Target Information
| Target General Information | Top | |||||
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| Target ID |
T02677
(Former ID: TTDC00273)
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| Target Name |
Apoptosis inhibitor survivin (BIRC5)
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| Synonyms |
Survivin; IAP4; Baculoviral IAP repeat-containing protein 5; Apoptosis inhibitor 4; API4
Click to Show/Hide
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| Gene Name |
BIRC5
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. 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. Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis. 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. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform. Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis.
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| BioChemical Class |
Acyltransferase
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| UniProt ID | ||||||
| Sequence |
MGAPTLPPAWQPFLKDHRISTFKNWPFLEGCACTPERMAEAGFIHCPTENEPDLAQCFFC
FKELEGWEPDDDPIEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIAKETNNK KKEFEETAKKVRRAIEQLAAMD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T36B1Q | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | ISIS 23722 | Drug Info | Phase 3 | Solid tumour/cancer | [2] | |
| 2 | SurVaxM | Drug Info | Phase 2 | Glioblastoma of brain | [3] | |
| 3 | CV-9201 | Drug Info | Phase 1/2 | Non-small-cell lung cancer | [4] | |
| 4 | EZN-3042 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | ISIS 23722 | Drug Info | [1] | |||
| 2 | EZN-3042 | Drug Info | [8] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | SurVaxM | Drug Info | [6] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Apoptosis | hsa04210 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Apoptosis - multiple species | hsa04215 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Hippo signaling pathway | hsa04390 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Hippo signaling pathway | |||||
| 2 | Hepatitis B | |||||
| 3 | Pathways in cancer | |||||
| 4 | Colorectal cancer | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Angiogenesis | |||||
| PID Pathway | [+] 4 PID Pathways | + | ||||
| 1 | Aurora B signaling | |||||
| 2 | Validated targets of C-MYC transcriptional activation | |||||
| 3 | FOXM1 transcription factor network | |||||
| 4 | Aurora A signaling | |||||
| Reactome | [+] 4 Reactome Pathways | + | ||||
| 1 | Separation of Sister Chromatids | |||||
| 2 | Resolution of Sister Chromatid Cohesion | |||||
| 3 | RHO GTPases Activate Formins | |||||
| 4 | Mitotic Prometaphase | |||||
| WikiPathways | [+] 7 WikiPathways | + | ||||
| 1 | IL-4 Signaling Pathway | |||||
| 2 | Apoptosis-related network due to altered Notch3 in ovarian cancer | |||||
| 3 | Mitotic Metaphase and Anaphase | |||||
| 4 | Mitotic Prometaphase | |||||
| 5 | Apoptosis | |||||
| 6 | Interleukin-11 Signaling Pathway | |||||
| 7 | Apoptosis Modulation and Signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Targeted BIRC5 silencing using YM155 causes cell death in neuroblastoma cells with low ABCB1 expression.Eur J Cancer.2012 Mar;48(5):763-71. | |||||
| REF 2 | ClinicalTrials.gov (NCT01630733) A Multinational, Randomized, Open-Label Study of Custirsen In Patients With Advanced or Metastatic (Stage IV) Non-Small Cell Lung Cancer. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT04013672) Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT00923312) Trial of an RNActive-Derived Cancer Vaccine in Stage IIIB/IV Non Small Cell Lung Cancer (NSCLC). U.S. National Institutes of Health. | |||||
| REF 5 | 2011 Pipeline of Santaris Pharma. | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | National Cancer Institute Drug Dictionary (drug id 648549). | |||||
| REF 8 | SPC3042: a proapoptotic survivin inhibitor.Mol Cancer Ther.2008 Sep;7(9):2736-45. | |||||
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