id: O15392
gene_symbol: BIRC5
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
existing_annotations:
  - term:
      id: GO:0007059
      label: chromosome segregation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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].
      action: ACCEPT
      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].
      supported_by:
        - reference_id: PMID:16322459
          supporting_text: "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."
        - reference_id: PMID:17956729
          supporting_text: "The chromosomal passenger complex (CPC) is a key regulator
            of chromosome segregation and cytokinesis."

        - reference_id: file:human/BIRC5/BIRC5-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0032133
      label: chromosome passenger complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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].
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:17956729
          supporting_text: "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."

  - term:
      id: GO:0000281
      label: mitotic cytokinesis
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Survivin localizes to the midbody during cytokinesis and is required for completion
        of cell
        division [PMID:16344111, PMID:17956729].
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:16344111
          supporting_text: "Survivin is a fascinating little protein that acts as
            a component of the chromosomal passenger complex, which is essential for
            cell division"
        - reference_id: PMID:17956729
          supporting_text: "The complex first localizes to centromeres and later associates
            with the central spindle and midbody."

  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Survivin is present in cytoplasm, particularly during certain cell cycle phases
        and in cancer
        cells with a mitochondrial pool [PMID:20627126, PMID:21364656].
      action: ACCEPT
      reason: >-
        Cytoplasmic localization is well-documented. Survivin shows nucleocytoplasmic
        shuttling
        controlled by CRM1/exportin-dependent nuclear export.
      supported_by:
        - reference_id: PMID:21364656
          supporting_text: "survivin was specifically detectable as a cytoplasmic
            and nuclear protein in the organ of Corti"

  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:21536684
          supporting_text: "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"

  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Survivin localizes to kinetochores during metaphase as part of the CPC, which
        is essential
        for kinetochore-microtubule attachment [PMID:15665297].
      action: ACCEPT
      reason: >-
        Kinetochore localization is a core aspect of survivin's CPC function during
        prometaphase and
        metaphase. Well-supported by IDA evidence.
      supported_by:
        - reference_id: PMID:15665297
          supporting_text: "Survivin, another IAP family member, and cIAP1 were both
            localized on midbody microtubules at telophase"

  - term:
      id: GO:0007052
      label: mitotic spindle organization
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Survivin, through its interaction with RAN-GTP, plays a role in mitotic spindle
        formation by
        delivering TPX2 to microtubules [PMID:18591255].
      action: ACCEPT
      reason: >-
        This is a core function of survivin as CPC component. The survivin-RAN complex
        regulates
        spindle assembly, particularly in tumor cells.
      supported_by:
        - reference_id: PMID:18591255
          supporting_text: "it inhibits the delivery of the Ran effector molecule
            TPX2 to microtubules. In turn, this results in aberrant mitotic spindle
            formation"

  - term:
      id: GO:0051233
      label: spindle midzone
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Survivin localizes to the spindle midzone during anaphase as part of normal
        CPC dynamics
        [PMID:17956729, PMID:16239925].
      action: ACCEPT
      reason: >-
        Spindle midzone localization during anaphase is a well-documented aspect of
        survivin's
        dynamic CPC localization pattern.
      supported_by:
        - reference_id: PMID:17956729
          supporting_text: "The complex first localizes to centromeres and later associates
            with the central spindle and midbody."
        - reference_id: PMID:16239925
          supporting_text: "Survivin mediates targeting of the chromosomal passenger
            complex to the centromere and midbody."

  - term:
      id: GO:0000775
      label: chromosome, centromeric region
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Survivin localizes to centromeres during early mitosis where it anchors the
        CPC via recognition
        of histone H3 phosphorylated at Thr-3 [PMID:16322459].
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:16322459
          supporting_text: "The chromosome passenger complex containing Survivin and
            the kinase Aurora B regulates this process from the centromeres."

  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Kinetochore localization during metaphase is supported by experimental evidence
        [PMID:15665297].
      action: ACCEPT
      reason: >-
        Duplicate of IBA annotation. Both are valid; kinetochore localization is well-documented.

  - term:
      id: GO:0004869
      label: cysteine-type endopeptidase inhibitor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Survivin has been reported to inhibit caspases (CASP3, CASP7), but this activity
        is controversial
        and may be indirect through XIAP interactions [PMID:21536684].
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:21536684
          supporting_text: "survivin monomer interacts with Smac/DIABLO and X-linked
            inhibitor of apoptosis protein (XIAP) both in vitro and in vivo"

  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Nuclear localization is well-documented, particularly for acetylated survivin
        and during
        mitosis when it associates with chromosomes [PMID:20627126, PMID:21364656].
      action: ACCEPT
      reason: >-
        Nuclear localization supported by multiple IDA studies. Acetylation at Lys-129
        promotes
        nuclear retention by enhancing homodimerization and inhibiting CRM1-mediated
        export.
      supported_by:
        - reference_id: PMID:21364656
          supporting_text: "survivin was specifically detectable as a cytoplasmic
            and nuclear protein in the organ of Corti"

  - term:
      id: GO:0005694
      label: chromosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Survivin associates with chromosomes during mitosis as part of the CPC [PMID:16322459].
      action: ACCEPT
      reason: >-
        Chromosome association is part of the core CPC function. Appropriately general
        term.

  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Duplicate of IBA annotation - cytoplasmic localization is well-documented.
      action: ACCEPT
      reason: >-
        Valid IEA annotation consistent with experimental evidence.

  - term:
      id: GO:0005819
      label: spindle
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Spindle localization is part of survivin's mitotic function [PMID:18591255].
      action: ACCEPT
      reason: >-
        Spindle association is essential for CPC function during anaphase.

  - term:
      id: GO:0005874
      label: microtubule
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Survivin associates with microtubules, particularly during anaphase and cytokinesis
        [PMID:15665297].
      action: ACCEPT
      reason: >-
        Microtubule association is well-documented, particularly at spindle midzone
        and midbody.
      supported_by:
        - reference_id: PMID:15665297
          supporting_text: "Survivin, another IAP family member, and cIAP1 were both
            localized on midbody microtubules at telophase"

  - term:
      id: GO:0006915
      label: apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.

