EHD1 (also RME-1/PAST1 homolog) is a member of the C-terminal Eps15 homology domain-containing (EHD) family of dynamin-related ATPases. It has an N-terminal G-like domain that binds and hydrolyzes ATP, a helical membrane-binding region, and a C-terminal EH domain with an EF-hand that binds NPF-motif partners such as MICAL-L1, rabenosyn-5, rabankyrin-5 and syndapin-2. ATP-bound EHD1 dimerizes and oligomerizes on membranes, where it tubulates and promotes fission (vesiculation) of tubular recycling endosomes. It is a key regulator of endocytic recycling, controlling exit of internalized receptors such as transferrin receptor and MHC class I from the perinuclear endocytic recycling compartment back to the plasma membrane, and it also contributes to retromer-dependent endosome-to-Golgi retrieval. In early primary ciliogenesis EHD1, together with its close paralog EHD3, is recruited to the mother centriole (via MICAL-L1), associates with preciliary vesicles and tubulates distal appendage vesicles so that they fuse, with SNAP29, into the ciliary vesicle; this step is required for removal of CP110 from the mother centriole and recruitment of transition zone proteins and IFT20. EHD1 later localizes to the ciliary pocket membrane. In other cell types EHD1 has been implicated in cholesterol homeostasis, myoblast fusion and neurotrophin-receptor trafficking. A homozygous EHD1 missense variant (p.R398W) causes an autosomal recessive syndrome of low-molecular-weight proteinuria and sensorineural hearing loss.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Calcium ion binding (IEA, EF-hand). Reason: The EH domain contains an EF-hand motif; calcium binding by EHD EF-hands is supported by family structural data. |
| GO:0005515 protein binding | IPI PMID:12121420 EHD3: a protein that resides in recycling tubular and vesicu... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:15020713 Rabenosyn-5 and EHD1 interact and sequentially regulate prot... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:15020713 Rabenosyn-5 and EHD1 interact and sequentially regulate prot... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:19864458 MICAL-L1 links EHD1 to tubular recycling endosomes and regul... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:22284051 Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endoc... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:22284051 Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endoc... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:23596323 Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:26226295 SUMOylation of EHD3 Modulates Tubulation of the Endocytic Re... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:27189942 EHD3 Protein Is Required for Tubular Recycling Endosome Stab... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:27189942 EHD3 Protein Is Required for Tubular Recycling Endosome Stab... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding (IPI) for EHD1. Partners include EHD3 and other EHDs, rabenosyn-5, MICAL-L1, rabankyrin-5, syndapin-2 and interactome hits; the functional content is captured by the adaptor, oligomerization and recycling terms. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | MODIFY | Summary: GTP binding (IEA, InterPro dynamin-like G domain) for EHD1. Reason: Although EHD proteins have a dynamin-related G domain, they bind and hydrolyze ATP rather than GTP; purified RME-1/EHD1 family proteins showed no significant GTP binding or hydrolysis, and ATP binding drives their oligomerization and membrane association. The correct nucleotide-binding term is ATP binding. Proposed replacements: ATP binding Supporting Evidence: PMID:15710626 we show that both Caenorhabditis elegans and mouse RME-1 proteins bind and hydrolyze ATP. No significant GTP binding or hydrolysis was detected. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasm (IBA). Reason: Consistent with EHD1 association with endocytic carriers and the perinuclear endocytic recycling compartment. Supporting Evidence: PMID:15020713 depletion of EHD1 caused the accumulation of internalized cargo in a compact juxtanuclear compartment |
| GO:0005768 endosome | IEA GO_REF:0000107 | ACCEPT | Summary: endosome (IEA). Reason: EHD1 associates with endosomal membranes, including early/sorting endosome compartments where it partially colocalizes with rabenosyn-5, as well as tubular recycling endosomes. Supporting Evidence: PMID:15020713 EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo |
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: early endosome (IBA). Reason: EHD1 associates with endosomal membranes, including early/sorting endosome compartments where it partially colocalizes with rabenosyn-5, as well as tubular recycling endosomes. Supporting Evidence: PMID:15020713 EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo |
| GO:0005769 early endosome | IEA GO_REF:0000107 | ACCEPT | Summary: early endosome (IEA). Reason: EHD1 associates with endosomal membranes, including early/sorting endosome compartments where it partially colocalizes with rabenosyn-5, as well as tubular recycling endosomes. Supporting Evidence: PMID:15020713 EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo |
| GO:0005811 lipid droplet | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: lipid droplet (IEA), transferred from rodent Ehd1 studies. Reason: Rodent Ehd1 has been linked to cholesterol uptake/storage and lipid droplets, plausibly secondary to its role in endocytic recycling of lipoprotein receptors; retained as a non-core, cell-type-specific role. |
| GO:0005811 lipid droplet | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: lipid droplet (ISS), transferred from rodent Ehd1 studies. Reason: Rodent Ehd1 has been linked to cholesterol uptake/storage and lipid droplets, plausibly secondary to its role in endocytic recycling of lipoprotein receptors; retained as a non-core, cell-type-specific role. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane (IBA). Reason: EHD1 associates with the plasma membrane and with recycling carriers delivering cargo to it; HPA main location is plasma membrane. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane from HPA immunofluorescence (IDA, GO_REF:0000052). Reason: HPA main location for EHD1 is plasma membrane, consistent with EHD1 on recycling carriers returning to the cell surface and its ciliary pocket localization. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane (IEA). Reason: EHD1 associates with the plasma membrane and with recycling carriers delivering cargo to it; HPA main location is plasma membrane. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Plasma membrane (ISS). Reason: EHD1 associates with the plasma membrane and with recycling carriers delivering cargo to it; HPA main location is plasma membrane. |
| GO:0005929 cilium | IDA GO_REF:0000052 | ACCEPT | Summary: cilium localization from the Human Protein Atlas cilium atlas immunofluorescence (IDA, GO_REF:0000052). Reason: HPA reports EHD1 at the primary cilium and primary cilium transition zone (Supported) with a main plasma membrane location; this agrees with the proximal-cilium/ciliary-pocket localization of EHD1/EHD3 shown by CLEM and SIM. Supporting Evidence: PMID:25686250 Interestingly, only GFP-EHD1 and GFP-EHD3 were detected at the proximal ciliary region |
| GO:0005929 cilium | IDA PMID:31615969 MICAL-L1 coordinates ciliogenesis by recruiting EHD1 to the ... | ACCEPT | Summary: Cilium (IDA). Reason: EHD1 is recruited to the basal body/proximal cilium in a MICAL-L1-dependent manner and localizes to the ciliary pocket region. Supporting Evidence: PMID:31615969 upon MICAL-L1-depletion, EHD1 fails to localize to basal bodies |
| GO:0006886 intracellular protein transport | IMP PMID:15020713 Rabenosyn-5 and EHD1 interact and sequentially regulate prot... | ACCEPT | Summary: Intracellular protein transport (IMP). Reason: General but correct: EHD1 depletion delays recycling of transferrin receptor and MHC class I to the cell surface. Supporting Evidence: PMID:15020713 Depletion of either EHD1 or Rabenosyn-5 delayed the recycling of transferrin and major histocompatibility complex class I to the plasma membrane. |
| GO:0006897 endocytosis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Endocytosis (IBA). Reason: EHD1 acts mainly after internalization, in sorting and recycling of endocytosed cargo (depletion relocalizes internalized transferrin to the recycling compartment). Endocytic trafficking in the broad sense is appropriate but the specific core process is endocytic recycling. Supporting Evidence: PMID:20801876 Upon Crmp2 depletion, we observed dramatic relocalization of internalized transferrin (Tf) from peripheral vesicles to the endocytic recycling compartment (ERC), similar to the effect of depleting either MICAL-L1 or EHD1. |
| GO:0006897 endocytosis | IMP PMID:20801876 Collapsin response mediator protein-2 (Crmp2) regulates traf... | KEEP AS NON CORE | Summary: Endocytosis (IMP). Reason: EHD1 acts mainly after internalization, in sorting and recycling of endocytosed cargo (depletion relocalizes internalized transferrin to the recycling compartment). Endocytic trafficking in the broad sense is appropriate but the specific core process is endocytic recycling. Supporting Evidence: PMID:20801876 Upon Crmp2 depletion, we observed dramatic relocalization of internalized transferrin (Tf) from peripheral vesicles to the endocytic recycling compartment (ERC), similar to the effect of depleting either MICAL-L1 or EHD1. |
| GO:0010008 endosome membrane | IEA GO_REF:0000107 | ACCEPT | Summary: endosome membrane (IEA). Reason: EHD1 associates with endosomal membranes, including early/sorting endosome compartments where it partially colocalizes with rabenosyn-5, as well as tubular recycling endosomes. Supporting Evidence: PMID:15020713 EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo |
| GO:0010008 endosome membrane | ISS GO_REF:0000024 | ACCEPT | Summary: endosome membrane (ISS). Reason: EHD1 associates with endosomal membranes, including early/sorting endosome compartments where it partially colocalizes with rabenosyn-5, as well as tubular recycling endosomes. Supporting Evidence: PMID:15020713 EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-1011576 | ACCEPT | Summary: endosome membrane (TAS). Reason: EHD1 associates with endosomal membranes, including early/sorting endosome compartments where it partially colocalizes with rabenosyn-5, as well as tubular recycling endosomes. Supporting Evidence: PMID:15020713 EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo |
| GO:0010886 positive regulation of cholesterol storage | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: positive regulation of cholesterol storage (IEA), transferred from rodent Ehd1 studies. Reason: Rodent Ehd1 has been linked to cholesterol uptake/storage and lipid droplets, plausibly secondary to its role in endocytic recycling of lipoprotein receptors; retained as a non-core, cell-type-specific role. |
| GO:0010886 positive regulation of cholesterol storage | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of cholesterol storage (ISS), transferred from rodent Ehd1 studies. Reason: Rodent Ehd1 has been linked to cholesterol uptake/storage and lipid droplets, plausibly secondary to its role in endocytic recycling of lipoprotein receptors; retained as a non-core, cell-type-specific role. |
| GO:0010976 positive regulation of neuron projection development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: positive regulation of neuron projection development (IEA), transferred from rodent neuronal studies. Reason: Ehd1 participates in neurotrophin receptor and synaptic membrane recycling in rodent neurons; consistent with its general recycling function but tissue-specific and non-core. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | ACCEPT | Summary: membrane (HDA). Reason: Consistent with EHD1 association with endocytic carriers and the perinuclear endocytic recycling compartment. Supporting Evidence: PMID:15020713 depletion of EHD1 caused the accumulation of internalized cargo in a compact juxtanuclear compartment |
| GO:0020018 ciliary pocket membrane | IDA PMID:25686250 Early steps in primary cilium assembly require EHD1/EHD3-dep... | ACCEPT | Summary: Ciliary pocket membrane (IDA) for EHD1. Reason: EHD1 and EHD3 localize to preciliary membranes and to the ciliary pocket membrane. Supporting Evidence: PMID:25686250 EHD1 and EHD3 localize to preciliary membranes and the ciliary pocket. |
| GO:0030139 endocytic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: endocytic vesicle (IBA). Reason: Consistent with EHD1 association with endocytic carriers and the perinuclear endocytic recycling compartment. Supporting Evidence: PMID:15020713 depletion of EHD1 caused the accumulation of internalized cargo in a compact juxtanuclear compartment |
| GO:0030139 endocytic vesicle | IEA GO_REF:0000107 | ACCEPT | Summary: endocytic vesicle (IEA). Reason: Consistent with EHD1 association with endocytic carriers and the perinuclear endocytic recycling compartment. Supporting Evidence: PMID:15020713 depletion of EHD1 caused the accumulation of internalized cargo in a compact juxtanuclear compartment |
| GO:0030674 protein-macromolecule adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein-macromolecule adaptor activity (IBA) for EHD1. Reason: The C-terminal EH domain of EHD proteins binds NPF-motif proteins (MICAL-L1, rabenosyn-5, syndapins, Rab11-FIP2), linking these partners to EHD oligomers on recycling membranes. The phylogenetic inference is consistent with this conserved EH-domain function. Supporting Evidence: PMID:27189942 EHD proteins have an EH domain that interacts with proteins containing an NPF motif. |
| GO:0031095 platelet dense tubular network membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: platelet dense tubular network membrane (IEA). Reason: Platelet-specific membrane compartment transferred from rodent data; tissue-specific location not central to EHD1 function. |
| GO:0031095 platelet dense tubular network membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: platelet dense tubular network membrane (ISS). Reason: Platelet-specific membrane compartment transferred from rodent data; tissue-specific location not central to EHD1 function. |
| GO:0031175 neuron projection development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: neuron projection development (IEA), transferred from rodent neuronal studies. Reason: Ehd1 participates in neurotrophin receptor and synaptic membrane recycling in rodent neurons; consistent with its general recycling function but tissue-specific and non-core. |
| GO:0031175 neuron projection development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: neuron projection development (ISS), transferred from rodent neuronal studies. Reason: Ehd1 participates in neurotrophin receptor and synaptic membrane recycling in rodent neurons; consistent with its general recycling function but tissue-specific and non-core. |
| GO:0031267 small GTPase binding | IPI PMID:19864458 MICAL-L1 links EHD1 to tubular recycling endosomes and regul... | MARK AS OVER ANNOTATED | Summary: Small GTPase binding (IPI) with RAB8A, from the MICAL-L1 study. Reason: The study shows that MICAL-L1 links EHD1 and RAB8A on tubular endosomes, and MICAL-L1 depletion abolishes the EHD1-RAB8A interaction, indicating that the association is bridged by MICAL-L1 rather than a direct EHD1-GTPase binding activity. Supporting Evidence: PMID:19864458 endogenous MICAL-L1 can link both EHD1 and Rab8a to these structures, as its depletion leads to loss of the EHD1-Rab8a interaction |
| GO:0031901 early endosome membrane | IDA PMID:15020713 Rabenosyn-5 and EHD1 interact and sequentially regulate prot... | ACCEPT | Summary: early endosome membrane (IDA). Reason: EHD1 associates with endosomal membranes, including early/sorting endosome compartments where it partially colocalizes with rabenosyn-5, as well as tubular recycling endosomes. Supporting Evidence: PMID:15020713 EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo |
| GO:0031901 early endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: early endosome membrane (IEA). Reason: EHD1 associates with endosomal membranes, including early/sorting endosome compartments where it partially colocalizes with rabenosyn-5, as well as tubular recycling endosomes. Supporting Evidence: PMID:15020713 EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo |
| GO:0032456 endocytic recycling | IBA GO_REF:0000033 | ACCEPT | Summary: Endocytic recycling (IBA) for EHD1. Reason: Core non-ciliary function of EHD1/EHD3: membrane remodeling on tubular recycling endosomes controlling exit of receptors (e.g. transferrin receptor, MHC class I) from the endocytic recycling compartment. Supporting Evidence: PMID:17233914 loss of EHD1 and 3 (and to a lesser extent EHD4) but not EHD2 function retarded transferrin exit from the endocytic recycling compartment |
| GO:0032456 endocytic recycling | IEA GO_REF:0000117 | ACCEPT | Summary: Endocytic recycling (IEA) for EHD1. Reason: Core non-ciliary function of EHD1/EHD3: membrane remodeling on tubular recycling endosomes controlling exit of receptors (e.g. transferrin receptor, MHC class I) from the endocytic recycling compartment. Supporting Evidence: PMID:17233914 loss of EHD1 and 3 (and to a lesser extent EHD4) but not EHD2 function retarded transferrin exit from the endocytic recycling compartment |
| GO:0032456 endocytic recycling | IGI PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by... | ACCEPT | Summary: Endocytic recycling (IGI) for EHD1. Reason: Core non-ciliary function of EHD1/EHD3: membrane remodeling on tubular recycling endosomes controlling exit of receptors (e.g. transferrin receptor, MHC class I) from the endocytic recycling compartment. Supporting Evidence: PMID:17233914 loss of EHD1 and 3 (and to a lesser extent EHD4) but not EHD2 function retarded transferrin exit from the endocytic recycling compartment |
| GO:0032456 endocytic recycling | IMP PMID:15020713 Rabenosyn-5 and EHD1 interact and sequentially regulate prot... | ACCEPT | Summary: Endocytic recycling (IMP). Reason: EHD1 depletion delays recycling of transferrin and MHC class I to the plasma membrane. Supporting Evidence: PMID:15020713 Depletion of either EHD1 or Rabenosyn-5 delayed the recycling of transferrin and major histocompatibility complex class I to the plasma membrane. |
| GO:0034383 low-density lipoprotein particle clearance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: low-density lipoprotein particle clearance (IEA), transferred from rodent Ehd1 studies. Reason: Rodent Ehd1 has been linked to cholesterol uptake/storage and lipid droplets, plausibly secondary to its role in endocytic recycling of lipoprotein receptors; retained as a non-core, cell-type-specific role. |
| GO:0034383 low-density lipoprotein particle clearance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: low-density lipoprotein particle clearance (ISS), transferred from rodent Ehd1 studies. Reason: Rodent Ehd1 has been linked to cholesterol uptake/storage and lipid droplets, plausibly secondary to its role in endocytic recycling of lipoprotein receptors; retained as a non-core, cell-type-specific role. |
| GO:0035869 ciliary transition zone | IDA GO_REF:0000052 | ACCEPT | Summary: ciliary transition zone localization from the Human Protein Atlas cilium atlas immunofluorescence (IDA, GO_REF:0000052). Reason: HPA reports EHD1 at the primary cilium and primary cilium transition zone (Supported) with a main plasma membrane location; this agrees with the proximal-cilium/ciliary-pocket localization of EHD1/EHD3 shown by CLEM and SIM. Supporting Evidence: PMID:25686250 Interestingly, only GFP-EHD1 and GFP-EHD3 were detected at the proximal ciliary region |
| GO:0042632 cholesterol homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cholesterol homeostasis (IEA), transferred from rodent Ehd1 studies. Reason: Rodent Ehd1 has been linked to cholesterol uptake/storage and lipid droplets, plausibly secondary to its role in endocytic recycling of lipoprotein receptors; retained as a non-core, cell-type-specific role. |
| GO:0042632 cholesterol homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cholesterol homeostasis (ISS), transferred from rodent Ehd1 studies. Reason: Rodent Ehd1 has been linked to cholesterol uptake/storage and lipid droplets, plausibly secondary to its role in endocytic recycling of lipoprotein receptors; retained as a non-core, cell-type-specific role. |
| GO:0042802 identical protein binding | IPI PMID:12121420 EHD3: a protein that resides in recycling tubular and vesicu... | ACCEPT | Summary: Identical protein binding (IPI). Reason: EHD1 forms homodimers and higher-order oligomers, which are required for its membrane association and remodeling activity; self-association is a defining property. Supporting Evidence: PMID:17233914 In our analyses, we found that each EHD protein homo- and hetero-oligomerized |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | ACCEPT | Summary: Identical protein binding (IPI). Reason: EHD1 forms homodimers and higher-order oligomers, which are required for its membrane association and remodeling activity; self-association is a defining property. Supporting Evidence: PMID:17233914 In our analyses, we found that each EHD protein homo- and hetero-oligomerized |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: Cadherin binding (HDA) from an E-cadherin interactome screen. Reason: High-throughput proximity/affinity proteomics does not establish direct cadherin binding as a function of EHD1. |
| GO:0048471 perinuclear region of cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: perinuclear region of cytoplasm (IBA). Reason: Consistent with EHD1 association with endocytic carriers and the perinuclear endocytic recycling compartment. Supporting Evidence: PMID:15020713 depletion of EHD1 caused the accumulation of internalized cargo in a compact juxtanuclear compartment |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: perinuclear region of cytoplasm (IEA). Reason: Consistent with EHD1 association with endocytic carriers and the perinuclear endocytic recycling compartment. Supporting Evidence: PMID:15020713 depletion of EHD1 caused the accumulation of internalized cargo in a compact juxtanuclear compartment |
| GO:0048786 presynaptic active zone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: presynaptic active zone (IEA), transferred from rodent neuronal studies. Reason: Ehd1 participates in neurotrophin receptor and synaptic membrane recycling in rodent neurons; consistent with its general recycling function but tissue-specific and non-core. |
| GO:0051260 protein homooligomerization | IPI PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by... | ACCEPT | Summary: Protein homooligomerization (IPI) for EHD1. Reason: EHD proteins form ATP-dependent dimers that oligomerize into ring-like assemblies on membranes; homo- and hetero-oligomerization among EHD paralogs was shown directly. Supporting Evidence: PMID:17233914 In our analyses, we found that each EHD protein homo- and hetero-oligomerized, however, hetero-oligomerization between EHD proteins was variable. |
| GO:0055038 recycling endosome membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Recycling endosome membrane (IBA) for EHD1. Reason: EHD1/EHD3 associate with tubular recycling endosome membranes and colocalize with RAB11. Supporting Evidence: PMID:17233914 variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker |
| GO:0055038 recycling endosome membrane | IDA PMID:15020713 Rabenosyn-5 and EHD1 interact and sequentially regulate prot... | ACCEPT | Summary: Recycling endosome membrane (IDA) for EHD1. Reason: EHD1/EHD3 associate with tubular recycling endosome membranes and colocalize with RAB11. Supporting Evidence: PMID:17233914 variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker |
| GO:0055038 recycling endosome membrane | IDA PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by... | ACCEPT | Summary: Recycling endosome membrane (IDA) for EHD1. Reason: EHD1/EHD3 associate with tubular recycling endosome membranes and colocalize with RAB11. Supporting Evidence: PMID:17233914 variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker |
| GO:0055038 recycling endosome membrane | IDA PMID:19864458 MICAL-L1 links EHD1 to tubular recycling endosomes and regul... | ACCEPT | Summary: Recycling endosome membrane (IDA) for EHD1. Reason: EHD1/EHD3 associate with tubular recycling endosome membranes and colocalize with RAB11. Supporting Evidence: PMID:17233914 variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker |
| GO:0055038 recycling endosome membrane | IDA PMID:23596323 Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in... | ACCEPT | Summary: Recycling endosome membrane (IDA) for EHD1. Reason: EHD1/EHD3 associate with tubular recycling endosome membranes and colocalize with RAB11. Supporting Evidence: PMID:17233914 variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker |
| GO:0055038 recycling endosome membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Recycling endosome membrane (IEA) for EHD1. Reason: EHD1/EHD3 associate with tubular recycling endosome membranes and colocalize with RAB11. Supporting Evidence: PMID:17233914 variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker |
| GO:0060170 ciliary membrane | IEA GO_REF:0000044 | MODIFY | Summary: Ciliary membrane (IEA, UniProt subcellular location mapping) for EHD1. Reason: Super-resolution and immuno-EM show EHD1 and EHD3 primarily at the ciliary pocket membrane rather than the ciliary membrane proper (unlike RAB8 and Smoothened); the more accurate term is ciliary pocket membrane. Proposed replacements: ciliary pocket membrane Supporting Evidence: PMID:25686250 demonstrated that EHD1 and EHD3 are primarily localized to the ciliary pocket membrane unlike Rab8 and Smoothened (Smo), largely present in the ciliary membrane |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Cilium assembly (IBA) for EHD1. Reason: EHD1 and EHD3 are required for early primary ciliogenesis: they tubulate distal appendage vesicles and, with SNAP29, drive their fusion into the ciliary vesicle, which is required for CP110 removal and recruitment of transition zone proteins and IFT20. Supporting Evidence: PMID:25686250 Here, we show that the membrane shaping proteins EHD1 and EHD3, in association with the Rab11-Rab8 cascade, function in early ciliogenesis. PMID:25686250 EHD-dependent membrane tubulation is essential for ciliary vesicle formation from smaller distal appendage vesicles (DAVs). |
| GO:0060271 cilium assembly | IDA PMID:31615969 MICAL-L1 coordinates ciliogenesis by recruiting EHD1 to the ... | ACCEPT | Summary: Cilium assembly (IDA) from the MICAL-L1 study. Reason: EHD1 facilitates ciliary vesicle fusion and CP110 removal; MICAL-L1 recruits EHD1 to the basal body to promote ciliogenesis. Supporting Evidence: PMID:31615969 The endocytic protein EHD1 plays an important role in ciliogenesis by facilitating fusion of the ciliary vesicle and removal of CP110 |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Cilium assembly (IEA) for EHD1. Reason: EHD1 and EHD3 are required for early primary ciliogenesis: they tubulate distal appendage vesicles and, with SNAP29, drive their fusion into the ciliary vesicle, which is required for CP110 removal and recruitment of transition zone proteins and IFT20. Supporting Evidence: PMID:25686250 Here, we show that the membrane shaping proteins EHD1 and EHD3, in association with the Rab11-Rab8 cascade, function in early ciliogenesis. PMID:25686250 EHD-dependent membrane tubulation is essential for ciliary vesicle formation from smaller distal appendage vesicles (DAVs). |
| GO:0060271 cilium assembly | IMP PMID:25686250 Early steps in primary cilium assembly require EHD1/EHD3-dep... | ACCEPT | Summary: Cilium assembly (IMP) for EHD1. Reason: EHD1 and EHD3 are required for early primary ciliogenesis: they tubulate distal appendage vesicles and, with SNAP29, drive their fusion into the ciliary vesicle, which is required for CP110 removal and recruitment of transition zone proteins and IFT20. Supporting Evidence: PMID:25686250 Here, we show that the membrane shaping proteins EHD1 and EHD3, in association with the Rab11-Rab8 cascade, function in early ciliogenesis. PMID:25686250 EHD-dependent membrane tubulation is essential for ciliary vesicle formation from smaller distal appendage vesicles (DAVs). |
| GO:0061512 protein localization to cilium | IMP PMID:25686250 Early steps in primary cilium assembly require EHD1/EHD3-dep... | KEEP AS NON CORE | Summary: Protein localization to cilium (IMP). Reason: EHD1 depletion blocks ciliary vesicle formation and thereby the subsequent recruitment of transition zone proteins and IFT20; the localization defects are a downstream consequence of failed ciliary vesicle assembly rather than EHD1 directly targeting proteins to the cilium. Supporting Evidence: PMID:25686250 Importantly, this step functions in M-centriole to basal body transformation and recruitment of transition zone proteins and IFT20. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: Extracellular exosome (HDA) for EHD1. Reason: Detection in exosome/extracellular vesicle proteomes reflects incidental inclusion of an abundant membrane-associated cytoplasmic protein; there is no evidence that it functions in exosomes. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | MARK AS OVER ANNOTATED | Summary: Extracellular exosome (HDA) for EHD1. Reason: Detection in exosome/extracellular vesicle proteomes reflects incidental inclusion of an abundant membrane-associated cytoplasmic protein; there is no evidence that it functions in exosomes. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | MARK AS OVER ANNOTATED | Summary: Extracellular exosome (HDA) for EHD1. Reason: Detection in exosome/extracellular vesicle proteomes reflects incidental inclusion of an abundant membrane-associated cytoplasmic protein; there is no evidence that it functions in exosomes. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: Extracellular exosome (HDA) for EHD1. Reason: Detection in exosome/extracellular vesicle proteomes reflects incidental inclusion of an abundant membrane-associated cytoplasmic protein; there is no evidence that it functions in exosomes. |
| GO:0072659 protein localization to plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Protein localization to plasma membrane (IBA). Reason: EHD1-mediated recycling returns internalized membrane proteins to the cell surface. Supporting Evidence: PMID:15020713 Depletion of either EHD1 or Rabenosyn-5 delayed the recycling of transferrin and major histocompatibility complex class I to the plasma membrane. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: glutamatergic synapse (IEA), transferred from rodent neuronal studies. Reason: Ehd1 participates in neurotrophin receptor and synaptic membrane recycling in rodent neurons; consistent with its general recycling function but tissue-specific and non-core. |
| GO:1901741 positive regulation of myoblast fusion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: positive regulation of myoblast fusion (IEA), transferred from rodent myoblast studies. Reason: Ehd1-dependent membrane trafficking contributes to myoblast fusion in rodent models; tissue-specific, non-core. |
