BIRC5 (survivin) is a member of the inhibitor of apoptosis (IAP) family that functions primarily as an essential component of the chromosomal passenger complex (CPC). Despite its historical name "apoptosis inhibitor survivin," contemporary evidence establishes that survivin's best-characterized and evolutionarily conserved function is in mitotic regulation, not apoptosis inhibition. As a CPC component, survivin associates with Aurora B kinase, INCENP, and borealin to regulate chromosome alignment, kinetochore-microtubule attachment, spindle midzone assembly, and cytokinesis. The protein localizes dynamically during mitosis: to centromeres during prometaphase/metaphase, to the spindle midzone during anaphase, and to the midbody during cytokinesis. While survivin has been implicated in anti-apoptotic activity, this appears to be indirect and context-dependent, likely mediated through interactions with XIAP and sequestration of SMAC/DIABLO, rather than direct caspase inhibition. Unlike other IAP family members, survivin lacks the full RING domain required for direct caspase ubiquitination. Expression peaks at G2/M phase and is largely absent from most normal adult tissues but highly overexpressed in cancers.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007059 chromosome segregation | IBA GO_REF:0000033 | ACCEPT | Summary: Chromosome segregation is a core function of survivin as a CPC component. The CPC containing survivin regulates kinetochore-microtubule attachment and chromosome bi-orientation essential for proper segregation [PMID:16322459, PMID:17956729]. Reason: This annotation accurately reflects survivin's essential role in chromosome segregation as a CPC component. IBA annotations from phylogenetic analysis support this as a conserved function. Multiple studies demonstrate that survivin depletion causes chromosome missegregation and aneuploidy [PMID:16322459]. Supporting Evidence: PMID:16322459 Proper chromosome segregation requires the attachment of sister kinetochores to microtubules from opposite spindle poles to form bi-oriented chromosomes on the metaphase spindle. The chromosome passenger complex containing Survivin and the kinase Aurora B regulates this process from the centromeres. PMID:17956729 The chromosomal passenger complex (CPC) is a key regulator of chromosome segregation and cytokinesis. PMID:22357620 the Haspin kinase phosphorylates histone H3 on T3 (Dai et al., 2005), which is directly bound by a baculoviral IAP repeat (BIR) domain in the Survivin subunit, providing a binding site for CPC on mitotic centromeres file:human/BIRC5/BIRC5-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0032133 chromosome passenger complex | IBA GO_REF:0000033 | ACCEPT | Summary: Survivin is an essential structural component of the CPC, forming a triple-helix bundle with INCENP and borealin that anchors Aurora B kinase [PMID:17956729]. As the CPC subunit that reads the histone code, the Survivin BIR domain binds the phosphorylated histone H3 N-terminal tail (H3T3ph) to recruit the whole complex to inner centromeres; crystal structures of the Survivin BIR domain bound to the H3T3ph tail peptide (PDB 3UEC) define this targeting interaction [PMID:22357620]. Reason: This is the core cellular component annotation for survivin. Crystal structure studies at 1.4 A resolution demonstrate that survivin forms the structural core of the CPC regulatory complex [PMID:17956729]. This is survivin's primary, non-redundant cellular role. Supporting Evidence: PMID:17956729 Survivin, Borealin, and INCENP are the three components of the CPC that regulate the activity and localization of its enzymatic component, the kinase Aurora B. We determined the 1.4 A resolution crystal structure of the regulatory core of the CPC, revealing that Borealin and INCENP associate with the helical domain of Survivin to form a tight three-helical bundle. PMID:22357620 Survivin, a subunit of the chromosome passenger complex (CPC), binds the N-terminal tail of histone H3, which is phosphorylated on T3 by Haspin kinase, and localizes the complex to the inner centromeres. PMID:22357620 The histone H3 tail binds to the BIR domain on a face that is adjacent to the extended C-terminal Ξ±-helix that is responsible for interaction with Borealin and INCENP |
| GO:0000281 mitotic cytokinesis | IBA GO_REF:0000033 | ACCEPT | Summary: Survivin localizes to the midbody during cytokinesis and is required for completion of cell division [PMID:16344111, PMID:17956729]. Reason: Mitotic cytokinesis is a core function of the CPC. Survivin mediates CPC targeting to the midbody where it is essential for cytokinesis completion. This IBA annotation is well-supported. Supporting Evidence: PMID:16344111 Survivin is a fascinating little protein that acts as a component of the chromosomal passenger complex, which is essential for cell division PMID:17956729 The complex first localizes to centromeres and later associates with the central spindle and midbody. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Survivin is present in cytoplasm, particularly during certain cell cycle phases and in cancer cells with a mitochondrial pool [PMID:20627126, PMID:21364656]. Reason: Cytoplasmic localization is well-documented. Survivin shows nucleocytoplasmic shuttling controlled by CRM1/exportin-dependent nuclear export. Supporting Evidence: PMID:21364656 survivin was specifically detectable as a cytoplasmic and nuclear protein in the organ of Corti |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: While survivin has documented anti-apoptotic activity, this is likely indirect and context-dependent, mediated through XIAP interactions and SMAC sequestration rather than direct caspase inhibition. Contemporary reviews emphasize that survivin's primary function is mitotic regulation via CPC. Reason: The deep research review states: "survivin's best-established function is as an essential CPC component regulating mitotic progression" and "Anti-apoptotic effects are context-dependent and likely mediated by networks (XIAP, SMAC) rather than direct caspase inhibition." Unlike other IAPs, survivin lacks a full RING domain for caspase ubiquitination. The apoptosis-related function is real but secondary and indirect - keep as non-core. Supporting Evidence: PMID:21536684 We showed that survivin monomer interacts with Smac/DIABLO and X-linked inhibitor of apoptosis protein (XIAP) both in vitro and in vivo. Due to this feature, it protects cells from caspase-dependent apoptosis |
| GO:0000776 kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: Survivin localizes to kinetochores during metaphase as part of the CPC, which is essential for kinetochore-microtubule attachment [PMID:15665297]. Reason: Kinetochore localization is a core aspect of survivin's CPC function during prometaphase and metaphase. Well-supported by IDA evidence. Supporting Evidence: PMID:15665297 Survivin, another IAP family member, and cIAP1 were both localized on midbody microtubules at telophase |
| GO:0007052 mitotic spindle organization | IBA GO_REF:0000033 | ACCEPT | Summary: Survivin, through its interaction with RAN-GTP, plays a role in mitotic spindle formation by delivering TPX2 to microtubules [PMID:18591255]. Reason: This is a core function of survivin as CPC component. The survivin-RAN complex regulates spindle assembly, particularly in tumor cells. Supporting Evidence: PMID:18591255 it inhibits the delivery of the Ran effector molecule TPX2 to microtubules. In turn, this results in aberrant mitotic spindle formation |
| GO:0051233 spindle midzone | IBA GO_REF:0000033 | ACCEPT | Summary: Survivin localizes to the spindle midzone during anaphase as part of normal CPC dynamics [PMID:17956729, PMID:16239925]. Reason: Spindle midzone localization during anaphase is a well-documented aspect of survivin's dynamic CPC localization pattern. Supporting Evidence: PMID:17956729 The complex first localizes to centromeres and later associates with the central spindle and midbody. PMID:16239925 Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody. |
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000044 | ACCEPT | Summary: Survivin localizes to centromeres during early mitosis where it anchors the CPC via recognition of histone H3 phosphorylated at Thr-3 [PMID:16322459]. The crystal structure of the Survivin BIR domain bound to the H3T3ph tail peptide (PDB 3UEC; with mutant/unphosphorylated complexes 3UEG-3UEI) defines this phospho-histone reading as the molecular basis of CPC targeting to the inner centromere [PMID:22357620]. Reason: Centromeric localization is well-established and essential for CPC function in early mitosis. IEA annotation is appropriately broad and supported by multiple IDA studies. Supporting Evidence: PMID:16322459 The chromosome passenger complex containing Survivin and the kinase Aurora B regulates this process from the centromeres. PMID:22357620 Survivin, a subunit of the chromosome passenger complex (CPC), binds the N-terminal tail of histone H3, which is phosphorylated on T3 by Haspin kinase, and localizes the complex to the inner centromeres. PMID:22357620 the Haspin kinase phosphorylates histone H3 on T3 (Dai et al., 2005), which is directly bound by a baculoviral IAP repeat (BIR) domain in the Survivin subunit, providing a binding site for CPC on mitotic centromeres PMID:22357620 Mutation of amino acids that interact with the histone N-terminus lowered in vitro tail binding affinity and reduced CPC recruitment to the inner centromere in cells, validating our solved structures. PMID:22357620 We determined the crystal structure of human Survivin bound to a fourβamino acid peptide ARTphK (H3T3ph(1-4)), which is the sequence of the N-terminus of the histone H3. |
| GO:0000776 kinetochore | IEA GO_REF:0000043 | ACCEPT | Summary: Kinetochore localization during metaphase is supported by experimental evidence [PMID:15665297]. Reason: Duplicate of IBA annotation. Both are valid; kinetochore localization is well-documented. |
| GO:0004869 cysteine-type endopeptidase inhibitor activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Survivin has been reported to inhibit caspases (CASP3, CASP7), but this activity is controversial and may be indirect through XIAP interactions [PMID:21536684]. Reason: Deep research indicates "Direct caspase inhibition by survivin remains unproven." Unlike other IAPs such as XIAP, survivin lacks the structural features (full RING domain) for direct caspase inhibition. Anti-apoptotic effects appear mediated through XIAP binding and SMAC sequestration. This annotation implies direct caspase inhibition which is over-annotation. Supporting Evidence: PMID:21536684 survivin monomer interacts with Smac/DIABLO and X-linked inhibitor of apoptosis protein (XIAP) both in vitro and in vivo |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization is well-documented, particularly for acetylated survivin and during mitosis when it associates with chromosomes [PMID:20627126, PMID:21364656]. Reason: Nuclear localization supported by multiple IDA studies. Acetylation at Lys-129 promotes nuclear retention by enhancing homodimerization and inhibiting CRM1-mediated export. Supporting Evidence: PMID:21364656 survivin was specifically detectable as a cytoplasmic and nuclear protein in the organ of Corti |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: Survivin associates with chromosomes during mitosis as part of the CPC [PMID:16322459]. Reason: Chromosome association is part of the core CPC function. Appropriately general term. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Duplicate of IBA annotation - cytoplasmic localization is well-documented. Reason: Valid IEA annotation consistent with experimental evidence. |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: Spindle localization is part of survivin's mitotic function [PMID:18591255]. Reason: Spindle association is essential for CPC function during anaphase. |
| GO:0005874 microtubule | IEA GO_REF:0000043 | ACCEPT | Summary: Survivin associates with microtubules, particularly during anaphase and cytokinesis [PMID:15665297]. Reason: Microtubule association is well-documented, particularly at spindle midzone and midbody. Supporting Evidence: PMID:15665297 Survivin, another IAP family member, and cIAP1 were both localized on midbody microtubules at telophase |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This annotation from UniProtKB keyword mapping reflects survivin's historical classification as an IAP. However, survivin's primary function is mitotic regulation, not apoptosis. Reason: This IEA annotation from SPKW mapping is based on survivin's IAP family membership and gene name "apoptosis inhibitor survivin." However, deep research clearly states: "survivin's best-established function is as an essential CPC component regulating mitotic progression" and "anti-apoptotic effects are context-dependent and likely mediated by networks (XIAP, SMAC) rather than direct caspase inhibition." The core evolved function is mitosis (CPC), not apoptosis. This represents historical over-annotation based on misleading gene nomenclature. |
| GO:0007059 chromosome segregation | IEA GO_REF:0000043 | ACCEPT | Summary: Duplicate of IBA annotation - chromosome segregation is core CPC function. Reason: Consistent with IBA annotation and experimental evidence. |
| GO:0030414 peptidase inhibitor activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Parent term of cysteine-type endopeptidase inhibitor activity. Same concerns apply. Reason: Same rationale as GO:0004869. Direct peptidase inhibition by survivin is not well-established. Anti-apoptotic effects are indirect. |
| GO:0030496 midbody | IEA GO_REF:0000044 | ACCEPT | Summary: Midbody localization during cytokinesis is well-documented [PMID:15665297, PMID:17956729]. Reason: Core CPC localization during cytokinesis. Essential for cell division completion. Supporting Evidence: PMID:15665297 Survivin, another IAP family member, and cIAP1 were both localized on midbody microtubules at telophase |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine learning annotation for anti-apoptotic activity. Same caveats as IBA annotation. Reason: Anti-apoptotic activity is documented but secondary to mitotic function. Keep as non-core. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: Survivin coordinates zinc ions through its BIR domain [PMID:17956729]. Reason: Crystal structure demonstrates zinc coordination. Zinc binding is essential for BIR domain structure and function. Supporting Evidence: PMID:17956729 We determined the 1.4 A resolution crystal structure of the regulatory core of the CPC |
| GO:0051301 cell division | IEA GO_REF:0000043 | ACCEPT | Summary: Cell division is the core biological process for survivin function [PMID:16344111]. Reason: This appropriately captures survivin's primary role in mitotic cell division as a CPC component. Supporting Evidence: PMID:16344111 Survivin is a fascinating little protein that acts as a component of the chromosomal passenger complex, which is essential for cell division |
| GO:0005515 protein binding | IPI PMID:16239925 Survivin mediates targeting of the chromosomal passenger com... | REMOVE | Summary: Study demonstrates survivin interaction with borealin/CDCA8 for CPC targeting [PMID:16239925]. Reason: Generic protein binding annotation is uninformative. The specific interaction with CDCA8 is captured by CPC annotations. More specific MF terms should be used. Proposed replacements: chromosome passenger complex Supporting Evidence: PMID:16239925 Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody. |
| GO:0005515 protein binding | IPI PMID:16291752 Molecular analysis of survivin isoforms - evidence that alte... | REMOVE | Summary: Study examines survivin isoform interactions and binding to borealin [PMID:16291752]. Reason: Generic protein binding is uninformative. Specific interactions captured elsewhere. Supporting Evidence: PMID:16291752 survivin-2beta and survivin-deltaEx3 can interact with wild type survivin but have reduced affinity for the partner protein of survivin, borealin |
| GO:0005515 protein binding | IPI PMID:17099693 The Survivin-Crm1 interaction is essential for chromosomal p... | REMOVE | Summary: Study examines survivin-CRM1 interaction for CPC localization. Reason: Generic protein binding uninformative. Publication not available for detailed review. Supporting Evidence: PMID:17099693 The Survivin-Crm1 interaction is essential for chromosomal passenger complex localization and function. |