  - term:
      id: GO:0007059
      label: chromosome segregation
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Duplicate of IBA annotation - chromosome segregation is core CPC function.
      action: ACCEPT
      reason: >-
        Consistent with IBA annotation and experimental evidence.

  - term:
      id: GO:0030414
      label: peptidase inhibitor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Parent term of cysteine-type endopeptidase inhibitor activity. Same concerns
        apply.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Same rationale as GO:0004869. Direct peptidase inhibition by survivin is not
        well-established.
        Anti-apoptotic effects are indirect.

  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Midbody localization during cytokinesis is well-documented [PMID:15665297,
        PMID:17956729].
      action: ACCEPT
      reason: >-
        Core CPC localization during cytokinesis. Essential for cell division completion.
      supported_by:
        - reference_id: PMID:15665297
          supporting_text: "Survivin, another IAP family member, and cIAP1 were both
            localized on midbody microtubules at telophase"

  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ARBA machine learning annotation for anti-apoptotic activity. Same caveats
        as IBA annotation.
      action: KEEP_AS_NON_CORE
      reason: >-
        Anti-apoptotic activity is documented but secondary to mitotic function. Keep
        as non-core.

  - term:
      id: GO:0046872
      label: metal ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Survivin coordinates zinc ions through its BIR domain [PMID:17956729].
      action: ACCEPT
      reason: >-
        Crystal structure demonstrates zinc coordination. Zinc binding is essential
        for BIR domain
        structure and function.
      supported_by:
        - reference_id: PMID:17956729
          supporting_text: "We determined the 1.4 A resolution crystal structure of
            the regulatory core of the CPC"

  - term:
      id: GO:0051301
      label: cell division
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Cell division is the core biological process for survivin function [PMID:16344111].
      action: ACCEPT
      reason: >-
        This appropriately captures survivin's primary role in mitotic cell division
        as a CPC component.
      supported_by:
        - reference_id: PMID:16344111
          supporting_text: "Survivin is a fascinating little protein that acts as
            a component of the chromosomal passenger complex, which is essential for
            cell division"

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16239925
    review:
      summary: >-
        Study demonstrates survivin interaction with borealin/CDCA8 for CPC targeting
        [PMID:16239925].
      action: REMOVE
      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_replacement_terms:
        - id: GO:0032133
          label: chromosome passenger complex

      supported_by:
        - reference_id: PMID:16239925
          supporting_text: Survivin mediates targeting of the chromosomal 
            passenger complex to the centromere and midbody.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16291752
    review:
      summary: >-
        Study examines survivin isoform interactions and binding to borealin [PMID:16291752].
      action: REMOVE
      reason: >-
        Generic protein binding is uninformative. Specific interactions captured elsewhere.
      supported_by:
        - reference_id: PMID:16291752
          supporting_text: "survivin-2beta and survivin-deltaEx3 can interact with
            wild type survivin but have reduced affinity for the partner protein of
            survivin, borealin"

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17099693
    review:
      summary: >-
        Study examines survivin-CRM1 interaction for CPC localization.
      action: REMOVE
      reason: >-
        Generic protein binding uninformative. Publication not available for detailed
        review.

      supported_by:
        - reference_id: PMID:17099693
          supporting_text: The Survivin-Crm1 interaction is essential for 
            chromosomal passenger complex localization and function.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17681274
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:17681274
          supporting_text: 'Cell death in leukemia: passenger protein regulation by
            topoisomerase inhibitors.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17956729
    review:
      summary: >-
        Crystal structure study demonstrating survivin-borealin-INCENP complex [PMID:17956729].
      action: REMOVE
      reason: >-
        Generic protein binding uninformative. The specific CPC interactions are captured
        by
        GO:0032133 (chromosome passenger complex).
      supported_by:
        - reference_id: PMID:17956729
          supporting_text: "Borealin and INCENP associate with the helical domain
            of Survivin to form a tight three-helical bundle"

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18243099
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:18243099
          supporting_text: Mps1 phosphorylates Borealin to control Aurora B 
            activity and chromosome alignment.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19357306
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:19357306
          supporting_text: A single amino acid change converts Aurora-A into 
            Aurora-B-like kinase in terms of partner specificity and cellular 
            function.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20638385
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:20638385
          supporting_text: Epub 2010 Jul 16. Interaction of Beclin 1 with 
            survivin regulates sensitivity of human glioma cells to 
            TRAIL-induced apoptosis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20739936
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:20739936
          supporting_text: Phosphorylation of the CPC by Cdk1 promotes 
            chromosome bi-orientation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21051298
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:21051298
          supporting_text: Oct 16. Spatio-temporal composition of the mitotic 
            Chromosomal Passenger Complex detected using in situ proximity 
            ligation assay.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21225229
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:21225229
          supporting_text: PAR, a protein involved in the cell cycle, is 
            functionally related to chromosomal passenger proteins.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21988832
    review:
      summary: >-
        Large-scale interactome study.
      action: REMOVE
      reason: >-
        Generic protein binding from high-throughput studies is uninformative.

      supported_by:
        - reference_id: PMID:21988832
          supporting_text: Toward an understanding of the protein interaction 
            network of the human liver.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23251006
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:23251006
          supporting_text: Epub 2012 Dec 18. Impairment of glioma stem cell 
            survival and growth by a novel inhibitor for Survivin-Ran protein 
            complex.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24571573
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:24571573
          supporting_text: 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.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:27332895
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner and
        relevance.

      supported_by:
        - reference_id: PMID:27332895
          supporting_text: eCollection 2016. Aurora-C Interactions with Survivin
            and INCENP Reveal Shared and Distinct Features Compared with 
            Aurora-B Chromosome Passenger Protein Complex.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28514442
    review:
      summary: >-
        Large-scale interactome study.
      action: REMOVE
      reason: >-
        Generic protein binding from high-throughput studies is uninformative.

