Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000407 phagophore assembly site	IBA GO_REF:0000033	ACCEPT	Summary: ATG2B is active at autophagy initiation/elongation sites. Mammalian ATG2 proteins are required at a late step of autophagosome formation, with a direct mechanism of lipid transfer at the ER-phagophore interface. Reason: This cellular-component annotation matches the conserved ATG2/WIPI role at phagophore assembly sites and is supported by mammalian cell evidence for ATG2-dependent autophagosome formation. Supporting Evidence: PMID:22219374 both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0000422 autophagy of mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ATG2B is part of the core macroautophagy machinery required to build autophagosomal membranes, so it can participate in mitophagy when the macroautophagy machinery is recruited to mitochondria. Reason: The annotation is biologically plausible as a phylogenetic inference for a core autophagy factor, but it should not be interpreted as a mitochondria- selective recognition role for ATG2B. The core function remains phagophore lipid transfer. Supporting Evidence: PMID:22219374 these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation
GO:0061908 phagophore	IBA GO_REF:0000033	ACCEPT	Summary: ATG2B functions on nascent autophagic membranes during phagophore expansion and forms a WIPI/ATG18-associated lipid-transfer module. Reason: The phagophore is the core location for ATG2B lipid-transfer activity in autophagosome biogenesis. Supporting Evidence: PMID:22219374 these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0000425 pexophagy	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ATG2B can support pexophagy indirectly as part of the general autophagosome-building machinery used by selective autophagy pathways. Reason: This is best retained as a non-core phylogenetic selective-autophagy annotation. The evidence does not show ATG2B as a peroxisome-selective cargo receptor or specificity factor. Supporting Evidence: PMID:22219374 both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions
GO:0043495 protein-membrane adaptor activity	IBA GO_REF:0000033	ACCEPT	Summary: ATG2B binds membranes and WDR45/WIPI4 and functions with this WIPI partner at autophagic membranes, consistent with a protein-membrane adaptor or tethering role in addition to lipid transfer. Reason: Direct biochemical and structural evidence supports ATG2B membrane binding, ATG2B-WDR45 complex formation, and membrane tethering/lipid-transfer activity. The more specific core molecular function is lipid transfer activity, but this term captures a supported tether/adaptor aspect. Supporting Evidence: PMID:28820312 mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs PMID:31721365 ATG2B possesses the membrane tethering (MT) and LT activity
GO:0061723 glycophagy	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ATG2B may be required for glycophagy insofar as glycophagy uses the core macroautophagy membrane expansion machinery. Reason: Retain as a non-core inferred selective-autophagy annotation. The direct evidence for ATG2B is autophagosome membrane formation, not glycogen cargo recognition. Supporting Evidence: PMID:22219374 both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions
GO:0032266 phosphatidylinositol-3-phosphate binding	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: The ATG2-WIPI module is recruited to PI3P-positive autophagic membranes, but the direct PI3P-binding effector is the WIPI/ATG18 family partner, not clearly ATG2B itself. Reason: This term overstates the available gene-level evidence for ATG2B. Direct evidence supports liposome binding and WDR45/WIPI4-dependent association with PI3P-containing membranes, but not a specific ATG2B PI3P headgroup binding activity. Supporting Evidence: PMID:28820312 PtdIns3P-binding effectors which can form complexes with proteins in the Atg2 family PMID:28820312 ATG2B and found that it could bind to liposomes independently of PtdIns3P or WDR45
GO:0034727 piecemeal microautophagy of the nucleus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ATG2B is a conserved autophagy factor and may support this process where the conserved machinery is used, but human ATG2B is not established as a process-specific PMN factor. Reason: Keep as a non-core phylogenetic inference. The strongest mammalian evidence supports general phagophore/autophagosome biogenesis rather than a human PMN-specific role. Supporting Evidence: PMID:22219374 both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions
GO:0061709 reticulophagy	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ATG2B can support reticulophagy as part of the core autophagy membrane expansion system, especially because ATG2B acts at ER-phagophore contact sites. Reason: Retain as non-core. ATG2B is not a reticulophagy cargo receptor or ER quality-control factor; its direct role is lipid transfer for phagophore expansion. Supporting Evidence: PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: ER membrane localization is consistent with the accepted model in which ATG2B tethers the isolation membrane/phagophore edge to the ER and transfers lipids from ER-derived membranes to the growing phagophore. Reason: Although this GOA row is electronically inferred from UniProt subcellular location, it is consistent with experimental and biochemical evidence for ATG2-dependent ER-to-phagophore lipid transfer. Supporting Evidence: PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0005811 lipid droplet	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Mammalian ATG2 proteins associate with lipid droplets and affect lipid droplet morphology and dispersion, but this is a secondary cellular context relative to ATG2B's core phagophore lipid-transfer role. Reason: Retain the localization, but mark non-core because the publication notes that the precise lipid-droplet mechanism and directness of the association remain unresolved. Supporting Evidence: PMID:22219374 One novel aspect of the present study is the finding that mammalian Atg2 proteins are present on lipid droplets PMID:22219374 Further experiments will be required to test whether Atg2 proteins directly or indirectly associate with lipid droplets
GO:0006914 autophagy	IEA GO_REF:0000002	MODIFY	Summary: The broad InterPro-derived autophagy annotation is directionally correct but less informative than the experimentally supported role in autophagosome assembly/phagophore expansion. Reason: Modify to GO:0000045 autophagosome assembly. ATG2B is not merely associated with autophagy in general; it is required for formation and closure/expansion of autophagosomal membranes. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:22219374 these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0034045 phagophore assembly site membrane	IEA GO_REF:0000044	ACCEPT	Summary: The phagophore assembly site membrane is a supported location for ATG2B function and matches its WIPI-associated lipid-transfer role at the growing isolation membrane. Reason: The electronic UniProt location mapping is supported by the experimental ATG2A/B depletion phenotype and by ATG2B membrane tethering/lipid-transfer activity. Supporting Evidence: PMID:22219374 these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0120009 intermembrane lipid transfer	IEA GO_REF:0000108	ACCEPT	Summary: ATG2B has membrane tethering and lipid-transfer activity and transfers lipids between membranes during isolation membrane expansion. Reason: This BP annotation follows directly from the experimentally demonstrated lipid-transfer activity and the model of ER-to-isolation-membrane lipid movement. Supporting Evidence: PMID:31721365 ATG2B possesses the membrane tethering (MT) and LT activity PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0005515 protein binding	IPI PMID:20562859 Network organization of the human autophagy system.	MARK AS OVER ANNOTATED	Summary: This interaction record reflects WDR45/WIPI4 association in the human autophagy interaction network, but generic protein binding is not an informative ATG2B molecular function. Reason: The WDR45 interaction is biologically relevant, but the curation should be represented by the ATG2-ATG18 complex/component context and ATG2B lipid transfer/tethering function rather than by GO:0005515. Supporting Evidence: PMID:20562859 association between ATG2A, ATG2B, and WDR45 was unaltered by mTOR inhibition PMID:28820312 mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: This BioPlex interaction row is a high-throughput WDR45 association, but GO:0005515 is too generic for ATG2B. Reason: Retaining a generic protein binding MF would obscure the supported biology: ATG2B forms a WDR45/WIPI4-associated autophagy lipid-transfer complex. The interaction can inform complex membership but should not be treated as a core molecular function by itself. Supporting Evidence: PMID:33961781 These networks model the interactome whose structure encodes protein function, localization, and complex membership. PMID:28820312 mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs
GO:0005515 protein binding	IPI PMID:34524948 Global Proximity Interactome of the Human Macroautophagy Pat...	MARK AS OVER ANNOTATED	Summary: This proximity-interactome annotation supports ATG2B's placement in the human macroautophagy interaction network, but it is not an adequate molecular-function description. Reason: Generic protein binding should not be propagated as ATG2B's function. The informative curation is lipid transfer activity and ATG2-WIPI complex membership. Supporting Evidence: PMID:34524948 Here, we applied BioID to the study of macroautophagy in human cells, generating a proximity interaction map of 39 core macroautophagy proteins. PMID:31721365 ATG2B possesses the membrane tethering (MT) and LT activity
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: The OpenCell-derived interaction annotation is useful as interactome context, but GO:0005515 is too broad and uninformative for ATG2B curation. Reason: The interaction should be interpreted conservatively as supporting complex context, not as the gene product's molecular function. ATG2B's curated molecular function is lipid transfer activity. Supporting Evidence: PMID:35271311 well-curated localization and interactome measurements PMID:28820312 We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: ER localization is consistent with ATG2B's role at ER-associated autophagosome biogenesis sites. Reason: The ER is central to ATG2B-mediated lipid transfer to the isolation membrane; this broader ER localization is valid alongside the more specific ER membrane annotation. Supporting Evidence: PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: The ER membrane annotation transferred by sequence similarity is consistent with the experimentally supported ATG2 lipid-transfer model. Reason: ATG2B acts at an ER-to-isolation-membrane interface, so ER membrane localization is a core cellular context. Supporting Evidence: PMID:31721365 direct lipid transfer (LT) from ER to IM for IM expansion
GO:0005811 lipid droplet	EXP PMID:22219374 Mammalian Atg2 proteins are essential for autophagosome form...	KEEP AS NON CORE	Summary: ATG2 proteins were observed on lipid droplets, and ATG2A/B depletion altered lipid droplet size and distribution. Reason: This direct localization should be retained, but it is not the main ATG2B core function. The lipid-droplet role is experimentally observed but mechanistically less resolved than ER- phagophore lipid transfer. Supporting Evidence: PMID:22219374 One novel aspect of the present study is the finding that mammalian Atg2 proteins are present on lipid droplets PMID:22219374 These data suggest that mammalian Atg2A and Atg2B function both in autophagosome formation and regulation of lipid droplet volume and distribution.
GO:0034045 phagophore assembly site membrane	EXP PMID:22219374 Mammalian Atg2 proteins are essential for autophagosome form...	ACCEPT	Summary: Direct mammalian evidence supports ATG2 localization/function at autophagic membranes and shows defective autophagosome formation after combined ATG2A/B depletion. Reason: This is a core location for ATG2B lipid transfer and membrane tethering during phagophore expansion. Supporting Evidence: PMID:22219374 these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation
GO:0120013 lipid transfer activity	IDA PMID:31721365 Human ATG2B possesses a lipid transfer activity which is acc...	ACCEPT	Summary: Human ATG2B directly possesses lipid-transfer activity, and this activity is promoted by negatively charged membranes and WIPI4. Reason: This is the most informative supported molecular-function annotation for ATG2B and should be treated as the core molecular function. Supporting Evidence: PMID:31721365 ATG2B possesses the membrane tethering (MT) and LT activity PMID:31721365 negatively charged membranes and an Atg18 ortholog WIPI4
GO:0062079 ATG2-ATG18 complex	IDA PMID:28820312 Architecture of the ATG2B-WDR45 complex and an aromatic Y/HF...	NEW	Summary: NEW annotation. ATG2B forms an ATG2-WIPI/ATG18 complex with WDR45/WIPI4, consistent with direct structural and biochemical evidence for complex membership. Reason: This is the conservative way to use the PN projection. The projection is not evidence for a new proteostasis function by itself, but it points to an existing GO complex term that is directly supported by ATG2B-WDR45 structural and biochemical evidence. Supporting Evidence: PMID:28820312 We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex PMID:28820312 conserved aromatic H/YF motif in the C terminus of ATG2A and ATG2B that is crucial for complex formation PMID:20562859 association between ATG2A, ATG2B, and WDR45 was unaltered by mTOR inhibition

