P55957 (BID_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
BH3-interacting domain death agonist

Alternative name(s):
p22 BID
Short name=BID

Cleaved into the following 3 chains:

1. BH3-interacting domain death agonist p15
   Alternative name(s):
   p15 BID
2. BH3-interacting domain death agonist p13
   Alternative name(s):
   p13 BID
3. BH3-interacting domain death agonist p11
   Alternative name(s):
   p11 BID

Gene names

Name:

BID

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	195 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The major proteolytic product p15 BID allows the release of cytochrome c By similarity. Isoform 1, isoform 2 and isoform 4 induce ICE-like proteases and apoptosis. Isoform 3 does not induce apoptosis. Counters the protective effect of Bcl-2. Ref.3
Subunit structure	Forms heterodimers either with the pro-apoptotic protein BAX or the anti-apoptotic protein Bcl-2 By similarity. p15 BID interacts with ITCH. Ref.11
Subcellular location	Cytoplasm By similarity. Mitochondrion membrane By similarity. Note: When uncleaved, it is predominantly cytoplasmic. Ref.3 BH3-interacting domain death agonist p15: Mitochondrion membrane By similarity. Note: Translocates to mitochondria as an integral membrane protein By similarity. Ref.3 BH3-interacting domain death agonist p13: Mitochondrion membrane By similarity. Note: Associated with the mitochondrial membrane By similarity. Ref.3 Isoform 1: Cytoplasm Ref.3. Isoform 3: Cytoplasm Ref.3. Isoform 2: Mitochondrion membrane. Note: A significant proportion of isoform 2 localizes to mitochondria, it may be cleaved constitutively. Ref.3
Tissue specificity	Isoform 2 and isoform 3 are expressed in spleen, bone marrow, cerebral and cerebellar cortex. Isoform 2 is expressed in spleen, pancreas and placenta (at protein level). Isoform 3 is expressed in lung, pancreas and spleen (at protein level). Isoform 4 is expressed in lung and pancreas (at protein level). Ref.3
Domain	Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.
Post-translational modification	TNF-alpha induces a caspase-mediated cleavage of p22 BID into a major p15 and minor p13 and p11 products By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.9 Ref.10 p15 BID is ubiquitinated by ITCH; ubiquitination results in proteasome-dependent degradation.
Sequence caution	The sequence AAH22072.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Membrane Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of pro-apoptotic gene products Traceable author statement. Source: Reactome establishment of protein localization in membrane Inferred from direct assay. Source: BHF-UCL induction of apoptosis by intracellular signals Traceable author statement. Source: Reactome induction of apoptosis via death domain receptors Traceable author statement. Source: ProtInc neuron apoptosis Traceable author statement. Source: HGNC positive regulation of protein homooligomerization Inferred from direct assay. Source: BHF-UCL positive regulation of release of cytochrome c from mitochondria Inferred from genetic interaction. Source: BHF-UCL release of cytochrome c from mitochondria Inferred from direct assay. Source: HGNC
Cellular component	cytosol Traceable author statement. Source: Reactome membrane fraction Traceable author statement. Source: ProtInc mitochondrial outer membrane Traceable author statement. Source: Reactome
Molecular function	death receptor binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	3	EBI-519672,EBI-77694
BCL2L2	Q92843	2	EBI-519672,EBI-707714
CAV1	Q03135	3	EBI-519672,EBI-603614

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P55957-1)

Also known as: BID(L);

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P55957-2)

Also known as: BID(EL);

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MCSGAGVMMARWAARGRAGWRSTVRILSPLGHCEPGVSRSCRAAQAM

Isoform 3 (identifier: P55957-3)

Also known as: BID(S);

The sequence of this isoform differs from the canonical sequence as follows:
     75-137: DSESQEDIIR...ATALEQLLQA → GASDNNTASA...AWTVASLRAW
     138-195: Missing.

Isoform 4 (identifier: P55957-4)

Also known as: BID(ES);

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 195

195

BH3-interacting domain death agonist

PRO_0000143101

Chain

62 – 195

134

BH3-interacting domain death agonist p15 By similarity

PRO_0000223233

Chain

77 – 195

119

BH3-interacting domain death agonist p13 By similarity

PRO_0000223232

Chain

100 – 195

96

BH3-interacting domain death agonist p11 By similarity

PRO_0000223231

Regions

Motif

86 – 100

15

BH3

Sites

Site

61 – 62

2

Cleavage By similarity

Site

76 – 77

2

Cleavage By similarity

Site

99 – 100

2

Cleavage By similarity

Amino acid modifications

Modified residue

54

1

Phosphotyrosine Ref.9

Modified residue

78

1

Phosphoserine Ref.10

Natural variations

Alternative sequence

1 – 96

96

Missing in isoform 4.

