACT_578; Apoptosis.
DR ChiTaRS; BID; human.
DR EvolutionaryTrace; P55957; -.
DR GeneWiki; BH3_interacting-domain_death_agonist; -.
DR GeneWiki; BH3_interacting_domain_death_agonist; -.
DR GenomeRNAi; 637; -.
DR NextBio; 2578; -.
DR PMAP-CutDB; P55957; -.
DR PRO; PR:P55957; -.
DR ArrayExpress; P55957; -.
DR Bgee; P55957; -.
DR CleanEx; HS_BID; -.
DR Genevestigator; P55957; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032592; C:integral to mitochondrial membrane; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0005123; F:death receptor binding; TAS:ProtInc.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0090150; P:establishment of protein localization to membrane; IDA:BHF-UCL.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:ProtInc.
DR GO; GO:0034349; P:glial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0051402; P:neuron apoptotic process; TAS:HGNC.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:1901030; P:positive regulation of mitochondrial outer membrane permeabilization; TAS:Reactome.
DR GO; GO:0032464; P:positive regulation of protein homooligomerization; IDA:BHF-UCL.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IEA:Ensembl.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:HGNC.
DR GO; GO:0032355; P:response to estradiol stimulus; IEA:Ensembl.
DR InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR InterPro; IPR010479; BID.
DR Pfam; PF06393; BID; 1.
DR PIRSF; PIRSF038018; BID; 1.
DR PROSITE; PS01259; BH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Complete proteome; Cytoplasm; Membrane; Mitochondrion; Phosphoprotein;
KW Polymorphism; Reference proteome; Ubl conjugation.
FT CHAIN 1 195 BH3-interacting domain death agonist.
FT /FTId=PRO_0000143101.
FT CHAIN 62 195 BH3-interacting domain death agonist p15
FT (By similarity).
FT /FTId=PRO_0000223233.
FT CHAIN 77 195 BH3-interacting domain death agonist p13
FT (By similarity).
FT /FTId=PRO_0000223232.
FT CHAIN 100 195 BH3-interacting domain death agonist p11
FT (By similarity).
FT /FTId=PRO_0000223231.
FT MOTIF 86 100 BH3.
FT SITE 61 62 Cleavage (By similarity).
FT SITE 76 77 Cleavage (By similarity).
FT SITE 99 100 Cleavage (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 54 54 Phosphotyrosine.
FT MOD_RES 78 78 Phosphoserine.
FT VAR_SEQ 1 96 Missing (in isoform 4).
FT /FTId=VSP_017266.
FT VAR_SEQ 1 1 M -> MCSGAGVMMARWAARGRAGWRSTVRILSPLGHCEPG
FT VSRSCRAAQAM (in isoform 2).
FT /FTId=VSP_017267.
FT VAR_SEQ 75 137 DSESQEDIIRNIARHLAQVGDSMDRSIPPGLVNGLALQLRN
FT TSRSEEDRNRDLATALEQLLQA -> GASDNNTASAEEETE
FT AAGSVAVERGLHGAATVILKVKKTSSGILPGTSPRSGTAWT
FT VASLRAW (in isoform 3).
FT /FTId=VSP_017268.
FT VAR_SEQ 138 195 Missing (in isoform 3).
FT /FTId=VSP_017269.
FT VARIANT 10 10 S -> G (in dbSNP:rs8190315).
FT /FTId=VAR_018845.
FT VARIANT 162 162 H -> Q (in dbSNP:rs17853595).
FT /FTId=VAR_025332.
FT VARIANT 194 194 M -> T (in dbSNP:rs59225839).
FT /FTId=VAR_061041.
FT HELIX 15 27
FT STRAND 31 33
FT HELIX 34 40
FT HELIX 41 43
FT HELIX 77 96
FT HELIX 97 99
FT STRAND 100 102
FT HELIX 106 114
FT HELIX 116 118
FT HELIX 119 135
FT HELIX 145 162
FT HELIX 167 179
FT TURN 180 182
FT HELIX 183 191
SQ SEQUENCE 195 AA; 21995 MW; B17A07334C1AFBEF CRC64;
MDCEVNNGSS LRDECITNLL VFGFLQSCSD NSFRRELDAL GHELPVLAPQ WEGYDELQTD
GNRSSHSRLG RIEADSESQE DIIRNIARHL AQVGDSMDRS IPPGLVNGLA LQLRNTSRSE
EDRNRDLATA LEQLLQAYPR DMEKEKTMLV LALLLAKKVA SHTPSLLRDV FHTTVNFINQ
NLRTYVRSLA RNGMD
//

