Summary: Inhibitor of Apoptosis domain

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Wikipedia: Inhibitor of apoptosis domain
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Inhibitor of apoptosis domain

Inhibitor of Apoptosis domain

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.

Identifiers

Symbol

BIR

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

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.

References

^ 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.
^ ^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.
^ 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 139420. PMID 11516343. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139420.
^ 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 236730. PMID 8139034. http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=8139034.

External links

Eukaryotic Linear Motif resource motif class LIG_BIR_II_1
Eukaryotic Linear Motif resource motif class LIG_BIR_III_1
Eukaryotic Linear Motif resource motif class LIG_BIR_III_2
Eukaryotic Linear Motif resource motif class LIG_BIR_III_3
Eukaryotic Linear Motif resource motif class LIG_BIR_III_4

v t e Protein domains

BAR BIR BZIP CARD C1 C2 DED ENTH FYVE HEAT Kringle LIM LRR NACHT PAS PDZ Pyrin PH PX SH2 SH3 SUN TRIO WD40 zinc finger

References

^ 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.
^ ^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.
^ 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 139420. PMID 11516343. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139420.
^ 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 236730. PMID 8139034. http://jvi.asm.org/cgi/pmidlookup?view=long&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

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

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

Clan

This family is a member of clan BIR-like (CL0417), which has a total of 3 members.

External database links

HOMSTRAD:	BIR
PANDIT:	PF00653
PROSITE:	PDOC00987
PROSITE profile:	PS50143
Pseudofam:	PF00653
SCOP:	1qbh
SYSTERS:	BIR

This tab holds annotation information from the InterPro database.

InterPro entry IPR001370

Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.

The baculovirus inhibitor of apoptosis protein repeat (BIR) is a domain of tandem repeats separated by a variable length linker that seems to confer cell death-preventing activity [PUBMED:8139034, PUBMED:8552191]. The BIR domains characterise the Inhibitor of Apoptosis (IAP) family of proteins (MEROPS proteinase inhibitor family I32, clan IV) that suppress apoptosis by interacting with and inhibiting the enzymatic activity of both initiator and effector caspases (MEROPS peptidase family C14, INTERPRO). Several distinct mammalian IAPs including XIAP, c-IAP1, c-IAP2, and ML-IAP, have been identified, and they all exhibit antiapoptotic activity in cell culture. The functional unit in each IAP protein is the baculoviral IAP repeat (BIR), which contains approximately 80 amino acids folded around a zinc atom. Most mammalian IAPs have more than one BIR domain, with the different BIR domains performing distinct functions. For example, in XIAP, the third BIR domain (BIR3) potently inhibits the catalytic activity of caspase-9, whereas the linker sequences immediately preceding the second BIR domain (BIR2) selectively targets caspase-3 or -7.

The first-recognised members of family MEROPS inhibitor family I32 were viral proteins that inhibited the apoptosis of infected cells: Cp-IAP from Cydia pomonella granulosis virus (CpGV) [PUBMED:8445726] and Op-IAP from Orgyia pseudotsugata multicapsid polyhedrosis virus(OpMNPV) [PUBMED:8139034]. The discovery of homologous proteins in mammals followed soon after with the recognition that mutations in the gene for neuronal apoptosis inhibitory protein (NIAP) underlie spinal muscular atrophy [PUBMED:7813013]. The inhibitors in family I32 all possess one or more 80-residue domains known as BIR (baculovirus inhibitor repeat) domains and have accordingly been termed 'BIR-containing' or 'BIRC' proteins as well as IAP proteins.

The mechanism of inhibition of caspases by the IAP proteins is complex, and reactive site residues cannot yet be identified with any confidence. Despite the conservation of the BIR or IAP (inhibitor of apoptosis) domains throughout the family it seems clear that other parts of the molecules also make essential contributions to inhibitory activity.

Homologs of most components in the mammalian apoptotic pathway have been identified in fruit flies. The Drosophila Apaf-1, known as Dapaf-1, HAC-1 or Dark, shares significant sequence similarity with its mammalian counterpart, and is critically important for the activation of the Drosophila initiator caspase Dronc. Dronc, in turn, cleaves and activates the effector caspase DrICE. The Drosophila IAP, DIAP1, binds to and in-activates both DrICE and Dronc through its BIR1 and BIR2 domains. During apoptosis, the anti-death function of DIAP1 is countered by at least four pro-apoptotic proteins, Reaper, Hid, Grim, and sickle, through direct physical interactions. These four proteins represent the functional homologs of the mammalian protein Smac, and they all share a conserved IAP-binding motif at their N termini. The three proteins Reaper, Hid, and Grim are collectively referred to as the RHG proteins [PUBMED:11511363, PUBMED:15273300].

Both XIAP and DIAP1 contain a RING domain at their C termini, and can act as an E3 ubiquitin ligase. Indeed, both XIAP and DIAP1 have been shown to promote self-ubiquitination and degradation as well as to negatively regulate the target caspases. Nonetheless, important differences exist between XIAP and DIAP1. The primary function of XIAP is thought to inhibit the catalytic activities of caspases; to what extent the ubiquitinating activity of XIAP contributes to its function remains unclear. For DIAP1, however, the ubiquitinating activity appears to be essential for its function.

Recently a Drosophila p53 protein has been identified that mediates apoptosis via a novel pathway involving the activation of the Reaper gene and subsequent inhibition of the inhibitors of apoptosis (IAPs). CIAP1, a major mammalian homologue of Drosophila IAPs, is irreversibly inhibited (cleaved) during p53-dependent apoptosis and this cleavage is mediated by a serine protease. Serine protease inhibitors that block CIAP1 cleavage inhibit p53-dependent apoptosis. Furthermore, activation of the p53 protein increases the transcription of the HTRA2 gene, which encodes a serine protease that interacts with CIAP1 and potentiates apoptosis. Therefore mammalian p53 protein activates apoptosis through a novel pathway functionally similar to that in Drosophila, which involves HTRA2 and subsequent inhibition of CIAP1 by cleavage [PUBMED:12569127].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Cellular component

intracellular (GO:0005622)

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 contains the following 3 members:

BIR Rsm1 zf-C3HC

Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

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Alignment:	Seed (189) Full (1194) NCBI (1597) Metagenomics (5)
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Alignment:	Seed (189) Full (1194)
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The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (189) Full (1194) NCBI (1597) Metagenomics (5)
Full length sequences	Full-sequences (1194)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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This page displays the phylogenetic tree for this family. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed or full alignments.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Prosite

Previous IDs:

none

Type:

Domain

Author:

Bateman A

Number in seed:

189

Number in full:

1194

Average length of the domain:

68.20 aa

Average identity of full alignment:

35 %

Average coverage of the sequence by the domain:

10.73 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 15929002 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	22.9	22.9
Trusted cut-off	23.0	23.1
Noise cut-off	22.8	22.8

Model length:

70

Family (HMM) version:

16

Download:

download the raw HMM for this family

Species distribution

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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

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Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

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Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

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Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

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Interactions

There are 3 interactions for this family. More...

Peptidase_C14 BIR PP2C

Structures

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 73 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 seqence.

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Family: BIR (PF00653)

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Summary: Inhibitor of Apoptosis domain

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Inhibitor of apoptosis domain

References

External links

References

Inhibitor of Apoptosis domain

Literature references

Clan

External database links

InterPro entry IPR001370

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Viewing

Downloading

View options

Formatting options

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures