Browse BIRC3

Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus
Domain PF00653 Inhibitor of Apoptosis domain
PF00619 Caspase recruitment domain
Function

Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8.

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0002218 activation of innate immune response
GO:0002221 pattern recognition receptor signaling pathway
GO:0002224 toll-like receptor signaling pathway
GO:0002697 regulation of immune effector process
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0002757 immune response-activating signal transduction
GO:0002758 innate immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002831 regulation of response to biotic stimulus
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007283 spermatogenesis
GO:0009615 response to virus
GO:0010466 negative regulation of peptidase activity
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0010939 regulation of necrotic cell death
GO:0010951 negative regulation of endopeptidase activity
GO:0010955 negative regulation of protein processing
GO:0016485 protein processing
GO:0030522 intracellular receptor signaling pathway
GO:0031349 positive regulation of defense response
GO:0031396 regulation of protein ubiquitination
GO:0031398 positive regulation of protein ubiquitination
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0034121 regulation of toll-like receptor signaling pathway
GO:0034612 response to tumor necrosis factor
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038061 NIK/NF-kappaB signaling
GO:0039528 cytoplasmic pattern recognition receptor signaling pathway in response to virus
GO:0039529 RIG-I signaling pathway
GO:0039531 regulation of viral-induced cytoplasmic pattern recognition receptor signaling pathway
GO:0039535 regulation of RIG-I signaling pathway
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043900 regulation of multi-organism process
GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045861 negative regulation of proteolysis
GO:0048232 male gamete generation
GO:0050688 regulation of defense response to virus
GO:0050727 regulation of inflammatory response
GO:0050792 regulation of viral process
GO:0051259 protein oligomerization
GO:0051291 protein heterooligomerization
GO:0051346 negative regulation of hydrolase activity
GO:0051604 protein maturation
GO:0051607 defense response to virus
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0060544 regulation of necroptotic process
GO:0060546 negative regulation of necroptotic process
GO:0060547 negative regulation of necrotic cell death
GO:0060759 regulation of response to cytokine stimulus
GO:0070265 necrotic cell death
GO:0070266 necroptotic process
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070424 regulation of nucleotide-binding oligomerization domain containing signaling pathway
GO:0070613 regulation of protein processing
GO:0071356 cellular response to tumor necrosis factor
GO:0097300 programmed necrotic cell death
GO:0097340 inhibition of cysteine-type endopeptidase activity
GO:0097341 zymogen inhibition
GO:0098542 defense response to other organism
GO:0098586 cellular response to virus
GO:1903317 regulation of protein maturation
GO:1903318 negative regulation of protein maturation
GO:1903320 regulation of protein modification by small protein conjugation or removal
GO:1903322 positive regulation of protein modification by small protein conjugation or removal
GO:1990001 inhibition of cysteine-type endopeptidase activity involved in apoptotic process
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2000117 negative regulation of cysteine-type endopeptidase activity
Molecular Function GO:0004842 ubiquitin-protein transferase activity
GO:0004857 enzyme inhibitor activity
GO:0004866 endopeptidase inhibitor activity
GO:0004869 cysteine-type endopeptidase inhibitor activity
GO:0016874 ligase activity
GO:0019787 ubiquitin-like protein transferase activity
GO:0030414 peptidase inhibitor activity
GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process
GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process
GO:0061134 peptidase regulator activity
GO:0061135 endopeptidase regulator activity
Cellular Component GO:0045121 membrane raft
GO:0098589 membrane region
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG hsa04064 NF-kappa B signaling pathway
hsa04120 Ubiquitin mediated proteolysis
hsa04210 Apoptosis
hsa04510 Focal adhesion
hsa04621 NOD-like receptor signaling pathway
hsa04668 TNF signaling pathway
Reactome R-HSA-166054: Activated TLR4 signalling
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-73887: Death Receptor Signalling
R-HSA-5688426: Deubiquitination
R-HSA-937041: IKK complex recruitment mediated by RIP1
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-392499: Metabolism of proteins
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-168638: NOD1/2 Signaling Pathway
R-HSA-168643: Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-597592: Post-translational protein modification
R-HSA-5357801: Programmed Cell Death
R-HSA-5213460: RIPK1-mediated regulated necrosis
R-HSA-5218859: Regulated Necrosis
R-HSA-5357905: Regulation of TNFR1 signaling
R-HSA-5675482: Regulation of necroptotic cell death
R-HSA-162582: Signal Transduction
R-HSA-5676594: TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-75893: TNF signaling
R-HSA-5357956: TNFR1-induced NFkappaB signaling pathway
R-HSA-5668541: TNFR2 non-canonical NF-kB pathway
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168898: Toll-Like Receptors Cascades
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between BIRC3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between BIRC3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
21282461Bladder CarcinomaInhibit immunityDegradation of the RIP1 K63 ubiquitin ligases cIAP1/2 amplifies the CD40-mediated cytotoxic effect, whereas inhibition of CYLD, a RIP1 K63 deubiquitinating enzyme, reduces it.
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of BIRC3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of BIRC3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0790.906
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.7020.649
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.6340.55
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0830.885
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.6080.717
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5880.795
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.6150.313
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.2310.428
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.030.986
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9010.622
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.5370.858
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0150.941
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of BIRC3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of BIRC3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of BIRC3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by BIRC3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of BIRC3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of BIRC3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between BIRC3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolBIRC3
Namebaculoviral IAP repeat containing 3
Aliases cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location11q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting BIRC3 collected from DrugBank database.
> Drugs from DrugBank database
 

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