TISIDB

Summary
Symbol	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
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 Chromosome Chromosome, centromere Cytoplasm, cytoskeleton, spindle Chromosome, centromere, kinetochore Midbody Note=Localizes at the centromeres from prophase to metaphase, at the spindle midzone during anaphase and a the midbody during telophase and cytokinesis. Accumulates in the nucleus upon treatment with leptomycin B (LMB), a XPO1/CRM1 nuclear export inhibitor (By similarity). Localizes on chromosome arms and inner centromeres from prophase through metaphase. Localizes to kinetochores in metaphase, distributes to the midzone microtubules in anaphase and at telophase, localizes exclusively to the midbody (PubMed:11084331). Colocalizes with AURKB at mitotic chromosomes (PubMed:14610074). Acetylation at Lys-129 directs its localization to the nucleus by enhancing homodimerization and thereby inhibiting XPO1/CRM1-mediated nuclear export (PubMed:20826784).
Domain	PF00653 Inhibitor of Apoptosis domain
Function	Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:9859993, PubMed:21364656, PubMed:20627126). Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis (PubMed:16322459). Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules (PubMed:20826784). Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis (PubMed:20929775). The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255). May counteract a default induction of apoptosis in G2/M phase (PubMed:9859993). The acetylated form represses STAT3 transactivation of target gene promoters (PubMed:20826784). May play a role in neoplasia (PubMed:10626797). Inhibitor of CASP3 and CASP7 (PubMed:21536684). Isoform 2 and isoform 3 do not appear to play vital roles in mitosis (PubMed:12773388, PubMed:16291752). Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform (PubMed:10626797).

> Gene Ontology [ TOP ]
Biological Process	GO:0000226 microtubule cytoskeleton organization GO:0000819 sister chromatid segregation GO:0007051 spindle organization GO:0007059 chromosome segregation GO:0007062 sister chromatid cohesion GO:0007067 mitotic nuclear division GO:0010466 negative regulation of peptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0010955 negative regulation of protein processing GO:0016485 protein processing GO:0016925 protein sumoylation GO:0018205 peptidyl-lysine modification GO:0031503 protein complex localization 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:0045861 negative regulation of proteolysis GO:0051225 spindle assembly GO:0051346 negative regulation of hydrolase activity GO:0051604 protein maturation GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0070613 regulation of protein processing GO:0090307 mitotic spindle assembly GO:0097340 inhibition of cysteine-type endopeptidase activity GO:0097341 zymogen inhibition GO:0098813 nuclear chromosome segregation GO:1902850 microtubule cytoskeleton organization involved in mitosis GO:1903317 regulation of protein maturation GO:1903318 negative regulation of protein maturation 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:0008017 microtubule binding GO:0008536 Ran GTPase binding GO:0015631 tubulin binding GO:0017016 Ras GTPase binding GO:0019787 ubiquitin-like protein transferase activity GO:0030414 peptidase inhibitor activity GO:0031267 small GTPase binding GO:0051020 GTPase binding GO:0051087 chaperone binding GO:0061134 peptidase regulator activity GO:0061135 endopeptidase regulator activity
Cellular Component	GO:0000775 chromosome, centromeric region GO:0000776 kinetochore GO:0000777 condensed chromosome kinetochore GO:0000779 condensed chromosome, centromeric region GO:0000793 condensed chromosome GO:0005819 spindle GO:0005874 microtubule GO:0005875 microtubule associated complex GO:0030496 midbody GO:0032133 chromosome passenger complex GO:0098687 chromosomal region

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04210 Apoptosis hsa04390 Hippo signaling pathway
Reactome	R-HSA-1640170: Cell Cycle R-HSA-69278: Cell Cycle, Mitotic R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-168256: Immune System R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-68886: M Phase R-HSA-392499: Metabolism of proteins R-HSA-68882: Mitotic Anaphase R-HSA-2555396: Mitotic Metaphase and Anaphase R-HSA-68877: Mitotic Prometaphase R-HSA-597592: Post-translational protein modification R-HSA-195258: RHO GTPase Effectors R-HSA-5663220: RHO GTPases Activate Formins R-HSA-2500257: Resolution of Sister Chromatid Cohesion R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins R-HSA-2990846: SUMOylation R-HSA-4615885: SUMOylation of DNA replication proteins R-HSA-2467813: Separation of Sister Chromatids R-HSA-162582: Signal Transduction R-HSA-449147: Signaling by Interleukins R-HSA-194315: Signaling by Rho GTPases R-HSA-5633008: TP53 Regulates Transcription of Cell Death Genes R-HSA-6803205: TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain R-HSA-3700989: Transcriptional Regulation by TP53

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04210 Apoptosis
hsa04390 Hippo signaling pathway

