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312  structures 1159  species 0  interactions 6995  sequences 131  architectures

Family: BIR (PF00653)

Summary: Inhibitor of Apoptosis domain

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Inhibitor of apoptosis domain Edit Wikipedia article

Inhibitor of Apoptosis domain
1QBH BIRC2.png
NMR solution structure of the BIR domain of human BIRC2 protein.[1] The protein is rainbow colored cartoon diagram (N-terminus = blue, C-terminus = red) while the coordinated zinc is represented by a grey sphere.
Symbol BIR
Pfam PF00653
InterPro IPR001370
SCOP 1qbh

The inhibitor of apoptosis domain -- also known as IAP repeat, Baculovirus Inhibitor of apoptosis protein Repeat, or BIR -- is a structural motif found in proteins with roles in apoptosis, cytokine production, and chromosome segregation.[2] Proteins containing BIR are known as inhibitor of apoptosis proteins (IAPs), or BIR-containing proteins (BIRPs or BIRCs), and include BIRC1 (NAIP), BIRC2 (cIAP1), BIRC3 (cIAP2), BIRC4 (xIAP), BIRC5 (survivin) and BIRC6.[2][3]

BIR domains belong to the zinc-finger domain family and characteristically have a number of invariant amino acid residues, including 3 conserved cysteines and one conserved histidine, which coordinate a zinc ion.[4] They are typically composed of 4-5 alpha helices and a three-stranded beta sheet.

External links


  1. ^ PDB: 1QBH​;Hinds MG, Norton RS, Vaux DL, Day CL (July 1999). "Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat". Nat. Struct. Biol. 6 (7): 648–51. doi:10.1038/10701. PMID 10404221. 
  2. ^ a b Silke J, Vaux DL (May 2001). "Two kinds of BIR-containing protein - inhibitors of apoptosis, or required for mitosis". J. Cell Sci. 114 (Pt 10): 1821–7. PMID 11329368. 
  3. ^ Verhagen AM, Coulson EJ, Vaux DL (2001). "Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs". Genome Biol. 2 (7): REVIEWS3009. doi:10.1186/gb-2001-2-7-reviews3009. PMC 139420Freely accessible. PMID 11516343. 
  4. ^ Birnbaum MJ, Clem RJ, Miller LK (April 1994). "An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs". J. Virol. 68 (4): 2521–8. PMC 236730Freely accessible. PMID 8139034. 

This article incorporates text from the public domain Pfam and InterPro IPR001370

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Inhibitor of Apoptosis domain Provide feedback

BIR stands for 'Baculovirus Inhibitor of apoptosis protein Repeat'. It is found repeated in inhibitor of apoptosis proteins (IAPs), and in fact it is also known as IAP repeat. These domains characteristically have a number of invariant residues, including 3 conserved cysteines and one conserved histidine that coordinate a zinc ion. They are usually made up of 4-5 alpha helices and a three-stranded beta-sheet. BIR is also found in other proteins known as BIR-domain-containing proteins (BIRPs), such as Survivin (O15392) [2].

Literature references

  1. Birnbaum MJ, Clem RJ, Miller LK; , J Virol 1994;68:2521-2528.: An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs. PUBMED:8139034 EPMC:8139034

  2. Verhagen AM, Coulson EJ, Vaux DL; , Genome Biol 2001;2:REVIEWS3009.: Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. PUBMED:11516343 EPMC:11516343

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001370

The 'baculovirus inhibitior of apoptosis protein repeat' (BIR) [ PUBMED:8139034 , PUBMED:8552191 ] is a domain of about 70 residues arranged in tandem repeats separated by a variable length linker, that seems to confer cell death-preventing activity. It is found in proteins belonging to the IAP (inhibitor of apoptosis proteins) family. The critical motifs required for anti-apoptotic activity of IAP proteins are the BIRs. All IAP proteins contain from one to three BIRs, and all known interactions between IAPs and other proteins are mediated by one or more BIRs [ PUBMED:10404221 ]. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. Proteins with BIR domains are considered peptidase inhibitors in family I32. In yeast, BIR domains are involved in regulating cytokinesis. This novel fold is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues and resembles a classical zinc finger [ PUBMED:8445726 ].

The BIR domain has a fold that is stabilised by zinc tetrahedrally coordinated by one histidine and three cysteine residues. The structure consists of three short alpha-helices and turns with the zinc packed in an unusually hydrophobic environment created by residues that are highly conserved among all BIRs. A subclass of repeats, comprising those at the C terminus of a series of BIR repeats from IAP proteins bearing RING finger domains, are likely to contain a C-terminal region that form an alpha-helix [ PUBMED:10404221 ].

Proteins that are known to contain this domain include:

  • Baculoviruses apoptosis inhibitors (IAPs).
  • Mammalian apoptosis inhibitors 1 and 2 (IAP1 and IAP2; BIRC-2 and BIRC-3; MEROPS identifiers I32.002 and I32.003, respectively).
  • Mammalian X-linked inhibitor of apoptosis protein (X-linked IAP; MEROPS identifier I32.004).
  • Chicken IAP (ITA).
  • Human neuronal apoptosis inhibitory protein (NAIP, BIRC-1; MEROPS identifier I32.001).
  • Drosophila apoptosis inhibitors 1 and 2 (Iap1 and Iap2; MEROPS identifiers I32.009 and I32.011, respectively)).
  • African Swine Fever Virus (ASFV) protein p27.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan BIR-like (CL0417), which has the following description:

Clan of domains all involved in binding nucleic acid and sharing the sequence motif C3HC.

The clan contains the following 3 members:

BIR Rsm1 zf-C3HC


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Curation and family details

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Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 71
Number in full: 6995
Average length of the domain: 69.10 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 12.37 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.9 22.9
Trusted cut-off 22.9 23.0
Noise cut-off 22.7 22.8
Model length: 73
Family (HMM) version: 23
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Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the BIR domain has been found. There are 312 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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