TISIDB

Summary
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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

> KEGG and Reactome Pathway

[ TOP ]

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
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
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

[ TOP ]

Literatures describing the relation between BIRC3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21282461	Bladder Carcinoma	Inhibit immunity	Degradation 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
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
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

[ TOP ]

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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.079	0.906
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.702	0.649
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.634	0.55
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.083	0.885
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.608	0.717
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.588	0.795
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.615	0.313
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.231	0.428
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.03	0.986
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.901	0.622
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.537	0.858
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.015	0.941

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
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 [ TOP ]

Summary
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of BIRC3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between BIRC3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Aliases	cIAP2; hiap-1; RNF49; MALT2; c-IAP2; apoptosis inhibitor 2; TNFR2-TRAF signaling complex protein; mammalian ......
Chromosomal Location	11q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting BIRC3 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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