MIM 601997
*RECORD*
*FIELD* NO
601997
*FIELD* TI
*601997 BH3-INTERACTING DOMAIN DEATH AGONIST; BID
*FIELD* TX

CLONING

The BCL2 family of proteins consists of both antagonists (e.g., BCL2;
read more151430) and agonists (e.g., BAX; 600040 and BAK; 600516) that regulate
apoptosis and compete through dimerization. The BH1 and BH2 domains of
BCL2 are required to heterodimerize with BAX and to repress cell death.
Conversely, the BH3 domain of BAX is required to heterodimerize with
BCL2 and to promote cell death. Wang et al. (1996) identified a gene
they termed BID (BH3 Interacting domain Death agonist) that encodes a
novel death agonist that heterodimerizes with either agonists (BAX) or
antagonists (BCL2). BID possesses only the BH3 domain, lacks a
C-terminal signal-anchor segment, and is found in both cytosolic and
membrane locations. BID's only homology with the BCL2 family is the
conserved BH3 domain. BID counters the protective effect of BCL2.
Expression of BID induces ICE-like proteases which are thought to be
downstream of BCL2, activated in apoptosis, and required for aspects of
cell death. Wang et al. (1996) stated that the discovery of this
BH3-only molecule supports the identification of BH3 as a death domain
and favors a model in which BID represents a death ligand for the
membrane-bound receptor BAX.

GENE FUNCTION

Luo et al. (1998) reported the purification of a cytosolic protein that
induces cytochrome c release from mitochondria in response to caspase-8
(CASP8; 601763), the apical caspase activated by cell surface death
receptors such as FAS (134637) and TNF (191160). Peptide mass
fingerprinting identified this protein as BID. CASP8 cleaves BID, and
the COOH-terminal part translocates to mitochondria where it triggers
cytochrome c release. Immunodepletion of BID from cell extracts
eliminated the cytochrome c releasing activity. The cytochrome c
releasing activity of BID was antagonized by BCL2. A mutation at the BH3
domain diminished its cytochrome c releasing activity. BID, therefore,
relays an apoptotic signal from the cell surface to mitochondria.

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.

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.

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.

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

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 (600040) and BAK (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, 603827; BID; and
PUMA, 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.

Yeretssian et al. (2011) used genomewide RNA interference to identify
candidate genes that modulate the NOD1 (605980) inflammatory response in
intestinal epithelial cells. Their results revealed a significant
crosstalk between innate immunity and apoptosis and identified BID as a
critical component of the inflammatory response. Colonocytes depleted of
BID or macrophages from Bid-null mice are markedly defective in cytokine
production in response to NOD activation. Furthermore, Bid-null mice are
unresponsive to local or systemic exposure to NOD agonists or their
protective effect in experimental colitis. Mechanistically, BID
interacts with NOD1, NOD2 (605956), and the I-kappa-B kinase complex
(see 600664), impacting NF-kappa-B (see 164011) and extracellular
signal-regulated kinase (ERK; see 601795) signaling. Yeretssian et al.
(2011) concluded that their results defined a novel role of BID in
inflammation and immunity independent of its apoptotic function,
furthering the evidence of evolutionary conservation between the
mechanisms of apoptosis and immunity.