| GO:0005515 protein binding | IPI PMID:17681274 Cell death in leukemia: passenger protein regulation by topo... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:17681274 Cell death in leukemia: passenger protein regulation by topoisomerase inhibitors. |
| GO:0005515 protein binding | IPI PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | REMOVE | Summary: Crystal structure study demonstrating survivin-borealin-INCENP complex [PMID:17956729]. Reason: Generic protein binding uninformative. The specific CPC interactions are captured by GO:0032133 (chromosome passenger complex). Supporting Evidence: PMID:17956729 Borealin and INCENP associate with the helical domain of Survivin to form a tight three-helical bundle |
| GO:0005515 protein binding | IPI PMID:18243099 Mps1 phosphorylates Borealin to control Aurora B activity an... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:18243099 Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. |
| GO:0005515 protein binding | IPI PMID:19357306 A single amino acid change converts Aurora-A into Aurora-B-l... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:19357306 A single amino acid change converts Aurora-A into Aurora-B-like kinase in terms of partner specificity and cellular function. |
| GO:0005515 protein binding | IPI PMID:20638385 Interaction of Beclin 1 with survivin regulates sensitivity ... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:20638385 Epub 2010 Jul 16. Interaction of Beclin 1 with survivin regulates sensitivity of human glioma cells to TRAIL-induced apoptosis. |
| GO:0005515 protein binding | IPI PMID:20739936 Phosphorylation of the CPC by Cdk1 promotes chromosome bi-or... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:20739936 Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation. |
| GO:0005515 protein binding | IPI PMID:21051298 Spatio-temporal composition of the mitotic Chromosomal Passe... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:21051298 Oct 16. Spatio-temporal composition of the mitotic Chromosomal Passenger Complex detected using in situ proximity ligation assay. |
| GO:0005515 protein binding | IPI PMID:21225229 PAR, a protein involved in the cell cycle, is functionally r... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:21225229 PAR, a protein involved in the cell cycle, is functionally related to chromosomal passenger proteins. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Large-scale interactome study. Reason: Generic protein binding from high-throughput studies is uninformative. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:23251006 Impairment of glioma stem cell survival and growth by a nove... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:23251006 Epub 2012 Dec 18. Impairment of glioma stem cell survival and growth by a novel inhibitor for Survivin-Ran protein complex. |
| GO:0005515 protein binding | IPI PMID:24571573 The GAR domain of GAS2L3 mediates binding to the chromosomal... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:24571573 The GAR domain of GAS2L3 mediates binding to the chromosomal passenger complex and is required for localization of GAS2L3 to the constriction zone during abscission. |
| GO:0005515 protein binding | IPI PMID:27332895 Aurora-C Interactions with Survivin and INCENP Reveal Shared... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner and relevance. Supporting Evidence: PMID:27332895 eCollection 2016. Aurora-C Interactions with Survivin and INCENP Reveal Shared and Distinct Features Compared with Aurora-B Chromosome Passenger Protein Complex. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Large-scale interactome study. Reason: Generic protein binding from high-throughput studies is uninformative. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... | REMOVE | Summary: Large-scale interactome/BioID study. Reason: Generic protein binding from high-throughput studies is uninformative. Supporting Evidence: PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Large-scale interactome study. Reason: Generic protein binding from high-throughput studies is uninformative. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Large-scale interactome study related to neurodegeneration. Reason: Generic protein binding from high-throughput studies is uninformative. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Large-scale proteomics study. Reason: Generic protein binding from high-throughput studies is uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0042802 identical protein binding | IPI PMID:17099693 The Survivin-Crm1 interaction is essential for chromosomal p... | ACCEPT | Summary: Survivin forms homodimers in the apo state [PMID:10949038, PMID:21536684]. Reason: Survivin homodimerization is well-documented and functionally relevant. The dimer-monomer equilibrium affects function (dimers enhance tubulin stability, monomers better inhibit apoptosis). Supporting Evidence: PMID:17099693 The Survivin-Crm1 interaction is essential for chromosomal passenger complex localization and function. |
| GO:0042802 identical protein binding | IPI PMID:23251006 Impairment of glioma stem cell survival and growth by a nove... | ACCEPT | Summary: Publication not available for detailed review, but homodimerization is well-established. Reason: Consistent with known homodimerization. Supporting Evidence: PMID:23251006 Epub 2012 Dec 18. Impairment of glioma stem cell survival and growth by a novel inhibitor for Survivin-Ran protein complex. |
