ATL3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0007029 endoplasmic reticulum organization	IBA GO_REF:0000033	ACCEPT	Summary: ATL3 is a conserved atlastin-family ER-shaping GTPase whose experimentally supported role is maintaining tubular ER network organization. Reason: The IBA term is broad but consistent with the direct ATL3 literature showing ER network maintenance and with the more specific reviewed ER tubular network membrane organization annotations. Supporting Evidence: PMID:27619977 ATL is needed to not only form, but also maintain, the ER network.
GO:0051260 protein homooligomerization	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ATL3 forms transient atlastin dimers as part of the GTPase-dependent membrane fusion cycle. Reason: Homooligomerization is an important mechanistic step in ATL3 fusion catalysis, but the core biological role is ER membrane fusion and ER network maintenance rather than oligomerization as an independent outcome. Supporting Evidence: PMID:28602821 from nucleotide binding and hydrolysis to ATL dimerization and phosphate release.
GO:0005525 GTP binding	IBA GO_REF:0000033	ACCEPT	Summary: ATL3 contains the conserved atlastin GTPase domain and binds nucleotide during its catalytic cycle. Reason: GTP binding is an intrinsic molecular function required for ATL3 GTPase activity and fusogenic activity. Supporting Evidence: PMID:28602821 from nucleotide binding and hydrolysis to ATL dimerization and phosphate release.
GO:0003924 GTPase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated GTPase annotation is supported by experimental ATL3 kinetic and structural studies. Reason: ATL3 hydrolyzes GTP as part of the atlastin catalytic cycle that drives ER membrane fusion. Supporting Evidence: PMID:28602821 A crystal structure of ATL3 suggests a mechanism for the displacement of the catalytic Mg2+ ion following guanosine triphosphate (GTP) hydrolysis.
GO:0005525 GTP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-derived GTP binding is consistent with the ATL3 GB1/RHD3-type GTPase domain and experimental catalytic-cycle data. Reason: ATL3 nucleotide binding is directly coupled to GTP hydrolysis, dimerization, and fusion. Supporting Evidence: PMID:28602821 from nucleotide binding and hydrolysis to ATL dimerization and phosphate release.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping to ER membrane is consistent with multiple experimental localization studies. Reason: ATL3 is a multi-pass ER membrane protein localized to ER tubules and junctions. Supporting Evidence: PMID:18270207 atlastin-2 and -3 are localized to the endoplasmic reticulum (ER)
GO:0016320 endoplasmic reticulum membrane fusion	IEA GO_REF:0000117	ACCEPT	Summary: ARBA propagation to ER membrane fusion is strongly supported by direct ATL3 fusion experiments. Reason: Purified human ATL3 catalyzes GTP-dependent lipid bilayer fusion in vitro and rescues ER network morphology in ATL knockout cells. Supporting Evidence: PMID:37102997 purified human ATL3 catalyzes efficient membrane fusion in vitro and is sufficient to sustain the ER network in triple knockout cells.
GO:0098826 endoplasmic reticulum tubular network membrane	IEA GO_REF:0000117	ACCEPT	Summary: Automated localization to the ER tubular network membrane matches ATL3 localization at ER tubules and three-way junctions. Reason: ATL3 is an ER membrane atlastin whose fusion function is active on ER tubules and junctions. Supporting Evidence: PMID:24459106 ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network.
GO:0140523 GTPase-dependent fusogenic activity	IEA GO_REF:0000117	ACCEPT	Summary: Automated fusogenic-activity annotation is directly supported by purified ATL3 fusion assays. Reason: The most specific molecular function for ATL3 is GTPase-dependent fusogenic activity, integrating GTPase activity with membrane fusion. Supporting Evidence: PMID:37102997 ATL3 incorporated at a 1:1,000 M protein/lipid ratio catalyzed robust lipid mixing.
GO:1990809 endoplasmic reticulum tubular network membrane organization	IEA GO_REF:0000117	ACCEPT	Summary: Automated ER tubular network membrane organization annotation is supported by ATL3 rescue and ER morphology studies. Reason: ATL3-mediated ER membrane fusion maintains the branched tubular ER network. Supporting Evidence: PMID:37102997 ATL3 can restore and maintain a normal ER network.
GO:0005515 protein binding	IPI PMID:23969831 Protrudin binds atlastins and endoplasmic reticulum-shaping ...	MARK AS OVER ANNOTATED	Summary: ATL3 interacts with ZFYVE27/protrudin in ER network biology, but GO:0005515 is uninformative as a molecular-function annotation. Reason: The evidence supports a physical interaction in an ER-shaping protein network, not a specific ATL3 molecular activity beyond its GTPase-dependent fusogenic function. Supporting Evidence: PMID:23969831 Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation.