      supported_by:
        - reference_id: PMID:28514442
          supporting_text: Architecture of the human interactome defines protein
            communities and disease networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:29568061
    review:
      summary: >-
        Large-scale interactome/BioID study.
      action: REMOVE
      reason: >-
        Generic protein binding from high-throughput studies is uninformative.

      supported_by:
        - reference_id: PMID:29568061
          supporting_text: An AP-MS- and BioID-compatible MAC-tag enables 
            comprehensive mapping of protein interactions and subcellular 
            localizations.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: >-
        Large-scale interactome study.
      action: REMOVE
      reason: >-
        Generic protein binding from high-throughput studies is uninformative.

      supported_by:
        - reference_id: PMID:32296183
          supporting_text: Apr 8. A reference map of the human binary protein 
            interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32814053
    review:
      summary: >-
        Large-scale interactome study related to neurodegeneration.
      action: REMOVE
      reason: >-
        Generic protein binding from high-throughput studies is uninformative.

      supported_by:
        - reference_id: PMID:32814053
          supporting_text: Interactome Mapping Provides a Network of 
            Neurodegenerative Disease Proteins and Uncovers Widespread Protein 
            Aggregation in Affected Brains.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: >-
        Large-scale proteomics study.
      action: REMOVE
      reason: >-
        Generic protein binding from high-throughput studies is uninformative.

      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:17099693
    review:
      summary: >-
        Survivin forms homodimers in the apo state [PMID:10949038, PMID:21536684].
      action: ACCEPT
      reason: >-
        Survivin homodimerization is well-documented and functionally relevant. The
        dimer-monomer
        equilibrium affects function (dimers enhance tubulin stability, monomers better
        inhibit apoptosis).

      supported_by:
        - reference_id: PMID:17099693
          supporting_text: The Survivin-Crm1 interaction is essential for 
            chromosomal passenger complex localization and function.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:23251006
    review:
      summary: >-
        Publication not available for detailed review, but homodimerization is well-established.
      action: ACCEPT
      reason: >-
        Consistent with known homodimerization.

      supported_by:
        - reference_id: PMID:23251006
          supporting_text: Epub 2012 Dec 18. Impairment of glioma stem cell 
            survival and growth by a novel inhibitor for Survivin-Ran protein 
            complex.
  - term:
      id: GO:0045171
      label: intercellular bridge
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        Immunofluorescence data showing localization to intercellular bridge during
        cytokinesis.
      action: ACCEPT
      reason: >-
        Consistent with midbody localization during cytokinesis.

  - term:
      id: GO:0000278
      label: mitotic cell cycle
    evidence_type: NAS
    original_reference_id: PMID:17956729
    review:
      summary: >-
        Survivin is essential for mitotic cell cycle progression as a CPC component
        [PMID:17956729].
      action: ACCEPT
      reason: >-
        Core function. CPC is essential for mitosis.
      supported_by:
        - reference_id: PMID:17956729
          supporting_text: "The chromosomal passenger complex (CPC) is a key regulator
            of chromosome segregation and cytokinesis."

  - term:
      id: GO:0000281
      label: mitotic cytokinesis
    evidence_type: NAS
    original_reference_id: PMID:17956729
    review:
      summary: >-
        Duplicate annotation - mitotic cytokinesis is core CPC function.
      action: ACCEPT
      reason: >-
        Consistent with IBA annotation.

      supported_by:
        - reference_id: PMID:17956729
          supporting_text: Structure of a Survivin-Borealin-INCENP core complex 
            reveals how chromosomal passengers travel together.
  - term:
      id: GO:0015630
      label: microtubule cytoskeleton
    evidence_type: IDA
    original_reference_id: PMID:9859993
    review:
      summary: >-
        Early study demonstrating survivin association with microtubule cytoskeleton.
      action: ACCEPT
      reason: >-
        Well-supported cellular component annotation.

      supported_by:
        - reference_id: PMID:9859993
          supporting_text: Control of apoptosis and mitotic spindle checkpoint 
            by survivin.
  - term:
      id: GO:0051256
      label: mitotic spindle midzone assembly
    evidence_type: NAS
    original_reference_id: PMID:17956729
    review:
      summary: >-
        CPC including survivin is involved in spindle midzone assembly [PMID:17956729].
      action: ACCEPT
      reason: >-
        Core CPC function during anaphase.
      supported_by:
        - reference_id: PMID:17956729
          supporting_text: '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'

  - term:
      id: GO:0090267
      label: positive regulation of mitotic cell cycle spindle assembly 
        checkpoint
    evidence_type: NAS
    original_reference_id: PMID:17956729
    review:
      summary: >-
        CPC regulates spindle assembly checkpoint signaling.
      action: ACCEPT
      reason: >-
        CPC function in checkpoint regulation is well-documented.

      supported_by:
        - reference_id: PMID:17956729
          supporting_text: Structure of a Survivin-Borealin-INCENP core complex 
            reveals how chromosomal passengers travel together.
  - term:
      id: GO:0090307
      label: mitotic spindle assembly
    evidence_type: NAS
    original_reference_id: PMID:17956729
    review:
      summary: >-
        Survivin-RAN complex involved in spindle assembly [PMID:18591255].
      action: ACCEPT
      reason: >-
        Core mitotic function supported by experimental evidence.
      supported_by:
        - reference_id: PMID:18591255
          supporting_text: "survivin is a novel effector of Ran signaling, and this
            pathway may be preferentially exploited for spindle assembly"

        - reference_id: PMID:17956729
          supporting_text: Structure of a Survivin-Borealin-INCENP core complex 
            reveals how chromosomal passengers travel together.
  - term:
      id: GO:1901970
      label: positive regulation of mitotic sister chromatid separation
    evidence_type: NAS
    original_reference_id: PMID:17956729
    review:
      summary: >-
        CPC including survivin is essential for sister chromatid separation [PMID:16322459].
      action: ACCEPT
      reason: >-
        Core CPC function in chromosome segregation.