| GO:0045171 intercellular bridge | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence data showing localization to intercellular bridge during cytokinesis. Reason: Consistent with midbody localization during cytokinesis. |
| GO:0000278 mitotic cell cycle | NAS PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | ACCEPT | Summary: Survivin is essential for mitotic cell cycle progression as a CPC component [PMID:17956729]. Reason: Core function. CPC is essential for mitosis. Supporting Evidence: PMID:17956729 The chromosomal passenger complex (CPC) is a key regulator of chromosome segregation and cytokinesis. |
| GO:0000281 mitotic cytokinesis | NAS PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | ACCEPT | Summary: Duplicate annotation - mitotic cytokinesis is core CPC function. Reason: Consistent with IBA annotation. Supporting Evidence: PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. |
| GO:0015630 microtubule cytoskeleton | IDA PMID:9859993 Control of apoptosis and mitotic spindle checkpoint by survi... | ACCEPT | Summary: Early study demonstrating survivin association with microtubule cytoskeleton. Reason: Well-supported cellular component annotation. Supporting Evidence: PMID:9859993 Control of apoptosis and mitotic spindle checkpoint by survivin. |
| GO:0051256 mitotic spindle midzone assembly | NAS PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | ACCEPT | Summary: CPC including survivin is involved in spindle midzone assembly [PMID:17956729]. Reason: Core CPC function during anaphase. Supporting Evidence: PMID:17956729 Association of the core "passenger" proteins creates a single structural unit, whose composite molecular surface presents conserved residues essential for central spindle and midbody localization |
| GO:0090267 positive regulation of mitotic cell cycle spindle assembly checkpoint | NAS PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | ACCEPT | Summary: CPC regulates spindle assembly checkpoint signaling. Reason: CPC function in checkpoint regulation is well-documented. Supporting Evidence: PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. |
| GO:0090307 mitotic spindle assembly | NAS PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | ACCEPT | Summary: Survivin-RAN complex involved in spindle assembly [PMID:18591255]. Reason: Core mitotic function supported by experimental evidence. Supporting Evidence: PMID:18591255 survivin is a novel effector of Ran signaling, and this pathway may be preferentially exploited for spindle assembly PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. |
| GO:1901970 positive regulation of mitotic sister chromatid separation | NAS PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | ACCEPT | Summary: CPC including survivin is essential for sister chromatid separation [PMID:16322459]. Reason: Core CPC function in chromosome segregation. Supporting Evidence: PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. |
| GO:1902425 positive regulation of attachment of mitotic spindle microtubules to kinetochore | NAS PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | ACCEPT | Summary: CPC regulates kinetochore-microtubule attachment [PMID:16322459]. Reason: Core CPC function during prometaphase/metaphase. Supporting Evidence: PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. |
| GO:1903490 positive regulation of mitotic cytokinesis | NAS PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals... | ACCEPT | Summary: CPC is essential for cytokinesis completion. Reason: Core CPC function at midbody during cytokinesis. Supporting Evidence: PMID:17956729 Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:10949038 Crystal structure and mutagenic analysis of the inhibitor-of... | KEEP AS NON CORE | Summary: Crystal structure study with mutagenesis showing survivin's role in apoptosis inhibition. However, this is indirect via dimerization and interaction surfaces [PMID:10949038]. Reason: The study demonstrates structural features required for anti-apoptotic activity, but this is secondary to the core mitotic function. Keep as non-core. Supporting Evidence: PMID:10949038 Mutagenesis analysis revealed that survivin dimerization and an extended negatively charged surface surrounding Asp-71 are required to counteract apoptosis and preserve ploidy. |
| GO:0005515 protein binding | IPI PMID:28218735 Aurora kinase A regulates Survivin stability through targeti... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to determine specific interaction partner. Supporting Evidence: PMID:28218735 Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:28218735 Aurora kinase A regulates Survivin stability through targeti... | KEEP AS NON CORE | Summary: Study on Aurora kinase A regulation of survivin stability through FBXL7. Reason: Anti-apoptotic function documented but secondary to core mitotic function. Supporting Evidence: PMID:28218735 Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis. |
| GO:0005515 protein binding | IPI PMID:25778398 The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial... | REMOVE | Summary: Study demonstrates survivin-FBXL7 interaction for ubiquitination. Reason: Generic protein binding uninformative. The specific E3 ligase interaction could be better captured by more specific terms. Supporting Evidence: PMID:25778398 2015 Mar 16. The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:25778398 The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial... | KEEP AS NON CORE | Summary: Study links survivin to mitochondrial function and apoptosis regulation. Reason: Anti-apoptotic function documented but secondary. Supporting Evidence: PMID:25778398 2015 Mar 16. The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin. |