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: HPA ER localization is consistent with the broader experimental literature. Reason: ATL3 is an ER-localized multi-pass membrane protein, although more specific ER membrane and ER tubular network membrane terms capture the main localization. Supporting Evidence: PMID:18270207 atlastin-2 and -3 are localized to the endoplasmic reticulum (ER)
GO:0003924 GTPase activity	EXP PMID:28602821 Timing and Reset Mechanism of GTP Hydrolysis-Driven Conforma...	ACCEPT	Summary: ATL3 GTPase activity is directly examined in structural and kinetic studies of the atlastin catalytic cycle. Reason: GTP hydrolysis is the enzymatic activity that powers ATL3 dimerization-cycle progression and membrane remodeling. Supporting Evidence: PMID:28602821 the data extend the mechanistic framework for how GTP hydrolysis drives conformational changes in ATL
GO:0003924 GTPase activity	EXP PMID:34546351 The hypervariable region of atlastin-1 is a site for intrins...	ACCEPT	Summary: ATL3 was included in comparative atlastin biochemical analyses supporting conserved GTPase activity. Reason: The study treats ATL3 as a catalytically active atlastin and reports ATL3 GTPase/tethering comparisons with ATL1. Supporting Evidence: PMID:34546351 The N-terminal, cytosol-facing portion of ATL, composed of the G and middle domains, constitutes the protein's catalytic core.
GO:0003924 GTPase activity	EXP PMID:37102997 Human atlastin-3 is a constitutive ER membrane fusion cataly...	ACCEPT	Summary: Direct ATL3 fusion work includes GTPase assays and GTP-dependent fusion requirements. Reason: ATL3 fusion is GTP dependent, and GTPase activity is part of the catalytic fusion mechanism. Supporting Evidence: PMID:37102997 ATL3 incorporated at a 1:1,000 M protein/lipid ratio catalyzed robust lipid mixing.
GO:0005789 endoplasmic reticulum membrane	EXP PMID:19665976 A class of dynamin-like GTPases involved in the generation o...	ACCEPT	Summary: Mammalian atlastins, including ATL3, localize predominantly to tubular ER membranes. Reason: The publication shows atlastins localize to tubular ER and interact with ER tubule-shaping proteins. Supporting Evidence: PMID:19665976 Similar results were obtained with Myc-ATL2 and Myc-ATL3
GO:0005789 endoplasmic reticulum membrane	EXP PMID:23969831 Protrudin binds atlastins and endoplasmic reticulum-shaping ...	ACCEPT	Summary: Protrudin-network work places ATL proteins in the tubular ER network. Reason: Although the cached abstract is not detailed for ATL3 sublocalization, it supports an atlastin/tubular-ER context and the annotation is independently supported by ATL3 localization literature. Supporting Evidence: PMID:23969831 Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation.
GO:0005789 endoplasmic reticulum membrane	EXP PMID:24459106 Sensory neuropathy with bone destruction due to a mutation i...	ACCEPT	Summary: Disease-variant work supports ATL3 as an ER-shaping protein at ER branch points. Reason: The wild-type ATL3 localization and mutant mislocalization/disruption support ER membrane localization. Supporting Evidence: PMID:24459106 ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network.
GO:0005789 endoplasmic reticulum membrane	EXP PMID:25548161 Lunapark stabilizes nascent three-way junctions in the endop...	ACCEPT	Summary: The accessible cached Lunapark abstract supports the ER three-way-junction context but not ATL3-specific localization; other ATL3-specific sources support retaining the term. Reason: The term is well supported for ATL3 by multiple other accessible references, but this specific abstract is not the strongest source for ATL3. Supporting Evidence: PMID:25548161 The endoplasmic reticulum (ER) consists of a polygonal network of sheets and tubules interconnected by three-way junctions.
