DIABLO

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005515 protein binding	IPI PMID:11604410 HtrA2 promotes cell death through its serine protease activi...	MODIFY	Summary: SMAC associates with XIAP and relieves its caspase inhibition. Reason: The human SMAC–XIAP anti-tag co-immunoprecipitation record EBI-4565754 is positive, despite the paper focusing on HTRA2. Its abstract explicitly compares SMAC-dependent relief of XIAP inhibition. Independent SMAC–XIAP domain experiments establish BIR binding, supporting this refinement; HTRA2 protease activity is not transferred to DIABLO. Proposed replacements: BIR domain binding Supporting Evidence: PMID:11604410 prevent XIAP inhibition of active caspase 3
GO:0005515 protein binding	IPI PMID:11801603 SMAC negatively regulates the anti-apoptotic activity of mel...	MODIFY	Summary: SMAC binds the XIAP BIR region. Reason: The source records include SMAC residues 56–64 with XIAP residues 241–356 in pull-down and fluorescence-polarization assays, plus human-cell co-immunoprecipitation. These construct-specific binding data support BIR domain binding. Peptide measurements do not establish the affinity of every full-length splice product. Proposed replacements: BIR domain binding Supporting Evidence: PMID:11801603 Cleaved SMAC binds X-IAP and antagonizes its anti-apoptotic activity.
GO:0005515 protein binding	IPI PMID:11801603 SMAC negatively regulates the anti-apoptotic activity of mel...	MODIFY	Summary: SMAC binds the BIRC7/ML-IAP BIR domain. Reason: The abstract and source interaction records map SMAC binding to ML-IAP residues 63–179, including SMAC N-terminal peptides, BIR mutations and human-cell co-immunoprecipitation. This is direct domain-specific support for BIR binding, not an inference from the presence of a BIR domain alone. Proposed replacements: BIR domain binding Supporting Evidence: PMID:11801603 physically interacts with SMAC through its BIR (baculovirus IAP repeat) domain.
GO:0005515 protein binding	IPI PMID:12559088 Comparative gene identification-94--a pivotal regulator of a...	REMOVE	Summary: Remove the generic binding annotation while preserving the reported UTP11/CGI-94 interaction. Reason: The source abstract explicitly reports CGI-94 binding to SMAC. The neurite-outgrowth and apoptosis experiments foreground CGI-94, and do not establish a distinct DIABLO catalytic, adaptor or RNA-processing activity. No more specific DIABLO binding class was established from the available assay description. Remove the uninformative GO:0005515 annotation under the generic-binding policy. The reported positive interaction and its assay limitations remain documented; this action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:15200957 Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2...	MODIFY	Summary: SMAC binds and antagonizes BIRC6/BRUCE. Reason: The original abstract reports both BRUCE antagonism by SMAC binding and SMAC ubiquitination as a BRUCE substrate. The latter observation alone cannot support antagonism. Independent BIRC6 structural and binding evidence supports a multivalent interaction involving its BIR site and another binding surface, making BIR domain binding an informative component of this interaction without reducing it to a single-site mechanism or assigning ligase activity to DIABLO. Proposed replacements: BIR domain binding Supporting Evidence: PMID:15200957 BRUCE is antagonized by three mechanisms: first, through binding to Smac;
GO:0005515 protein binding	IPI PMID:15628841 Solution structure of human survivin and its binding interfa...	MODIFY	Summary: SMAC engages the BIR-containing binding surface of survivin. Reason: The published NMR abstract identifies a human survivin 1–120 construct and SMAC-dependent perturbations near alpha4/beta3, with peptide binding across the third beta strand. Together with controlled survivin-fragment experiments, this supports BIR domain binding while preserving the contribution of adjacent survivin sequence; it does not establish that an isolated BIR fragment is sufficient in every assay. Proposed replacements: BIR domain binding Supporting Evidence: PMID:15628841 specific residues near alpha4 and beta3 are perturbed.
GO:0005515 protein binding	IPI PMID:16282325 Distinct BIR domains of cIAP1 mediate binding to and ubiquit...	MODIFY	Summary: SMAC binds the XIAP BIR3 region. Reason: The original human HEK293T experiments recover SMAC with tagged XIAP and show competition by AVPI but not the control GVPF peptide; XIAP BIR3 also competes. The source interaction record maps the necessary XIAP region to residues 260–356. BIR domain binding captures the observed specificity without assigning the TRAF2/NF-kappaB experiments to SMAC. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:16282325 Distinct BIR domains of cIAP1 mediate binding to and ubiquit...	MODIFY	Summary: SMAC binds the BIRC2/cIAP1 BIR3 domain. Reason: The original maps SMAC binding to BIRC2 BIR3, with reciprocal co-immunoprecipitation, W316A/D320A binding defects, protein-expression controls and AVPI competition. BIR1/BIR2 control mutations retain binding. These experiments support BIR domain binding; BIRC2-dependent ubiquitination makes SMAC a substrate, not a ubiquitin ligase. Proposed replacements: BIR domain binding Supporting Evidence: PMID:16282325 necessary and sufficient for binding TRAF2 and SMAC, respectively.