      supported_by:
        - reference_id: PMID:17956729
          supporting_text: Structure of a Survivin-Borealin-INCENP core complex 
            reveals how chromosomal passengers travel together.
  - term:
      id: GO:1902425
      label: positive regulation of attachment of mitotic spindle microtubules 
        to kinetochore
    evidence_type: NAS
    original_reference_id: PMID:17956729
    review:
      summary: >-
        CPC regulates kinetochore-microtubule attachment [PMID:16322459].
      action: ACCEPT
      reason: >-
        Core CPC function during prometaphase/metaphase.

      supported_by:
        - reference_id: PMID:17956729
          supporting_text: Structure of a Survivin-Borealin-INCENP core complex 
            reveals how chromosomal passengers travel together.
  - term:
      id: GO:1903490
      label: positive regulation of mitotic cytokinesis
    evidence_type: NAS
    original_reference_id: PMID:17956729
    review:
      summary: >-
        CPC is essential for cytokinesis completion.
      action: ACCEPT
      reason: >-
        Core CPC function at midbody during cytokinesis.

      supported_by:
        - reference_id: PMID:17956729
          supporting_text: Structure of a Survivin-Borealin-INCENP core complex 
            reveals how chromosomal passengers travel together.
  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IDA
    original_reference_id: PMID:10949038
    review:
      summary: >-
        Crystal structure study with mutagenesis showing survivin's role in apoptosis
        inhibition.
        However, this is indirect via dimerization and interaction surfaces [PMID:10949038].
      action: KEEP_AS_NON_CORE
      reason: >-
        The study demonstrates structural features required for anti-apoptotic activity,
        but this
        is secondary to the core mitotic function. Keep as non-core.
      supported_by:
        - reference_id: PMID:10949038
          supporting_text: "Mutagenesis analysis revealed that survivin dimerization
            and an extended negatively charged surface surrounding Asp-71 are required
            to counteract apoptosis and preserve ploidy."

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28218735
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to determine specific interaction partner.

      supported_by:
        - reference_id: PMID:28218735
          supporting_text: Aurora kinase A regulates Survivin stability through 
            targeting FBXL7 in gastric cancer drug resistance and prognosis.
  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IMP
    original_reference_id: PMID:28218735
    review:
      summary: >-
        Study on Aurora kinase A regulation of survivin stability through FBXL7.
      action: KEEP_AS_NON_CORE
      reason: >-
        Anti-apoptotic function documented but secondary to core mitotic function.

      supported_by:
        - reference_id: PMID:28218735
          supporting_text: Aurora kinase A regulates Survivin stability through 
            targeting FBXL7 in gastric cancer drug resistance and prognosis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25778398
    review:
      summary: >-
        Study demonstrates survivin-FBXL7 interaction for ubiquitination.
      action: REMOVE
      reason: >-
        Generic protein binding uninformative. The specific E3 ligase interaction
        could be
        better captured by more specific terms.

      supported_by:
        - reference_id: PMID:25778398
          supporting_text: 2015 Mar 16. The Proapoptotic F-box Protein Fbxl7 
            Regulates Mitochondrial Function by Mediating the Ubiquitylation and
            Proteasomal Degradation of Survivin.
  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IMP
    original_reference_id: PMID:25778398
    review:
      summary: >-
        Study links survivin to mitochondrial function and apoptosis regulation.
      action: KEEP_AS_NON_CORE
      reason: >-
        Anti-apoptotic function documented but secondary.

      supported_by:
        - reference_id: PMID:25778398
          supporting_text: 2015 Mar 16. The Proapoptotic F-box Protein Fbxl7 
            Regulates Mitochondrial Function by Mediating the Ubiquitylation and
            Proteasomal Degradation of Survivin.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23825075
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication.

      supported_by:
        - reference_id: PMID:23825075
          supporting_text: Renal uptake of the antiapoptotic protein survivin is
            mediated by megalin at the apical membrane of the proximal tubule.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:20627126
    review:
      summary: >-
        Nuclear localization demonstrated in cochlea studies [PMID:20627126].
      action: ACCEPT
      reason: >-
        Nuclear localization well-documented.
      supported_by:
        - reference_id: PMID:20627126
          supporting_text: "the apoptosis inhibitor protein Birc5 is expressed in
            cell types critical for hearing perception"

  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:21364656
    review:
      summary: >-
        Nuclear localization confirmed in cochlea studies [PMID:21364656].
      action: ACCEPT
      reason: >-
        Consistent with other IDA evidence.
      supported_by:
        - reference_id: PMID:21364656
          supporting_text: "survivin was specifically detectable as a cytoplasmic
            and nuclear protein in the organ of Corti"

  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:20627126
    review:
      summary: >-
        Cytoplasmic localization demonstrated [PMID:20627126].
      action: ACCEPT
      reason: >-
        Well-documented.

      supported_by:
        - reference_id: PMID:20627126
          supporting_text: Epub 2010 Jul 17. Expression analysis suggests a 
            potential cytoprotective role of Birc5 in the inner ear.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:21364656
    review:
      summary: >-
        Cytoplasmic localization confirmed [PMID:21364656].
      action: ACCEPT
      reason: >-
        Consistent with other evidence.

      supported_by:
        - reference_id: PMID:21364656
          supporting_text: An otoprotective role for the apoptosis inhibitor 
            protein survivin.
  - term:
      id: GO:0007605
      label: sensory perception of sound
    evidence_type: IEP
    original_reference_id: PMID:20627126
    review:
      summary: >-
        Survivin expression correlates with auditory function in cochlea studies [PMID:20627126].
      action: KEEP_AS_NON_CORE
      reason: >-
        This is a tissue-specific expression pattern correlation, not a core function.
        The
        cytoprotective role in auditory cells is context-dependent.
      supported_by:
        - reference_id: PMID:20627126
          supporting_text: "the apoptosis inhibitor protein Birc5 is expressed in
            cell types critical for hearing perception"