| GO:0005515 protein binding | IPI PMID:23825075 Renal uptake of the antiapoptotic protein survivin is mediat... | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication. Supporting Evidence: PMID:23825075 Renal uptake of the antiapoptotic protein survivin is mediated by megalin at the apical membrane of the proximal tubule. |
| GO:0005634 nucleus | IDA PMID:20627126 Expression analysis suggests a potential cytoprotective role... | ACCEPT | Summary: Nuclear localization demonstrated in cochlea studies [PMID:20627126]. Reason: Nuclear localization well-documented. Supporting Evidence: PMID:20627126 the apoptosis inhibitor protein Birc5 is expressed in cell types critical for hearing perception |
| GO:0005634 nucleus | IDA PMID:21364656 An otoprotective role for the apoptosis inhibitor protein su... | ACCEPT | Summary: Nuclear localization confirmed in cochlea studies [PMID:21364656]. Reason: Consistent with other IDA evidence. Supporting Evidence: PMID:21364656 survivin was specifically detectable as a cytoplasmic and nuclear protein in the organ of Corti |
| GO:0005737 cytoplasm | IDA PMID:20627126 Expression analysis suggests a potential cytoprotective role... | ACCEPT | Summary: Cytoplasmic localization demonstrated [PMID:20627126]. Reason: Well-documented. Supporting Evidence: PMID:20627126 Epub 2010 Jul 17. Expression analysis suggests a potential cytoprotective role of Birc5 in the inner ear. |
| GO:0005737 cytoplasm | IDA PMID:21364656 An otoprotective role for the apoptosis inhibitor protein su... | ACCEPT | Summary: Cytoplasmic localization confirmed [PMID:21364656]. Reason: Consistent with other evidence. Supporting Evidence: PMID:21364656 An otoprotective role for the apoptosis inhibitor protein survivin. |
| GO:0007605 sensory perception of sound | IEP PMID:20627126 Expression analysis suggests a potential cytoprotective role... | KEEP AS NON CORE | Summary: Survivin expression correlates with auditory function in cochlea studies [PMID:20627126]. Reason: This is a tissue-specific expression pattern correlation, not a core function. The cytoprotective role in auditory cells is context-dependent. Supporting Evidence: PMID:20627126 the apoptosis inhibitor protein Birc5 is expressed in cell types critical for hearing perception |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:20627126 Expression analysis suggests a potential cytoprotective role... | KEEP AS NON CORE | Summary: Cytoprotective activity demonstrated against ototoxins [PMID:20627126]. Reason: Anti-apoptotic activity in specific cellular context, but not core function. Supporting Evidence: PMID:20627126 The cytoprotective activity of the guinea pig and human Birc5 protein was confirmed by cloning of the gene and by subsequent ectopic expression and challenging studies against the ototoxin gentamicin |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:21364656 An otoprotective role for the apoptosis inhibitor protein su... | KEEP AS NON CORE | Summary: Otoprotective role demonstrated [PMID:21364656]. Reason: Secondary function in specific tissue context. Supporting Evidence: PMID:21364656 overexpression of survivin from both species significantly counteracted PCD as determined by quantitating apoptotic nuclei and caspase-3 activity |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8956026 | ACCEPT | Summary: Reactome pathway annotation for cytosolic localization. Reason: Consistent with general cytoplasmic localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4655355 | ACCEPT | Summary: Reactome pathway annotation for nucleoplasm localization. Reason: Consistent with nuclear localization during CPC function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6790036 | ACCEPT | Summary: Reactome annotation - duplicate. Reason: Consistent annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6797763 | ACCEPT | Summary: Reactome annotation for TP53-BIRC5 regulation. Reason: Consistent annotation. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:21536684 Survivin monomer plays an essential role in apoptosis regula... | KEEP AS NON CORE | Summary: Study demonstrates survivin monomer role in apoptosis regulation through XIAP and SMAC interactions [PMID:21536684]. Reason: This study actually supports that anti-apoptotic effects are indirect through XIAP/SMAC interactions. Keep as non-core. Supporting Evidence: PMID:21536684 survivin monomer interacts with Smac/DIABLO and X-linked inhibitor of apoptosis protein (XIAP) both in vitro and in vivo. Due to this feature, it protects cells from caspase-dependent apoptosis |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141409 | ACCEPT | Summary: Reactome annotation for spindle checkpoint pathway. Reason: Consistent with cytosolic localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141422 | ACCEPT | Summary: Reactome spindle checkpoint annotation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141431 | ACCEPT | Summary: Reactome spindle checkpoint annotation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141439 | ACCEPT | Summary: Reactome spindle checkpoint annotation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638803 | ACCEPT | Summary: Reactome annotation for cohesin phosphorylation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638821 | ACCEPT | Summary: Reactome annotation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467809 | ACCEPT | Summary: Reactome annotation for separase/cohesin cleavage. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467811 | ACCEPT | Summary: Reactome annotation for sister chromatid separation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2468287 | ACCEPT | Summary: Reactome annotation for CDK1 phosphorylation of sororin. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2484822 | ACCEPT | Summary: Reactome annotation for kinetochore assembly. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-375302 | ACCEPT | Summary: Reactome annotation for kinetochore capture. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4655355 | ACCEPT | Summary: Reactome annotation for CPC SUMOylation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666129 | ACCEPT | Summary: Reactome annotation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666160 | ACCEPT | Summary: Reactome annotation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666169 | ACCEPT | Summary: Reactome annotation. Reason: Consistent annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9648114 | ACCEPT | Summary: Reactome annotation for mitotic spindle. Reason: Consistent annotation. |
| GO:0000776 kinetochore | IDA PMID:15665297 cIAP1 Localizes to the nuclear compartment and modulates the... | ACCEPT | Summary: Kinetochore localization demonstrated [PMID:15665297]. Reason: Core CPC localization during metaphase. Supporting Evidence: PMID:15665297 Survivin, another IAP family member, and cIAP1 were both localized on midbody microtubules at telophase |
| GO:0005515 protein binding | IPI PMID:20826784 Acetylation directs survivin nuclear localization to repress... | REMOVE | Summary: Study demonstrates survivin-STAT3 and survivin-CRM1 interactions. Reason: Generic protein binding uninformative. Specific interactions could be captured by more specific terms. Supporting Evidence: PMID:20826784 2010 Sep 8. Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity. |
| GO:0005515 protein binding | IPI PMID:21536684 Survivin monomer plays an essential role in apoptosis regula... | REMOVE | Summary: Study demonstrates survivin interactions with XIAP and SMAC [PMID:21536684]. Reason: Generic protein binding uninformative. The specific XIAP and SMAC interactions are functionally important but should be captured by more specific terms. Supporting Evidence: PMID:21536684 2011 May 2. Survivin monomer plays an essential role in apoptosis regulation. |
| GO:0005634 nucleus | IDA PMID:15665297 cIAP1 Localizes to the nuclear compartment and modulates the... | ACCEPT | Summary: Nuclear localization demonstrated [PMID:15665297]. Reason: Well-documented localization. Supporting Evidence: PMID:15665297 cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. |
| GO:0005634 nucleus | IDA PMID:20826784 Acetylation directs survivin nuclear localization to repress... | ACCEPT | Summary: Nuclear localization controlled by acetylation at Lys-129. Reason: Well-documented with mechanistic detail. Supporting Evidence: PMID:20826784 2010 Sep 8. Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity. |
| GO:0008017 microtubule binding | TAS PMID:21536684 Survivin monomer plays an essential role in apoptosis regula... | ACCEPT | Summary: Survivin dimers enhance tubulin stability [PMID:21536684]. Reason: Microtubule binding is part of survivin's mitotic function. Supporting Evidence: PMID:21536684 only wild-type survivin, but not the monomer mutant form, enhances tubulin stability in cells |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:16344111 Survivin - a protein with dual roles in mitosis and apoptosi... | ACCEPT | Summary: Survivin promotes cell proliferation through its role in mitosis [PMID:16344111]. Reason: Cell proliferation is a consequence of survivin's essential mitotic function. Supporting Evidence: PMID:16344111 Survivin is a fascinating little protein that acts as a component of the chromosomal passenger complex, which is essential for cell division, and as an inhibitor of apoptosis. With dual roles in promoting cell proliferation and preventing apoptosis |
| GO:0030496 midbody | IDA PMID:15665297 cIAP1 Localizes to the nuclear compartment and modulates the... | ACCEPT | Summary: Midbody localization during cytokinesis [PMID:15665297]. Reason: Core CPC localization. Supporting Evidence: PMID:15665297 Survivin, another IAP family member, and cIAP1 were both localized on midbody microtubules at telophase |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:20826784 Acetylation directs survivin nuclear localization to repress... | KEEP AS NON CORE | Summary: Acetylated survivin represses STAT3 transactivation. Reason: Transcriptional repression is a secondary, context-dependent function. Supporting Evidence: PMID:20826784 2010 Sep 8. Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity. |
| GO:0005515 protein binding | IPI PMID:15665297 cIAP1 Localizes to the nuclear compartment and modulates the... | REMOVE | Summary: Survivin-cIAP1 interaction demonstrated [PMID:15665297]. Reason: Generic protein binding uninformative. Supporting Evidence: PMID:15665297 cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | ACCEPT | Summary: Cytoplasmic localization from fusion protein studies. Reason: Consistent with other evidence. |