Core Functions

ATG2B is a WDR45/WIPI4-associated lipid-transfer and membrane-tethering protein that transfers lipids between ER-derived membrane sources and the growing isolation membrane/phagophore during autophagosome assembly.

Molecular Function:

lipid transfer activity

Directly Involved In:

intermembrane lipid transfer autophagosome assembly

Cellular Locations:

phagophore assembly site membrane endoplasmic reticulum membrane phagophore

In Complex:

ATG2-ATG18 complex

Supporting Evidence:

PMID:31721365
ATG2B possesses the membrane tethering (MT) and LT activity
PMID:28820312
We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex
PMID:22219374
these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on inter-ontology links

PMID:20562859

Network organization of the human autophagy system.

ATG2B is a known autophagy protein in a human autophagy interaction network and associates with WDR45.

"association between ATG2A, ATG2B, and WDR45 was unaltered by mTOR inhibition"

PMID:22219374

Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets.

Mammalian ATG2A and ATG2B are required for autophagosome formation and also affect lipid droplet morphology.

"These data suggest that mammalian Atg2A and Atg2B function both in autophagosome formation and regulation of lipid droplet volume and distribution."

PMID:28820312

Architecture of the ATG2B-WDR45 complex and an aromatic Y/HF motif crucial for complex formation.

ATG2B forms a complex with WDR45/WIPI4, supporting ATG2-ATG18 complex membership.

"We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex"

PMID:31721365

Human ATG2B possesses a lipid transfer activity which is accelerated by negatively charged lipids and WIPI4.

Human ATG2B has membrane tethering and lipid-transfer activity stimulated by WIPI4.

"ATG2B possesses the membrane tethering (MT) and LT activity"

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

BioPlex AP-MS data provide proteome-scale interaction context for high-throughput protein-binding annotations.

"Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks."

PMID:34524948

Global Proximity Interactome of the Human Macroautophagy Pathway.

BioID mapping places core macroautophagy proteins in a proximity-interaction network and supports cautious interpretation of high-throughput interaction annotations.

"Here, we applied BioID to the study of macroautophagy in human cells, generating a proximity interaction map of 39 core macroautophagy proteins."

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

OpenCell provides endogenous tagging, localization, and interactome measurements for human cellular organization.

"well-curated localization and interactome measurements"

PMID:32009292

A conserved ATG2-GABARAP family interaction is critical for phagophore formation.

A conserved ATG2 LIR mediates binding of ATG2A/ATG2B to GABARAP-subfamily ATG8 proteins; this interaction is required for phagophore formation and closure, whereas the ATG2-WIPI4 interaction is dispensable for autophagy flux.
Endogenous ATG2B co-localizes with ATG2A on early autophagic membranes positive for WIPI2 and ATG16L1, providing direct ATG2B localization evidence at phagophore assembly sites.

PMID:30952800

ATG2 transports lipids to promote autophagosome biogenesis.

ATG2 is a lipid-transfer protein operating at the ER-autophagosome interface; lipid transfer is the major autophagy-dependent activity, since a lipid-transfer-competent ATG2 N-terminal fragment rescues autophagosome biogenesis in ATG2A/ATG2B double-knockout cells whereas lipid-transport-defective mutants do not.

PMID:38622126

ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores.

The endosomal PI3P-binding protein ANKFY1 binds ATG2A and enhances ATG2-mediated lipid transfer, identifying PI3P-enriched endosomes as an additional lipid source for ATG2-mediated phagophore expansion; ANKFY1 depletion impairs autophagosome growth and largely phenocopies ATG2A/ATG2B depletion.

PMID:26280900

Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies.

An autosomal-dominant germline 14q32 duplication spanning ATG2B and GSKIP predisposes to familial myeloid malignancies, and overexpression of ATG2B/GSKIP enhances hematopoietic progenitor differentiation and cooperates with JAK2/MPL/CALR driver mutations; the disease effect is a dosage-sensitive locus-level property shared with GSKIP rather than an ATG2B-specific molecular function.

Suggested Experiments

Experiment: Use endogenous ATG2B knockout/rescue cells expressing wild-type ATG2B or WDR45-binding motif mutants, then measure ATG2B-WDR45 colocalization, autophagic flux, and phagophore closure under starvation.

Hypothesis: ATG2B-WDR45 complex formation is required for efficient ATG2B recruitment to PI3P-positive phagophore membranes and for autophagosome membrane expansion.

Type: genome editing, rescue, live-cell imaging, and autophagy flux assay

Experiment: In ATG2A/ATG2B double-knockout cells reconstituted with ATG2B, test whether ANKFY1 depletion reduces ATG2B-dependent autophagosome growth and PI3P distribution on phagophores, and assay ANKFY1-ATG2B binding and ATG2B-mediated lipid transfer between PI3P-containing liposomes in vitro.

Hypothesis: ATG2B, like ATG2A, can transfer lipids from PI3P-enriched endosomes (via ANKFY1) in addition to the ER, contributing endosome-derived lipid to phagophore expansion.

Type: knockout/rescue, proximity imaging, in vitro lipid-transfer assay

Deep Research

Falcon

(ATG2B-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 25 citations 2 artifacts 2026-06-07T05:07:26.597040

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000017 Figure 3 in the document provides the requested data showing the autophagy flux phenotype of ATG2A/ATG2B double knockout (ATG2 DKO) (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Human ATG2B (UniProt: Q96BY7; gene: ATG2B/C14orf103) — functional annotation and current evidence

0) Scope, gene/protein identity verification, and ambiguity checks

ATG2B is a human autophagy gene encoding a large ATG2-family protein that acts in autophagosome biogenesis, particularly phagophore expansion. Mammals have two paralogs, ATG2A and ATG2B, which share substantial but incomplete sequence identity (~44.5%) and are frequently functionally redundant, such that single depletion often has limited effects while combined perturbation yields strong defects. (duarte2023theorganizationand pages 4-5)

Critical limitation (identifier mapping): In the retrieved full-text sources, an explicit statement mapping human ATG2B to UniProt accession Q96BY7 was not found. Therefore, the UniProt accession assignment is taken from the user-provided UniProt record, while functional and mechanistic statements are supported by primary literature and reviews cited below. (duarte2023theorganizationand pages 4-5, bozic2020aconservedatg2‐gabarap pages 2-4)

1) Key concepts and definitions (current understanding)

1.1 Macroautophagy, phagophore expansion, and membrane contact sites

Macroautophagy (“autophagy” in much of the mammalian literature) involves de novo formation of a double-membrane phagophore/isolation membrane that expands and closes into an autophagosome, which subsequently fuses with lysosomes for degradation. The expansion step requires large lipid input and is organized at phagophore–ER membrane contact sites (MCSs) that concentrate lipid-handling ATG proteins. (duarte2023theorganizationand pages 4-5, duarte2023theorganizationand pages 5-7)

1.2 ATG2-family proteins as bulk lipid transfer “bridges”

A major conceptual advance of the past several years is that ATG2-family proteins (including ATG2A/ATG2B in mammals) are rod-like lipid transfer/tether proteins capable of transferring lipids between adjacent membranes. Reviews summarizing biochemical and structural evidence describe ATG2 proteins as having a long hydrophobic cavity/groove consistent with bulk phospholipid transport, functioning together with lipid scramblases (notably ATG9A) to expand autophagic membranes. (duarte2023theorganizationand pages 4-5, mcewan2022atg2andvps13 pages 7-7)

2) Molecular function of ATG2B: what does it do?

2.1 Primary function: non-vesicular lipid transfer that enables phagophore expansion

Although many direct in vitro transfer assays are performed using ATG2A, mammalian ATG2A and ATG2B are generally treated as redundant lipid-transfer modules in cells. A 2023 review summarizes that ATG2 proteins transfer lipids between membranes and that the N-terminus associates with ER while C-terminal regions contribute to phagophore binding, placing ATG2-mediated lipid transfer at the ER–phagophore interface where expansion occurs. (duarte2023theorganizationand pages 5-7, duarte2023theorganizationand pages 4-5)

Strong functional evidence from combined loss-of-function: In human cells, deletion of both ATG2A and ATG2B (ATG2 DKO) blocks autophagic flux, with accumulation of LC3B-II and p62 and reduced lysosomal flux; re-expression of ATG2A rescues these phenotypes. (valverde2019atg2transportslipids pages 4-6)

Lipid-transfer dependence: A key mechanistic finding is that a lipid-transfer competent N-terminal fragment (“mini-ATG2A”, residues 1–345) can rescue autophagy in ATG2 DKO cells, whereas lipid-transport-defective mutants fail to rescue; near-complete rescue required ~10× endogenous-level expression of the mini-fragment. This supports a model in which ATG2’s essential cellular role is lipid transfer that provides membrane material for phagophore growth. (valverde2019atg2transportslipids pages 4-6)

Figure evidence (direct experimental readout): Immunoblot and imaging panels show the ATG2 DKO flux defect and rescue by full-length or mini-ATG2A, and failure of lipid-transport-dead mutants to rescue. (valverde2019atg2transportslipids media f607665f)

2.2 ATG2B is not an enzyme catalyzing a classical reaction

ATG2B is best described as a lipid transfer/tether protein rather than a catalytic enzyme with a single defined reaction. Its “substrate” is bulk membrane lipid (phospholipids) transported between donor membranes (classically ER; increasingly also other organelles) and the expanding phagophore. (mcewan2022atg2andvps13 pages 7-7, duarte2023theorganizationand pages 4-5)

3) Subcellular localization: where does ATG2B act?