Nachbur et al. (2012) used the same strain of Bid-null mice as
Yeretssian et al. (2012) and found that the mice responded like wildtype
mice to NOD ligands and that the levels of NFK-beta or ERK activation
cytokine secretion from BID-null bone marrow-derived macrophages (BMDMs)
were indistinguishable from the wildtype response. Nachbur et al. (2012)
therefore proposed that the nonapoptotic role of BID in inflammation and
innate immunity should be reassessed. To understand the discrepancy
between their results and those of Yeretssian et al. (2012), Nachbur et
al. (2012) generated BMDMs from wildtype, Bid-null, and Ripk2-null mice
and activated NOD signaling in these cells in vitro by 2 separate
methods. Regardless of the method used, Nachbur et al. (2012) observed
comparable levels of IL6 (147620) secretion in Bid-null and wildtype
BMDMs, whereas Ripk2-null cells were unresponsive to any of the
treatments. Nachbur et al. (2012) evaluated activation of NFK-beta and
ERK signaling using 4 different protocols for NOD activation and,
regardless of method, detected normal levels of NFK-beta activation and
ERK phosphorylation in Bid-deficient BMDMs. They concluded that BID is
not essential for NOD signaling. Yeretssian et al. (2012) replied that
it is difficult to draw any conclusions based on the divergent data
presented by Nachbur et al. (2012) and that although the extent to which
BID is required for NOD signaling may vary with cellular context and
with environmental and disease conditions, their conclusion that BID
contributes to NOD-mediated responses is reproducible and has been
repeated independently.

BIOCHEMICAL FEATURES

Chou et al. (1999) and McDonnell et al. (1999) determined the solution
structure of BID using NMR spectroscopy.

MAPPING

By fluorescence in situ hybridization, Wang et al. (1998) mapped the
human BID gene to 22q11. By interspecific backcross analysis, they
mapped the mouse Bid gene to chromosome 6 near the Atp6e gene.

Footz et al. (1998) reported mapping of the BID gene to human chromosome
22 by study of genomic DNA from a human/hamster hybrid cell line
containing chromosome 22 as the only human component. The gene was found
to fall within the segment of 22q11.2 that is duplicated in the cat eye
syndrome (CES; 115470). Only 1 gene, ATP6E (108746), had previously been
mapped to this duplicated region. Dosage analysis demonstrated that BID
is located just distal to the CES region critical for most malformations
associated with the syndrome. Bid and the adjacent gene Atp6e were found
to map to mouse chromosome 6, whereas the region homologous to the
DiGeorge syndrome critical region (188400) is known to map to mouse
chromosome 16.

ANIMAL MODEL

Yin et al. (1999) generated mice deficient in Bid by homologous
recombination. Bid -/- mice were born at the expected frequency and had
no developmental abnormalities. When Bid -/- mice were injected with an
antibody against Fas, nearly all survived, whereas wildtype mice died
from hepatocellular apoptosis and hemorrhagic necrosis. About half of
the Bid -/- mice had no apparent liver injury and showed no evidence of
activation of the effector caspases 3 (600636) and 7 (601761), although
the initiator caspase-8 had been activated. Other Bid-deficient mice
survived with only moderate damage: all 3 caspases (3, 7, and 8) were
activated, but their cell nuclei were intact, and no mitochondrial
cytochrome c was released. Yin et al. (1999) also investigated the
effects of Bid deficiency in cultured cells treated with anti-Fas
antibody or with TNF-alpha. 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 signaling by death-receptor agonists that mediates
a mitochondrial amplification loop that is essential for the apoptosis
of selected cells.

Budinger et al. (2006) observed significantly less pulmonary fibrosis in
response to intratracheal bleomycin in Bid-null mice than in wildtype
mice, despite similar levels of inflammation, lung injury, and active
TGFB1 (190180) in bronchoalveolar lavage fluid. Bleomycin induced
similar levels of cell death in vitro in alveolar epithelial cells
isolated from wildtype and Bid-null mice; however, alveolar epithelial
cells from Bid-null mice were resistant to TGFB1-induced cell death.
Budinger et al. (2006) concluded that BCL2 family members are critical
regulators in the development of pulmonary fibrosis downstream of TGFB1
activation.

