EHD3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001881 receptor recycling	IMP PMID:21791287 Endocytosis promotes rapid dopaminergic signaling.	ACCEPT	Summary: Receptor recycling (IMP) from a study of D1 dopamine receptor endocytosis and signaling. Reason: The cached abstract does not name EHD3, but recycling inhibition was assayed and EHD3 is an established regulator of endocytic recycling; deferring to the curator who read the full text. Supporting Evidence: PMID:21791287 Although endocytic inhibition markedly attenuated acute cAMP accumulation, inhibiting the subsequent recycling of receptors had no effect.
GO:0003676 nucleic acid binding	TAS PMID:10673336 EHD2, EHD3, and EHD4 encode novel members of a highly conser...	REMOVE	Summary: Nucleic acid binding (TAS) from the EHD2-4 cloning paper. Reason: The cloning paper describes only predicted sequence features (a nucleotide-binding consensus site and a predicted bipartite nuclear localization signal); it contains no evidence of nucleic acid binding, and EHD proteins are ATP-binding membrane-remodeling ATPases. Supporting Evidence: PMID:10673336 multiple conserved regions that include a nucleotide-binding consensus site at the N-terminus, a bipartite nuclear localization signal
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.
GO:0005515 protein binding	IPI PMID:15020713 Rabenosyn-5 and EHD1 interact and sequentially regulate prot...	REMOVE	Summary: Generic protein binding (IPI) for EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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:20489164 EH domain proteins regulate cardiac membrane protein targeti...	REMOVE	Summary: Generic protein binding (IPI) for EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. Partners include EHD1 and other EHDs, rabenosyn-5, MICAL-L1, ankyrin-B and interactome hits; functional content is captured by the adaptor, oligomerization, recycling and cardiac targeting 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 EHD3. 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:0005634 nucleus	TAS PMID:10673336 EHD2, EHD3, and EHD4 encode novel members of a highly conser...	REMOVE	Summary: Nucleus (TAS) from the EHD2-4 cloning paper. Reason: Based only on a predicted bipartite nuclear localization signal; experimental studies place EHD3 on endocytic recycling membranes, the plasma membrane and the ciliary pocket, not in the nucleus. Supporting Evidence: PMID:10673336 a bipartite nuclear localization signal PMID:12121420 implying that EHD3 resides within the endocytic recycling compartment
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: cytoplasm (IBA). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0005737 cytoplasm	IEA GO_REF:0000107	ACCEPT	Summary: cytoplasm (IEA). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0005737 cytoplasm	ISS GO_REF:0000024	ACCEPT	Summary: cytoplasm (ISS). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0005769 early endosome	IBA GO_REF:0000033	ACCEPT	Summary: early endosome (IBA). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0005829 cytosol	IEA GO_REF:0000108	ACCEPT	Summary: cytosol (IEA). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0005886 plasma membrane	EXP PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by...	ACCEPT	Summary: Plasma membrane (EXP). Reason: EHD3 associates with the plasma membrane and recycling carriers; HPA main location is plasma membrane.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Plasma membrane (IBA). Reason: EHD3 associates with the plasma membrane and recycling carriers; 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 EHD3 is plasma membrane, consistent with recycling-carrier and ciliary pocket association.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: Plasma membrane (IEA). Reason: EHD3 associates with the plasma membrane and recycling carriers; HPA main location is plasma membrane.
GO:0005925 focal adhesion	HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome...	MARK AS OVER ANNOTATED	Summary: Focal adhesion (HDA) from a focal adhesion proteome. Reason: Detection in a biochemically isolated focal adhesion fraction is not evidence of a function of EHD3 at focal adhesions.
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 EHD3 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:0006897 endocytosis	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Endocytosis (IBA). Reason: EHD3 functions in post-internalization endosomal sorting and recycling rather than the internalization step; retained as broad, non-core.
GO:0010008 endosome membrane	TAS Reactome:R-HSA-1011576	ACCEPT	Summary: endosome membrane (TAS). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
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 EHD3. 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: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0030139 endocytic vesicle	IEA GO_REF:0000107	ACCEPT	Summary: endocytic vesicle (IEA). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0030674 protein-macromolecule adaptor activity	IBA GO_REF:0000033	ACCEPT	Summary: Protein-macromolecule adaptor activity (IBA) for EHD3. 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:0032456 endocytic recycling	IBA GO_REF:0000033	ACCEPT	Summary: Endocytic recycling (IBA) for EHD3. 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	IDA PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by...	ACCEPT	Summary: Endocytic recycling (IDA) for EHD3. 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 EHD3. 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:0034498 early endosome to Golgi transport	IMP PMID:19139087 EHD3 regulates early-endosome-to-Golgi transport and preserv...	ACCEPT	Summary: Early endosome to Golgi transport (IMP). Reason: EHD3 knockdown disrupts SNX1 distribution and transport of internalized Shiga toxin B subunit and M6PR from endosomes to the Golgi. Supporting Evidence: PMID:19139087 Our findings support a role for EHD3 in regulating endosome-to-Golgi transport file:human/EHD3/EHD3-deep-research-falcon.md accumulated sorting nexin-1 on enlarged early endosomes, impaired Shiga-toxin B delivery to the Golgi, and mislocalized the mannose-6-phosphate receptor
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 EHD3 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:0048471 perinuclear region of cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: perinuclear region of cytoplasm (IBA). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000107	ACCEPT	Summary: perinuclear region of cytoplasm (IEA). Reason: EHD3 localizes to endocytic vesicles and microtubule-dependent tubules of the perinuclear endocytic recycling compartment, and cycles between cytosol and membranes. Supporting Evidence: PMID:12121420 EHD3, expressed as a green fluorescent fusion protein was localized to endocytic vesicles and to microtubule-dependent, membrane tubules.
GO:0051260 protein homooligomerization	IPI PMID:17233914 Shared as well as distinct roles of EHD proteins revealed by...	ACCEPT	Summary: Protein homooligomerization (IPI) for EHD3. 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 EHD3. 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 EHD3. 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 EHD3. 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:0055117 regulation of cardiac muscle contraction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of cardiac muscle contraction (IEA). Reason: Ehd3 loss in mouse cardiomyocytes impairs targeting of ankyrin-associated ion transporters (NCX1, Cav1.2), affecting membrane excitability and conduction; physiologically important but a tissue-specific consequence of its membrane-targeting role. Supporting Evidence: PMID:20489164 these proteins may play a key role in regulating membrane excitability in normal and diseased heart
GO:0060170 ciliary membrane	IEA GO_REF:0000044	MODIFY	Summary: Ciliary membrane (IEA, UniProt subcellular location mapping) for EHD3. 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 EHD3. 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	IEA GO_REF:0000107	ACCEPT	Summary: Cilium assembly (IEA) for EHD3. 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). Reason: siRNA-resistant EHD3 rescues ciliation in EHD-depleted cells, and zebrafish ehd3 morphants show tissue-specific ciliogenesis defects; EHD3 acts partly redundantly with EHD1 (in RPE cells EHD1 is much more abundant and EHD3 appears dispensable). Supporting Evidence: PMID:25686250 Importantly, an siRNA resistant form of GFP-EHD1 or GFP-EHD3 but not GFP, GFP-EHD2 or GFP-EHD4 rescued ciliation PMID:25686250 Together these results indicate that Ehd1 and Ehd3 have overlapping, albeit tissue specific, functions in ciliogenesis in zebrafish embryos.