3.1 ER–phagophore contact sites and early autophagy membranes

ATG2 proteins localize to ER–phagophore MCSs, consistent with their tethering and lipid transfer roles. A 2023 synthesis notes localization at the phagophore rim and ER MCSs, with the N-terminus engaging ER and C-terminal elements supporting phagophore association. (duarte2023theorganizationand pages 5-7)

3.2 Direct ATG2B localization evidence

In mammalian starvation conditions, endogenous ATG2B co-localizes with GFP-ATG2A on punctate and ring-like LC3B-positive structures and with early autophagy markers including WIPI2 and ATG16L1, consistent with recruitment to early autophagic membranes/omegasome–isolation membrane structures. (bozic2020aconservedatg2‐gabarap pages 2-4)

4) Interaction partners and pathway placement

4.1 WIPI4/WDR45 (Atg18 family)

ATG2 proteins interact with WIPI family PI3P effectors, including WIPI4/WDR45, which can recruit ATG2A to PI3P-containing membranes in vitro and is widely discussed as a targeting/tethering partner. (maeda2019theautophagicmembrane pages 12-14)

However, in mammalian cells, ATG2–WIPI4 binding appears less critical for autophagy flux than ATG2’s interaction with ATG8-family proteins: ATG2A mutants defective in WIPI4 binding can still restore autophagy flux, whereas mutants defective in GABARAP binding cannot. (bozic2020aconservedatg2‐gabarap pages 1-2, mcewan2022atg2andvps13 pages 7-7)

4.2 ATG8-family proteins (GABARAP subfamily) via an ATG2 LIR

A major experimentally supported mechanism placing ATG2B in the pathway is binding to ATG8-family proteins (especially GABARAP/GABARAP-L1) through a conserved ATG2 LC3-interaction region (LIR).

ATG2A/ATG2B preferentially interact with GABARAP family members; starvation enhances ATG2–GABARAP co-precipitation, while LC3B interaction is comparatively weak in the cited experiments. (bozic2020aconservedatg2‐gabarap pages 2-4)
Disrupting the ATG2–GABARAP interaction blocks phagophore formation/closure and phenocopies ATG2A/ATG2B double knockout. (bozic2020aconservedatg2‐gabarap pages 1-2)

These findings underpin an expert consensus that ATG2’s GABARAP interaction is essential for late phagophore maturation/closure, while WIPI4 may be a stabilizer/recruitment factor rather than the primary essential linkage in mammals. (mcewan2022atg2andvps13 pages 7-7, duarte2023theorganizationand pages 4-5)

4.3 ATG9A and lipid scrambling

Autophagosome biogenesis requires coordination of lipid transfer with lipid scrambling; ATG9A is widely discussed as a scramblase that cooperates with ATG2-mediated bulk transfer. ATG9A also binds ATG2A in mammalian systems, consistent with a coupled lipid-handling module at phagophore–ER MCSs. (duarte2023theorganizationand pages 4-5, mcewan2022atg2andvps13 pages 7-7)

5) Recent developments and latest research (prioritizing 2023–2024)

5.1 2023: Noncanonical ATG2 engagement after lysosome damage

A 2023 Journal of Cell Biology study reported that lysosome damage induces a noncanonical ATG8 conjugation response (CASM) in which ATG8s are directly conjugated to lysosomal single membranes. This response promotes robust LC3A engagement with ATG2, linking ATG2 lipid-transfer machinery to lysosomal damage responses and repair-associated pathways beyond canonical autophagosome formation. (cross2023lysosomedamagetriggers pages 1-2)

5.2 2024: Endosomes as an additional lipid source for ATG2-mediated phagophore growth (ANKFY1)

A 2024 Cell Discovery paper identified ANKFY1 as an endosome-localized ATG2A-binding protein that binds PI3P via a FYVE domain and enhances ATG2A-mediated lipid transfer between PI3P-containing liposomes. In cells, ANKFY1 depletion impaired autophagosome growth and reduced autophagy flux, largely phenocopying ATG2A/B depletion, and ANKFY1 co-localized with ATG2A between endosomes and phagophores. The authors propose that PI3P-enriched endosomes can donate lipids (including PI3P-associated lipid pools) to phagophores via ATG2-mediated transfer, extending the lipid-source model beyond ER-only. (wei2024ankfy1bridgesatg2amediated pages 1-2)

5.3 2023: Updated expert synthesis of phagophore–ER contact site organization

A 2023 review focused on phagophore–ER MCSs emphasized that mammalian ATG2A and ATG2B are key phagophore expansion factors, are rod-like lipid transfer proteins, and function together with ATG9 and WIPI/PI3P machinery; it highlights remaining open questions regarding how ATG9, ATG2, and WIPI4 coordinate directionality and efficiency of lipid flux. (duarte2023theorganizationand pages 4-5)

6) Current applications and real-world implementations

6.1 Clinical genetics: germline 14q32 duplication involving ATG2B and GSKIP

A highly actionable real-world context for ATG2B is germline predisposition to myeloid malignancies through copy-number duplication.

A 2015 Nature Genetics study identified an autosomal-dominant ~700-kb germline duplication on chromosome 14q32 that includes ATG2B and GSKIP and co-segregates with familial myeloid malignancies (including essential thrombocythemia and other MPNs, with progression in some cases to myelofibrosis or AML). Mechanistically, ATG2B/GSKIP overexpression in patient-derived systems increased progenitor differentiation and sensitivity to thrombopoietin and appeared to cooperate with common somatic MPN drivers (JAK2/MPL/CALR), consistent with a “germline fitness” effect that increases the likelihood of malignant evolution. (saliba2015germlineduplicationof pages 1-3, saliba2015germlineduplicationof pages 4-5)

A 2022 mechanistic genetics study in mice reported that combined loss of Atg2b and Gskip (but not either gene alone) causes severe hematopoietic defects (including reduced HSC pools), emphasizing that the locus has dosage-sensitive biology relevant to hematopoiesis, although effects in that model were described as not driven by canonical autophagy changes. (sakai2022lossofatg2b pages 1-2, sakai2022lossofatg2b pages 2-5)

Implementation in practice: The 14q32 duplication is used in hereditary hematologic malignancy workups and genetic counseling as part of germline predisposition evaluation; although management guidance was not directly retrieved here, the original Nature Genetics evidence supports its role as a familial predisposition allele. (saliba2015germlineduplicationof pages 1-3)

6.2 Hypothesis-generating disease associations from Open Targets

Open Targets lists multiple disease associations for ATG2B (e.g., Sjögren syndrome, heart disease, neurodegenerative disease, colorectal carcinoma), each supported by limited evidence items and PubMed links; these associations can be used to prioritize follow-up but should not be interpreted as causal without reviewing the underlying studies. (OpenTargets Search: -ATG2B)

7) Relevant statistics and data points from recent/authoritative studies

ATG2 DKO autophagy flux defect and rescue: ATG2A/ATG2B double knockout causes LC3B-II and p62 accumulation with reduced lysosomal flux; mini-ATG2A(1–345) can rescue, with near-complete rescue requiring ~10× endogenous expression. (valverde2019atg2transportslipids pages 4-6)
Clinical genetics functional impact (14q32 duplication): Patient iPSC differentiation showed a ~10-fold increase in colony formation, and patient megakaryocytes showed ~2–3× overexpression of ATG2B/GSKIP; knockdown reduced CFU-MK output to ~40% of maximal under TPO stimulation. (saliba2015germlineduplicationof pages 4-5, saliba2015germlineduplicationof pages 7-8)

8) Expert opinions and analysis (authoritative syntheses)

Two expert reviews provide a coherent interpretation of ATG2B’s role within modern autophagy models:

ATG2A/ATG2B are described as “molecular highways” enabling bulk lipid transfer to drive membrane expansion and organelle communication, acting together with ATG9A scramblase activity and PI3P/WIPI scaffolding at ER–phagophore contact sites. (mcewan2022atg2andvps13 pages 7-7)
A focused 2023 MCS review emphasizes the centrality of ATG2A/ATG2B at phagophore–ER MCSs while noting that mechanistic coupling among ATG9, ATG2, and WIPI4 and the directionality of lipid flux remain incompletely resolved. (duarte2023theorganizationand pages 4-5)

9) Summary table of evidence

The following table consolidates primary and review evidence for ATG2B functional annotation, including 2023–2024 developments and clinical genetics.

Aspect	Key finding	Evidence type (review/primary)	System/model	Key experimental readout or statistic	Citation (first author year)	URL/DOI	Notes on ATG2A vs ATG2B specificity
Identity/family	Human ATG2B is the ATG2-family paralog of ATG2A; both are very large rod-like autophagy factors with conserved N-terminal chorein/VPS13-like region, ATG2_CAD, ATG_C, a C-terminal localization region, and a conserved LIR near the WIPI4-interaction region.	Review	Mammalian/yeast comparative literature synthesis	ATG2A is ~44.5% identical to ATG2B; single depletion of either paralog does not abolish autophagy. (duarte2023theorganizationand pages 4-5)	Duarte 2023	https://doi.org/10.1177/25152564231183898	Strong family-level evidence; most mechanistic papers test ATG2A directly and infer partial redundancy with ATG2B.
Function	ATG2 proteins act as lipid transfer proteins and membrane tethers that support phagophore expansion at ER–phagophore contact sites.	Review	Mammalian autophagy field overview	ATG2 transfers phospholipids from ER to phagophore; ATG9A scramblase activity complements transfer by equilibrating leaflets. (mcewan2022atg2andvps13 pages 7-7, duarte2023theorganizationand pages 5-7)	McEwan 2022	https://doi.org/10.1111/febs.16280	Function generally assigned to ATG2A/ATG2B together in mammals; direct in vitro assays are mostly with ATG2A.
Function	ATG2-mediated lipid transfer is sufficient to restore autophagy in ATG2A/ATG2B double-knockout cells when an active N-terminal ATG2A mini-fragment is expressed.	Primary	Human ATG2 DKO cells with rescue constructs	Mini-ATG2A(1–345) rescued autophagy; near-complete rescue required ~10× endogenous expression; lipid-transfer-defective mutants failed to rescue. (valverde2019atg2transportslipids pages 4-6, valverde2019atg2transportslipids media f607665f)	Valverde 2019	https://doi.org/10.1083/jcb.201811139	Rescue tested with ATG2A, but phenotype is defined in ATG2A/ATG2B DKO cells, supporting redundancy.
Interaction	A conserved ATG2 LIR mediates preferential binding to GABARAP-family proteins and is critical for phagophore maturation/closure.	Primary	Mammalian cells; biochemical binding assays	Mutation of the ATG2 LIR abolished ATG8-family binding and blocked phagophore formation/closure, phenocopying ATG2A/ATG2B DKO; starvation increased ATG2–GABARAP co-precipitation. (bozic2020aconservedatg2‐gabarap pages 2-4, bozic2020aconservedatg2‐gabarap pages 1-2)	Bozic 2020	https://doi.org/10.15252/embr.201948412	Demonstrated for both ATG2A and ATG2B family architecture; endogenous ATG2B co-localized with GFP-ATG2A.
Interaction	WIPI4/WDR45 binds mammalian ATG2 proteins, but ATG2–WIPI4 binding appears less essential than ATG2–GABARAP binding for autophagy flux in mammalian cells.	Primary + review	Mammalian cells; literature synthesis	WIPI4-binding mutants retained autophagy rescue, whereas GABARAP-binding mutants did not. (bozic2020aconservedatg2‐gabarap pages 1-2, mcewan2022atg2andvps13 pages 7-7)	Bozic 2020	https://doi.org/10.15252/embr.201948412	WIPI4 interacts with both ATG2A and ATG2B; functional importance may differ from yeast precedent.
Localization	ATG2 localizes to ER–phagophore/omegasome contact sites; N-terminus associates with ER and C-terminal regions contribute to phagophore binding.	Review	Mammalian/yeast literature synthesis	Overexpressed GFP-ATG2A localizes to phagophore rim and ER MCSs; coincidence binding to ATG9 and PI3P helps phagophore-edge association. (duarte2023theorganizationand pages 5-7)	Duarte 2023	https://doi.org/10.1177/25152564231183898	Localization model is derived mainly from ATG2A and yeast Atg2, but considered applicable to mammalian ATG2B as a redundant paralog.
Localization	Endogenous ATG2B and GFP-ATG2A co-localize on punctate/ring-like LC3B-positive starvation-induced structures together with early autophagy markers WIPI2 and ATG16L1.	Primary	Starved mammalian cells	Co-localization with LC3B, WIPI2, ATG16L1 on early autophagic structures. (bozic2020aconservedatg2‐gabarap pages 2-4)	Bozic 2020	https://doi.org/10.15252/embr.201948412	One of the clearer pieces of direct ATG2B localization evidence in human/mammalian cells.
Phenotype	Simultaneous loss of ATG2A and ATG2B causes accumulation of small, open, immature phagophores and blocks autophagic flux.	Primary	Mammalian double depletion/KO systems	LC3B-II, GABARAPL1, and p62 accumulate; bafilomycin A1 fails to further increase LC3B-II in ATG2 DKO; large LC3-positive structures accumulate. (valverde2019atg2transportslipids pages 4-6, valverde2019atg2transportslipids media f607665f, bozic2020aconservedatg2‐gabarap pages 2-4)	Valverde 2019	https://doi.org/10.1083/jcb.201811139	Strongest functional evidence is for combined ATG2A/ATG2B loss, indicating partial redundancy.
Phenotype	ATG2A/B deficiency can shift stress responses away from cytoprotective autophagy toward apoptosis/caspase-8 activation.	Primary	Mammalian cells	Combined ATG2A/B loss caused immature autophagosomal membrane accumulation and altered death signaling. (context from paper search result; summarized in retrieved metadata)	Tang 2017	https://doi.org/10.1038/cdd.2017.133	Study addresses combined deficiency, not ATG2B alone.
New mechanism (2024)	ANKFY1 is a new ATG2A-binding factor that recruits/promotes ATG2-mediated lipid transfer from PI3P-positive endosomes to phagophores, identifying endosomes as an additional lipid source.	Primary	Mammalian cells; purified proteins/liposomes	ANKFY1 depletion impaired autophagosome growth and autophagy flux and largely phenocopied ATG2A/B depletion; recombinant ANKFY1 enhanced ATG2A-mediated lipid transfer; UVRAG, ANKFY1, or ATG2A/B depletion reduced PI3P on phagophores. (wei2024ankfy1bridgesatg2amediated pages 1-2)	Wei 2024	https://doi.org/10.1038/s41421-024-00659-y	Direct binding was shown for ATG2A, but authors state ATG2A and ATG2B are functionally redundant in mammalian autophagy.
New mechanism (2023)	Lysosome damage triggers non-canonical ATG8 conjugation that engages ATG2 in a repair-associated pathway, extending ATG2 function beyond canonical autophagosome biogenesis.	Primary	Mammalian lysosome damage model	CASM generated direct ATG8 conjugation to lysosomal membranes and promoted robust LC3A engagement with ATG2. (cross2023lysosomedamagetriggers pages 1-2)	Cross 2023	https://doi.org/10.1083/jcb.202303078	Study discusses mammalian ATG2A/ATG2B collectively; isoform-specific distinctions were not emphasized.
Pathway context	ATG2 functions with ATG9A scramblase and WIPI/PI3P machinery at phagophore–ER contact sites; GABARAP interaction is especially important for late phagophore maturation.	Review	Autophagy pathway synthesis	Integrates lipid transfer, ATG9A scrambling, PI3P/WIPI scaffolding, and ATG8-family interactions in autophagosome biogenesis. (duarte2023theorganizationand pages 4-5, mcewan2022atg2andvps13 pages 7-7)	Duarte 2023	https://doi.org/10.1177/25152564231183898	Pathway assignment applies to mammalian ATG2A and ATG2B together.
Disease genetics	A germline ~700-kb duplication at 14q32 including ATG2B and GSKIP segregates with familial myeloid malignancies.	Primary	Human pedigrees with familial MPN/AML spectrum	Duplication predisposed to ET/MPN and progression to AML/myelofibrosis/CMML; overexpression of ATG2B/GSKIP enhanced hematopoietic progenitor differentiation and cooperated with JAK2/MPL/CALR driver mutations. (saliba2015germlineduplicationof pages 1-3)	Saliba 2015	https://doi.org/10.1038/ng.3380	Disease association is not ATG2B-only because the duplicated interval also contains GSKIP.
Disease mechanism	In patient-derived models, increased ATG2B/GSKIP dosage promoted hematopoietic output and megakaryopoiesis.	Primary	Patient cells, iPSC differentiation, megakaryocyte assays	~10-fold increase in colony formation in iPSC differentiation assays; two- to threefold overexpression in megakaryocytes; shRNA silencing reduced TPO-independent megakaryocyte formation and CFU-MK output to ~40% of maximal stimulated colonies. (saliba2015germlineduplicationof pages 4-5, saliba2015germlineduplicationof pages 7-8)	Saliba 2015	https://doi.org/10.1038/ng.3380	Mechanistic attribution remains shared between ATG2B and GSKIP.
Disease relevance/update	Mouse combined loss of Atg2b and Gskip impaired hematopoietic stem cell maintenance, supporting dosage-sensitive biology of the 14q32 locus, though effects were reported as autophagy-independent in that context.	Primary	Mouse knockout	Double knockout caused in utero lethality, decreased HSC pool size, and increased apoptosis; single knockouts showed little hematopoietic phenotype. (sakai2022lossofatg2b pages 1-2, sakai2022lossofatg2b pages 2-5)	Sakai 2022	https://doi.org/10.1128/mcb.00024-21	Again a locus-level effect (Atg2b + Gskip), not cleanly ATG2B-specific.

Table: This table summarizes the main functional, localization, interaction, phenotype, and disease-association evidence relevant to human ATG2B/Q96BY7. It emphasizes recent 2023-2024 studies while retaining foundational mechanistic and clinical genetics papers needed for a robust annotation.

10) Conclusions (functional annotation)

Best-supported primary function: Human ATG2B (as part of the mammalian ATG2A/ATG2B module) is a core autophagy factor that supports phagophore expansion by non-vesicular bulk lipid transfer at ER–phagophore membrane contact sites, in coordination with lipid scrambling (ATG9A) and PI3P/WIPI scaffolding. (duarte2023theorganizationand pages 4-5, mcewan2022atg2andvps13 pages 7-7, duarte2023theorganizationand pages 5-7)

Best-supported interaction logic: A conserved ATG2 LIR mediating GABARAP-family binding is essential for phagophore maturation/closure and for productive autophagy flux in mammalian cells; WIPI4 binding is important for recruitment in vitro and is part of the canonical complex, but appears less essential than GABARAP engagement in mammalian flux assays. (bozic2020aconservedatg2‐gabarap pages 1-2, bozic2020aconservedatg2‐gabarap pages 2-4, mcewan2022atg2andvps13 pages 7-7)

Most relevant 2023–2024 updates: ATG2 engagement is implicated in lysosome damage responses via noncanonical ATG8 conjugation (2023), and endosome-to-phagophore lipid transfer via ATG2 can be promoted by ANKFY1, expanding the set of lipid donor organelles beyond the ER (2024). (cross2023lysosomedamagetriggers pages 1-2, wei2024ankfy1bridgesatg2amediated pages 1-2)

Translational relevance: Germline 14q32 duplication including ATG2B and GSKIP is a well-supported familial predisposition to myeloid malignancy spectrum disorders, with functional evidence for altered hematopoietic progenitor behavior. (saliba2015germlineduplicationof pages 1-3, saliba2015germlineduplicationof pages 4-5)

References

(duarte2023theorganizationand pages 4-5): Prado Vargas Duarte and Fulvio Reggiori. The organization and function of the phagophore-er membrane contact sites. Contact, Jan 2023. URL: https://doi.org/10.1177/25152564231183898, doi:10.1177/25152564231183898. This article has 15 citations.
(bozic2020aconservedatg2‐gabarap pages 2-4): Mihaela Bozic, Luuk van den Bekerom, Beth A Milne, Nicola Goodman, Lisa Roberston, Alan R Prescott, Thomas J Macartney, Nina Dawe, and David G McEwan. A conserved atg2‐gabarap family interaction is critical for phagophore formation. EMBO reports, Feb 2020. URL: https://doi.org/10.15252/embr.201948412, doi:10.15252/embr.201948412. This article has 113 citations and is from a highest quality peer-reviewed journal.
(duarte2023theorganizationand pages 5-7): Prado Vargas Duarte and Fulvio Reggiori. The organization and function of the phagophore-er membrane contact sites. Contact, Jan 2023. URL: https://doi.org/10.1177/25152564231183898, doi:10.1177/25152564231183898. This article has 15 citations.
(mcewan2022atg2andvps13 pages 7-7): David G. McEwan and Kevin M. Ryan. Atg2 and vps13 proteins: molecular highways transporting lipids to drive membrane expansion and organelle communication. The FEBS Journal, 289:7113-7127, Nov 2022. URL: https://doi.org/10.1111/febs.16280, doi:10.1111/febs.16280. This article has 26 citations.
(valverde2019atg2transportslipids pages 4-6): Diana P. Valverde, Shenliang Yu, Venkata Boggavarapu, Nikit Kumar, Joshua A. Lees, Thomas Walz, Karin M. Reinisch, and Thomas J. Melia. Atg2 transports lipids to promote autophagosome biogenesis. The Journal of Cell Biology, 218:1787-1798, Apr 2019. URL: https://doi.org/10.1083/jcb.201811139, doi:10.1083/jcb.201811139. This article has 598 citations.
(valverde2019atg2transportslipids media f607665f): Diana P. Valverde, Shenliang Yu, Venkata Boggavarapu, Nikit Kumar, Joshua A. Lees, Thomas Walz, Karin M. Reinisch, and Thomas J. Melia. Atg2 transports lipids to promote autophagosome biogenesis. The Journal of Cell Biology, 218:1787-1798, Apr 2019. URL: https://doi.org/10.1083/jcb.201811139, doi:10.1083/jcb.201811139. This article has 598 citations.
(maeda2019theautophagicmembrane pages 12-14): Shintaro Maeda, Chinatsu Otomo, and Takanori Otomo. The autophagic membrane tether atg2a transfers lipids between membranes. Jul 2019. URL: https://doi.org/10.7554/elife.45777, doi:10.7554/elife.45777. This article has 387 citations and is from a domain leading peer-reviewed journal.
(bozic2020aconservedatg2‐gabarap pages 1-2): Mihaela Bozic, Luuk van den Bekerom, Beth A Milne, Nicola Goodman, Lisa Roberston, Alan R Prescott, Thomas J Macartney, Nina Dawe, and David G McEwan. A conserved atg2‐gabarap family interaction is critical for phagophore formation. EMBO reports, Feb 2020. URL: https://doi.org/10.15252/embr.201948412, doi:10.15252/embr.201948412. This article has 113 citations and is from a highest quality peer-reviewed journal.
(cross2023lysosomedamagetriggers pages 1-2): Jake Cross, Joanne Durgan, David G. McEwan, Matthew Tayler, Kevin M. Ryan, and Oliver Florey. Lysosome damage triggers direct atg8 conjugation and atg2 engagement via non-canonical autophagy. The Journal of Cell Biology, Oct 2023. URL: https://doi.org/10.1083/jcb.202303078, doi:10.1083/jcb.202303078. This article has 94 citations.
(wei2024ankfy1bridgesatg2amediated pages 1-2): Bin Wei, Yuhui Fu, Xiuzhi Li, Fang Chen, Yiqing Zhang, Hanmo Chen, Mindan Tong, Linsen Li, Yi Pan, Shen Zhang, She Chen, Xiaoxia Liu, and Qing Zhong. Ankfy1 bridges atg2a-mediated lipid transfer from endosomes to phagophores. Cell Discovery, Apr 2024. URL: https://doi.org/10.1038/s41421-024-00659-y, doi:10.1038/s41421-024-00659-y. This article has 13 citations and is from a peer-reviewed journal.
(saliba2015germlineduplicationof pages 1-3): Joseph Saliba, Cécile Saint-Martin, Antonio Di Stefano, Gaëlle Lenglet, Caroline Marty, Boris Keren, Florence Pasquier, Véronique Della Valle, Lise Secardin, Gwendoline Leroy, Emna Mahfoudhi, Sarah Grosjean, Nathalie Droin, M'boyba Diop, Philippe Dessen, Sabine Charrier, Alberta Palazzo, Jane Merlevede, Jean-Côme Meniane, Christine Delaunay-Darivon, Pascal Fuseau, Françoise Isnard, Nicole Casadevall, Eric Solary, Najet Debili, Olivier A Bernard, Hana Raslova, Albert Najman, William Vainchenker, Christine Bellanné-Chantelot, and Isabelle Plo. Germline duplication of atg2b and gskip predisposes to familial myeloid malignancies. Nature Genetics, 47:1131-1140, Aug 2015. URL: https://doi.org/10.1038/ng.3380, doi:10.1038/ng.3380. This article has 163 citations and is from a highest quality peer-reviewed journal.
(saliba2015germlineduplicationof pages 4-5): Joseph Saliba, Cécile Saint-Martin, Antonio Di Stefano, Gaëlle Lenglet, Caroline Marty, Boris Keren, Florence Pasquier, Véronique Della Valle, Lise Secardin, Gwendoline Leroy, Emna Mahfoudhi, Sarah Grosjean, Nathalie Droin, M'boyba Diop, Philippe Dessen, Sabine Charrier, Alberta Palazzo, Jane Merlevede, Jean-Côme Meniane, Christine Delaunay-Darivon, Pascal Fuseau, Françoise Isnard, Nicole Casadevall, Eric Solary, Najet Debili, Olivier A Bernard, Hana Raslova, Albert Najman, William Vainchenker, Christine Bellanné-Chantelot, and Isabelle Plo. Germline duplication of atg2b and gskip predisposes to familial myeloid malignancies. Nature Genetics, 47:1131-1140, Aug 2015. URL: https://doi.org/10.1038/ng.3380, doi:10.1038/ng.3380. This article has 163 citations and is from a highest quality peer-reviewed journal.
(sakai2022lossofatg2b pages 1-2): Shun-suke Sakai, Atsushi Hasegawa, Ryosuke Ishimura, Naoki Tamura, Shun Kageyama, Satoko Komatsu-Hirota, Manabu Abe, Yiwei Ling, Shujiro Okuda, Manabu Funayama, Mika Kikkawa, Yoshiki Miura, Kenji Sakimura, Ichiei Narita, Satoshi Waguri, Ritsuko Shimizu, and Masaaki Komatsu. Loss of atg2b and gskip impairs the maintenance of the hematopoietic stem cell pool size. Jan 2022. URL: https://doi.org/10.1128/mcb.00024-21, doi:10.1128/mcb.00024-21. This article has 8 citations and is from a domain leading peer-reviewed journal.
(sakai2022lossofatg2b pages 2-5): Shun-suke Sakai, Atsushi Hasegawa, Ryosuke Ishimura, Naoki Tamura, Shun Kageyama, Satoko Komatsu-Hirota, Manabu Abe, Yiwei Ling, Shujiro Okuda, Manabu Funayama, Mika Kikkawa, Yoshiki Miura, Kenji Sakimura, Ichiei Narita, Satoshi Waguri, Ritsuko Shimizu, and Masaaki Komatsu. Loss of atg2b and gskip impairs the maintenance of the hematopoietic stem cell pool size. Jan 2022. URL: https://doi.org/10.1128/mcb.00024-21, doi:10.1128/mcb.00024-21. This article has 8 citations and is from a domain leading peer-reviewed journal.
(OpenTargets Search: -ATG2B): Open Targets Query (-ATG2B, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(saliba2015germlineduplicationof pages 7-8): Joseph Saliba, Cécile Saint-Martin, Antonio Di Stefano, Gaëlle Lenglet, Caroline Marty, Boris Keren, Florence Pasquier, Véronique Della Valle, Lise Secardin, Gwendoline Leroy, Emna Mahfoudhi, Sarah Grosjean, Nathalie Droin, M'boyba Diop, Philippe Dessen, Sabine Charrier, Alberta Palazzo, Jane Merlevede, Jean-Côme Meniane, Christine Delaunay-Darivon, Pascal Fuseau, Françoise Isnard, Nicole Casadevall, Eric Solary, Najet Debili, Olivier A Bernard, Hana Raslova, Albert Najman, William Vainchenker, Christine Bellanné-Chantelot, and Isabelle Plo. Germline duplication of atg2b and gskip predisposes to familial myeloid malignancies. Nature Genetics, 47:1131-1140, Aug 2015. URL: https://doi.org/10.1038/ng.3380, doi:10.1038/ng.3380. This article has 163 citations and is from a highest quality peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

duarte2023theorganizationand pages 4-5
duarte2023theorganizationand pages 5-7
maeda2019theautophagicmembrane pages 12-14
cross2023lysosomedamagetriggers pages 1-2
saliba2015germlineduplicationof pages 1-3
saliba2015germlineduplicationof pages 4-5
saliba2015germlineduplicationof pages 7-8
https://doi.org/10.1177/25152564231183898
https://doi.org/10.1111/febs.16280
https://doi.org/10.1083/jcb.201811139
https://doi.org/10.15252/embr.201948412
https://doi.org/10.1038/cdd.2017.133
https://doi.org/10.1038/s41421-024-00659-y
https://doi.org/10.1083/jcb.202303078
https://doi.org/10.1038/ng.3380
https://doi.org/10.1128/mcb.00024-21
https://doi.org/10.1177/25152564231183898,
https://doi.org/10.15252/embr.201948412,
https://doi.org/10.1111/febs.16280,
https://doi.org/10.1083/jcb.201811139,
https://doi.org/10.7554/elife.45777,
https://doi.org/10.1083/jcb.202303078,
https://doi.org/10.1038/s41421-024-00659-y,
https://doi.org/10.1038/ng.3380,
https://doi.org/10.1128/mcb.00024-21,

📚 Additional Documentation

Notes

(ATG2B-notes.md)

ATG2B notes

Deep research provenance

Falcon deep research was attempted with the requested perplexity-lite fallback using:

just deep-research-falcon human ATG2B --fallback perplexity-lite

The Falcon child process timed out after 600 seconds. The fallback attempt then failed with a Perplexity API quota error, so no ATG2B-deep-research-falcon.md or fallback provider artifact was written. Per repository guidance, this manual notes file records the evidence review instead of creating a fake provider-named deep-research file.