VSP_017266

Alternative sequence

1

1

M → MCSGAGVMMARWAARGRAGW RSTVRILSPLGHCEPGVSRS CRAAQAM in isoform 2.

VSP_017267

Alternative sequence

75 – 137

63

DSESQ…QLLQA → GASDNNTASAEEETEAAGSV AVERGLHGAATVILKVKKTS SGILPGTSPRSGTAWTVASL RAW in isoform 3.

VSP_017268

Alternative sequence

138 – 195

58

Missing in isoform 3.

VSP_017269

Natural variant

10

1

S → G. Ref.7
Corresponds to variant rs8190315 [ dbSNP | Ensembl ].

VAR_018845

Natural variant

162

1

H → Q. Ref.8
Corresponds to variant rs17853595 [ dbSNP | Ensembl ].

VAR_025332

Natural variant

194

1

M → T.
Corresponds to variant rs59225839 [ dbSNP | Ensembl ].

VAR_061041

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

195

Helix Strand Turn

Details...

Helix

15 – 27

13

Beta strand

31 – 33

3

Helix

34 – 40

7

Helix

41 – 43

3

Helix

84 – 98

15

Helix

106 – 114

9

Helix

116 – 118

3

Helix

119 – 135

17

Helix

145 – 162

18

Helix

167 – 179

13

Turn

180 – 182

3

Helix

183 – 191

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (BID(L)) [UniParc]. Last modified November 1, 1997. Version 1. Checksum: B17A07334C1AFBEF	FASTA	195	21,995
	10 20 30 40 50 60 MDCEVNNGSS LRDECITNLL VFGFLQSCSD NSFRRELDAL GHELPVLAPQ WEGYDELQTD 70 80 90 100 110 120 GNRSSHSRLG RIEADSESQE DIIRNIARHL AQVGDSMDRS IPPGLVNGLA LQLRNTSRSE 130 140 150 160 170 180 EDRNRDLATA LEQLLQAYPR DMEKEKTMLV LALLLAKKVA SHTPSLLRDV FHTTVNFINQ 190 NLRTYVRSLA RNGMD
	Isoform 2 (BID(EL)) [UniParc]. Checksum: 437706F65542B380	FASTA	241	26,836
	10 20 30 40 50 60 MCSGAGVMMA RWAARGRAGW RSTVRILSPL GHCEPGVSRS CRAAQAMDCE VNNGSSLRDE 70 80 90 100 110 120 CITNLLVFGF LQSCSDNSFR RELDALGHEL PVLAPQWEGY DELQTDGNRS SHSRLGRIEA 130 140 150 160 170 180 DSESQEDIIR NIARHLAQVG DSMDRSIPPG LVNGLALQLR NTSRSEEDRN RDLATALEQL 190 200 210 220 230 240 LQAYPRDMEK EKTMLVLALL LAKKVASHTP SLLRDVFHTT VNFINQNLRT YVRSLARNGM D
	Isoform 3 (BID(S)) [UniParc]. Checksum: 00B4D060E01FA1B8	FASTA	137	14,620
	10 20 30 40 50 60 MDCEVNNGSS LRDECITNLL VFGFLQSCSD NSFRRELDAL GHELPVLAPQ WEGYDELQTD 70 80 90 100 110 120 GNRSSHSRLG RIEAGASDNN TASAEEETEA AGSVAVERGL HGAATVILKV KKTSSGILPG 130 TSPRSGTAWT VASLRAW
	Isoform 4 (BID(ES)) [UniParc]. Checksum: 482F50C9C7DF86B0	FASTA	99	11,263
	10 20 30 40 50 60 MDRSIPPGLV NGLALQLRNT SRSEEDRNRD LATALEQLLQ AYPRDMEKEK TMLVLALLLA 70 80 90 KKVASHTPSL LRDVFHTTVN FINQNLRTYV RSLARNGMD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"BID: a novel BH3 domain-only death agonist." Wang K., Yin X.-M., Chao D.T., Milliman C.L., Korsmeyer S.J. Genes Dev. 10:2859-2869(1996) [PubMed: 8918887] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[2]	"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." Footz T.K., Birren B., Minoshima S., Asakawa S., Shimizu N., Riazi M.A., McDermid H.E. Genomics 51:472-475(1998) [PubMed: 9721221] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Three novel Bid proteins generated by alternative splicing of the human Bid gene." Renshaw S.A., Dempsey C.E., Barnes F.A., Bagstaff S.M., Dower S.K., Bingle C.D., Whyte M.K. J. Biol. Chem. 279:2846-2855(2004) [PubMed: 14583606] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION.
[4]	"Cloning and expression of a new human cDNA homology to murine apoptic death agonist (BID) mRNA." Dai F.Y., Yu L., Huang H.B., Jiang C.L., Cui Y.Y., Zhao S.Y. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	NIEHS SNPs program Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-10.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT GLN-162. Tissue: Brain and Skin.
[9]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-54, MASS SPECTROMETRY.
[10]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid." Azakir B.A., Desrochers G., Angers A. FEBS J. 277:1319-1330(2010) [PubMed: 20392206] [Abstract] Cited for: INTERACTION WITH ITCH, UBIQUITINATION BY ITCH.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Solution structure of BID, an intracellular amplifier of apoptotic signaling." Chou J.J., Li H., Salvesen G.S., Yuan J., Wagner G. Cell 96:615-624(1999) [PubMed: 10089877] [Abstract] Cited for: STRUCTURE BY NMR.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF042083 mRNA. Translation: AAC34365.1.
AF250233 mRNA. Translation: AAO32633.1.
AY005151 mRNA. Translation: AAF89091.1.
AF087891 mRNA. Translation: AAP97190.1.
CR456389 mRNA. Translation: CAG30275.1.
CR407603 mRNA. Translation: CAG28531.1.
AY309922 Genomic DNA. Translation: AAP50259.1.
BC009197 mRNA. Translation: AAH09197.1.
BC022072 mRNA. Translation: AAH22072.2. Different initiation.
BC033634 mRNA. Translation: AAH33634.1.
BC036364 mRNA. Translation: AAH36364.2.