GO:0005515 protein binding	IPI PMID:16729033 Livin promotes Smac/DIABLO degradation by ubiquitin-proteaso...	MODIFY	Summary: BIRC7 recognizes SMAC through its BIR domain. Reason: The published abstract explicitly reports that a BIRC7 BIR mutation abolishes SMAC binding, while both BIR and RING regions are needed for SMAC degradation. Independent ML-IAP binding experiments support the same domain-specific interaction. The full original was not accessible, so no unreported construct details or DIABLO ubiquitin-ligase activity are inferred. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:19153467 The structure of the BIR3 domain of cIAP1 in complex with th...	MODIFY	Summary: A SMAC N-terminal peptide binds the BIRC2 BIR3 groove. Reason: The published abstract and exact IntAct records establish crystallography and surface-plasmon-resonance experiments with human SMAC residues 56–61 and BIRC2 BIR3 constructs. This supports BIR domain binding directly. The reported peptide affinity and PDB 3D9U are not measurements of intact SMAC or of every alternative product. Proposed replacements: BIR domain binding Supporting Evidence: PMID:19153467 the SMAC and caspase-9 peptides bind with comparable affinities
GO:0005515 protein binding	IPI PMID:21185211 ARTS and Siah collaborate in a pathway for XIAP degradation.	MODIFY	Summary: SMAC–XIAP binding depends on the canonical IAP-binding interface. Reason: The original includes a controlled comparison in which AVPI inhibits SMAC–XIAP binding, whereas ARTS uses a different interaction mechanism. The source pull-down is a SMAC–XIAP experiment; it is not misattributed merely because ARTS is the paper’s main subject. Independent XIAP BIR mapping supports this refinement. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:21536684 Survivin monomer plays an essential role in apoptosis regula...	MODIFY	Summary: SMAC binds the BIR-containing region of survivin. Reason: The original compares purified mature SMAC and an engineered N-terminal deletion, survivin monomers/dimers, pull-down and cellular FRET. Survivin residues 1–109 bind whereas the dimerization segment 84–109 alone does not. BIR involvement is supported, but the adjoining dimerization region contributes and isolated-domain sufficiency is not claimed. Proposed replacements: BIR domain binding Supporting Evidence: PMID:21536684 survivin monomer interacts with Smac/DIABLO
GO:0005515 protein binding	IPI PMID:21695558 ARTS binds to a distinct domain in XIAP-BIR3 and promotes ap...	MODIFY	Summary: SMAC recognizes an established XIAP BIR3 interface. Reason: The published abstract explicitly distinguishes the ARTS interface in XIAP BIR3 from the known SMAC interface. The complete source assay was not recovered, so its specific construct comparisons remain unverified. Curator-supported SMAC–XIAP association and independent original BIR-binding experiments justify the more specific term without transferring ARTS-dependent XIAP degradation to DIABLO. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:22465666 Identification of a novel protein kinase Cδ-Smac complex tha...	MODIFY	Summary: SMAC associates with XIAP in the PKCdelta-regulated system. Reason: The source contains a positive human SMAC–XIAP anti-tag co-immunoprecipitation record in COS-7 cells, distinct from the human PKCdelta pairs. The abstract describes regulation of the cytosolic SMAC–XIAP complex. Independent domain mapping supports BIR binding, while this source alone is not a purified binary-affinity measurement. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:22465666 Identification of a novel protein kinase Cδ-Smac complex tha...	MODIFY	Summary: SMAC associates with the serine/threonine kinase PKCdelta. Reason: Four positive source co-immunoprecipitation records identify human PRKCD, including an interaction-disrupting SMAC N-terminal alteration in MCF7 cells. The published abstract describes the same regulated interaction. PRKCD’s experimentally supported serine/threonine kinase activity justifies the partner-class refinement. Association does not establish that SMAC is a kinase, a substrate, or a direct regulator of the catalytic reaction. Proposed replacements: protein serine/threonine kinase binding
GO:0005515 protein binding	IPI PMID:23251006 Impairment of glioma stem cell survival and growth by a nove...	MODIFY	Summary: SMAC binds survivin in a controlled recombinant-protein assay. Reason: The original Figure 4 uses immobilized His-SMAC and GST-GFP-survivin, with XIAP as a comparison. This positive binding result is consistent with independent mapping of the survivin BIR-containing interface. The study’s survivin–Ran and mitotic phenotypes are not evidence for a separate DIABLO cell-cycle function. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:23251006 Impairment of glioma stem cell survival and growth by a nove...	MODIFY	Summary: SMAC binds the BIR-containing XIAP fragment. Reason: The original controlled recombinant pull-down and source interaction record identify XIAP residues 125–356, encompassing its BIR-containing caspase-regulatory region. Together with direct domain mapping, this supports BIR domain binding. The compound-response comparison does not imply that DIABLO acts as a drug-metabolizing enzyme. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:23479728 Identification of a novel anti-apoptotic E3 ubiquitin ligase...	REMOVE	Summary: SMAC binds AREL1 as an IAP-antagonist substrate. Reason: The original shows human AREL1 HECT-region association with SMAC in lysates and endogenous association after etoposide; SMAC is also an AREL1 ubiquitination substrate. The grouped source lists AREL1, SEPTIN4/ARTS and HTRA2. The latter two are other AREL1 substrates in the read experiments, so separate binary SMAC binding to each is not established. Preserve the positive broad association without converting the grouped record into DIABLO ligase or adaptor activity. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false. Supporting Evidence: PMID:23479728 AREL1 interacted with and ubiquitinated IAP antagonists such as SMAC, HtrA2, and ARTS.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: A validated binary screen detects SMAC–ARL6IP1 interaction. Reason: The exact human pair appears in validated two-hybrid, array and pooled-screen records. The 2014 study retested candidate pairs in quadruplicate from fresh colonies and retained sequence-confirmed pairs positive in at least three attempts. ARL6IP1’s ER-membrane role does not establish a more specific DIABLO activity; yeast binding capacity does not prove a native ER complex or ER-shaping function. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ...	REMOVE	Summary: The isoform-interaction study detects SMAC–ARL6IP1 binding. Reason: Three exact human pair records include validated two-hybrid and screen stages. The study pairwise-tested isoforms against candidate partners; the mapped DIABLO sequence is the canonical precursor. The interaction supports contextual binding capacity, without demonstrating an ER-shaping or trafficking role for DIABLO. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ...	REMOVE	Summary: SMAC binds the tested AGTRAP alternative product in yeast. Reason: The exact pair maps to AGTRAP Q6RW13-2, reconstructed as 152 residues with the annotated seven-residue deletion, and to canonical DIABLO. Validated two-hybrid and screen records support the interaction. Binding an angiotensin-receptor-associated regulator does not establish DIABLO receptor activity, adaptor function or participation in angiotensin signaling. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: HuRI detects DIABLO binding to MPC2. Reason: The exact human DIABLO–MPC2 pair has validated two-hybrid, array and pooled-screen records in HuRI. MPC2 is a directly characterized mitochondrial pyruvate carrier. The yeast assay does not establish an inner-membrane complex with mature SMAC or control of pyruvate transport. Proposed replacements: transmembrane transporter binding
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to synaptophysin. Reason: The exact human DIABLO–synaptophysin pair has validated two-hybrid, array and pooled-screen records in HuRI. Synaptophysin is a synaptic-vesicle membrane protein; this record does not establish a more specific DIABLO binding activity. No DIABLO vesicle-release or neurotransmission role follows from this isolated pair. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: HuRI detects DIABLO binding to ATP6V0C. Reason: The exact human DIABLO–ATP6V0C pair has validated two-hybrid, array and pooled-screen records in HuRI. ATP6V0C forms the proton-conducting membrane pore of the V-ATPase complex. The pore subunit is not the ATP-hydrolyzing V1 catalytic subunit; the interaction neither assigns ATPase activity to DIABLO nor demonstrates regulation of organelle acidification. Proposed replacements: transmembrane transporter binding
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to APOC4. Reason: The exact human DIABLO–APOC4 pair has validated two-hybrid, array and pooled-screen records in HuRI. APOC4 is a secreted lipoprotein-associated protein, and no appropriate more specific DIABLO binding activity is established. Its secretory context and the yeast fusion assay leave a native encounter unresolved; secretion or lipid transport is not assigned to DIABLO. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: HuRI detects DIABLO binding to EHHADH. Reason: The exact human DIABLO–EHHADH pair has validated two-hybrid, array and pooled-screen records in HuRI. EHHADH is a bifunctional peroxisomal enzyme with curated hydratase/dehydrogenase reactions. The pair establishes assay binding capacity, not a native intraperoxisomal encounter, DIABLO beta-oxidation activity or regulation of that enzyme. Proposed replacements: enzyme binding
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to ARL6IP1. Reason: The exact human DIABLO–ARL6IP1 pair has validated two-hybrid, array and pooled-screen records in HuRI. ARL6IP1 is an ER membrane-shaping protein; its name does not make it a small GTPase. The interaction, also reported in earlier maps, does not establish DIABLO-mediated membrane shaping or a particular adaptor mechanism. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to MTFR1. Reason: The exact human DIABLO–MTFR1 pair has validated two-hybrid, array and pooled-screen records in HuRI. MTFR1 participates in mitochondrial morphology, but no demonstrated catalytic partner class supplies a more specific term here. Binding capacity alone does not establish a DIABLO mitochondrial-fission function. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to MIC13. Reason: The exact human DIABLO–MIC13 pair has validated two-hybrid, array and pooled-screen records in HuRI. MIC13 is a MICOS assembly component rather than an independently established enzyme or transmembrane transporter. The pair does not establish DIABLO participation in crista-junction assembly or stoichiometric MICOS membership. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to RHBDD2. Reason: The exact human DIABLO–RHBDD2 pair has validated two-hybrid, array and pooled-screen records in HuRI. The tested RHBDD2 product is Q6NTF9-3, 223 residues after deletion of canonical residues 1–141. A rhomboid-family name does not establish active protease function, and this shortened membrane-protein construct does not justify DIABLO protease binding or cleavage activity. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to AGTRAP. Reason: The exact human DIABLO–AGTRAP pair has validated two-hybrid, array and pooled-screen records in HuRI. The partner is Q6RW13-2, the 152-residue alternative product also represented in the earlier isoform map. Association with a receptor-associated regulator does not establish DIABLO receptor signaling or adaptor activity. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: HuRI detects DIABLO binding to DGAT2L6. Reason: The exact human DIABLO–DGAT2L6 pair has validated two-hybrid, array and pooled-screen records in HuRI. DGAT2L6 has experimentally supported acyl-CoA-dependent glycerolipid acyltransferase activity. The ER-membrane context is not recreated by the yeast fusion assay; no DIABLO lipid synthesis or enzyme regulation is inferred. Proposed replacements: enzyme binding
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: HuRI detects DIABLO binding to HSD17B13. Reason: The exact human DIABLO–HSD17B13 pair has validated two-hybrid, array and pooled-screen records in HuRI. The exact mapped 300-residue sequence is the displayed Q7Z5P4 product, named isoform 2 by UniProt, which has documented lipid oxidoreductase activity. This is distinct from the shorter product with different activity; the yeast interaction does not establish native lipid-droplet association or DIABLO oxidoreductase activity. Proposed replacements: enzyme binding
