ANK1 encodes ankyrin-1, also called ankyrin-R, a set of membrane-associated cytoskeletal adaptor isoforms generated by alternative promoters and splicing. In erythrocytes, large ankyrin-1 proteins bind beta-spectrin and integral membrane proteins including band 3 and Rhesus-complex components, organizing the connection between the lipid bilayer and the spectrinβactin skeleton. This linkage supports membrane shape and mechanical stability, and ANK1 defects cause hereditary spherocytosis. Ankyrin-R also assists trafficking and surface organization of selected membrane proteins and organizes membrane proteins in subsets of neurons. Short muscle isoforms associate with the sarcoplasmic reticulum and bind obscurin near the contractile apparatus, supporting SR organization through an architecture distinct from the large erythroid products.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005198 structural molecule activity | NAS PMID:9430667 An alternate promoter directs expression of a truncated, mus... | MODIFY | Summary: The structural role is a membrane-to-cytoskeleton linkage. Reason: PMID:9430667 describes the established erythroid linker role while identifying a short human muscle transcript. Cytoskeletal adaptor activity expresses that role more precisely than generic structural molecule activity, with direct linkage evidence in PMID:379653. This does not assign all erythroid binding domains to the truncated muscle product. Proposed replacements: cytoskeletal anchor activity Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005200 structural constituent of cytoskeleton | IEA GO_REF:0000117 | ACCEPT | Summary: Ankyrin-1 is a structural component of the erythrocyte membrane skeleton. Reason: The electronic structural annotation agrees with the spectrinβband-3 linkage and the native human ankyrin-1 complex. The ARBA rule itself is not treated as an experiment. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
| GO:0005200 structural constituent of cytoskeleton | TAS PMID:8640229 Ankyrin-1 mutations are a major cause of dominant and recess... | ACCEPT | Summary: ANK1 provides a structural linkage whose disruption causes hereditary spherocytosis. Reason: PMID:8640229 identifies ankyrin-1 as the principal linker between spectrin and the membrane and documents human loss-of-function variants. The structural role is independently established biochemically, rather than inferred solely from disease association. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005515 protein binding | IPI PMID:12719424 Rh-RhAG/ankyrin-R, a new interaction site between the membra... | MODIFY | Summary: RhAG binding contributes to membraneβcytoskeleton attachment. Reason: The original study tests Rh/RhAG cytoplasmic-tail binding to ankyrin-R and membrane-skeleton association. Cytoskeletal adaptor activity describes the measured anchoring role; it is already represented in the seed. The later native complex structure identifies additional RhCE contacts and does not negate the earlier RhAG-tail experiment. Proposed replacements: cytoskeletal anchor activity Supporting Evidence: PMID:12719424 We report here that ankyrin-R is capable of interacting directly with the C-terminal cytoplasmic domain of Rh and RhAG polypeptides. |
| GO:0005515 protein binding | IPI PMID:16580865 Functional interaction between Rh proteins and the spectrin-... | MODIFY | Summary: The erythroid Rh/RhAG interaction is a cytoskeletal anchoring activity. Reason: PMID:16580865 explicitly distinguishes Rh/RhAGβankyrin-R anchoring from epithelial RhBGβankyrin-G. Refine the generic binding assertion to the existing adaptor function without transferring the ankyrin-G mechanism to ANK1. Proposed replacements: cytoskeletal anchor activity Supporting Evidence: PMID:12719424 We report here that ankyrin-R is capable of interacting directly with the C-terminal cytoplasmic domain of Rh and RhAG polypeptides. |
| GO:0005515 protein binding | IPI PMID:16962094 Molecular interactions with obscurin are involved in the loc... | MODIFY | Summary: Small muscle ankyrin-1 isoforms associate with obscurin at the sarcomere. Reason: PMID:16962094 demonstrates binding of small ank1.5/ank1.9 to obscurin and colocalization at the M-band region. SR membrane integration/targeting and independent rat-myofiber knockdown/rescue in PMID:22045734 strengthen the membrane-to-cytoskeleton anchoring model. GO:0008093 captures that bridging interpretation; the original binding assay alone does not prove that obscurin tethering accounts for every SR-maintenance effect. This concerns short muscle products, without assigning their properties to every isoform or converting historical names into new tested-isoform tags. Proposed replacements: cytoskeletal anchor activity Supporting Evidence: PMID:16962094 was able to bind to obscurin in yeast two-hybrid assay and in pull-down experiments. PMID:22045734 Our results show that sAnk1 stabilizes the nSR and that its absence causes the nSR to fragment into distinct membrane compartments. |