IPI

IPI00385121.
IPI00413587.
IPI00420084.
IPI00472003.

RefSeq

NP_001187.1. NM_001196.3.
NP_001231496.1. NM_001244567.1.
NP_001231498.1. NM_001244569.1.
NP_001231499.1. NM_001244570.1.
NP_001231501.1. NM_001244572.1.
NP_932070.1. NM_197966.2.
NP_932071.1. NM_197967.2.

UniGene

Hs.591054.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZY3	NMR	-	B	82-101	[»]
2BID	NMR	-	A	1-195	[»]
2KBW	NMR	-	B	76-106	[»]

ProteinModelPortal

P55957.

SMR

P55957. Positions 1-195.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34937N.

IntAct

P55957. 9 interactions.

MINT

MINT-270277.

STRING

P55957.

PTM databases

PhosphoSite

P55957.

Polymorphism databases

DMDM

2493285.

2D gel databases

OGP

P55957.

Proteomic databases

PRIDE

P55957.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000317361; ENSP00000318822; ENSG00000015475.
ENST00000399774; ENSP00000382674; ENSG00000015475.

GeneID

637.

KEGG

hsa:637.

UCSC

uc002znd.1. human.
uc002zne.1. human.

Organism-specific databases

CTD

637.

GeneCards

GC22M018216.

HGNC

HGNC:1050. BID.

HPA

CAB003771.
HPA000722.

MIM

601997. gene.

neXtProt

NX_P55957.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07914.

GeneTree

ENSGT00390000002868.

HOVERGEN

HBG001703.

InParanoid

P55957.

OMA

DSEVSNG.

OrthoDB

EOG4J9N1J.

Enzyme and pathway databases

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.
ceramidepathway. Ceramide signaling pathway.
faspathway. FAS signaling pathway (CD95).
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P55957.

Bgee

P55957.

CleanEx

HS_BID.

Genevestigator

P55957.

GermOnline

ENSG00000015475. Homo sapiens.

Family and domain databases

InterPro

IPR020728. Bcl2_BH3_motif_CS.
IPR010479. BID.
[Graphical view]

KO

K04726.

Pfam

PF06393. BID. 1 hit.
[Graphical view]

PIRSF

PIRSF038018. BID. 1 hit.

PROSITE

PS01259. BH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

2578.

PMAP-CutDB

P55957.

SOURCE

Search...

Entry information

Entry name

BID_HUMAN

Accession

Primary (citable) accession number: P55957
Secondary accession number(s): Q549M7 , Q71T04, Q7Z4M9, Q8IY86

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.