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to CMTM4. Reason: The exact human DIABLO–CMTM4 pair has validated two-hybrid, array and pooled-screen records in HuRI. The exact partner is Q8IZR5-2, 208 residues after deletion of the canonical C-terminal 26 residues. Its membrane and PD-L1-stability biology does not establish a particular DIABLO binding class or immune-regulatory function. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Remove the generic binding annotation without denying the HuRI DIABLO–SLC66A2 interaction. Reason: The exact human DIABLO–SLC66A2 pair has validated two-hybrid, array and pooled-screen records in HuRI. The partner is a lysosomal membrane protein, but the read official record does not establish a specific transported substrate or catalytic reaction. A solute-carrier name alone is insufficient to impose transporter-binding specificity; remove the uninformative GO:0005515 annotation under the generic-binding policy. The positive yeast interaction and its construct and assay limitations remain documented. This action neither denies that measured interaction nor establishes a native lysosomal encounter.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to FADS6. Reason: The exact human DIABLO–FADS6 pair has validated two-hybrid, array and pooled-screen records in HuRI. The three source records identify FADS6, but their sequence checksum differs from the current 368-residue official sequence. No cause of that sequence-version discrepancy is established. Preserve the curated positive pair with this limitation; the name alone does not justify enzyme-binding specificity or transfer of desaturase activity. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to SFT2A. Reason: The exact human DIABLO–SFT2A pair has validated two-hybrid, array and pooled-screen records in HuRI. The current official name for Q8WV19 is vesicle-trafficking protein SFT2A. The interaction does not establish DIABLO vesicle fusion, tethering or SNARE-regulator activity. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to SEC22A. Reason: The exact human DIABLO–SEC22A pair has validated two-hybrid, array and pooled-screen records in HuRI. SEC22A is a vesicle-trafficking SNARE-family protein, not a syntaxin established by this record. A binary pair does not show DIABLO-mediated SNARE-complex assembly or membrane fusion, so no adaptor or syntaxin-binding activity is inferred. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: HuRI detects DIABLO binding to DHRS1. Reason: The exact human DIABLO–DHRS1 pair has validated two-hybrid, array and pooled-screen records in HuRI. DHRS1 has measured NADPH-dependent oxidoreductase activity on steroid and other substrates. The pair does not demonstrate an endogenous ER encounter, regulation of this reaction or catalytic activity of DIABLO. Proposed replacements: enzyme binding
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to RMDN2. Reason: The exact human DIABLO–RMDN2 pair has validated two-hybrid, array and pooled-screen records in HuRI. The source marks RMDN2 residues 14–410 as the sufficient binding region. The mapped pair does not establish a distinct DIABLO microtubule, mitochondrial-distribution or adaptor activity. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: HuRI detects DIABLO binding to SLC17A9. Reason: The exact human DIABLO–SLC17A9 pair has validated two-hybrid, array and pooled-screen records in HuRI. SLC17A9 is an experimentally characterized voltage-driven purine-nucleotide transporter. The yeast assay does not demonstrate native lysosomal or secretory-vesicle association, regulation of nucleotide transport or transport activity by DIABLO. Proposed replacements: transmembrane transporter binding
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to DERL2. Reason: The exact human DIABLO–DERL2 pair has validated two-hybrid, array and pooled-screen records in HuRI. DERL2 is an ER-associated degradation component with a proposed retrotranslocation role. The pair alone does not establish binding to a demonstrated catalytic enzyme or transporter, and does not assign DIABLO ER quality-control or retrotranslocation activity. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to STMN4. Reason: The exact human DIABLO–STMN4 pair has validated two-hybrid, array and pooled-screen records in HuRI. The partner is the 216-residue STMN4 Q9H169-2 product, whose inserted segment was reconstructed from the official record. Its microtubule-destabilizing family role does not establish DIABLO binding to microtubules or regulation of their dynamics. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI detects DIABLO binding to TIMMDC1. Reason: The exact human DIABLO–TIMMDC1 pair has validated two-hybrid, array and pooled-screen records in HuRI. TIMMDC1 assists mitochondrial complex-I assembly. An assembly factor is not automatically a protein-folding chaperone; this pair does not establish DIABLO respiratory-complex assembly or a more specific chaperone-binding function. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MODIFY	Summary: HuRI detects DIABLO binding to FKBP7. Reason: The exact human DIABLO–FKBP7 pair has validated two-hybrid, array and pooled-screen records in HuRI. FKBP7 is an ER-lumen peptidyl-prolyl cis-trans isomerase. Its normal lumenal location is not reproduced by the yeast assay; no native encounter, DIABLO protein-folding role or isomerase activity is inferred. Proposed replacements: enzyme binding
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MODIFY	Summary: BioPlex recovers DIABLO with XIAP. Reason: The exact human pair is present in anti-tag AP–MS records from HEK293T and HCT116 cells. These records establish co-complex association, not direct binary binding by themselves. Independent XIAP domain experiments establish the SMAC–BIR interaction and support this refinement; no new complex stoichiometry or affinity is inferred from the screen. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MODIFY	Summary: BioPlex recovers DIABLO with BIRC2. Reason: The exact human pair is present in anti-tag AP–MS records from HEK293T and HCT116 cells. These records establish co-complex association, not direct binary binding by themselves. Independent BIRC2 domain experiments establish the SMAC–BIR interaction and support this refinement; no new complex stoichiometry or affinity is inferred from the screen. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: BioPlex recovers a DIABLO–MTFR1 association. Reason: Positive HEK293T and HCT116 AP–MS records place MTFR1 with C-terminally tagged DIABLO. These are co-complex associations, not direct binding or evidence that DIABLO performs mitochondrial fission. No more specific DIABLO molecular activity follows from the pair. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MODIFY	Summary: BioPlex recovers DIABLO with BIRC7. Reason: The exact human pair is present in anti-tag AP–MS records from HEK293T and HCT116 cells. These records establish co-complex association, not direct binary binding by themselves. Independent BIRC7 domain experiments establish the SMAC–BIR interaction and support this refinement; no new complex stoichiometry or affinity is inferred from the screen. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MODIFY	Summary: The U2OS interactome recovers DIABLO with XIAP. Reason: The published AP–MS network contains the exact DIABLO–XIAP edge. Human ORFs were expressed with C-terminal HA–Flag tags and captured from U2OS lysates. The association supports the independently mapped SMAC–BIR interaction, while the screen itself neither resolves a binary interface nor measures native stoichiometry. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MODIFY	Summary: The U2OS interactome recovers DIABLO with BIRC2. Reason: The published AP–MS network contains the exact DIABLO–BIRC2 edge. Human ORFs were expressed with C-terminal HA–Flag tags and captured from U2OS lysates. The association supports the independently mapped SMAC–BIR interaction, while the screen itself neither resolves a binary interface nor measures native stoichiometry. Proposed replacements: BIR domain binding
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	REMOVE	Summary: The U2OS interactome recovers DIABLO with MTFR1. Reason: The published AP–MS network contains the exact DIABLO–MTFR1 edge from tagged-bait human U2OS experiments. Together with earlier screens this supports an association, but does not establish direct binding or a DIABLO role in mitochondrial fission; no more informative molecular-function term is demonstrated. For this systematic re-review the current generic-binding policy supersedes the earlier task-specific retention decision: remove the uninformative GO:0005515 annotation, while preserving the measured interaction and all construct, isoform, and assay limitations above. This action does not assert that the interaction is false.
GO:0005739 mitochondrion	EXP PMID:14523016 Smac3, a novel Smac/DIABLO splicing variant, attenuates the ...	ACCEPT	Summary: Mitochondrial localization is supported and remains informative at organelle resolution. Reason: The original human SMAC3 study localizes the tagged 195-residue splice product to mitochondria by microscopy and fractionation, with cytochrome-c colocalization and stimulus-dependent release. The authors infer IMS residence from colocalization, but these assays do not directly resolve submitochondrial topology. This directly supports the organelle claim. The canonical PARL processing route and inner-membrane intermediate are not assigned to SMAC3 from these experiments. Retain the informative mitochondrion assertion under the root-organelle policy; supported intermembrane-space annotations remain separate. Supporting Evidence: PMID:14523016 Smac3 is released from mitochondria into the cytosol
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: Mitochondrial localization is supported and remains informative at organelle resolution. Reason: The MitoCoP workbook includes a DIABLO protein group containing canonical and SMAC3 identifiers through the literature-supported pool, with zero valid localization ratios. It therefore does not independently establish a quantitative localization profile or distinguish products. The organelle claim is nevertheless correct and independently grounded by target localization and processing evidence. Canonical processing intermediates and mature IMS protein must not be conflated, or generalized to every splice product. Retain the informative mitochondrion assertion under the root-organelle policy; supported intermembrane-space annotations remain separate. Supporting Evidence: PMID:34800366 PMID:14523016 Smac3 is released from mitochondria into the cytosol
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Mitochondrial localization is supported and remains informative at organelle resolution. Reason: The mitochondrial PAINT IBD at PTN001283560 on the lineage leading to human DIABLO is grounded by target and mouse experimental sources. Target self-inclusion is legitimate experimental grounding, not circularity. Mitochondrial residence is inherited and independently supported; more specific processing and mature-chain locations do not constitute a granularity defect in this informative organelle assertion. Retain the informative mitochondrion assertion under the root-organelle policy; supported intermembrane-space annotations remain separate.
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Mitochondrial localization is supported and remains informative at organelle resolution. Reason: The HPA ICC/IF record reports mitochondrial staining and cytosol. This directly supports the organelle-resolution claim without resolving a mitochondrial subcompartment or product-specific processing. Independent processing and mature-chain evidence supplies more specific locations separately. Retain the informative mitochondrion assertion under the root-organelle policy; supported intermembrane-space annotations remain separate.
GO:0005739 mitochondrion	IDA PMID:28288130 PARL mediates Smac proteolytic maturation in mitochondria to...	ACCEPT	Summary: Mitochondrial localization is supported and remains informative at organelle resolution. Reason: The published abstract explicitly reports intramembrane cleavage of SMAC by the inner-membrane protease PARL. Genuine publisher supplementary experiments distinguish precursor, intermediate and mature forms in human HEK293 fractionation and HA-SMAC/MPP perturbation assays. These observations support mitochondrial residence. The mature-chain IMS Reactome entity provides separate compartment context. The predicted W42–A60 segment is not an independent topology measurement, and the published main Methods/Results remain unavailable. This neither assigns PARL protease activity to DIABLO nor transfers the processing route to alternative products. Retain the informative mitochondrion assertion under the root-organelle policy; supported intermembrane-space annotations remain separate.
