BIRC3 Gene

HGNC Family	Baculoviral IAP repeat containing (BIRC), Zinc fingers
Name	baculoviral IAP repeat containing 3
Description	This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified. [provided by RefSeq, Aug 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BIRC3, also known as cellular inhibitor of apoptosis protein‐2 (cIAP2), plays a multifaceted role in regulating cell fate by modulating key ubiquitination‐dependent signaling pathways. Functioning primarily as an E3 ubiquitin ligase, BIRC3 ubiquitinates signaling adaptors such as RIP1, thereby promoting the assembly of prosurvival complexes that activate NF‑κB pathways and inhibit apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, BIRC3 targets proapoptotic proteins such as Smac for proteasomal degradation, contributing further to its antiapoptotic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Transcriptional regulation of BIRC3 is also critical; for example, SIRT1‐mediated deacetylation can enhance chromatin occupancy at the cIAP2 promoter, leading to reduced NF‑κB‐driven gene expression and increased sensitivity to TNFα‐induced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, treatment with Smac mimetics triggers the auto‐ubiquitination and subsequent proteasomal degradation of BIRC3, which disrupts RIP1 ubiquitination and thereby shifts TNF receptor signaling from prosurvival to caspase‑8‐dependent apoptotic pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic alterations in BIRC3 have been implicated in various malignancies. Loss‐of‐function mutations in BIRC3 have been associated with constitutive activation of the noncanonical NF‑κB pathway in multiple myeloma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and recurrent BIRC3 lesions have been identified in mantle cell lymphoma, linking aberrant BIRC3 activity to tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, BIRC3 interacts with adaptor molecules such as TRAF2 to regulate TNF receptor 1 signal transduction, ensuring proper RIP1 ubiquitination and balanced NF‑κB activation, while also functioning to limit excessive TNFα production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Elevated expression of BIRC3 in certain cancer stem cell populations has also been linked to enhanced survival and chemoresistance, further emphasizing its role in sustaining tumor cell viability under stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these studies underscore BIRC3 as a critical regulator of cell survival and apoptosis whose E3 ligase activity and interactions within TNF receptor complexes balance prosurvival NF‑κB signals with the induction of cell death, thereby influencing both normal cellular homeostasis and cancer pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shimin Hu, Xiaolu Yang "}, {"type": "b", "children": [{"type": "t", "text": "Cellular inhibitor of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis inducer Smac/DIABLO."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207197200"}], "href": "https://doi.org/10.1074/jbc.M207197200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12525502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12525502"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mathieu J M Bertrand, Snezana Milutinovic, Kathleen M Dickson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2008.05.014"}], "href": "https://doi.org/10.1016/j.molcel.2008.05.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18570872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18570872"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jasmin N Dynek, Tatiana Goncharov, Erin C Dueber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2010.300"}], "href": "https://doi.org/10.1038/emboj.2010.300"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21113135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21113135"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fan Yeung, Jamie E Hoberg, Catherine S Ramsey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600244"}], "href": "https://doi.org/10.1038/sj.emboj.7600244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15152190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15152190"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lai Wang, Fenghe Du, Xiaodong Wang "}, {"type": "b", "children": [{"type": "t", "text": "TNF-alpha induces two distinct caspase-8 activation pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.03.036"}], "href": "https://doi.org/10.1016/j.cell.2008.03.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18485876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18485876"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "N Vanlangenakker, T Vanden Berghe, P Bogaert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2010.138"}], "href": "https://doi.org/10.1038/cdd.2010.138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21052097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21052097"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jonathan J Keats, Rafael Fonseca, Marta Chesi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2007.07.003"}], "href": "https://doi.org/10.1016/j.ccr.2007.07.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17692805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17692805"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rami Rahal, Mareike Frick, Rodrigo Romero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3435"}], "href": "https://doi.org/10.1038/nm.3435"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24362935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24362935"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "James E Vince, Delara Pantaki, Rebecca Feltham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.072256"}], "href": "https://doi.org/10.1074/jbc.M109.072256"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19815541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19815541"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "D E Christofferson, Y Li, J Hitomi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel role for RIP1 kinase in mediating TNFα production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2012.64"}], "href": "https://doi.org/10.1038/cddis.2012.64"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22695613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22695613"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Lili Yang, Mark P Boldin, Yang Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-146a controls the resolution of T cell responses in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20112218"}], "href": "https://doi.org/10.1084/jem.20112218"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22891274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22891274"}]}]}]}
Synonyms	CIAP2, API2, MALT2, AIP1, HAIP1, MIHC, HIAP1, RNF49, C-IAP2
Proteins	BIRC3_HUMAN
NCBI Gene ID	330
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BIRC3 has 14,195 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 122 datasets.

Click the + buttons to view associations for BIRC3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BIRC3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BIRC3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of BIRC3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of BIRC3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of BIRC3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of BIRC3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BIRC3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving BIRC3 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of BIRC3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BIRC3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BIRC3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of BIRC3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of BIRC3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with BIRC3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with BIRC3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of BIRC3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BIRC3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of BIRC3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of BIRC3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BIRC3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BIRC3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing BIRC3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BIRC3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with BIRC3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing BIRC3 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of BIRC3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BIRC3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BIRC3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BIRC3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by BIRC3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with BIRC3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with BIRC3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with BIRC3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with BIRC3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BIRC3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at BIRC3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of BIRC3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BIRC3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing BIRC3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with BIRC3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with BIRC3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.