Evidence synthesis

ATG2B is one of the two mammalian ATG2 orthologs. The core mammalian phenotype is a redundant ATG2A/ATG2B requirement for autophagy: combined ATG2A/B depletion blocks autophagic flux, accumulates unclosed autophagic structures, and leaves other ATG proteins on abnormal LC3-positive membranes [PMID:22219374 "both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions"; PMID:22219374 "these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation"].

The best-supported molecular function is membrane tethering plus lipid transfer. Osawa et al. report that human ATG2B has membrane tethering and lipid-transfer activity, promoted by negatively charged membranes and WIPI4 [PMID:31721365 "ATG2B possesses the membrane tethering (MT) and LT activity"; PMID:31721365 "negatively charged membranes and an Atg18 ortholog WIPI4"]. This supports GO:0120013 lipid transfer activity and GO:0120009 intermembrane lipid transfer, with GO:0000045 autophagosome assembly as the best replacement for broad GO:0006914 autophagy.

The PN projection report lists ATG2B under Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition|ATG2-WIPI complex component, projecting GO:0062079 ATG2-ATG18 complex as a candidate addition. This projection is biologically plausible and conservative when treated as a component annotation, not as evidence for a new proteostasis/chaperone/degradation role. Direct evidence supports ATG2B-WDR45/WIPI4 complex membership [PMID:28820312 "We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex"; PMID:28820312 "conserved aromatic H/YF motif in the C terminus of ATG2A and ATG2B that is crucial for complex formation"]. A human autophagy interaction-network paper also detects ATG2A/ATG2B/WDR45 association PMID:20562859.

The PI3P-binding IBA annotation should be interpreted cautiously. WIPI/ATG18 proteins are the PI3P-binding effectors in the complex, while ATG2B binds liposomes without requiring PI3P or WDR45 in the cited abstract [PMID:28820312 "PtdIns3P-binding effectors which can form complexes with proteins in the Atg2 family"; PMID:28820312 "ATG2B and found that it could bind to liposomes independently of PtdIns3P or WDR45"]. I marked GO:0032266 phosphatidylinositol-3-phosphate binding as over-annotated for ATG2B.

Lipid droplet localization is experimentally supported but not the main PN-relevant role. Velikkakath et al. report mammalian ATG2 proteins on lipid droplets and altered lipid droplet size/distribution after ATG2A/B depletion [PMID:22219374 "One novel aspect of the present study is the finding that mammalian Atg2 proteins are present on lipid droplets"; PMID:22219374 "These data suggest that mammalian Atg2A and Atg2B function both in autophagosome formation and regulation of lipid droplet volume and distribution."]. The same paper notes the directness/mechanism remains unresolved PMID:22219374, so I kept lipid-droplet annotations as non-core.

Selective autophagy terms such as mitophagy, pexophagy, glycophagy, reticulophagy, and piecemeal microautophagy of the nucleus are plausible for a conserved core autophagy membrane-expansion factor, but they should not be read as cargo-specific receptor or recognition functions. I kept those as non-core rather than adding proteostasis-projection-driven cargo-specific conclusions.

Falcon deep research findings (2026-06-07)

A real Falcon report (ATG2B-deep-research-falcon.md, Edison Scientific) was generated, superseding the earlier failed attempt noted above. Key findings vs the existing COMPLETE review (CONFIRMS / NEW / PROVISIONAL). PMIDs resolved via PubMed.

CONFIRMS core lipid-transfer/tether role at the ER-phagophore interface and ATG2A/ATG2B partial redundancy. Adds the strongest mechanistic primary source: in ATG2A/ATG2B double-knockout (DKO) cells a lipid-transfer-competent N-terminal mini-ATG2A(1-345) rescues autophagy whereas lipid-transport-dead mutants do not, establishing lipid transfer as the essential cellular activity [PMID:30952800 "ATG2 transports lipids to promote autophagosome biogenesis"; Valverde 2019]. Note: rescue assays were done with ATG2A; the DKO phenotype defines the shared module.
NEW interaction/mechanism: a conserved ATG2 LIR drives preferential binding to GABARAP-subfamily ATG8 proteins (GABARAP/GABARAP-L1); disrupting this interaction blocks phagophore formation/closure and phenocopies ATG2A/ATG2B DKO, while a WIPI4-binding mutant still rescues autophagy. Endogenous ATG2B co-localizes with GFP-ATG2A on LC3B/WIPI2/ATG16L1-positive early autophagic structures [PMID:32009292 "A conserved ATG2-GABARAP family interaction is critical for phagophore formation"; Bozic 2020]. This is the clearest direct ATG2B localization evidence and reframes WIPI4 binding as dispensable relative to GABARAP binding in mammalian flux — supports a possible future GABARAP/ATG8 LIR-based MF or interaction annotation (not added now; ATG2B-specific LIR not separately mapped to a cached supporting substring).
NEW lipid-source mechanism (2024): ANKFY1, an endosome-localized PI3P/FYVE protein, binds ATG2A and enhances ATG2A-mediated lipid transfer between PI3P liposomes; ANKFY1 depletion impairs autophagosome growth and largely phenocopies ATG2A/B depletion, identifying endosomes (not just ER) as a lipid donor for phagophore expansion [PMID:38622126 "ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores"; Wei 2024]. Direct binding shown for ATG2A; relevance to ATG2B is by redundancy.
NEW noncanonical context (2023): lysosome damage triggers CASM (direct ATG8 conjugation to single membranes) and promotes LC3A engagement with ATG2, extending ATG2 lipid-transfer machinery to lysosomal damage/repair beyond canonical autophagosome biogenesis [PMID:37796195 "Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via non-canonical autophagy"; Cross 2023]. Mammalian ATG2A/ATG2B treated collectively.
NEW disease link: an autosomal-dominant germline ~700-kb 14q32 duplication spanning ATG2B AND GSKIP predisposes to familial myeloid malignancies (MPN/ET progressing to AML/myelofibrosis); ATG2B/GSKIP overexpression increases hematopoietic progenitor differentiation and TPO sensitivity and cooperates with JAK2/MPL/CALR drivers [PMID:26280900 "Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies"; Saliba 2015]. Mouse Atg2b+Gskip double loss reduces the HSC pool, reportedly autophagy-independently [PMID:34751431-? Sakai 2022, DOI 10.1128/mcb.00024-21 — PMID not separately verified, kept notes-only]. PROVISIONAL/locus-level: causality is shared between ATG2B and GSKIP (dosage-sensitive locus), so this is NOT an ATG2B-specific molecular function and does not change annotations; recorded as disease/translational context only.
PROVISIONAL/low-confidence (not used to change annotations): Tang 2017 (cited as DOI 10.1038/cdd.2017.133 in the Falcon table from search-result metadata only) suggesting ATG2A/B deficiency shifts stress responses toward caspase-8/apoptosis; and Open Targets disease associations (Sjogren, neurodegeneration, colorectal carcinoma) flagged as hypothesis-generating only. Maeda 2019 (ATG2A lipid transfer, eLife) reinforces the tether/transfer model but is ATG2A-focused.

Net effect on review: existing annotations and actions remain appropriate. I added the four well-resolved primary references (Bozic 2020, Valverde 2019, Wei 2024, Saliba 2015) as statement-only entries (none cached in publications/), one suggested question (GABARAP/ATG8 LIR), and one suggested experiment (endosomal/ANKFY1 lipid source). No annotation action changed.

Pn Notes

(ATG2B-pn-notes.md)

ATG2B PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q96BY7
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-03 (PR 1377)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/ATG2B/ATG2B-ai-review.yaml
AIGR review HTML: present - genes/human/ATG2B/ATG2B-ai-review.html
Gene notes: present - genes/human/ATG2B/ATG2B-notes.md
GOA TSV: present - genes/human/ATG2B/ATG2B-goa.tsv
UniProt record: present - genes/human/ATG2B/ATG2B-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/ATG2B.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/ATG2B.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/ATG2B/ATG2B-deep-research-falcon.md

AIGR Review Snapshot

Description: ATG2B is a large conserved autophagy-related lipid-transfer protein that acts at endoplasmic reticulum-phagophore membrane contact sites during autophagosome biogenesis. It binds membranes and forms an ATG2-WIPI/ATG18 complex with WDR45/WIPI4, which promotes ATG2B recruitment to PI3P-containing autophagic membranes and stimulates lipid-transfer activity. Mammalian ATG2 proteins are also associated with lipid droplets and affect lipid droplet morphology and dispersion, but the best-supported core role of ATG2B is membrane tethering and lipid transfer for phagophore expansion.
Existing/core annotation action counts: ACCEPT: 10; KEEP_AS_NON_CORE: 7; MARK_AS_OVER_ANNOTATED: 5; MODIFY: 1; NEW: 1

PN Consistency Summary

Consistency: Fully consistent. Deep research/notes, review YAML, PN annotation, and PN-node mapping all converge on ATG2B as a WDR45/WIPI4-associated lipid-transfer/membrane-tethering protein of the ATG2-WIPI complex. The review explicitly adds GO:0062079 as a NEW annotation, citing it as "the conservative way to use the PN projection." No contradictions.
PN story / NEW pressure: PN asserts ATG2-WIPI complex membership not previously in GOA. This is a real term, directly supported by ATG2B-WDR45 structural/biochemical evidence (PMID:28820312, 20562859). Review correctly ADDED it (action: NEW, part_of, IDA). Core molecular function (GO:0120013 lipid transfer activity) and process (autophagosome assembly via MODIFY of GO:0006914) are independently captured. Verdict: PN story is correctly captured/ADDED — well-aligned, no over-reach.
Evidence alignment: Strong overlap. PN cites Mizushima reviews plus the ATG2A-WIPI4/PNAS structural work and the lipid-droplet paper (PMID:22219374); review uses the same PMID:22219374 plus PMID:28820312 (ATG2B-WDR45 architecture) and PMID:31721365 (ATG2B lipid transfer) for the complex/MF claims. Convergent evidence base.
Verdict: Consistent; PN ATG2-ATG18 complex projection correctly ADDED as NEW. No edits required.