GO:0005739 mitochondrion	IEA GO_REF:0000120	ACCEPT	Summary: Mitochondrial localization is supported and remains informative at organelle resolution. Reason: The current InterPro family/fold matches and UniProt location mapping support mitochondrial residence, corroborated by independent target localization and processing evidence. They do not themselves resolve precursor processing or mature-protein topology. Their correct organelle assignment is not a propagation failure merely because finer locations are supported separately. Retain the informative mitochondrion assertion under the root-organelle policy; supported intermembrane-space annotations remain separate.
GO:0005739 mitochondrion	TAS PMID:10929711 Smac, a mitochondrial protein that promotes cytochrome c-dep...	ACCEPT	Summary: Mitochondrial localization is supported and remains informative at organelle resolution. Reason: The published abstract establishes mitochondrial storage and release of SMAC into cytosol during apoptosis; the complete original was not recovered. This supports the existing organelle claim. The mature-DIABLO Reactome entity independently places the release-competent 56–239 chain in IMS, but that separate evidence does not require replacement of mitochondrion or turn the abstract into a topology assay. Retain the informative mitochondrion assertion under the root-organelle policy; supported intermembrane-space annotations remain separate.
GO:0005758 mitochondrial intermembrane space	TAS PMID:18309324 No death without life: vital functions of apoptotic effector...	ACCEPT	Summary: DIABLO is stored in the mitochondrial intermembrane space before release. Reason: The cited review describes the established IMS-to-cytosol transition. Independent maturation/fractionation evidence and the exact Reactome mature-protein entity support this location. Storage in IMS is distinct from the cytosolic location at which released SMAC antagonizes IAPs.
GO:0005758 mitochondrial intermembrane space	TAS Reactome:R-HSA-114307	ACCEPT	Summary: Reactome explicitly places mature DIABLO in the IMS. Reason: Event R-HSA-114307 consumes entity R-HSA-64637, human Q9NR28 residues 56–239 in GO:0005758, and produces cytosolic entity R-HSA-114298. The reaction compartment is the outer membrane, but the source protein entity is explicitly in the IMS; transport context is not mistaken for a DIABLO membrane topology.
GO:0005829 cytosol	IDA PMID:28288130 PARL mediates Smac proteolytic maturation in mitochondria to...	ACCEPT	Summary: Processed DIABLO is released into the cytosol. Reason: The source abstract and recovered published supplementary experiments support PARL-dependent maturation and cytosolic release during apoptosis. Cytosol is the site at which mature SMAC can antagonize IAPs. Cleavage by MPP/PARL does not make DIABLO a protease or an active participant in its own processing.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: The cytosolic location mapping is supported experimentally. Reason: The UniProt SL-0091 mapping is consistent with direct fractionation, microscopy and IAP-antagonism evidence for released SMAC. This is a functional cytosolic pool, not a default assignment from the absence of membrane features.
GO:0005829 cytosol	TAS Reactome:R-HSA-114307	ACCEPT	Summary: The curated reaction contains cytosolic DIABLO. Reason: R-HSA-114307 transfers mature DIABLO from the IMS entity R-HSA-64637 to the cytosolic entity R-HSA-114298. The explicit component chain resolves to human Q9NR28 residues 56–239; this is a source-specific protein location, not an inference that DIABLO catalyzes the other participants’ reactions.
GO:0005829 cytosol	TAS Reactome:R-HSA-114354	ACCEPT	Summary: The curated reaction contains cytosolic DIABLO. Reason: R-HSA-114354 uses the cytosolic DIABLO dimer R-HSA-9627054 and produces DIABLO:XIAP:caspase-7 R-HSA-114353. The explicit component chain resolves to human Q9NR28 residues 56–239; this is a source-specific protein location, not an inference that DIABLO catalyzes the other participants’ reactions.
GO:0005829 cytosol	TAS Reactome:R-HSA-114392	ACCEPT	Summary: The curated reaction contains cytosolic DIABLO. Reason: R-HSA-114392 consumes DIABLO:XIAP:caspase-7 and releases caspase-7, retaining the cytosolic DIABLO dimer:XIAP entity R-HSA-9627391. The explicit component chain resolves to human Q9NR28 residues 56–239; this is a source-specific protein location, not an inference that DIABLO catalyzes the other participants’ reactions.
GO:0005829 cytosol	TAS Reactome:R-HSA-9627106	ACCEPT	Summary: The curated reaction contains cytosolic DIABLO. Reason: R-HSA-9627106 assembles the cytosolic DIABLO dimer from two copies of entity R-HSA-114298. The explicit component chain resolves to human Q9NR28 residues 56–239; this is a source-specific protein location, not an inference that DIABLO catalyzes the other participants’ reactions.
GO:0005829 cytosol	TAS Reactome:R-HSA-9627350	ACCEPT	Summary: The curated reaction contains cytosolic DIABLO. Reason: R-HSA-9627350 binds the cytosolic DIABLO dimer to XIAP, producing R-HSA-9627391. The explicit component chain resolves to human Q9NR28 residues 56–239; this is a source-specific protein location, not an inference that DIABLO catalyzes the other participants’ reactions.
GO:0006915 apoptotic process	IEA GO_REF:0000002	MODIFY	Summary: The broad apoptosis mapping can be refined to intrinsic signaling. Reason: Current InterPro family and fold matches genuinely map DIABLO to apoptotic process. Direct IAP-antagonism experiments establish participation in the cytochrome-c/Apaf-1/caspase-9 signaling system, providing a more informative existing term. This refinement does not deny the contextual death-receptor or oxidative-stress roles. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR015142 SUPPORTS TRANSFER Current family match spans residues 1–239 and maps to apoptotic process. Proposed replacements: intrinsic apoptotic signaling pathway
GO:0006915 apoptotic process	TAS PMID:10929712 Identification of DIABLO, a mammalian protein that promotes ...	MODIFY	Summary: The original IAP-antagonism finding supports intrinsic apoptotic signaling. Reason: The source abstract describes processed DIABLO associating with IAPs and counteracting their suppression of apoptosis. Independent biochemical reconstitution places this activity in intrinsic apoptotic signaling. GO:0097193 is more informative than the general apoptotic-process term and is already represented in the source annotations. Proposed replacements: intrinsic apoptotic signaling pathway Supporting Evidence: PMID:10929712 preventing them from inhibiting caspases.
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors	TAS PMID:10950947 Molecular determinants of the caspase-promoting activity of ...	KEEP AS NON CORE	Summary: SMAC can contribute downstream of death-domain receptor activation. Reason: The actual original uses an engineered cytosolic GFP–SMAC construct with a caspase-8-cleavable junction to potentiate TRAIL-induced apoptosis and bypass Bcl-xL inhibition. The term covers the signaling sequence from receptor activation to apoptotic execution; it does not require SMAC to bind the receptor. Retain this contextual participation with its engineered-construct limit, rather than replacing it solely because SMAC acts downstream. Supporting Evidence: PMID:10950947 allowed TRAIL to bypass Bcl-xL inhibition of death receptor-induced apoptosis.
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Inherited oxidative-stress apoptotic participation is retained as contextual. Reason: The PAINT IBD at PTN001283560 lies on the human lineage and is grounded in mouse Diablo IDA evidence from PMID:16085184. Its abstract reports peroxide-associated SMAC release and reciprocal overexpression/antisense effects in C2C12 cells. The mouse sequence retains the corresponding mature IAP-binding motif, and no target-specific loss or divergence was demonstrated. The source full text remains unavailable; stimulus specificity alone is not grounds to erase a valid phylogenetic placement. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001283560 SUPPORTS TRANSFER The oxidative-stress IBD lies on the human lineage. No target-specific loss or divergent placement is established. MGI:MGI:1913843 SUPPORTS TRANSFER Mouse Diablo IDA/PMID:16085184 is supported by peroxide-stress release and expression/antisense phenotypes in C2C12 cells; the full paper was unavailable. Supporting Evidence: PMID:16085184 significantly enhanced H(2)O(2)-induced apoptosis
GO:0009898 cytoplasmic side of plasma membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Mouse CD40 recruitment supports a contextual membrane-side location inference. Reason: The actual original detects endogenous SMAC in activated CD40 complexes in mouse B-cell lines, using receptor-capture controls and a human-ectodomain/mouse-tail chimera whose cytoplasmic-tail deletion loses recruitment. This supports the imported ISS location on the cytoplasmic side of the plasma membrane. It is not a direct human localization experiment or evidence that SMAC is an integral membrane receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9JIQ3 SUPPORTS TRANSFER PMID:20614026 directly detects mouse SMAC in activated CD40 complexes using receptor-tail and TRAF2 controls. Human ISS remains a species transfer, not a direct human experiment. Supporting Evidence: PMID:20614026 Recruitment of all three proteins was largely dependent on TRAF2
GO:0035631 CD40 receptor complex	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Mouse experiments support a contextual CD40-complex association. Reason: The original identifies SMAC in activated CD40 receptor captures by mass spectrometry and immunoblotting in mouse B cells, with tail-deletion and TRAF2-dependence controls. This grounds the human ISS inference. Preserve the species and activation context; co-complex recruitment does not prove direct SMAC–CD40 binding or a separate DIABLO receptor-signaling core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9JIQ3 SUPPORTS TRANSFER PMID:20614026 directly detects mouse SMAC in activated CD40 complexes using receptor-tail and TRAF2 controls. Human ISS remains a species transfer, not a direct human experiment.
