ANKRD26 is an ankyrin-repeat-containing protein with distinct membrane-associated and centriolar functions. Its N-terminal region binds membranes through an amphipathic element and senses membrane curvature through ankyrin repeats. The complete N-terminal module also deforms membranes. At mature centrioles, a coiled-coil region recruits PIDD1 to distal appendages, coupling centrosome number to PIDDosome signaling. ANKRD26 also affects cytokine-receptor internalization and signaling in hematopoietic cells. Regulatory-region variants that disrupt its normal downregulation during megakaryocyte differentiation cause inherited thrombocytopenia with predisposition to myeloid malignancy. Its interaction with transcriptional coregulators and effects on adipocyte differentiation provide additional cellular contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:22666460 ANKRD26 and its interacting partners TRIO, GPS2, HMMR and DI... | REMOVE | Summary: The ANKRD26 C-terminal region interacts with HMMR. Reason: The original yeast two-hybrid and co-immunoprecipitation experiments support the interaction. The co-IP used human ANKRD26 residues 1212–1710 in 293T cells with a partner recovered from a mouse embryo library. Remove the uninformative generic binding annotation; this does not mean that the reported interaction is false. Neither direct microtubule binding nor a defined HMMR adaptor mechanism is established by this pairwise interaction. |
| GO:0005515 protein binding | IPI PMID:22666460 ANKRD26 and its interacting partners TRIO, GPS2, HMMR and DI... | REMOVE | Summary: The ANKRD26 C-terminal region interacts with a TRIO fragment. Reason: Human ANKRD26 residues 1212–1710 co-immunoprecipitated with the mouse-library-derived TRIO fragment in human 293T cells. Remove the uninformative generic binding annotation; this does not mean that the reported interaction is false. The experiment establishes neither nucleotide-exchange activity of ANKRD26 nor assembly of a functional GEF-containing complex, so partner identity alone does not justify a specific replacement. |
| GO:0005515 protein binding | IPI PMID:22666460 ANKRD26 and its interacting partners TRIO, GPS2, HMMR and DI... | MODIFY | Summary: ANKRD26 interacts with the transcriptional coregulator GPS2. Reason: The original study experimentally supports interaction with GPS2, a transcriptional coregulator. Transcription coregulator binding describes the partner class more precisely than generic protein binding. The human ANKRD26 C-terminal fragment and mouse-library partner constructs are distinguished from full-length endogenous proteins. Fragment-driven cytoplasmic redistribution in 3T3-L1 cells does not establish DNA binding or transcription coregulator activity of ANKRD26 itself. Proposed replacements: transcription coregulator binding |
| GO:0005515 protein binding | IPI PMID:22666460 ANKRD26 and its interacting partners TRIO, GPS2, HMMR and DI... | MODIFY | Summary: ANKRD26 interacts with the transcriptional coregulator CCDC85B/DIPA. Reason: PMID:22666460 supports the ANKRD26–CCDC85B/DIPA interaction. The partner classification is independently supported by the official UniProt Q15834 transcriptional-repressor record and primary human CCDC85B–TCF4/TCF7L2 binding, competition and transcriptional assays in PMID:17873903, documented with public article locators in the notes. It is not inferred from nuclear residence. Thus transcription coregulator binding is more informative than generic binding. The original ANKRD26 C-terminal fragment and mouse-library partner constructs remain distinguished from full-length endogenous proteins; their redistribution in 3T3-L1 cells does not establish ANKRD26 transcription coregulator activity. Proposed replacements: transcription coregulator binding Supporting Evidence: file:human/ANKRD26/ANKRD26-notes.md CCDC85B is a transcriptional coregulator independently of its interaction with ANKRD26: human CCDC85B binds TCF4/TCF7L2 and competes with beta-catenin in the primary study PMID:17873903. |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: ANKRD26 localizes to the centrosomal region, including mature-centriolar distal appendages. Reason: The available extraction of the original proteomics paper omits candidate-specific tables and the ANKRD26 localization image. Retain the experimental curator’s broad centrosome assertion: independent human-cell localization, recruitment and complementation experiments directly corroborate it. Later distal-appendage mapping refines the spatial description but is not represented as a reconstruction of the 2011 assay. PIDD1 recruitment can occur at non-ciliated mature centrioles, so the cilium-defined transition-fiber term is not imposed on this broad assertion. |