Full Consistency Review

UniProt: Q96BY7 · batch: proteostasis-batch-2026-06-03 · review status: COMPLETE
PN placement: ALP|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition|ATG2-WIPI complex component ; PN-node mapping: type-leaf mapped, ok_for_propagation_to_go → GO:0062079 ATG2-ATG18 complex (verified real, OLS); goa_status=more_specific_than_existing_goa.
Consistency: Fully consistent. Deep research/notes, review YAML, PN annotation, and PN-node mapping all converge on ATG2B as a WDR45/WIPI4-associated lipid-transfer/membrane-tethering protein of the ATG2-WIPI complex. The review explicitly adds GO:0062079 as a NEW annotation, citing it as "the conservative way to use the PN projection." No contradictions.
PN story / NEW pressure: PN asserts ATG2-WIPI complex membership not previously in GOA. This is a real term, directly supported by ATG2B-WDR45 structural/biochemical evidence (PMID:28820312, 20562859). Review correctly ADDED it (action: NEW, part_of, IDA). Core molecular function (GO:0120013 lipid transfer activity) and process (autophagosome assembly via MODIFY of GO:0006914) are independently captured. Verdict: PN story is correctly captured/ADDED — well-aligned, no over-reach.
Mapping strategy: Gene supports the existing node mapping rather than changing it; projected component term is narrower than (and complementary to) the review's MF/BP terms — an appropriate complex-membership refinement, not a broad over-propagation.
Evidence alignment: Strong overlap. PN cites Mizushima reviews plus the ATG2A-WIPI4/PNAS structural work and the lipid-droplet paper (PMID:22219374); review uses the same PMID:22219374 plus PMID:28820312 (ATG2B-WDR45 architecture) and PMID:31721365 (ATG2B lipid transfer) for the complex/MF claims. Convergent evidence base.
Verdict: Consistent; PN ATG2-ATG18 complex projection correctly ADDED as NEW. No edits required.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-03
review_yaml: genes/human/ATG2B/ATG2B-ai-review.yaml
PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Regulation of autophagophore membrane composition | ATG2-WIPI complex component

UniProt: Q96BY7
In branches: ALP
Notes: Component of ATG2-WIPI complex, which recruits ATG9 to the autophagosome. ATG2A and ATG2B are lipid transporters, carry phospholipids to the phagophore
PN references (titles):
- Mammalian Autophagy: How Does It Work? | Annual Review of Biochemistry (annualreviews.org)
- Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2A-WIPI4 complex | PNAS
- Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets | Molecular Biology of the Cell (molbiolcell.org)
- Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells[S] - Journal of Lipid Research (jlr.org)
- Autophagosome biogenesis comes out of the black box | Nature Cell Biology
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition|ATG2-WIPI complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0062079 ATG2-ATG18 complex]
  rationale: This PN component bucket corresponds to the ATG2-WIPI/ATG18 lipid-transfer complex used during autophagophore membrane expansion. The GO ATG2-ATG18 complex term is the closest component-level target.
- [group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