GO:0005789 endoplasmic reticulum membrane	EXP PMID:27619977 Cooperation of the ER-shaping proteins atlastin, lunapark, a...	ACCEPT	Summary: ATL3 localization to ER tubule junctions supports ER membrane annotation. Reason: Tagged ATL3 localizes to ER three-way junctions and ATL function maintains the ER network. Supporting Evidence: PMID:27619977 wild type ATL-3 and ATL-2 localized in punctae at three-way junctions
GO:0005789 endoplasmic reticulum membrane	EXP PMID:37102997 Human atlastin-3 is a constitutive ER membrane fusion cataly...	ACCEPT	Summary: Direct ATL3 fusion/rescue study supports ATL3 as an ER membrane fusion catalyst. Reason: ATL3 is assayed as a membrane protein reconstituted into liposomes and as an ER network-maintenance factor in cells. Supporting Evidence: PMID:37102997 Purified protein (Fig. S1 A) was incorporated into synthetic liposomes
GO:0005789 endoplasmic reticulum membrane	IDA PMID:18270207 Atlastin GTPases are required for Golgi apparatus and ER mor...	ACCEPT	Summary: ATL2 and ATL3 were reported as ER-localized proteins. Reason: This is direct localization evidence for ATL3 at the ER membrane. Supporting Evidence: PMID:18270207 atlastin-2 and -3 are localized to the endoplasmic reticulum (ER)
GO:0016320 endoplasmic reticulum membrane fusion	IMP PMID:27619977 Cooperation of the ER-shaping proteins atlastin, lunapark, a...	ACCEPT	Summary: ATL function is required for ER network formation and maintenance, consistent with ER membrane fusion. Reason: Although the study is pan-atlastin and network-level, it supports the process that later ATL3-specific reconstitution confirms directly. Supporting Evidence: PMID:27619977 Connecting tubules into a network requires membrane fusion, which is mediated by membrane-anchored GTPases, the atlastins
GO:0016320 endoplasmic reticulum membrane fusion	IDA PMID:37102997 Human atlastin-3 is a constitutive ER membrane fusion cataly...	ACCEPT	Summary: Purified human ATL3 directly catalyzes membrane fusion. Reason: This is the strongest ATL3-specific evidence for ER membrane fusion. Supporting Evidence: PMID:37102997 purified human ATL3 catalyzes efficient membrane fusion in vitro and is sufficient to sustain the ER network in triple knockout cells.
GO:0098826 endoplasmic reticulum tubular network membrane	IDA PMID:37102997 Human atlastin-3 is a constitutive ER membrane fusion cataly...	ACCEPT	Summary: ATL3 fusogenic activity occurs on ER tubular network membranes. Reason: ATL3 restores and maintains ER network morphology as the sole atlastin source in triple-knockout cells. Supporting Evidence: PMID:37102997 ATL3 can restore and maintain a normal ER network.
GO:0140523 GTPase-dependent fusogenic activity	IDA PMID:37102997 Human atlastin-3 is a constitutive ER membrane fusion cataly...	ACCEPT	Summary: ATL3 has directly demonstrated GTP-dependent membrane fusogenic activity. Reason: This term is the best molecular-function description for ATL3 because it captures both GTPase dependence and membrane fusion activity. Supporting Evidence: PMID:37102997 purified human ATL3 catalyzes efficient membrane fusion in vitro
GO:1990809 endoplasmic reticulum tubular network membrane organization	IMP PMID:27619977 Cooperation of the ER-shaping proteins atlastin, lunapark, a...	ACCEPT	Summary: ATL activity is required for ER tubular network organization and maintenance. Reason: The term accurately reflects the cellular consequence of ATL3-family ER fusion activity. Supporting Evidence: PMID:27619977 ATL is needed to not only form, but also maintain, the ER network.
GO:1990809 endoplasmic reticulum tubular network membrane organization	IMP PMID:37102997 Human atlastin-3 is a constitutive ER membrane fusion cataly...	ACCEPT	Summary: ATL3-specific rescue of ATL knockout cells supports ER tubular network membrane organization. Reason: ATL3 is sufficient to restore a branched ER network, linking the molecular fusion activity to ER network organization. Supporting Evidence: PMID:37102997 ATL3 can restore and maintain a normal ER network.