Reactome

R-HSA-1640170: Cell Cycle
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-168256: Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-68886: M Phase
R-HSA-392499: Metabolism of proteins
R-HSA-68882: Mitotic Anaphase
R-HSA-2555396: Mitotic Metaphase and Anaphase
R-HSA-68877: Mitotic Prometaphase
R-HSA-597592: Post-translational protein modification
R-HSA-195258: RHO GTPase Effectors
R-HSA-5663220: RHO GTPases Activate Formins
R-HSA-2500257: Resolution of Sister Chromatid Cohesion
R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins
R-HSA-2990846: SUMOylation
R-HSA-4615885: SUMOylation of DNA replication proteins
R-HSA-2467813: Separation of Sister Chromatids
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-194315: Signaling by Rho GTPases
R-HSA-5633008: TP53 Regulates Transcription of Cell Death Genes
R-HSA-6803205: TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-3700989: Transcriptional Regulation by TP53

Summary
Symbol	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between BIRC5 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

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Literatures describing the relation between BIRC5 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18363997	Melanoma; Colon Carcinoma; Breast Carcinoma; Lung carcinoma	Promote immunity (T cell function); essential for immunotherapy	Four novel oral DNA vaccines provide protection against melanoma, colon, breast, and lung carcinoma in mouse models. Vaccines are delivered by attenuated Salmonella typhimurium to secondary lymphoid organs and respectively target vascular endothelial growth factor receptor-2, transcription factor Fos-related antigen-1, anti-apoptosis protein survivin and Legumain, an asparaginyl endopeptidase specifically overexpressed on tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Key mechanisms induced by these DNA vaccines include efficient suppression of angiogenesis in the tumor vasculature and marked activation of cytotoxic T cells, natural killer cells, and antigen-presenting dendritic cells.
19337999	Melanoma	Promote immunity	Survivin is overexpressed in several malignancies and in tumor-associated endothelium making it an attractive target for therapeutic cytotoxic T-cell responses. In summary, we demonstrated the immunogenicity of two K(b)-restricted peptide epitopes derived from the murine survivin protein; moreover, survivin-specific vaccination not only resulted in a reduction of tumor cells but also the tumor supplying blood vessels.
19291796	Neuroblastoma	Promote immunity	This response was as effective as a survivin full-length vaccine and was associated with an increased target cell lysis, increased presence of CD8(+) T-cells at the primary tumor site and enhanced production of proinflammatory cytokines by systemic CD8(+) T cells.
19454669	Lymphoma	Promote immunity (T cell function)	In vivo, with response to tumor-expressed Ag following adoptive T cell transfer, Ag-reactive CD8(+) T cells expressing both Bcl-x(L) and survivin displayed greatly enhanced tumor protective activity compared with CD8(+) T cells expressing either molecule introduced separately. These results indicate that Bcl-x(L) and survivin can critically contribute in a cooperative, nonredundant manner to augment the accumulation and persistence of CD8(+) T cells following encounter with Ag.
23838315	Childhood acute lymphoblastic leukemia	Promote immunity (T cell function); essential for immunotherapy	Peripheral blood mononuclear cells were stimulated with autologous dendritic cells pulsed with complete peptide libraries of WT1, Survivin, MAGE-A3, and PRAME, antigens frequently expressed on ALL blasts. Antigen-specificity was observed in more than 50% of patients after the initial stimulation and increased to more than 90% after three stimulations as assessed in IFN-γ-enzyme-linked immunospot (ELISpot) and (51)Cr-release assays. This study supports the use of immunotherapy with adoptively transferred autologous tumor antigen-specific T cells to prevent relapse and improve the prognosis of patients with high-risk ALL.
29600445	melanoma	Promote immunity	By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens.
24004671	Plasma Cell Myeloma	Inhibit immunity	Thus showing the induction of a cell adhesion-mediated immune resistance (CAM-IR) against CTL lysis. Further analyses revealed that adhesion to accessory cells downregulated Fas and upregulated the caspase-3 inhibitor survivin in multiple myeloma cells. Repressing survivin with the small-molecule YM155 synergized with CTLs and abrogated CAM-IR in vitro and in vivo.
18676762	Colorectal Cancinoma; Prostate Carcinoma	Promote immunity	The level of CD8(+) T cells capable of binding tetramers for the tumor-associated antigen survivin, which is overexpressed in both cancer types, was enumerated in HLA-A*0201 patient samples.

Summary
Symbol	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
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

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Statistical results of BIRC5 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	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
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 BIRC5 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	-0.396	0.277
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.078	0.969
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.63	0.67
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.63	0.366
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.362	0.776
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.98	0.567
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.108	0.803
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.692	0.638
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.599	0.699
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.068	0.942
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	0.011	0.994
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.54	0.000136

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of BIRC5 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	14.3	14.3	0.196
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of BIRC5. 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	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of BIRC5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by BIRC5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of BIRC5. 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	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of BIRC5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between BIRC5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	BIRC5
Name	baculoviral IAP repeat containing 5
Aliases	survivin; survivin variant 3 alpha; API4; apoptosis inhibitor 4; baculoviral IAP repeat-containing 5; apopto ......
Chromosomal Location	17q25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting BIRC5 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting BIRC5.

ID	Name	Drug Type	Targets	#Targets
DB00206	Reserpine	Small Molecule	BIRC5, SLC18A1, SLC18A2	3
DB04115	Berberine	Small Molecule	BIRC5	1
DB05141	LY2181308	Small Molecule	BIRC5	1

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