  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IDA
    original_reference_id: PMID:20627126
    review:
      summary: >-
        Cytoprotective activity demonstrated against ototoxins [PMID:20627126].
      action: KEEP_AS_NON_CORE
      reason: >-
        Anti-apoptotic activity in specific cellular context, but not core function.
      supported_by:
        - reference_id: PMID:20627126
          supporting_text: "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"

  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IDA
    original_reference_id: PMID:21364656
    review:
      summary: >-
        Otoprotective role demonstrated [PMID:21364656].
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary function in specific tissue context.
      supported_by:
        - reference_id: PMID:21364656
          supporting_text: "overexpression of survivin from both species significantly
            counteracted PCD as determined by quantitating apoptotic nuclei and caspase-3
            activity"

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8956026
    review:
      summary: >-
        Reactome pathway annotation for cytosolic localization.
      action: ACCEPT
      reason: >-
        Consistent with general cytoplasmic localization.

  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-4655355
    review:
      summary: >-
        Reactome pathway annotation for nucleoplasm localization.
      action: ACCEPT
      reason: >-
        Consistent with nuclear localization during CPC function.

  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6790036
    review:
      summary: >-
        Reactome annotation - duplicate.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6797763
    review:
      summary: >-
        Reactome annotation for TP53-BIRC5 regulation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: IMP
    original_reference_id: PMID:21536684
    review:
      summary: >-
        Study demonstrates survivin monomer role in apoptosis regulation through XIAP
        and SMAC
        interactions [PMID:21536684].
      action: KEEP_AS_NON_CORE
      reason: >-
        This study actually supports that anti-apoptotic effects are indirect through
        XIAP/SMAC
        interactions. Keep as non-core.
      supported_by:
        - reference_id: PMID:21536684
          supporting_text: "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"

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-141409
    review:
      summary: >-
        Reactome annotation for spindle checkpoint pathway.
      action: ACCEPT
      reason: >-
        Consistent with cytosolic localization.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-141422
    review:
      summary: >-
        Reactome spindle checkpoint annotation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-141431
    review:
      summary: >-
        Reactome spindle checkpoint annotation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-141439
    review:
      summary: >-
        Reactome spindle checkpoint annotation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1638803
    review:
      summary: >-
        Reactome annotation for cohesin phosphorylation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1638821
    review:
      summary: >-
        Reactome annotation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2467809
    review:
      summary: >-
        Reactome annotation for separase/cohesin cleavage.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2467811
    review:
      summary: >-
        Reactome annotation for sister chromatid separation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2468287
    review:
      summary: >-
        Reactome annotation for CDK1 phosphorylation of sororin.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2484822
    review:
      summary: >-
        Reactome annotation for kinetochore assembly.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-375302
    review:
      summary: >-
        Reactome annotation for kinetochore capture.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-4655355
    review:
      summary: >-
        Reactome annotation for CPC SUMOylation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5666129
    review:
      summary: >-
        Reactome annotation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5666160
    review:
      summary: >-
        Reactome annotation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5666169
    review:
      summary: >-
        Reactome annotation.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9648114
    review:
      summary: >-
        Reactome annotation for mitotic spindle.
      action: ACCEPT
      reason: >-
        Consistent annotation.

  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IDA
    original_reference_id: PMID:15665297
    review:
      summary: >-
        Kinetochore localization demonstrated [PMID:15665297].
      action: ACCEPT
      reason: >-
        Core CPC localization during metaphase.
      supported_by:
        - reference_id: PMID:15665297
          supporting_text: "Survivin, another IAP family member, and cIAP1 were both
            localized on midbody microtubules at telophase"

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20826784
    review:
      summary: >-
        Study demonstrates survivin-STAT3 and survivin-CRM1 interactions.
      action: REMOVE
      reason: >-
        Generic protein binding uninformative. Specific interactions could be captured
        by
        more specific terms.

      supported_by:
        - reference_id: PMID:20826784
          supporting_text: 2010 Sep 8. Acetylation directs survivin nuclear 
            localization to repress STAT3 oncogenic activity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21536684
    review:
      summary: >-
        Study demonstrates survivin interactions with XIAP and SMAC [PMID:21536684].
      action: REMOVE
      reason: >-
        Generic protein binding uninformative. The specific XIAP and SMAC interactions
        are
        functionally important but should be captured by more specific terms.

      supported_by:
        - reference_id: PMID:21536684
          supporting_text: 2011 May 2. Survivin monomer plays an essential role 
            in apoptosis regulation.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:15665297
    review:
      summary: >-
        Nuclear localization demonstrated [PMID:15665297].
      action: ACCEPT
      reason: >-
        Well-documented localization.

      supported_by:
        - reference_id: PMID:15665297
          supporting_text: cIAP1 Localizes to the nuclear compartment and 
            modulates the cell cycle.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:20826784
    review:
      summary: >-
        Nuclear localization controlled by acetylation at Lys-129.
      action: ACCEPT
      reason: >-
        Well-documented with mechanistic detail.

      supported_by:
        - reference_id: PMID:20826784
          supporting_text: 2010 Sep 8. Acetylation directs survivin nuclear 
            localization to repress STAT3 oncogenic activity.
  - term:
      id: GO:0008017
      label: microtubule binding
    evidence_type: TAS
    original_reference_id: PMID:21536684
    review:
      summary: >-
        Survivin dimers enhance tubulin stability [PMID:21536684].
      action: ACCEPT
      reason: >-
        Microtubule binding is part of survivin's mitotic function.
      supported_by:
        - reference_id: PMID:21536684
          supporting_text: "only wild-type survivin, but not the monomer mutant form,
            enhances tubulin stability in cells"