| GO:1901741 positive regulation of myoblast fusion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: positive regulation of myoblast fusion (ISS), transferred from rodent myoblast studies. Reason: Ehd1-dependent membrane trafficking contributes to myoblast fusion in rodent models; tissue-specific, non-core. |
| GO:1990090 cellular response to nerve growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to nerve growth factor stimulus (IEA), transferred from rodent neuronal studies. Reason: Ehd1 participates in neurotrophin receptor and synaptic membrane recycling in rodent neurons; consistent with its general recycling function but tissue-specific and non-core. |
| GO:1990090 cellular response to nerve growth factor stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cellular response to nerve growth factor stimulus (ISS), transferred from rodent neuronal studies. Reason: Ehd1 participates in neurotrophin receptor and synaptic membrane recycling in rodent neurons; consistent with its general recycling function but tissue-specific and non-core. |
| GO:2001137 positive regulation of endocytic recycling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of endocytic recycling (IEA). Reason: EHD1 participates directly in endocytic recycling (annotated separately); the regulatory framing is redundant but not incorrect. |
| GO:2001137 positive regulation of endocytic recycling | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of endocytic recycling (ISS). Reason: EHD1 participates directly in endocytic recycling (annotated separately); the regulatory framing is redundant but not incorrect. |
| GO:1905556 ciliary vesicle assembly | IMP PMID:25686250 Early steps in primary cilium assembly require EHD1/EHD3-dep... | NEW | Summary: Proposed: EHD1 drives assembly of the ciliary vesicle from distal appendage vesicles at the mother centriole. Reason: EHD1 does the work of this step: its membrane-tubulating activity reorganizes the small distal appendage vesicles, and with the SNARE regulator SNAP29 it promotes their fusion into the ciliary vesicle. This is more specific than the existing cilium assembly annotation and matches the GO definition (smaller vesicles dock at the transitional fibres and fuse to form the ciliary vesicle). No gene product currently carries this term, so there is no conflicting convention. Supporting Evidence: PMID:25686250 EHD-dependent membrane tubulation is essential for ciliary vesicle formation from smaller distal appendage vesicles (DAVs). PMID:25686250 Based on our findings for EHD1 and EHD3 functioning in CV assembly from DAVs, we predicted that the SNARE membrane fusion machinery would play a critical role in early ciliogenesis. PMID:25686250 Together, these results indicate that the EHD1 K483 membrane tubulation function is critical for DAV assembly into the CV and M-centriole reorganization |
| GO:0016887 ATP hydrolysis activity | ISS PMID:15710626 ATP binding regulates oligomerization and endosome associati... | NEW | Summary: Proposed: EHD1 is an ATPase (RME-1/EHD family proteins bind and hydrolyze ATP). Reason: Mouse RME-1/EHD1 (and C. elegans RME-1) bind and hydrolyze ATP, not GTP, and ATP binding is required for oligomerization and endosome association. Human EHD1 is highly conserved with mouse Ehd1, so ATP hydrolysis activity is the appropriate catalytic activity term and replaces the incorrect GTP-binding inference. Supporting Evidence: PMID:15710626 we show that both Caenorhabditis elegans and mouse RME-1 proteins bind and hydrolyze ATP. No significant GTP binding or hydrolysis was detected. file:human/EHD1/EHD1-deep-research-falcon.md ATP binding recruits EHD1, while hydrolysis promotes scaffold assembly, membrane bulging, local thinning, and fission. |
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Download this section (compressed HTML)Q: Is ATP hydrolysis by EHD1 required for distal appendage vesicle tubulation/fusion in ciliogenesis, as it is for oligomerization on recycling endosomes?
Q: Should EHD1 receive a membrane tubulation/fission-related molecular function term once GO provides one suited to dynamin-like ATPases, rather than only ATP hydrolysis activity?
Experiment: Rescue EHD1-knockout RPE1 cells with ATP-binding (P-loop) and ATP-hydrolysis mutants and quantify ciliary vesicle formation by EM, CP110 removal and ciliation.
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