| GO:0005515 protein binding | IPI PMID:379653 The membrane attachment protein for spectrin is associated w... | MODIFY | Summary: Band-3 binding forms the membrane arm of the spectrin linkage. Reason: PMID:379653 directly couples ankyrin-linked band 3 to spectrin in human erythrocyte extracts. Cytoskeletal adaptor activity captures the functional association and subsumes generic protein binding. Proposed replacements: cytoskeletal anchor activity Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: ANK1 acts on the cytoplasmic side of cellular membranes. Reason: The broad cytoplasm mapping is consistent with erythroid ankyrin, intracellular cargo-associated pools and short muscle products. Membrane association does not exclude a cytoplasmic compartment. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:18768923 These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of alpha(1)-Na(+)-K(+)-ATPase and presumably other selected proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392751 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-392751 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-443774 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-443774 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445076 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-445076 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807875 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-6807875 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807877 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-6807877 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809003 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-6809003 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809006 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-6809006 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809010 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-6809010 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809011 | ACCEPT | Summary: The cytosolic compartment is consistent with ankyrin-mediated complexes. Reason: The Reactome event places an ankyrin-containing entity on the cytosolic side, consistent with independently established ANK1 membrane-skeleton and cargo-adaptor functions. This supports location; family-set membership does not assign every event mechanism to ANK1. Supporting Evidence: Reactome:R-HSA-6809011 PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Erythroid ankyrin is a component of the membrane-associated cytoskeleton. Reason: The UniProt subcellular mapping agrees with direct spectrin linkage and native human erythrocyte complex isolation. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
| GO:0005856 cytoskeleton | NAS PMID:1833445 Immunocytochemical localization of fodrin and ankyrin in bov... | ACCEPT | Summary: A cytoskeletal ankyrin pool is compatible with the established ANK1 function. Reason: PMID:1833445 localizes erythrocyte-ankyrin-reactive antigen on filaments in bovine chromaffin cells. That is not a human ANK1-specific experiment, but the broad cytoskeleton annotation is independently established for human erythroid ankyrin. Retain the original NAS source without converting antibody cross-reactivity into a gene-specific functional assay. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma-membrane association is an experimentally grounded ancestral ankyrin property. Reason: The local PTHR24123 PAINT slice records the GO:0005886 IBD at PTN002380879. ANK1 itself supplies legitimate descendant evidence, while human erythrocyte studies independently establish membrane association. The complete tree/MSA was not reconstructed; no node-placement defect is inferred. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
| GO:0005886 plasma membrane | IDA PMID:379653 The membrane attachment protein for spectrin is associated w... | ACCEPT | Summary: Ankyrin links spectrin to integral proteins of the erythrocyte membrane. Reason: Human erythrocyte membrane extracts in PMID:379653 establish association with membrane-spanning band 3. This is peripheral cytoplasmic membrane association, not a transmembrane domain in the large erythroid product. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0005886 plasma membrane | NAS PMID:9430667 An alternate promoter directs expression of a truncated, mus... | ACCEPT | Summary: The broad plasma-membrane location applies to erythroid ANK1. Reason: PMID:9430667 states the established erythrocyte membrane-linker role before analyzing the distinct short muscle transcript. Retain this broad NAS assertion with independent human erythrocyte evidence, without relocating all short muscle products to the plasma membrane. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0006887 exocytosis | NAS PMID:1833445 Immunocytochemical localization of fodrin and ankyrin in bov... | MARK AS OVER ANNOTATED | Summary: The original localization study does not demonstrate an exocytotic step. Reason: The original bovine chromaffin-cell paper was inspected beyond its abstract: anti-rat erythrocyte ankyrin immunolabeling maps antigen to cytoskeletal filaments and coated membrane, but the authors explicitly leave its functional significance unresolved and consider membrane retrieval as well as secretion. They do not demonstrate ankyrin performing vesicle tethering, docking, fusion or content release, which define exocytosis. The source-specific NAS assertion therefore extends a localization-based hypothesis into a process assignment. This does not deny that ANK1 participates in selective cargo trafficking supported independently, and it does not identify the bovine antigen as a different ankyrin gene. The original-body access and primary URL are documented in the notes; the cached abstract-only flag is retained. Supporting Evidence: file:human/ANK1/ANK1-notes.md The bovine chromaffin study maps ankyrin-reactive antigen to filaments and coated membrane and leaves secretion versus membrane retrieval unresolved. |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IDA PMID:18768923 Ankyrin facilitates intracellular trafficking of alpha1-Na+-... | ACCEPT | Summary: Ankyrin-R helps selected membrane cargo enter the ER-to-Golgi pathway. Reason: PMID:18768923 distinguishes ankyrin-R from ankyrin-G knockdown, transfers ankyrin dependence through the ATPase ankyrin-binding segment, and restores cargo traffic with human erythrocyte ankyrin-R in semipermeabilized assays. This supports a selective cargo-adaptor role, not global control of all secretion. Rat ATPase constructs and the different host-cell systems remain distinct from the added human protein. Supporting Evidence: PMID:18768923 These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of alpha(1)-Na(+)-K(+)-ATPase and presumably other selected proteins. |
| GO:0007010 cytoskeleton organization | NAS PMID:9430667 An alternate promoter directs expression of a truncated, mus... | ACCEPT | Summary: ANK1 organizes the connection between the membrane and the spectrin network. Reason: The original NAS paper describes the erythroid scaffold role while examining alternative muscle transcription. Direct membraneβspectrin linkage and the native complex establish a structural contribution to cytoskeleton organization, beyond the existence of a disease phenotype or short transcript. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ANK1 can organize signaling components without being a signaling enzyme. Reason: The InterPro mapping derives from its death domain and does not alone establish a signaling mechanism. Independent CD45 association and surface organization in PMID:12354383 support a contextual scaffold contribution to lymphocyte signaling. Retain the broad process outside the compact structural core; do not infer apoptotic or kinase activity from the domain name. Supporting Evidence: PMID:12354383 Spectrin's effects are mediated by ankyrin, which binds directly to the cytoplasmic domain of CD45 (K(d) = 4.3 +/- 3.0 nM). |
| GO:0008093 cytoskeletal adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoskeletal adaptor activity is the conserved central function of ankyrin-1. Reason: PTN002380879 carries the corresponding IBD in the local PAINT slice, with ANK1 experimental evidence among its descendants. Target self-inclusion is valid grounding, not circularity. Direct human spectrinβmembrane linkage substantiates the activity independently of inference. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0008093 cytoskeletal adaptor activity | IDA PMID:379653 The membrane attachment protein for spectrin is associated w... | ACCEPT | Summary: Ankyrin physically bridges spectrin and band 3. Reason: The original human erythrocyte biochemistry demonstrates that spectrin binds ankyrin-linked band 3, defining an adaptor mechanism rather than uninformative binding alone. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0008093 cytoskeletal adaptor activity | TAS PMID:11427698 Spectrin and ankyrin-based pathways: metazoan inventions for... | ACCEPT | Summary: The family review describes the erythrocyte spectrinβanion-exchanger linkage. Reason: PMID:11427698 explicitly identifies ankyrin as the link between spectrin and the anion exchanger. This central erythroid function is independently supported by direct human experiments; broader tissue-specific functions discussed in the family review are assessed separately. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | ACCEPT | Summary: ANK1 participates in membrane-proximal complexes on the cytoplasmic side. Reason: PMID:12354383 associates ankyrin with CD45 and spectrin in human lymphocytes. Indexed publisher Methods specifically identify human erythrocyte ankyrin-R in the CD45 binding assay, resolving the gene context. The cytoplasmic membrane location also agrees with the erythroid linkage. Supporting Evidence: PMID:12354383 Spectrin's effects are mediated by ankyrin, which binds directly to the cytoplasmic domain of CD45 (K(d) = 4.3 +/- 3.0 nM). PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0014731 spectrin-associated cytoskeleton | IDA PMID:379653 The membrane attachment protein for spectrin is associated w... | ACCEPT | Summary: Ankyrin is part of the spectrin-associated erythrocyte cytoskeleton. Reason: The original human erythrocyte extraction and binding experiments establish the spectrin linkage directly. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0014731 spectrin-associated cytoskeleton | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA compartment assignment agrees with the native ankyrinβspectrin scaffold. Reason: Direct human biochemistry and native complex architecture support the cellular component independently of the uninspected historical rule execution. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Membrane association is shared across distinct ANK1 products. Reason: Large erythroid ankyrin binds integral membrane proteins from the cytoplasmic side, whereas short muscle products have a distinct hydrophobic N-terminus and sarcoplasmic-reticulum association. The broad membrane annotation is valid without treating their topologies as identical. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:16962094 In cultured myotubes, ank1.5 and ank1.9 colocalized with endogenous obscurin at the M-band region. |
| GO:0016323 basolateral plasma membrane | NAS PMID:12409278 Dissociation of spectrin-ankyrin complex as a basis for loss... | MARK AS OVER ANNOTATED | Summary: The inspected renal localization experiment uses an AnkG190-specific reagent. Reason: The indexed original publisher Introduction and Results explicitly identify an antibody against the unique N-terminal sequence of AnkG190, with rat-kidney and canine-MDCK immunoblot controls and basolateral staining. Thus the inspected localization experiment directly concerns that AnkG isoform. The generic kidney-specific wording of the cached abstract alone would not settle gene identity, but the inspected body identifies the reagent. The source-specific NAS transfer to ANK1 lacks support from this assayed reagent and is marked overannotated without claiming that ANK1 can never occupy a basolateral membrane or excluding other uninspected evidence. The original-body access and primary URL are documented in the notes; the cached abstract-only flag is retained. Supporting Evidence: file:human/ANK1/ANK1-notes.md The renal study's inspected primary body identifies an antibody to the unique AnkG190 N-terminal sequence, including the 15β31 region. |
| GO:0016529 sarcoplasmic reticulum | IEA GO_REF:0000120 | ACCEPT | Summary: Short muscle ANK1 products associate with the sarcoplasmic reticulum. Reason: Small muscle ANK1 products associate with the SR in PMID:16962094. Independent rat/mouse localization and rabbit SR fractionation in PMID:9024692, membrane-integration evidence in PMID:16308276 and adult-rat myofiber knockdown/rescue in PMID:22045734 corroborate this location. The original rat Ensembl donor chain remains unreconstructed; the independent evidence supports the location, not its assignment to every erythroid product. Supporting Evidence: PMID:16962094 interactions between muscle-specific ankyrin1 isoforms localized on the sarcoplasmic reticulum and obscurin a protein associated with the contractile apparatus. PMID:9024692 These results indicate that the small ankyrins associate tightly and preferentially with the sarcoplasmic reticulum of mammalian skeletal muscle. PMID:22045734 Our results show that sAnk1 stabilizes the nSR and that its absence causes the nSR to fragment into distinct membrane compartments. |
| GO:0019899 enzyme binding | IPI PMID:21177872 Asparagine and aspartate hydroxylation of the cytoskeletal a... | KEEP AS NON CORE | Summary: Ankyrin-R binds its modifying enzyme FIH/HIF1AN as a substrate. Reason: PMID:21177872 tests FIH-dependent hydroxylation of recombinant ankyrin-R repeats and native human erythrocyte ankyrin. The enzyme interaction is real, but ANK1 is the hydroxylated substrate, not the oxygenase or an established FIH inhibitor. Retain this post-translational interaction outside the structural core. The enzyme-binding definition includes selective interaction with an enzyme and does not itself require inhibition or activation. The source therefore supports a real substrate interaction, retained as non-core rather than reinterpreted as an FIH regulatory function. Supporting Evidence: PMID:21177872 Here we report that the cytoskeletal ankyrin family are substrates for FIH-catalyzed hydroxylations. |
| GO:0019899 enzyme binding | TAS PMID:11427698 Spectrin and ankyrin-based pathways: metazoan inventions for... | MODIFY | Summary: Na,K-ATPase binding supplies a supported, more specific enzyme interaction. Reason: The family reviewβs generic enzyme-binding assertion can be refined using independent PMID:8159688, which separately tests erythrocyte Ank1 and kidney Ank3 binding to Na,K-ATPase cytoplasmic domains. ATPase binding is already present in the seed; the later supporting source does not reconstruct an uninspected experiment in the review. This is a refinement of this source row to an already-seeded term, not a NEW annotation or additional independent core activity. Proposed replacements: ATPase binding |
| GO:0019903 protein phosphatase binding | IPI PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | KEEP AS NON CORE | Summary: ANK1 binds the CD45 protein phosphatase in lymphocyte-associated complexes. Reason: The source demonstrates direct CD45 cytoplasmic-domain binding, and indexed Methods identify human erythrocyte AnkR in surface plasmon resonance. This supports the specific partner-class function, without assigning phosphatase catalysis or a universal immune role to ANK1. Supporting Evidence: PMID:12354383 Spectrin's effects are mediated by ankyrin, which binds directly to the cytoplasmic domain of CD45 (K(d) = 4.3 +/- 3.0 nM). |
| GO:0030018 Z disc | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Comparative rat muscle staining supports a Z-line-associated AnkR pool. Reason: The original body of PMID:9664041 reports a thinner AnkR-positive band colocalizing with alpha-actinin at Z lines, alongside a major A-band signal. This independently supports the existing regional located_in assertion. PMID:9024692 separately places small Ank1 in SR surrounding Z/M levels, which must not be equated with an integral actin-anchoring-plate constituent. Retain the Z-region localization outside the compact mechanistic core using the same regional interpretation as the M/A-band evidence, without assigning it to every isoform or claiming the original rat donor chain has been recovered. Supporting Evidence: PMID:9664041 Both ankyrin isoforms codistributed over Z-lines and at the postsynaptic membrane. PMID:9024692 Thus, the p6 epitope is likely to be concentrated with desmin at the Z line surrounding the Z disk, but it is probably also present at other sites in the myoplasm. file:human/ANK1/ANK1-notes.md The comparative rat study reports a thin AnkR-positive band colocalizing with alpha-actinin at Z lines, beyond the separate small-Ank1 SR pool that surrounds Z/M levels. |
| GO:0030507 spectrin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Spectrin binding is both ancestral and directly demonstrated for ANK1. Reason: The PAINT slice records the spectrin-binding IBD at PTN002380879, including ANK1 descendant evidence. Direct target biochemistry supports the activity; the self-source is not circular. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:8159688 Spectrin binds both Ank1 and Ank3 avidly, as expected. |
| GO:0030507 spectrin binding | IDA PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | ACCEPT | Summary: Spectrin association is retained in the CD45βankyrin scaffold. Reason: PMID:12354383 reports beta-I spectrinβankyrinβCD45 association; indexed publisher Results identify an AnkR-reactive high-molecular-weight protein in human lymphocytes. Direct human erythrocyte spectrin binding provides independent support without converting every cellular co-precipitation into a purified binary assay. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0030507 spectrin binding | IDA PMID:379653 The membrane attachment protein for spectrin is associated w... | ACCEPT | Summary: Human erythrocyte ankyrin binds spectrin. Reason: The source directly tests spectrin binding to ankyrin-linked band 3 and distinguishes it from band 3 alone. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0030507 spectrin binding | IPI PMID:8159688 Ankyrin binds to two distinct cytoplasmic domains of Na,K-AT... | ACCEPT | Summary: Recombinant spectrin domains bind erythrocyte ankyrin-1. Reason: PMID:8159688 explicitly tests Ank1 separately from kidney Ank3. Both bind spectrin; the paperβs inclusion of another ankyrin does not make this ANK1 annotation a paralog misattribution. Supporting Evidence: PMID:8159688 Spectrin binds both Ank1 and Ank3 avidly, as expected. |
| GO:0030507 spectrin binding | NAS PMID:8640229 Ankyrin-1 mutations are a major cause of dominant and recess... | ACCEPT | Summary: The disease study correctly describes the established ankyrinβspectrin linkage. Reason: PMID:8640229 states that ankyrin-1 attaches spectrin to the cytoplasmic domain of band 3. Preserve the NAS statement with independent biochemical corroboration rather than treating genetic association itself as a new binding assay. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0030673 axolemma | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: AnkR can occupy axonal membrane at developing and compensatory nodes. Reason: Genetically resolved mouse experiments in PMID:25362473 demonstrate AnkR at nodal axonal membrane during early PNS development and after AnkG loss, with Ank1-deficient controls validating antibody identity. Mature control nodes have much less AnkR, and CNS developmental enrichment differs. This independently supports a context-dependent axolemmal pool without making AnkR the principal adult nodal ankyrin or reconstructing the original rat donor chain. Historical PMID:2139035 antibody staining alone would not settle gene identity. Supporting Evidence: PMID:25362473 Although we transiently detected AnkR at developing PNS nodes, we only rarely detected AnkR at developing CNS nodes. PMID:25362473 The rescue of Na+ channel clustering by AnkR/Ξ²I spectrin is not a consequence of genetic reprogramming, but rather redistribution of a pre-existing pool of axonal AnkR/Ξ²I spectrin. |
| GO:0031430 M band | IEA GO_REF:0000120 | ACCEPT | Summary: Small muscle ankyrin-1 isoforms localize with obscurin at the M band. Reason: The read small-isoform study and the UniProt Mu17 statement independently support this compartment. Preserve the electronic donor fields, while restricting the biological interpretation to the relevant muscle products rather than all ANK1 isoforms. This is a peripheral M-band-region association through obscurin; PMID:9024692 distinguishes nearby SR small ankyrins from integral M-line proteins. Retaining the existing location does not make ANK1 a thick-filament crosslinker. Supporting Evidence: PMID:16962094 In cultured myotubes, ank1.5 and ank1.9 colocalized with endogenous obscurin at the M-band region. PMID:9024692 Thus, the small ankyrins are not integral to the M lines but instead appear to surround the myosin filaments at the level of the M lines. |
| GO:0031672 A band | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Independent rat muscle staining supports an A-band-associated AnkR pool. Reason: PMID:9664041 directly compares rat AnkG and AnkR and reports Ank1 products at sarcolemma and sarcoplasmic structures in register with A bands. Its inspected body distinguishes the major A-band-associated signal from thinner Z-level staining. GO:0031672 includes the M band by part_of, so the existing M-band evidence is compatible rather than anatomically unrelated. Retain this broader regional muscle location outside the compact mechanistic core, without claiming a separate thick-filament activity or recovery of the original electronic donor chain. Supporting Evidence: PMID:9664041 ankyrin(s)R (ank1 gene products) accumulate at the sarcolemma and at sarcoplasmic structures, in register with A-bands. PMID:16962094 In cultured myotubes, ank1.5 and ank1.9 colocalized with endogenous obscurin at the M-band region. |
