baculoviral IAP repeat containing 3

Target id: 2792

Nomenclature: baculoviral IAP repeat containing 3

Family: Inhibitors of apoptosis (IAP) protein family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     baculoviral IAP repeat containing 3 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 604 11q22 BIRC3 baculoviral IAP repeat containing 3
Mouse - 602 9 A2 Birc3 baculoviral IAP repeat-containing 3
Rat - 638 8q11 Birc3 baculoviral IAP repeat-containing 3
Previous and Unofficial Names
API2 | apoptosis inhibitor 2 | c-IAP2 | cIAP2 | MALT2
Database Links
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
SM-122 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 Affinity Units Reference
SM-337 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)
AT-406 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 Hs Antagonist 7.4 pKi 2
pKi 7.4 (Ki 4.3x10-8 M) [2]
Description: BIR3 domain of hcIPA2 (BIRC3)
AZD5582 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 ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of toll-like receptor signaling pathway (GO:0034121) TAS
TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
regulation of RIG-I signaling pathway (GO:0039535) TAS
regulation of innate immune response (GO:0045088) TAS
regulation of inflammatory response (GO:0050727) TAS
regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of toll-like receptor signaling pathway (GO:0034121) TAS
TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
regulation of RIG-I signaling pathway (GO:0039535) TAS
regulation of innate immune response (GO:0045088) TAS
regulation of inflammatory response (GO:0050727) TAS
regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
regulation of RIG-I signaling pathway (GO:0039535) TAS
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  ubiquitin-protein transferase activity (GO:0004842) IDA
positive regulation of protein ubiquitination (GO:0031398) IDA
regulation of toll-like receptor signaling pathway (GO:0034121) TAS
TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
regulation of RIG-I signaling pathway (GO:0039535) TAS
regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
References: 
Physiological Consequences of Altering Gene Expression
Birc2 and Birc3 null mice are resistant to inflammasome-dependent peritonitis.
Species:  Mouse
Tissue: 
Technique: 
References:  4
Clinically-Relevant Mutations and Pathophysiology
Disease:  Asthma, susceptibility to
Disease Ontology: DOID:2841
OMIM: 600807
Biologically Significant Variants
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: 
References:  6

References

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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. LabbĂ© 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. Immunity35 (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. (2016) BIRC3 single nucleotide polymorphism associate with asthma susceptibility and the abundance of eosinophils and neutrophils. J Asthma, : 1-9 [Epub ahead of print]. [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 12/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2792.