GO:0042981 regulation of apoptotic process	NAS PMID:19153467 The structure of the BIR3 domain of cIAP1 in complex with th...	MODIFY	Summary: SMAC positively regulates intrinsic apoptotic signaling by relieving IAP inhibition. Reason: The source abstract and curated structural records establish SMAC-peptide recognition by the human BIRC2 BIR3 groove; the complete source article remains unavailable. Independent purified-component reconstitution in PMID:10972280 shows SMAC relieving XIAP inhibition of procaspase activation and mature caspase activity. This performed positive-control step supports GO:2001244, a verified descendant of the imported apoptosis-regulation term. The reconstitution includes mouse XIAP 1–356 in the procaspase assay and human XIAP BIR2 in the mature-caspase assay; the peptide paper is not relabeled as a complete pathway experiment. Proposed replacements: positive regulation of intrinsic apoptotic signaling pathway Supporting Evidence: PMID:10972280
GO:0043065 positive regulation of apoptotic process	IEA GO_REF:0000117	MODIFY	Summary: SMAC positively regulates intrinsic apoptotic signaling by relieving IAP inhibition. Reason: The current ARBA00027745 condition set includes target-matching FunFam 1.20.58.70:FF:000012 with Vertebrata. Its positive-apoptosis conclusion is sound. Direct IAP-antagonism and purified-component reconstitution support the more specific GO:2001244, which retains positive regulation and is a verified descendant of GO:0043065. This refinement describes SMAC relieving inhibition, not catalyzing caspase cleavage. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00027745 SUPPORTS TRANSFER Exact FunFam 1.20.58.70:FF:000012 plus Vertebrata conditions match the human record. Independent target mechanism supports the positive-regulatory descendant GO:2001244. Proposed replacements: positive regulation of intrinsic apoptotic signaling pathway Supporting Evidence: PMID:10972280
GO:0043065 positive regulation of apoptotic process	TAS PMID:18309324 No death without life: vital functions of apoptotic effector...	MODIFY	Summary: SMAC positively regulates intrinsic apoptotic signaling by relieving IAP inhibition. Reason: The cited synthesis describes released SMAC neutralizing IAP restraint of caspases. Independent biochemical reconstitution identifies the performed positive-control step: relief of XIAP inhibition of procaspase activation and mature caspase activity. GO:2001244 preserves this regulatory sign and is a verified descendant of the original GO:0043065; pathway membership alone would not preserve that meaning. SMAC is not assigned caspase catalytic activity. Proposed replacements: positive regulation of intrinsic apoptotic signaling pathway Supporting Evidence: PMID:10972280
GO:0051402 neuron apoptotic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: The neuronal-apoptosis inference has experimental grounding. Reason: The valid PTN001283560 IBD is grounded in mouse sympathetic-neuron experiments. Recombinant SMAC plus cytochrome c promotes neuronal death, with an altered N-terminal-motif control, while endogenous release alone under peroxide stress is insufficient in the tested wild-type context. These results support conditional participation, not a universal death trigger. No target-specific loss was demonstrated; non-core neuronal context is not evidence of over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001283560 SUPPORTS TRANSFER The neuronal-apoptosis IBD lies on the human lineage. A contextual function is not a propagation failure merely because it is not the principal core. MGI:MGI:1913843 SUPPORTS TRANSFER PMID:14623868 directly tests SMAC/cytochrome-c-dependent death in mouse sympathetic neurons with a motif control; endogenous release has context-dependent sufficiency. Supporting Evidence: PMID:14623868 the release of endogenous Smac was not sufficient to overcome the XIAP resistance
GO:0051726 regulation of cell cycle	NAS PMID:19153467 The structure of the BIR3 domain of cIAP1 in complex with th...	KEEP AS NON CORE	Summary: Mature-SMAC overexpression can alter cell-cycle progression in leukemia cells. Reason: The imported NAS reference PMID:19153467 establishes a SMAC-peptide/BIRC2 binding system, and its particular cell-cycle linkage remains unverified. Independent PMID:12642862 explicitly reports mature-SMAC overexpression in human K562/CEM cells causing G0/G1 arrest and reduced BrdU incorporation, as also discussed in PMID:18309324. Retain a contextual cell-cycle effect with the overexpression and unresolved physiological-mechanism limits; no new process term or separate cell-cycle core is proposed. Supporting Evidence: PMID:12642862 Smac transfectants displayed significant G0/G1 arrest
GO:0097190 apoptotic signaling pathway	IMP PMID:10972280 Structural and biochemical basis of apoptotic activation by ...	MODIFY	Summary: The biochemical signaling activity is more specifically intrinsic apoptosis. Reason: The original SMAC reconstitution experiments relieve XIAP inhibition in the cytochrome-c/Apaf-1/caspase system and also test mature-caspase inhibition. The source therefore supports intrinsic apoptotic signaling more specifically than the broad signaling-pathway term. Human SMAC constructs and the assay-specific human or mouse XIAP reagents are kept distinct. Proposed replacements: intrinsic apoptotic signaling pathway
GO:0097193 intrinsic apoptotic signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: The intrinsic-apoptosis rule agrees with direct biochemical evidence. Reason: ARBA00028303 includes the matching FunFam 1.20.58.70:FF:000012 plus Mammalia condition set. Human DIABLO satisfies both. Its IAP-antagonist activity in the intrinsic pathway is independently established, so this is a supported electronic inference rather than unexamined family-name transfer. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028303 SUPPORTS TRANSFER Exact condition set FunFam 1.20.58.70:FF:000012 plus Mammalia matches the official human record; direct target biochemistry independently supports intrinsic signaling.
GO:0097193 intrinsic apoptotic signaling pathway	TAS PMID:18309324 No death without life: vital functions of apoptotic effector...	ACCEPT	Summary: Intrinsic apoptotic signaling is a central DIABLO function. Reason: The cited review’s pathway assignment agrees with direct original experiments showing SMAC-dependent relief of IAP inhibition in the cytochrome-c/Apaf-1/caspase-9 system. The molecular contribution is IAP binding and antagonism, not caspase catalysis.
GO:1990713 survivin complex	IPI PMID:19153467 The structure of the BIR3 domain of cIAP1 in complex with th...	KEEP AS NON CORE	Summary: The source supports association with a BIR-containing IAP complex. Reason: The current official GO:1990713 definition includes an anti-apoptotic complex containing a baculoviral-IAP-repeat-family component and explicitly cites PMID:19153467. The definition and source xref are reproduced with the official link in the evidence guide. The source abstract and curated SPR/crystallographic records establish human SMAC 56–61 peptide binding to BIRC2 BIR3. Retain this source-defined contextual complex annotation with curator deference, without interpreting the term name as proof of a stable endogenous full-length BIRC5 assembly or adding such a complex to the core.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

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