| GO:0042383 sarcolemma | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Large muscle Ank1 proteins form a distinct sarcolemmal pool. Reason: PMID:9024692 distinguishes large Ank1 at the rat sarcolemma from small Ank1 in internal SR membranes; loss of the large sarcolemmal signal in nb/nb mouse muscle supports Ank1 identity. PMID:9664041 independently compares rat AnkR and AnkG distributions. This is positive support for the muscle plasma-membrane pool, distinct from the short SR products. Retain the tissue-specific location without pretending to have recovered the exact rat donor chain. Supporting Evidence: PMID:9024692 Data from the nb/nb mouse confirm the fact that the products of the 9.0- and 7.5-kb Ank1 transcripts are associated with the sarcolemma. PMID:9664041 ankyrin(s)R (ank1 gene products) accumulate at the sarcolemma and at sarcoplasmic structures, in register with A-bands. |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Genetically resolved axonal AnkR supports the inherited neuron-projection location. Reason: The local PAINT slice records neuron projection at PTN002380879; the full tree and MSA remain uninspected. Independent PMID:25362473 directly locates AnkR in mouse axons, including developing and compensatory nodes, rather than inferring a projection from brain expression alone. Human somatic membrane staining in PMID:34180393 corroborates neuronal relevance but is not itself projection or postsynaptic evidence. No target-specific loss is established, and the original inherited assertion is retained outside the compact erythroid/short-muscle core. Supporting Evidence: PMID:25362473 The rescue of Na+ channel clustering by AnkR/Ξ²I spectrin is not a consequence of genetic reprogramming, but rather redistribution of a pre-existing pool of axonal AnkR/Ξ²I spectrin. PMID:34180393 AnkR is also highly expressed in Pv+ neurons in human brain. |
| GO:0044325 transmembrane transporter binding | IBA GO_REF:0000033 | ACCEPT | Summary: ANK1 binds integral membrane transporters as part of its adaptor role. Reason: The ancestral IBD at PTN002380879 is present in the local PAINT slice. Although its listed experimental seed is ANK2, ANK1 itself binds band 3 and Na,K-ATPase. The short donor list is not a reason to challenge a phylogenetic assertion corroborated on the target. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. |
| GO:0045199 maintenance of epithelial cell apical/basal polarity | TAS PMID:11427698 Spectrin and ankyrin-based pathways: metazoan inventions for... | UNDECIDED | Summary: The family review does not resolve an ANK1-specific epithelial polarity mechanism. Reason: The available PMID:11427698 abstract discusses spectrin/ankyrin pathways across tissues and family members. The exact ANK1 evidence for maintenance of epithelial apical/basal polarity has not been accessed. ANK1-selective cargo traffic in PMID:18768923 is relevant but does not itself establish maintenance of overall epithelial polarity. Supporting Evidence: PMID:18768923 These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of alpha(1)-Na(+)-K(+)-ATPase and presumably other selected proteins. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: The muscle postsynaptic AnkR signal retains a published antibody-specificity caveat. Reason: The original body of the rat comparative study PMID:9664041 explicitly considers cross-reaction with low-abundance subsynaptic AnkG480 as an explanation of postsynaptic AnkR-antibody staining. This is a source-stated unresolved possibility, not a wrong-paralog claim inferred from the paper title. Genetically resolved axonal AnkR and human cortical somatic membrane staining do not independently settle a postsynaptic compartment. Keep the electronic assertion unresolved rather than remove it or substitute another neuronal location. Supporting Evidence: file:human/ANK1/ANK1-notes.md Postsynaptic membrane remains UNDECIDED because the comparative 1998 paper itself allows antibody cross-reaction with low-abundance subsynaptic AnkG480. |
| GO:0048193 Golgi vesicle transport | IEA GO_REF:0000117 | ACCEPT | Summary: ANK1 supports Golgi-directed movement of selected cargo. Reason: The broad ARBA process agrees with PMID:18768923, which tests ankyrin-R-dependent ER-to-Golgi cargo entry and rescue. This is selective trafficking, not an assertion that ANK1 coats every Golgi vesicle or transports all cargo. Supporting Evidence: PMID:18768923 These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of alpha(1)-Na(+)-K(+)-ATPase and presumably other selected proteins. |
| GO:0051117 ATPase binding | IPI PMID:8159688 Ankyrin binds to two distinct cytoplasmic domains of Na,K-AT... | ACCEPT | Summary: Erythrocyte ankyrin-1 binds Na,K-ATPase cytoplasmic domains. Reason: PMID:8159688 directly separates Ank1 and Ank3 binding assays and finds two ATPase domains that bind both. The original nonhuman ATPase partner identifier is preserved; the binding partnerβs species does not change the identity of the tested ankyrin. Supporting Evidence: |