By generating novel Bid -/- mice and testing other Bid -/- mouse
strains, Kaufmann et al. (2007) ruled out a role for BID in DNA damage-
or replicative stress-induced apoptosis or cell cycle arrest.

Ren et al. (2010) provided in vivo evidence demonstrating an essential
role of the proteins BID, BIM (603827), and PUMA (605854) in activating
BAX (600040) and BAK (600516). Bid, Bim, and Puma triple-knockout mice
showed the same developmental defects that are associated with
deficiency of Bax and Bak, including persistent interdigital webs and
imperforate vaginas. Genetic deletion of Bid, Bim, and Puma prevented
the homooligomerization of Bax and Bak, and thereby cytochrome c
(123970)-mediated activation of caspases in response to diverse death
signals in neurons and T lymphocytes, despite the presence of other
BH3-only molecules. Thus, Ren et al. (2010) concluded that many forms of
apoptosis require direct activation of BAX and BAK at the mitochondria
by a member of the BID, BIM, or PUMA family of proteins.

*FIELD* RF
1. Budinger, G. R. S.; Mutlu, G. M.; Eisenbart, J.; Fuller, A. C.;
Bellmeyer, A. A.; Baker, C. M.; Wilson, M.; Ridge, K.; Barrett, T.
A.; Lee, V. Y.; Chandel, N. S.: Proapoptotic Bid is required for
pulmonary fibrosis. Proc. Nat. Acad. Sci. 103: 4604-4609, 2006.

2. Chou, J. J.; Li, H.; Salvesen, G. S.; Yuan, J.; Wagner, G.: Solution
structure of BID, an intracellular amplifier of apoptotic signaling. Cell 95:
615-624, 1999.

3. Footz, T. K.; Birren, B.; Minoshima, S.; Asakawa, S.; Shimizu,
N.; Ali Riazi, M.; McDermid, H. E.: The gene for death agonist BID
maps to the region of human 22q11.2 duplicated in cat eye syndrome
chromosomes and to mouse chromosome 6. Genomics 51: 472-475, 1998.

4. Kaufmann, T.; Tai, L.; Ekert, P. G.; Huang, D. C. S.; Norris, F.;
Lindemann, R. K.; Johnstone, R. W.; Dixit, V. M.; Strasser, A.: The
BH3-only protein Bid is dispensable for DNA damage- and replicative
stress-induced apoptosis or cell-cycle arrest. Cell 129: 423-433,
2007.

5. Li, H.; Zhu, H.; Xu, C.; Yuan, J.: Cleavage of BID by caspase
8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:
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6. Luo, X.; Budihardjo, I.; Zou, H.; Slaughter, C.; Wang, X.: Bid,
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7. McDonnell, J. M.; Fushman, D.; Milliman, C. L.; Korsmeyer, S. J.;
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8. Nachbur, U.; Vince, J. E.; O'Reilly, L. A.; Strasser, A.; Silke,
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2012. Note: Electronic Article.

9. Ren, D.; Tu, H.-C.; Kim, H.; Wang, G. X.; Bean, G. R.; Takeuchi,
O.; Jeffers, J. R.; Zambetti, G. P.; Hsieh, J. J.-D.; Cheng, E. H.-Y.
: BID, BIM, and PUMA are essential for activation of the BAX- and
BAK-dependent cell death program. Science 330: 1390-1393, 2010.

10. Sax, J. K.; Fei, P.; Murphy, M. E.; Bernhard, E.; Korsmeyer, S.
J.; El-Deiry, W.: BID regulation by p53 contributes to chemosensitivity. Nature
Cell Biol. 4: 842-849, 2002.

11. Wang, K.; Yin, X.-M.; Chao, D. T.; Milliman, C. L.; Korsmeyer,
S. J.: BID: a novel BH3 domain-only death agonist. Genes Dev. 10:
2859-2869, 1996.