GO:0072659 protein localization to plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Protein localization to plasma membrane (IBA). Reason: EHD-mediated recycling and targeting return membrane proteins to the cell surface; consistent with EHD3 cardiac targeting data.
GO:0072659 protein localization to plasma membrane	IGI PMID:20489164 EH domain proteins regulate cardiac membrane protein targeti...	ACCEPT	Summary: Protein localization to plasma membrane (IGI) in cardiomyocytes. Reason: EHD proteins bind ankyrin-B and are required for membrane targeting of cardiac ion transport proteins such as NCX1. Supporting Evidence: PMID:20489164 We show that EHD1-4 directly associate with ankyrin
GO:0086036 regulation of cardiac muscle cell membrane potential	IGI PMID:20489164 EH domain proteins regulate cardiac membrane protein targeti...	KEEP AS NON CORE	Summary: regulation of cardiac muscle cell membrane potential (IGI). Reason: Ehd3 loss in mouse cardiomyocytes impairs targeting of ankyrin-associated ion transporters (NCX1, Cav1.2), affecting membrane excitability and conduction; physiologically important but a tissue-specific consequence of its membrane-targeting role. Supporting Evidence: PMID:20489164 these proteins may play a key role in regulating membrane excitability in normal and diseased heart
GO:0090160 Golgi to lysosome transport	IMP PMID:19139087 EHD3 regulates early-endosome-to-Golgi transport and preserv...	KEEP AS NON CORE	Summary: Golgi to lysosome transport (IMP). Reason: Cathepsin D trapping at the Golgi and Golgi fragmentation after EHD3 depletion are attributed by the authors to impaired endosome-to-Golgi retrieval of M6PR and reduced AP-1 recruitment, i.e. indirect consequences of the primary endosome-to-Golgi transport defect. Supporting Evidence: PMID:19139087 These data also suggest that impaired endosome-to-Golgi transport and the resulting lack of recruitment of AP-1 gamma-adaptin to Golgi membranes affect Golgi morphology.
GO:1903358 regulation of Golgi organization	IMP PMID:19139087 EHD3 regulates early-endosome-to-Golgi transport and preserv...	KEEP AS NON CORE	Summary: regulation of Golgi organization (IMP). Reason: Cathepsin D trapping at the Golgi and Golgi fragmentation after EHD3 depletion are attributed by the authors to impaired endosome-to-Golgi retrieval of M6PR and reduced AP-1 recruitment, i.e. indirect consequences of the primary endosome-to-Golgi transport defect. Supporting Evidence: PMID:19139087 These data also suggest that impaired endosome-to-Golgi transport and the resulting lack of recruitment of AP-1 gamma-adaptin to Golgi membranes affect Golgi morphology.
GO:1903779 regulation of cardiac conduction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of cardiac conduction (IEA). Reason: Ehd3 loss in mouse cardiomyocytes impairs targeting of ankyrin-associated ion transporters (NCX1, Cav1.2), affecting membrane excitability and conduction; physiologically important but a tissue-specific consequence of its membrane-targeting role. Supporting Evidence: PMID:20489164 these proteins may play a key role in regulating membrane excitability in normal and diseased heart
GO:1905556 ciliary vesicle assembly	IMP PMID:25686250 Early steps in primary cilium assembly require EHD1/EHD3-dep...	NEW	Summary: Proposed: EHD3 drives assembly of the ciliary vesicle from distal appendage vesicles at the mother centriole. Reason: EHD3 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 Given these findings and the requirement for EHD1 and EHD3 tubulation function in CV assembly, we theorized that EHD proteins recruit SNAP29 to DAVs where the SNARE functions in fusion of tubulated DAVs.

Gene Description

Existing Annotations Review

Core Functions

Membrane-associated EHD ATPase (hetero-oligomerizing with EHD1) on tubular recycling endosomes that stabilizes recycling tubules and supports early endosome-to-recycling compartment and endosome-to-Golgi transport (non-ciliary core role).

Ciliary role, partly redundant with EHD1: membrane tubulation of distal appendage vesicles for ciliary vesicle assembly at the onset of primary ciliogenesis; localizes to the ciliary pocket membrane.

Cardiac membrane protein targeting: binds ankyrin-B and supports targeting of NCX1/Cav1.2 to the cardiomyocyte membrane, influencing excitability and conduction (tissue-specific).

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