  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: TAS
    original_reference_id: PMID:16344111
    review:
      summary: >-
        Survivin promotes cell proliferation through its role in mitosis [PMID:16344111].
      action: ACCEPT
      reason: >-
        Cell proliferation is a consequence of survivin's essential mitotic function.
      supported_by:
        - reference_id: PMID:16344111
          supporting_text: "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"

  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IDA
    original_reference_id: PMID:15665297
    review:
      summary: >-
        Midbody localization during cytokinesis [PMID:15665297].
      action: ACCEPT
      reason: >-
        Core CPC localization.
      supported_by:
        - reference_id: PMID:15665297
          supporting_text: "Survivin, another IAP family member, and cIAP1 were both
            localized on midbody microtubules at telophase"

  - term:
      id: GO:0045892
      label: negative regulation of DNA-templated transcription
    evidence_type: IMP
    original_reference_id: PMID:20826784
    review:
      summary: >-
        Acetylated survivin represses STAT3 transactivation.
      action: KEEP_AS_NON_CORE
      reason: >-
        Transcriptional repression is a secondary, context-dependent function.

      supported_by:
        - reference_id: PMID:20826784
          supporting_text: 2010 Sep 8. Acetylation directs survivin nuclear 
            localization to repress STAT3 oncogenic activity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15665297
    review:
      summary: >-
        Survivin-cIAP1 interaction demonstrated [PMID:15665297].
      action: REMOVE
      reason: >-
        Generic protein binding uninformative.

      supported_by:
        - reference_id: PMID:15665297
          supporting_text: cIAP1 Localizes to the nuclear compartment and 
            modulates the cell cycle.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: GO_REF:0000054
    review:
      summary: >-
        Cytoplasmic localization from fusion protein studies.
      action: ACCEPT
      reason: >-
        Consistent with other evidence.

  - term:
      id: GO:0000228
      label: nuclear chromosome
    evidence_type: IDA
    original_reference_id: PMID:16322459
    review:
      summary: >-
        Survivin associates with chromosomes during mitosis [PMID:16322459].
      action: ACCEPT
      reason: >-
        Core CPC function - chromosome association.
      supported_by:
        - reference_id: PMID:16322459
          supporting_text: "The chromosome passenger complex containing Survivin and
            the kinase Aurora B regulates this process from the centromeres."

  - term:
      id: GO:0000775
      label: chromosome, centromeric region
    evidence_type: IDA
    original_reference_id: PMID:16322459
    review:
      summary: >-
        Centromeric localization demonstrated [PMID:16322459].
      action: ACCEPT
      reason: >-
        Core CPC localization during early mitosis.

      supported_by:
        - reference_id: PMID:16322459
          supporting_text: Chromosome alignment and segregation regulated by 
            ubiquitination of survivin.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14610074
    review:
      summary: >-
        Survivin-INCENP interaction demonstrated.
      action: REMOVE
      reason: >-
        Generic protein binding. CPC interactions captured by GO:0032133.

      supported_by:
        - reference_id: PMID:14610074
          supporting_text: 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.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: PMID:18591255
    review:
      summary: >-
        Cytosolic localization during survivin-RAN complex function [PMID:18591255].
      action: ACCEPT
      reason: >-
        Well-documented localization.

      supported_by:
        - reference_id: PMID:18591255
          supporting_text: Jun 30. A survivin-ran complex regulates spindle 
            formation in tumor cells.
  - term:
      id: GO:0019899
      label: enzyme binding
    evidence_type: IPI
    original_reference_id: PMID:16322459
    review:
      summary: >-
        Survivin binds Aurora B kinase as part of CPC.
      action: ACCEPT
      reason: >-
        More informative than generic protein binding. Aurora B is the enzymatic component
        of CPC.

      supported_by:
        - reference_id: PMID:16322459
          supporting_text: Chromosome alignment and segregation regulated by 
            ubiquitination of survivin.
  - term:
      id: GO:0031267
      label: small GTPase binding
    evidence_type: IPI
    original_reference_id: PMID:18591255
    review:
      summary: >-
        Survivin binds RAN-GTP [PMID:18591255].
      action: ACCEPT
      reason: >-
        Well-characterized interaction with functional significance for spindle assembly.
      supported_by:
        - reference_id: PMID:18591255
          supporting_text: "survivin associates with the small GTPase Ran in an evolutionarily
            conserved recognition in mammalian cells"

  - term:
      id: GO:0032133
      label: chromosome passenger complex
    evidence_type: IPI
    original_reference_id: PMID:15260989
    review:
      summary: >-
        CPC component identification [PMID:15260989].
      action: ACCEPT
      reason: >-
        Core annotation for survivin's primary cellular role.
      supported_by:
        - reference_id: PMID:15260989
          supporting_text: "the vertebrate chromosomal passenger complex containing
            Incenp, Survivin, and the kinase Aurora B"

  - term:
      id: GO:0032133
      label: chromosome passenger complex
    evidence_type: IPI
    original_reference_id: PMID:18591255
    review:
      summary: >-
        CPC function confirmed [PMID:18591255].
      action: ACCEPT
      reason: >-
        Core annotation.
      supported_by:
        - reference_id: PMID:18591255
          supporting_text: "Disruption of a survivin-Ran complex does not affect the
            assembly of survivin within the chromosomal passenger complex"

  - term:
      id: GO:0051087
      label: protein-folding chaperone binding
    evidence_type: IPI
    original_reference_id: PMID:18086682
    review:
      summary: >-
        Publication not available for detailed review.
      action: UNDECIDED
      reason: >-
        Unable to access publication to evaluate Hsp60 interaction relevance.

      supported_by:
        - reference_id: PMID:18086682
          supporting_text: 2007 Dec 17. Hsp60 regulation of tumor cell 
            apoptosis.
  - term:
      id: GO:0031503
      label: protein-containing complex localization
    evidence_type: IMP
    original_reference_id: PMID:16239925
    review:
      summary: >-
        Survivin mediates CPC targeting to centromeres and midbody [PMID:16239925].
      action: ACCEPT
      reason: >-
        Core function - survivin directs CPC localization.
      supported_by:
        - reference_id: PMID:16239925
          supporting_text: "Survivin mediates targeting of the chromosomal passenger
            complex to the centromere and midbody."