| GO:0071944 cell periphery | IEA GO_REF:0000117 | ACCEPT | Summary: Ankyrin-1 is concentrated at the cytoplasmic cell periphery in erythrocytes. Reason: The broad electronic location agrees with direct membraneβspectrin tethering and native complex structure. Supporting Evidence: PMID:379653 It is concluded that a fraction of band 3 is attached to the erythrocyte cytoskeleton through association with ankyrin, which in turn is bound to spectrin. PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
| GO:0072657 protein localization to membrane | IEA GO_REF:0000117 | ACCEPT | Summary: ANK1 helps recruit and retain selected membrane proteins. Reason: The electronic process is supported by structural membrane-protein clustering and cargo-trafficking experiments. ANK1 supplies a binding scaffold that performs part of localization, not merely a protein whose loss causes an indirect phenotype. Supporting Evidence: PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. PMID:18768923 These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of alpha(1)-Na(+)-K(+)-ATPase and presumably other selected proteins. |
| GO:0072659 protein localization to plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ANK1 contributes to targeting and retention of plasma-membrane proteins. Reason: The local PTN002380879 IBD includes ANK1 descendant evidence and agrees with target cargo studies. Self-inclusion is valid experimental grounding. The scaffold participates in the localization step by binding cargo; no new process is added. Supporting Evidence: PMID:18768923 These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of alpha(1)-Na(+)-K(+)-ATPase and presumably other selected proteins. PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
| GO:0072659 protein localization to plasma membrane | IMP PMID:18768923 Ankyrin facilitates intracellular trafficking of alpha1-Na+-... | ACCEPT | Summary: Ankyrin-R-dependent trafficking supports Na,K-ATPase delivery to the surface. Reason: PMID:18768923 tests ankyrin-R depletion and selective cargo movement, with human erythrocyte ankyrin rescue of ER-to-Golgi transfer. The Na,K-ATPase surface phenotype supports the broad plasma-membrane localization process; the engineered VSV-MAB chimera reaching Golgi is not represented as proof that every chimera accumulates stably at the surface. Supporting Evidence: PMID:18768923 These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of alpha(1)-Na(+)-K(+)-ATPase and presumably other selected proteins. |
| GO:0170014 ankyrin-1 complex | IDA PMID:35835865 Architecture of the human erythrocyte ankyrin-1 complex. | ACCEPT | Summary: ANK1 is a directly resolved subunit of the native human erythrocyte complex. Reason: PMID:35835865 purifies ankyrin-1 complexes from human erythrocytes and resolves their membrane-partner interfaces. The structural evidence establishes complex membership; proposed gas-transport metabolon functions of other subunits do not confer catalysis on ANK1. Supporting Evidence: PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
| GO:1990778 protein localization to cell periphery | IEA GO_REF:0000117 | ACCEPT | Summary: ANK1 organizes delivery and stable association of proteins at the cell periphery. Reason: The broad localization process is consistent with the membrane-protein scaffold and selective secretory trafficking. The core synthesis uses the more specific plasma-membrane localization term rather than duplicating its ancestor. Supporting Evidence: PMID:18768923 These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of alpha(1)-Na(+)-K(+)-ATPase and presumably other selected proteins. PMID:35835865 Here we present structures of ankyrin-1 complexes purified from human erythrocytes. |
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Download this section (compressed HTML)Q: Which human ANK1 splice products underlie the rat-derived Z-disc, A-band, sarcolemmal, axolemmal and postsynaptic-membrane annotations, and what original experiments support those transfers?
Q: Does an ANK1-specific basolateral epithelial pool support the annotation citing PMID:12409278, whose inspected localization experiments use AnkG190-specific antibodies?
Q: How do the historical small-muscle ank1.5/ank1.9 constructs map by sequence to the current human alternative-product records?
Experiment: Use sequence-defined endogenous isoform tagging and isoform-selective rescue to distinguish erythroid, neuronal and short muscle ankyrin-1 localization and partner recruitment.
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