Top ▲

baculoviral IAP repeat containing 3

Click here for help

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2792

Nomenclature: baculoviral IAP repeat containing 3

Family: Inhibitors of apoptosis (IAP) protein family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 604 11q22.2 BIRC3 baculoviral IAP repeat containing 3
Mouse - 600 9 A1 Birc3 baculoviral IAP repeat-containing 3
Rat - 638 8q11 Birc3 baculoviral IAP repeat-containing 3
Previous and Unofficial Names Click here for help
API2 | apoptosis inhibitor 2 | c-IAP2 | cIAP2 | MALT2
Database Links Click here for help
Alphafold Q13489 (Hs), O08863 (Mm)
CATH/Gene3D 3.30.40.10
ChEMBL Target CHEMBL5335 (Hs)
Ensembl Gene ENSG00000023445 (Hs), ENSMUSG00000032000 (Mm), ENSRNOG00000005731 (Rn)
Entrez Gene 330 (Hs), 11796 (Mm), 78971 (Rn)
Human Protein Atlas ENSG00000023445 (Hs)
KEGG Gene hsa:330 (Hs), mmu:11796 (Mm), rno:78971 (Rn)
OMIM 601721 (Hs)
Pharos Q13489 (Hs)
RefSeq Nucleotide NM_001165 (Hs), NM_007464 (Mm), NM_023987 (Rn)
RefSeq Protein NP_001156 (Hs), NP_031490 (Mm), NP_076477 (Rn)
UniProtKB Q13489 (Hs), O08863 (Mm)
Wikipedia BIRC3 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SM-122 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pKi 5
⤷ pKi 8.7 (Ki 1.8x10-9 M) [5]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SM-337 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.4 pKi 5
⤷ pKi 8.4 (Ki 4.2x10-9 M) [5]
Description: Fluorescence polarization assay using hcIAP2 BIR3 domain (residues 238-349)
xevinapant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 1
⤷ pKi 8.3 (Ki 5.1x10-9 M) [1]
Description: Competitive inhibition of human cIAP2 BIR3 domain expressed in Escherichia coli.
GDC-0152 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.4 pKi 2
⤷ pKi 7.4 (Ki 4.3x10-8 M) [2]
Description: BIR3 domain of hcIPA2 (BIRC3)
AZD5582 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.7 pIC50 3
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [3]
Antagonist Comments
AZD5582 is a peptide mimetic. It consists of a dimeric structure, with sequences based on the AVPI motif of DIABLO (aka Smac; Q9NR28). DIABLO is a peptide of mitochondrial origin and is an endogenous pro-apoptotic antagonist of IAP protein function.
Immunopharmacology Comments
Cellular inhibitor of apoptosis proteins (cIAPs) suppress apoptosis thereby promoting cell survival, and participate in the immune response (e.g. negative regulation of the necrosome, inflammasome and ripoptosome. In asthma, cIAPs extend the survival of neutrophils, macrophages and eosinophils, prolonging the inflammation. The minor alleles of single nucleotide polymorphisms in BIRC3 are shown to correlate with reduced numbers of circulating eosinophils and neutrophils, suggesting a protective effect against the development of asthma[6].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Physiological Consequences of Altering Gene Expression Click here for help
Birc2 and Birc3 null mice are resistant to inflammasome-dependent peritonitis.
Species:  Mouse
Tissue: 
Technique: 
References:  4
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Asthma, susceptibility to
Disease Ontology: DOID:2841
OMIM: 600807
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  BIRC3 polymorphisms associate with a reduced susceptibility for asthma (rs3460) and a reduced load of circulating eosinophils and neutrophils (rs7928663, rs7127583).
SNP accession:  rs7127583, rs7928663, rs3460
References:  6

References

Show »

1. Cai Q, Sun H, Peng Y, Lu J, Nikolovska-Coleska Z, McEachern D, Liu L, Qiu S, Yang CY, Miller R et al.. (2011) A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. J Med Chem, 54 (8): 2714-26. [PMID:21443232]

2. Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S, Cohen F, Deshayes K, Doerner K, Eckhardt SG et al.. (2012) Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem, 55 (9): 4101-13. [PMID:22413863]

3. Hennessy EJ, Adam A, Aquila BM, Castriotta LM, Cook D, Hattersley M, Hird AW, Huntington C, Kamhi VM, Laing NM et al.. (2013) Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582). J Med Chem, 56 (24): 9897-919. [PMID:24320998]

4. Labbé K, McIntire CR, Doiron K, Leblanc PM, Saleh M. (2011) Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome. Immunity, 35 (6): 897-907. [PMID:22195745]

5. Peng Y, Sun H, Nikolovska-Coleska Z, Qiu S, Yang CY, Lu J, Cai Q, Yi H, Kang S, Yang D et al.. (2008) Potent, orally bioavailable diazabicyclic small-molecule mimetics of second mitochondria-derived activator of caspases. J Med Chem, 51 (24): 8158-62. [PMID:19049347]

6. Roscioli E, Hamon R, Ruffin RE, Grant J, Hodge S, Zalewski P, Lester S. (2017) BIRC3 single nucleotide polymorphism associate with asthma susceptibility and the abundance of eosinophils and neutrophils. J Asthma, 54 (2): 116-124. [PMID:27304223]

How to cite this page

Inhibitors of apoptosis (IAP) protein family: baculoviral IAP repeat containing 3. Last modified on 15/02/2017. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2792.