  - term:
      id: GO:0000775
      label: chromosome, centromeric region
    evidence_type: IDA
    original_reference_id: PMID:11084331
    review:
      summary: >-
        Centromeric localization demonstrated in foundational study.
      action: ACCEPT
      reason: >-
        Core CPC localization.

      supported_by:
        - reference_id: PMID:11084331
          supporting_text: Survivin and the inner centromere protein INCENP show
            similar cell-cycle localization and gene knockout phenotype.
  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IDA
    original_reference_id: PMID:11084331
    review:
      summary: >-
        Midbody localization demonstrated in foundational study.
      action: ACCEPT
      reason: >-
        Core CPC localization during cytokinesis.

      supported_by:
        - reference_id: PMID:11084331
          supporting_text: Survivin and the inner centromere protein INCENP show
            similar cell-cycle localization and gene knockout phenotype.
references:
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping
    findings: []
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000054
    title: Gene Ontology annotation based on curation of intracellular 
      localizations of expressed fusion proteins
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: PMID:10949038
    title: Crystal structure and mutagenic analysis of the 
      inhibitor-of-apoptosis protein survivin.
    findings:
      - statement: Crystal structure reveals survivin forms homodimer with 
          intermolecular zinc coordination
      - statement: Dimerization and Asp-71 surface required for anti-apoptotic 
          activity
  - id: PMID:11084331
    title: Survivin and the inner centromere protein INCENP show similar 
      cell-cycle localization and gene knockout phenotype.
    findings:
      - statement: Survivin localizes to centromeres, spindle midzone, and 
          midbody during mitosis
  - id: PMID:14610074
    title: 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.
    findings:
      - statement: Aurora B phosphorylates survivin at Thr-117
      - statement: Phosphorylation affects INCENP interaction and chromosome 
          localization
  - id: PMID:15260989
    title: The chromosomal passenger complex is required for chromatin-induced 
      microtubule stabilization and spindle assembly.
    findings:
      - statement: CPC containing survivin is essential for spindle assembly
      - statement: Regulates MCAK activity to permit spindle formation
  - id: PMID:15665297
    title: cIAP1 Localizes to the nuclear compartment and modulates the cell 
      cycle.
    findings:
      - statement: Survivin and cIAP1 both localize to midbody microtubules at 
          telophase
      - statement: cIAP1-survivin interaction during mitosis
  - id: PMID:16239925
    title: Survivin mediates targeting of the chromosomal passenger complex to 
      the centromere and midbody.
    findings:
      - statement: Survivin is critical for CPC localization to centromeres and 
          midbody
  - id: PMID:16291752
    title: Molecular analysis of survivin isoforms - evidence that alternatively
      spliced variants do not play a role in mitosis.
    findings:
      - statement: Splice variants have reduced borealin affinity and do not 
          localize with CPC
      - statement: Only wild-type survivin can rescue proliferation after RNAi 
          depletion
  - id: PMID:16322459
    title: Chromosome alignment and segregation regulated by ubiquitination of 
      survivin.
    findings:
      - statement: Survivin ubiquitination regulates centromere association
      - statement: Required for proper chromosome segregation
  - id: PMID:16344111
    title: Survivin - a protein with dual roles in mitosis and apoptosis.
    findings:
      - statement: Review establishing survivin's dual roles in cell division 
          and apoptosis inhibition
  - id: PMID:17956729
    title: Structure of a Survivin-Borealin-INCENP core complex reveals how 
      chromosomal passengers travel together.
    findings:
      - statement: 1.4 A crystal structure of CPC regulatory core
      - statement: Survivin, borealin, and INCENP form tight three-helical 
          bundle
      - statement: Complex creates composite surface essential for central 
          spindle/midbody localization
  - id: PMID:18591255
    title: A survivin-ran complex regulates spindle formation in tumor cells.
    findings:
      - statement: Survivin associates with RAN-GTP
      - statement: Complex delivers TPX2 to microtubules for spindle assembly
      - statement: Function preferentially exploited in tumor cells
  - id: PMID:20627126
    title: Expression analysis suggests a potential cytoprotective role of Birc5
      in the inner ear.
    findings:
      - statement: Survivin expressed in cochlear cell types critical for 
          hearing
      - statement: Noise exposure upregulates survivin expression
      - statement: Cytoprotective activity against gentamicin ototoxicity
  - id: PMID:21364656
    title: An otoprotective role for the apoptosis inhibitor protein survivin.
    findings:
      - statement: Survivin protects against ototoxin-induced cell death
      - statement: Detectable as cytoplasmic and nuclear protein in cochlea
  - id: PMID:21536684
    title: Survivin monomer plays an essential role in apoptosis regulation.
    findings:
      - statement: Survivin monomer interacts with XIAP and SMAC/DIABLO
      - statement: Monomer protects against caspase-dependent apoptosis through 
          these interactions
      - statement: Only dimeric form enhances tubulin stability
  - id: PMID:9859993
    title: Control of apoptosis and mitotic spindle checkpoint by survivin.
    findings: []
  - id: PMID:17099693
    title: The Survivin-Crm1 interaction is essential for chromosomal passenger 
      complex localization and function.
    findings: []
  - id: PMID:17681274
    title: "Cell death in leukemia: passenger protein regulation by topoisomerase
      inhibitors."
    findings: []
  - id: PMID:18086682
    title: Hsp60 regulation of tumor cell apoptosis.
    findings: []
  - id: PMID:18243099
    title: Mps1 phosphorylates Borealin to control Aurora B activity and 
      chromosome alignment.
    findings: []
  - id: PMID:19357306
    title: A single amino acid change converts Aurora-A into Aurora-B-like 
      kinase in terms of partner specificity and cellular function.
    findings: []
  - id: PMID:20638385
    title: Interaction of Beclin 1 with survivin regulates sensitivity of human 
      glioma cells to TRAIL-induced apoptosis.
    findings: []
  - id: PMID:20739936
    title: Phosphorylation of the CPC by Cdk1 promotes chromosome 
      bi-orientation.
    findings: []
  - id: PMID:20826784
    title: Acetylation directs survivin nuclear localization to repress STAT3 
      oncogenic activity.
    findings: []
  - id: PMID:21051298
    title: Spatio-temporal composition of the mitotic Chromosomal Passenger 
      Complex detected using in situ proximity ligation assay.
    findings: []
  - id: PMID:21225229
    title: PAR, a protein involved in the cell cycle, is functionally related to
      chromosomal passenger proteins.
    findings: []
  - id: PMID:21988832
    title: Toward an understanding of the protein interaction network of the 
      human liver.
    findings: []
  - id: PMID:23251006
    title: Impairment of glioma stem cell survival and growth by a novel 
      inhibitor for Survivin-Ran protein complex.
    findings: []
  - id: PMID:23825075
    title: Renal uptake of the antiapoptotic protein survivin is mediated by 
      megalin at the apical membrane of the proximal tubule.
    findings: []
  - id: PMID:24571573
    title: 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.
    findings: []
  - id: PMID:25778398
    title: The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function
      by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin.
    findings: []
  - id: PMID:27332895
    title: Aurora-C Interactions with Survivin and INCENP Reveal Shared and 
      Distinct Features Compared with Aurora-B Chromosome Passenger Protein 
      Complex.
    findings: []
  - id: PMID:28218735
    title: Aurora kinase A regulates Survivin stability through targeting FBXL7 
      in gastric cancer drug resistance and prognosis.
    findings: []
  - id: PMID:28514442
    title: Architecture of the human interactome defines protein communities and
      disease networks.
    findings: []
  - id: PMID:29568061
    title: An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping 
      of protein interactions and subcellular localizations.
    findings: []
  - id: PMID:32296183
    title: A reference map of the human binary protein interactome.
    findings: []
  - id: PMID:32814053
    title: Interactome Mapping Provides a Network of Neurodegenerative Disease 
      Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the 
      human interactome.
    findings: []
  - id: Reactome:R-HSA-8956026
    title: Reactome pathway annotation
    findings: []
  - id: Reactome:R-HSA-4655355
    title: SUMOylation of the CPC
    findings: []
  - id: Reactome:R-HSA-6790036
    title: Reactome mitosis pathway
    findings: []
  - id: Reactome:R-HSA-6797763
    title: TP53 regulation of BIRC5
    findings: []
  - id: Reactome:R-HSA-141409
    title: Spindle checkpoint signaling
    findings: []
  - id: Reactome:R-HSA-141422
    title: Spindle checkpoint
    findings: []
  - id: Reactome:R-HSA-141431
    title: Spindle checkpoint pathway
    findings: []
  - id: Reactome:R-HSA-141439
    title: Spindle checkpoint signaling
    findings: []
  - id: Reactome:R-HSA-1638803
    title: Cohesin phosphorylation
    findings: []
  - id: Reactome:R-HSA-1638821
    title: Mitotic pathway
    findings: []
  - id: Reactome:R-HSA-2467809
    title: Separase/cohesin cleavage
    findings: []
  - id: Reactome:R-HSA-2467811
    title: Sister chromatid separation
    findings: []
  - id: Reactome:R-HSA-2468287
    title: CDK1 phosphorylation of sororin
    findings: []
  - id: Reactome:R-HSA-2484822
    title: Kinetochore assembly
    findings: []
  - id: Reactome:R-HSA-375302
    title: Kinetochore capture
    findings: []
  - id: Reactome:R-HSA-5666129
    title: Mitosis pathway
    findings: []
  - id: Reactome:R-HSA-5666160
    title: Cell cycle pathway
    findings: []
  - id: Reactome:R-HSA-5666169
    title: Mitotic pathway
    findings: []
  - id: Reactome:R-HSA-9648114
    title: Mitotic spindle pathway
    findings: []
  - id: file:human/BIRC5/BIRC5-deep-research-falcon.md
    title: Deep research report on BIRC5
    findings: []