12. Wang, K.; Yin, X.-M.; Copeland, N. G.; Gilbert, D. J.; Jenkins,
N. A.; Keck, C. L.; Zimonjic, D. B.; Popescu, N. C.; Korsmeyer, S.
J.: BID, a proapoptotic BCL-2 family member, is localized to mouse
chromosome 6 and human chromosome 22q11. Genomics 53: 235-238, 1998.

13. Wei, M. C.; Zong, W.-X.; Cheng, E. H.-Y.; Lindsten, T.; Panoutsakopoulou,
V.; Ross, A. J.; Roth, K. A.; MacGregor, G. R.; Thompson, C. B.; Korsmeyer,
S. J.: Proapoptotic BAX or BAK: a requisite gateway to mitochondrial
dysfunction and death. Science 292: 727-730, 2001.

14. Willis, S. N.; Fletcher, J. I.; Kaufmann, T.; van Delft, M. F.;
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Bouillet, P.; Strasser, A.; Kluck, R. M.; Adams, J. M.; Huang, D.
C. S.: Apoptosis initiated when BH3 ligands engage multiple Bcl-2
homologs, not Bax or Bak. Science 315: 856-859, 2007.

15. Yeretssian, G.; Correa, R. G.; Doiron, K.; Fitzgerald, P.; Dillon,
C. P.; Green, D. R.; Reed, J. C.; Saleh, M.: Reply to Nachbur et
al. 2012. Nature 488: E6-E8, 2012. Note: Electronic Article. Erratum:
Nature 491: 784 only, 2012.

16. Yeretssian, G.; Correa, R. G.; Doiron, K.; Fitzgerald, P.; Dillon,
C. P.; Green, D. R.; Reed, J. C.; Saleh, M.: Non-apoptotic role of
BID in inflammation and innate immunity. Nature 474: 96-99, 2011.

17. Yin, X.-M.; Wang, K.; Gross, A.; Zhao, Y.; Zinkel, S.; Klocke,
B.; Roth, K. A.; Korsmeyer, S. J.: Bid-deficient mice are resistant
to Fas-induced hepatocellular apoptosis. Nature 400: 886-891, 1999.

18. Zha, J.; Weiler, S.; Oh, K. J.; Wei, M. C.; Korsmeyer, S. J.:
Posttranslational N-myristoylation of BID as a molecular switch for
targeting mitochondria and apoptosis. Science 290: 1761-1765, 2000.

*FIELD* CN
Ada Hamosh - updated: 1/9/2013
Ada Hamosh - updated: 6/22/2011
Ada Hamosh - updated: 12/28/2010
Paul J. Converse - updated: 11/9/2007
Ada Hamosh - updated: 4/17/2007
Marla J. F. O'Neill - updated: 6/7/2006
Patricia A. Hartz - updated: 3/25/2003
Ada Hamosh - updated: 5/7/2001
Ada Hamosh - updated: 12/6/2000
Ada Hamosh - updated: 2/7/2000
Stylianos E. Antonarakis - updated: 3/25/1999
Carol A. Bocchini - updated: 12/4/1998
Victor A. McKusick - updated: 11/30/1998
Stylianos E. Antonarakis - updated: 9/15/1998

*FIELD* CD
Ethylin Wang Jabs: 9/15/1997

*FIELD* ED
carol: 10/02/2013
alopez: 1/14/2013
terry: 1/9/2013
alopez: 6/23/2011
terry: 6/22/2011
alopez: 1/3/2011
terry: 12/28/2010
mgross: 11/9/2007
alopez: 4/19/2007
terry: 4/17/2007
wwang: 6/7/2006
mgross: 3/25/2003
alopez: 5/8/2001
terry: 5/7/2001
carol: 12/7/2000
terry: 12/6/2000
alopez: 2/9/2000
terry: 2/7/2000
mgross: 3/26/1999
terry: 3/25/1999
terry: 12/4/1998
dkim: 12/3/1998
carol: 11/30/1998
alopez: 10/23/1998
carol: 9/15/1998
joanna: 9/2/1998
mark: 9/16/1997