GO:0098826 endoplasmic reticulum tubular network membrane	IDA PMID:27619977 Cooperation of the ER-shaping proteins atlastin, lunapark, a...	ACCEPT	Summary: ATL3 localizes at ER three-way junctions in the tubular network. Reason: The active site of ATL3 function is the ER tubular network membrane, especially tubule junctions. Supporting Evidence: PMID:27619977 wild type ATL-3 and ATL-2 localized in punctae at three-way junctions
GO:1990809 endoplasmic reticulum tubular network membrane organization	IMP PMID:18270207 Atlastin GTPases are required for Golgi apparatus and ER mor...	ACCEPT	Summary: Dominant-negative atlastin perturbation affects ER reticularization, supporting ATL3-family roles in ER network organization. Reason: The annotation is supported by the publication's ATL2/ATL3 localization and ER morphogenesis data, and is reinforced by later ATL3-specific work. Supporting Evidence: PMID:18270207 expression of SPG3A mutant or dominant-negative atlastin proteins lacking GTPase activity causes prominent inhibition of ER reticularization
GO:1990809 endoplasmic reticulum tubular network membrane organization	IMP PMID:19665976 A class of dynamin-like GTPases involved in the generation o...	ACCEPT	Summary: Atlastins are required for tubular ER network formation and interconnection. Reason: ATL3 belongs to the mammalian atlastin group tested for ER tubular network formation; later direct ATL3 experiments confirm the assignment. Supporting Evidence: PMID:19665976 The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro.
GO:0005515 protein binding	IPI PMID:32075961 REEP5 depletion causes sarco-endoplasmic reticulum vacuoliza...	MARK AS OVER ANNOTATED	Summary: ATL3 is reported as an interactor in REEP5/SR-ER network biology, but protein binding is too generic for ATL3 molecular function. Reason: The physical interaction supports ER-shaping network context. It should not obscure the more specific ATL3 molecular function, GTPase-dependent fusogenic activity. Supporting Evidence: PMID:32075961 ER tubules are also stabilized by forming a characteristic polygonal network through membrane fusion mediated by the atlastin family of dynamin-related GTPases
GO:0098826 endoplasmic reticulum tubular network membrane	IDA PMID:25548161 Lunapark stabilizes nascent three-way junctions in the endop...	ACCEPT	Summary: The term is correct for ATL3, though the accessible cached abstract for this reference is not ATL3-specific. Reason: ATL3 localization to ER tubule junctions and ER tubular network membrane is supported by other accessible ATL3-specific references. Supporting Evidence: PMID:24459106 ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network.
GO:0005515 protein binding	IPI PMID:23969831 Protrudin binds atlastins and endoplasmic reticulum-shaping ...	MARK AS OVER ANNOTATED	Summary: The duplicated GOA ZFYVE27/protrudin interaction row supports an interaction but not a useful molecular-function annotation. Reason: Protein binding is a non-informative term for ATL3; the actionable molecular function is GTPase-dependent ER membrane fusion. This entry is retained separately because it reflects a duplicate seeded GOA row rather than a distinct ATL3 function. Supporting Evidence: PMID:23969831 Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation.
GO:0071782 endoplasmic reticulum tubular network	IDA PMID:23969831 Protrudin binds atlastins and endoplasmic reticulum-shaping ...	ACCEPT	Summary: ATL3 is located in the ER tubular network. Reason: The term is consistent with protrudin/atlastin ER network biology and with ATL3-specific junction localization in independent studies. Supporting Evidence: PMID:24459106 ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: High-throughput membrane proteomics is compatible with ATL3 being a membrane protein, but the term is very broad. Reason: ATL3 is specifically an ER membrane and ER tubular network membrane protein; the generic membrane term adds little beyond more precise accepted annotations. Supporting Evidence: PMID:19946888 The present study was initiated to define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS.
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport	IMP NOT PMID:18270207 Atlastin GTPases are required for Golgi apparatus and ER mor...	ACCEPT	Summary: The NOT annotation is supported: ATL perturbation did not generally block anterograde ER-to-Golgi trafficking in the VSVG-GFP assay. Reason: The negated annotation is important because ATL3's core role is ER morphology/fusion rather than general ER-to-Golgi vesicle-mediated transport. Supporting Evidence: PMID:18270207 secretory pathway trafficking as assessed using vesicular stomatitis virus G protein fused to green fluorescent protein (VSVG-GFP) as a reporter was essentially normal
GO:0042802 identical protein binding	IDA PMID:18270207 Atlastin GTPases are required for Golgi apparatus and ER mor...	ACCEPT	Summary: ATL3 homotypic interactions are part of the atlastin fusion mechanism. Reason: Identical protein binding is more informative than generic protein binding for ATL3 because trans homodimerization of atlastin molecules is mechanistically required for fusion. Supporting Evidence: PMID:37102997 GTP-binding induced GTPase (G) domain dimerization in trans

Gene Description

Existing Annotations Review

Core Functions

ATL3 is a constitutive ER membrane fusion catalyst. GTP binding and hydrolysis by cytosolic ATL3 domains promote transient atlastin homodimerization across apposed ER membranes, driving homotypic ER membrane fusion and maintaining the branched tubular ER network.

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