core_functions:
  - molecular_function:
      id: GO:0019899
      label: enzyme binding
    in_complex:
      id: GO:0032133
      label: chromosome passenger complex
    directly_involved_in:
      - id: GO:0007059
        label: chromosome segregation
      - id: GO:0000281
        label: mitotic cytokinesis
    description: >-
      Survivin is an essential structural component of the chromosomal passenger complex
      (CPC),
      forming a triple-helix bundle with INCENP and borealin that anchors and regulates
      the
      Aurora B kinase. As a CPC component, survivin is essential for proper chromosome
      segregation
      during mitosis and mediates CPC targeting to the midbody for cytokinesis completion.
  - molecular_function:
      id: GO:0031267
      label: small GTPase binding
    directly_involved_in:
      - id: GO:0090307
        label: mitotic spindle assembly
    description: >-
      Through interaction with RAN-GTP, survivin participates in spindle assembly
      by delivering
      TPX2 to microtubules.

proposed_new_terms: []

suggested_questions:
  - question: >-
      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?
  - question: >-
      Do the splice variants (survivin-2B, survivin-DeltaEx3) have any physiological
      function
      or are they non-functional products of alternative splicing?
  - question: >-
      What determines the balance between survivin's mitotic and potential apoptotic
      functions
      in different cellular contexts?

suggested_experiments:
  - description: >-
      Structure-function studies with BIR domain mutants that specifically disrupt
      caspase
      binding without affecting CPC assembly to determine direct vs. indirect anti-apoptotic
      mechanisms.
  - description: >-
      Isoform-specific knockdown/rescue experiments to determine if splice variants
      have
      any non-mitotic functions.