| GO:0045599 negative regulation of fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse perturbation evidence supports a negative effect on adipocyte differentiation. Reason: The donor Q811D2 is mouse Ankrd26. The original mouse 3T3-L1 knockdown and mouse mutant phenotypes support the transferred adipogenic association. Human ANKRD26 fragment interactions do not independently establish the whole differentiation mechanism in human adipocytes. Retain the curated orthology transfer as a non-core physiological context, without attributing a discrete adipogenesis reaction to ANKRD26. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q811D2 SUPPORTS TRANSFER Mouse Ankrd26 perturbation affects adipogenesis; the physiological association is retained without claiming a direct human adipocyte assay. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:33350495 ANKRD26 recruits PIDD1 to centriolar distal appendages to ac... | NEW | Summary: ANKRD26 docks PIDD1 at centriolar distal appendages. Reason: Two independent studies map a PIDD1-binding region and separate ANKRD26 centriolar localization from PIDD1 recruitment by deletion and rescue experiments. This establishes a physical recruiting activity. ANKRD26 is not assigned PIDD1 autoproteolysis or caspase-2 chemistry, and is not established as an integral scaffold holding the mature PIDDosome together. The generic adaptor term captures the demonstrated docking mechanism without inventing a partner-specific term. Supporting Evidence: PMID:33350495 The distal appendage protein ANKRD26 is found to interact with and recruit the PIDDosome component PIDD1 to centriole distal appendages PMID:33350486 ANKRD26 deficiency, but not CEP164 or FBF1 depletion, abrogated PIDD1 recruitment to DAs |
| GO:0140090 membrane curvature sensor activity | IDA PMID:38493476 Ankrd26 is a retinoic acid-responsive plasma membrane-bindin... | NEW | Summary: The ANKRD26 ankyrin-repeat region preferentially binds more strongly curved membranes. Reason: The externally read original Figure 3B–C tests purified human residues 45–217 and directly establishes curvature preference. The normal cache remains abstract-only. This activity is distinct from membrane bending; fragment measurements do not imply a physiological lipid ligand or constitutive occupancy of curved membranes. Supporting Evidence: file:human/ANKRD26/ANKRD26-notes.md The human 45–217 fragment preferentially binds SUVs over LUVs in Figure 3B–C; this is curvature sensing, distinct from membrane deformation. |
| GO:0180020 membrane bending activity | IDA PMID:38493476 Ankrd26 is a retinoic acid-responsive plasma membrane-bindin... | NEW | Summary: The human N-terminal module directly deforms membranes. Reason: Purified human N-Ank (1–217) reshapes liposomes in Figure 3F–J, unlike GST and truncation controls. Construct and assay Methods were read externally; the unchanged cached abstract corroborates bending. GO:0180020 is a distinct molecular function, not an ancestor or descendant of the curvature-sensor term. Supporting Evidence: PMID:38493476 Ankrd26 uses an N-terminal amphipathic structure for membrane binding and bending. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:38493476 Ankrd26 is a retinoic acid-responsive plasma membrane-bindin... | NEW | Summary: An endogenous ANKRD26 pool occupies the cytoplasmic plasma-membrane face. Reason: Original Figure 1G–J and Methods identify endogenous protein at the P-face in human SK-N-SH cells. This external full-text evidence is more specific than the unchanged cached abstract. It describes a demonstrated cellular pool, not exclusive localization. Supporting Evidence: file:human/ANKRD26/ANKRD26-notes.md Endogenous ANKRD26 labels the cytoplasmic plasma-membrane face in differentiated human SK-N-SH cells (Figure 1G–J), with E-face and ice controls. |
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Download this section (compressed HTML)Q: Which endogenous ANKRD26 interactions directly control type I cytokine-receptor internalization, as opposed to indirect associations detected by co-immunoprecipitation and proximity assays?
Q: How do ANKRD26 pools at centriolar distal appendages and the plasma membrane exchange during differentiation, and how do the two annotated alternative products differ?
Q: Does endogenous full-length ANKRD26 relocalize GPS2 or CCDC85B in human adipocyte precursors, reproducing the C-terminal-fragment effects observed in mouse 3T3-L1 cells?
Experiment: Compare endogenous ANKRD26 rescue with membrane-anchor and PIDD1-binding mutants at matched expression, resolving receptor internalization, centriolar PIDD1 recruitment and differentiation phenotypes separately.
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