| GO:0000228 nuclear chromosome | IDA PMID:16322459 Chromosome alignment and segregation regulated by ubiquitina... | ACCEPT | Summary: Survivin associates with chromosomes during mitosis [PMID:16322459]. Reason: Core CPC function - chromosome association. Supporting Evidence: PMID:16322459 The chromosome passenger complex containing Survivin and the kinase Aurora B regulates this process from the centromeres. |
| GO:0000775 chromosome, centromeric region | IDA PMID:16322459 Chromosome alignment and segregation regulated by ubiquitina... | ACCEPT | Summary: Centromeric localization demonstrated [PMID:16322459]. Reason: Core CPC localization during early mitosis. Supporting Evidence: PMID:16322459 Chromosome alignment and segregation regulated by ubiquitination of survivin. |
| GO:0005515 protein binding | IPI PMID:14610074 Aurora-B phosphorylation in vitro identifies a residue of su... | REMOVE | Summary: Survivin-INCENP interaction demonstrated. Reason: Generic protein binding. CPC interactions captured by GO:0032133. Supporting Evidence: PMID:14610074 2003 Nov 10. Aurora-B phosphorylation in vitro identifies a residue of survivin that is essential for its localization and binding to inner centromere protein (INCENP) in vivo. |
| GO:0005829 cytosol | IDA PMID:18591255 A survivin-ran complex regulates spindle formation in tumor ... | ACCEPT | Summary: Cytosolic localization during survivin-RAN complex function [PMID:18591255]. Reason: Well-documented localization. Supporting Evidence: PMID:18591255 Jun 30. A survivin-ran complex regulates spindle formation in tumor cells. |
| GO:0019899 enzyme binding | IPI PMID:16322459 Chromosome alignment and segregation regulated by ubiquitina... | ACCEPT | Summary: Survivin binds Aurora B kinase as part of CPC. Reason: More informative than generic protein binding. Aurora B is the enzymatic component of CPC. Supporting Evidence: PMID:16322459 Chromosome alignment and segregation regulated by ubiquitination of survivin. |
| GO:0031267 small GTPase binding | IPI PMID:18591255 A survivin-ran complex regulates spindle formation in tumor ... | ACCEPT | Summary: Survivin binds RAN-GTP [PMID:18591255]. Reason: Well-characterized interaction with functional significance for spindle assembly. Supporting Evidence: PMID:18591255 survivin associates with the small GTPase Ran in an evolutionarily conserved recognition in mammalian cells |
| GO:0032133 chromosome passenger complex | IPI PMID:15260989 The chromosomal passenger complex is required for chromatin-... | ACCEPT | Summary: CPC component identification [PMID:15260989]. Reason: Core annotation for survivin's primary cellular role. Supporting Evidence: PMID:15260989 the vertebrate chromosomal passenger complex containing Incenp, Survivin, and the kinase Aurora B |
| GO:0032133 chromosome passenger complex | IPI PMID:18591255 A survivin-ran complex regulates spindle formation in tumor ... | ACCEPT | Summary: CPC function confirmed [PMID:18591255]. Reason: Core annotation. Supporting Evidence: PMID:18591255 Disruption of a survivin-Ran complex does not affect the assembly of survivin within the chromosomal passenger complex |
| GO:0051087 protein-folding chaperone binding | IPI PMID:18086682 Hsp60 regulation of tumor cell apoptosis. | UNDECIDED | Summary: Publication not available for detailed review. Reason: Unable to access publication to evaluate Hsp60 interaction relevance. Supporting Evidence: PMID:18086682 2007 Dec 17. Hsp60 regulation of tumor cell apoptosis. |
| GO:0031503 protein-containing complex localization | IMP PMID:16239925 Survivin mediates targeting of the chromosomal passenger com... | ACCEPT | Summary: Survivin mediates CPC targeting to centromeres and midbody [PMID:16239925]. Reason: Core function - survivin directs CPC localization. Supporting Evidence: PMID:16239925 Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody. |
| GO:0000775 chromosome, centromeric region | IDA PMID:11084331 Survivin and the inner centromere protein INCENP show simila... | ACCEPT | Summary: Centromeric localization demonstrated in foundational study. Reason: Core CPC localization. Supporting Evidence: PMID:11084331 Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. |
| GO:0030496 midbody | IDA PMID:11084331 Survivin and the inner centromere protein INCENP show simila... | ACCEPT | Summary: Midbody localization demonstrated in foundational study. Reason: Core CPC localization during cytokinesis. Supporting Evidence: PMID:11084331 Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. |
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Download this section (compressed HTML)Q: What is the precise mechanism by which survivin contributes to anti-apoptotic activity? Is it entirely through XIAP potentiation and SMAC sequestration, or are there additional direct mechanisms?
Q: Do the splice variants (survivin-2B, survivin-DeltaEx3) have any physiological function or are they non-functional products of alternative splicing?
Q: What determines the balance between survivin's mitotic and potential apoptotic functions in different cellular contexts?
Experiment: Structure-function studies with BIR domain mutants that specifically disrupt caspase binding without affecting CPC assembly to determine direct vs. indirect anti-apoptotic mechanisms.
Experiment: Isoform-specific knockdown/rescue experiments to determine if splice variants have any non-mitotic functions.
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