GO:0062079 ATG2-ATG18 complex | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition|ATG2-WIPI complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q96BY7
gene_symbol: ATG2B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ATG2B is a large conserved autophagy-related lipid-transfer protein that acts
  at endoplasmic reticulum-phagophore membrane contact sites during
  autophagosome biogenesis. It binds membranes and forms an ATG2-WIPI/ATG18
  complex with WDR45/WIPI4, which promotes ATG2B recruitment to PI3P-containing
  autophagic membranes and stimulates lipid-transfer activity. Mammalian ATG2
  proteins are also associated with lipid droplets and affect lipid droplet
  morphology and dispersion, but the best-supported core role of ATG2B is
  membrane tethering and lipid transfer for phagophore expansion.
existing_annotations:
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      ATG2B is active at autophagy initiation/elongation sites. Mammalian ATG2
      proteins are required at a late step of autophagosome formation, with a
      direct mechanism of lipid transfer at the ER-phagophore interface.
    action: ACCEPT
    reason: >-
      This cellular-component annotation matches the conserved ATG2/WIPI role at
      phagophore assembly sites and is supported by mammalian cell evidence for
      ATG2-dependent autophagosome formation.
    additional_reference_ids:
    - PMID:22219374
    - PMID:31721365
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0000422
    label: autophagy of mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      ATG2B is part of the core macroautophagy machinery required to build
      autophagosomal membranes, so it can participate in mitophagy when the
      macroautophagy machinery is recruited to mitochondria.
    action: KEEP_AS_NON_CORE
    reason: >-
      The annotation is biologically plausible as a phylogenetic inference for a
      core autophagy factor, but it should not be interpreted as a mitochondria-
      selective recognition role for ATG2B. The core function remains
      phagophore lipid transfer.
    additional_reference_ids:
    - PMID:22219374
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation
- term:
    id: GO:0061908
    label: phagophore
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      ATG2B functions on nascent autophagic membranes during phagophore
      expansion and forms a WIPI/ATG18-associated lipid-transfer module.
    action: ACCEPT
    reason: >-
      The phagophore is the core location for ATG2B lipid-transfer activity in
      autophagosome biogenesis.
    additional_reference_ids:
    - PMID:22219374
    - PMID:31721365
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0000425
    label: pexophagy
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      ATG2B can support pexophagy indirectly as part of the general
      autophagosome-building machinery used by selective autophagy pathways.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is best retained as a non-core phylogenetic selective-autophagy
      annotation. The evidence does not show ATG2B as a peroxisome-selective
      cargo receptor or specificity factor.
    additional_reference_ids:
    - PMID:22219374
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions
- term:
    id: GO:0043495
    label: protein-membrane adaptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      ATG2B binds membranes and WDR45/WIPI4 and functions with this WIPI partner
      at autophagic membranes, consistent with a protein-membrane adaptor or
      tethering role in addition to lipid transfer.
    action: ACCEPT
    reason: >-
      Direct biochemical and structural evidence supports ATG2B membrane binding,
      ATG2B-WDR45 complex formation, and membrane tethering/lipid-transfer
      activity. The more specific core molecular function is lipid transfer
      activity, but this term captures a supported tether/adaptor aspect.
    additional_reference_ids:
    - PMID:28820312
    - PMID:31721365
    supported_by:
    - reference_id: PMID:28820312
      supporting_text: mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs
    - reference_id: PMID:31721365
      supporting_text: ATG2B possesses the membrane tethering (MT) and LT activity
- term:
    id: GO:0061723
    label: glycophagy
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      ATG2B may be required for glycophagy insofar as glycophagy uses the core
      macroautophagy membrane expansion machinery.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retain as a non-core inferred selective-autophagy annotation. The direct
      evidence for ATG2B is autophagosome membrane formation, not glycogen cargo
      recognition.
    additional_reference_ids:
    - PMID:22219374
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions
- term:
    id: GO:0032266
    label: phosphatidylinositol-3-phosphate binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      The ATG2-WIPI module is recruited to PI3P-positive autophagic membranes,
      but the direct PI3P-binding effector is the WIPI/ATG18 family partner,
      not clearly ATG2B itself.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This term overstates the available gene-level evidence for ATG2B. Direct
      evidence supports liposome binding and WDR45/WIPI4-dependent association
      with PI3P-containing membranes, but not a specific ATG2B PI3P headgroup
      binding activity.
    additional_reference_ids:
    - PMID:28820312
    - PMID:31721365
    supported_by:
    - reference_id: PMID:28820312
      supporting_text: PtdIns3P-binding effectors which can form complexes with proteins in the Atg2 family
    - reference_id: PMID:28820312
      supporting_text: ATG2B and found that it could bind to liposomes independently of PtdIns3P or WDR45
- term:
    id: GO:0034727
    label: piecemeal microautophagy of the nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      ATG2B is a conserved autophagy factor and may support this process where
      the conserved machinery is used, but human ATG2B is not established as a
      process-specific PMN factor.
    action: KEEP_AS_NON_CORE
    reason: >-
      Keep as a non-core phylogenetic inference. The strongest mammalian
      evidence supports general phagophore/autophagosome biogenesis rather than
      a human PMN-specific role.
    additional_reference_ids:
    - PMID:22219374
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: both Atg2A and Atg2B are required for autophagy and that they have redundant and overlapping functions
- term:
    id: GO:0061709
    label: reticulophagy
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      ATG2B can support reticulophagy as part of the core autophagy membrane
      expansion system, especially because ATG2B acts at ER-phagophore contact
      sites.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retain as non-core. ATG2B is not a reticulophagy cargo receptor or ER
      quality-control factor; its direct role is lipid transfer for phagophore
      expansion.
    additional_reference_ids:
    - PMID:31721365
    supported_by:
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      ER membrane localization is consistent with the accepted model in which
      ATG2B tethers the isolation membrane/phagophore edge to the ER and
      transfers lipids from ER-derived membranes to the growing phagophore.
    action: ACCEPT
    reason: >-
      Although this GOA row is electronically inferred from UniProt subcellular
      location, it is consistent with experimental and biochemical evidence for
      ATG2-dependent ER-to-phagophore lipid transfer.
    additional_reference_ids:
    - PMID:31721365
    supported_by:
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0005811
    label: lipid droplet
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Mammalian ATG2 proteins associate with lipid droplets and affect lipid
      droplet morphology and dispersion, but this is a secondary cellular
      context relative to ATG2B's core phagophore lipid-transfer role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retain the localization, but mark non-core because the publication notes
      that the precise lipid-droplet mechanism and directness of the association
      remain unresolved.
    additional_reference_ids:
    - PMID:22219374
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: One novel aspect of the present study is the finding that mammalian Atg2 proteins are present on lipid droplets
    - reference_id: PMID:22219374
      supporting_text: Further experiments will be required to test whether Atg2 proteins directly or indirectly associate with lipid droplets
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      The broad InterPro-derived autophagy annotation is directionally correct
      but less informative than the experimentally supported role in
      autophagosome assembly/phagophore expansion.
    action: MODIFY
    reason: >-
      Modify to GO:0000045 autophagosome assembly. ATG2B is not merely
      associated with autophagy in general; it is required for formation and
      closure/expansion of autophagosomal membranes.
    proposed_replacement_terms:
    - id: GO:0000045
      label: autophagosome assembly
    additional_reference_ids:
    - PMID:22219374
    - PMID:31721365
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0034045
    label: phagophore assembly site membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      The phagophore assembly site membrane is a supported location for ATG2B
      function and matches its WIPI-associated lipid-transfer role at the
      growing isolation membrane.
    action: ACCEPT
    reason: >-
      The electronic UniProt location mapping is supported by the experimental
      ATG2A/B depletion phenotype and by ATG2B membrane tethering/lipid-transfer
      activity.
    additional_reference_ids:
    - PMID:22219374
    - PMID:31721365
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0120009
    label: intermembrane lipid transfer
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: >-
      ATG2B has membrane tethering and lipid-transfer activity and transfers
      lipids between membranes during isolation membrane expansion.
    action: ACCEPT
    reason: >-
      This BP annotation follows directly from the experimentally demonstrated
      lipid-transfer activity and the model of ER-to-isolation-membrane lipid
      movement.
    additional_reference_ids:
    - PMID:31721365
    supported_by:
    - reference_id: PMID:31721365
      supporting_text: ATG2B possesses the membrane tethering (MT) and LT activity
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20562859
  qualifier: enables
  review:
    summary: >-
      This interaction record reflects WDR45/WIPI4 association in the human
      autophagy interaction network, but generic protein binding is not an
      informative ATG2B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The WDR45 interaction is biologically relevant, but the curation should be
      represented by the ATG2-ATG18 complex/component context and ATG2B lipid
      transfer/tethering function rather than by GO:0005515.
    additional_reference_ids:
    - PMID:28820312
    supported_by:
    - reference_id: PMID:20562859
      supporting_text: association between ATG2A, ATG2B, and WDR45 was unaltered by mTOR inhibition
    - reference_id: PMID:28820312
      supporting_text: mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      This BioPlex interaction row is a high-throughput WDR45 association, but
      GO:0005515 is too generic for ATG2B.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Retaining a generic protein binding MF would obscure the supported biology:
      ATG2B forms a WDR45/WIPI4-associated autophagy lipid-transfer complex. The
      interaction can inform complex membership but should not be treated as a
      core molecular function by itself.
    additional_reference_ids:
    - PMID:28820312
    - PMID:31721365
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: These networks model the interactome whose structure encodes protein function, localization, and complex membership.
    - reference_id: PMID:28820312
      supporting_text: mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34524948
  qualifier: enables
  review:
    summary: >-
      This proximity-interactome annotation supports ATG2B's placement in the
      human macroautophagy interaction network, but it is not an adequate
      molecular-function description.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein binding should not be propagated as ATG2B's function. The
      informative curation is lipid transfer activity and ATG2-WIPI complex
      membership.
    additional_reference_ids:
    - PMID:28820312
    - PMID:31721365
    supported_by:
    - reference_id: PMID:34524948
      supporting_text: Here, we applied BioID to the study of macroautophagy in human cells, generating a proximity interaction map of 39 core macroautophagy proteins.
    - reference_id: PMID:31721365
      supporting_text: ATG2B possesses the membrane tethering (MT) and LT activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: >-
      The OpenCell-derived interaction annotation is useful as interactome
      context, but GO:0005515 is too broad and uninformative for ATG2B curation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction should be interpreted conservatively as supporting complex
      context, not as the gene product's molecular function. ATG2B's curated
      molecular function is lipid transfer activity.
    additional_reference_ids:
    - PMID:28820312
    - PMID:31721365
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: well-curated localization and interactome measurements
    - reference_id: PMID:28820312
      supporting_text: We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      ER localization is consistent with ATG2B's role at ER-associated
      autophagosome biogenesis sites.
    action: ACCEPT
    reason: >-
      The ER is central to ATG2B-mediated lipid transfer to the isolation
      membrane; this broader ER localization is valid alongside the more
      specific ER membrane annotation.
    additional_reference_ids:
    - PMID:31721365
    supported_by:
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      The ER membrane annotation transferred by sequence similarity is
      consistent with the experimentally supported ATG2 lipid-transfer model.
    action: ACCEPT
    reason: >-
      ATG2B acts at an ER-to-isolation-membrane interface, so ER membrane
      localization is a core cellular context.
    additional_reference_ids:
    - PMID:31721365
    supported_by:
    - reference_id: PMID:31721365
      supporting_text: direct lipid transfer (LT) from ER to IM for IM expansion
- term:
    id: GO:0005811
    label: lipid droplet
  evidence_type: EXP
  original_reference_id: PMID:22219374
  qualifier: located_in
  review:
    summary: >-
      ATG2 proteins were observed on lipid droplets, and ATG2A/B depletion
      altered lipid droplet size and distribution.
    action: KEEP_AS_NON_CORE
    reason: >-
      This direct localization should be retained, but it is not the main
      ATG2B core function. The lipid-droplet role is experimentally observed
      but mechanistically less resolved than ER-
      phagophore lipid transfer.
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: One novel aspect of the present study is the finding that mammalian Atg2 proteins are present on lipid droplets
    - reference_id: PMID:22219374
      supporting_text: These data suggest that mammalian Atg2A and Atg2B function both in autophagosome formation and regulation of lipid droplet volume and distribution.
- term:
    id: GO:0034045
    label: phagophore assembly site membrane
  evidence_type: EXP
  original_reference_id: PMID:22219374
  qualifier: located_in
  review:
    summary: >-
      Direct mammalian evidence supports ATG2 localization/function at
      autophagic membranes and shows defective autophagosome formation after
      combined ATG2A/B depletion.
    action: ACCEPT
    reason: >-
      This is a core location for ATG2B lipid transfer and membrane tethering
      during phagophore expansion.
    supported_by:
    - reference_id: PMID:22219374
      supporting_text: these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation
- term:
    id: GO:0120013
    label: lipid transfer activity
  evidence_type: IDA
  original_reference_id: PMID:31721365
  qualifier: enables
  review:
    summary: >-
      Human ATG2B directly possesses lipid-transfer activity, and this activity
      is promoted by negatively charged membranes and WIPI4.
    action: ACCEPT
    reason: >-
      This is the most informative supported molecular-function annotation for
      ATG2B and should be treated as the core molecular function.
    supported_by:
    - reference_id: PMID:31721365
      supporting_text: ATG2B possesses the membrane tethering (MT) and LT activity
    - reference_id: PMID:31721365
      supporting_text: negatively charged membranes and an Atg18 ortholog WIPI4
- term:
    id: GO:0062079
    label: ATG2-ATG18 complex
  evidence_type: IDA
  original_reference_id: PMID:28820312
  qualifier: part_of
  review:
    summary: >-
      NEW annotation. ATG2B forms an ATG2-WIPI/ATG18 complex with WDR45/WIPI4,
      consistent with direct structural and biochemical evidence for complex
      membership.
    action: NEW
    reason: >-
      This is the conservative way to use the PN projection. The projection is
      not evidence for a new proteostasis function by itself, but it points to an
      existing GO complex term that is directly supported by ATG2B-WDR45
      structural and biochemical evidence.
    additional_reference_ids:
    - PMID:20562859
    - PMID:31721365
    supported_by:
    - reference_id: PMID:28820312
      supporting_text: We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex
    - reference_id: PMID:28820312
      supporting_text: conserved aromatic H/YF motif in the C terminus of ATG2A and ATG2B that is crucial for complex formation
    - reference_id: PMID:20562859
      supporting_text: association between ATG2A, ATG2B, and WDR45 was unaltered by mTOR inhibition
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on inter-ontology links
  findings: []
- id: PMID:20562859
  title: Network organization of the human autophagy system.
  findings:
  - statement: ATG2B is a known autophagy protein in a human autophagy interaction network and associates with WDR45.
    supporting_text: association between ATG2A, ATG2B, and WDR45 was unaltered by mTOR inhibition
- id: PMID:22219374
  title: Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets.
  findings:
  - statement: Mammalian ATG2A and ATG2B are required for autophagosome formation and also affect lipid droplet morphology.
    supporting_text: These data suggest that mammalian Atg2A and Atg2B function both in autophagosome formation and regulation of lipid droplet volume and distribution.
- id: PMID:28820312
  title: Architecture of the ATG2B-WDR45 complex and an aromatic Y/HF motif crucial for complex formation.
  full_text_unavailable: true
  findings:
  - statement: ATG2B forms a complex with WDR45/WIPI4, supporting ATG2-ATG18 complex membership.
    supporting_text: We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex
- id: PMID:31721365
  title: Human ATG2B possesses a lipid transfer activity which is accelerated by negatively charged lipids and WIPI4.
  full_text_unavailable: true
  findings:
  - statement: Human ATG2B has membrane tethering and lipid-transfer activity stimulated by WIPI4.
    supporting_text: ATG2B possesses the membrane tethering (MT) and LT activity
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings:
  - statement: BioPlex AP-MS data provide proteome-scale interaction context for high-throughput protein-binding annotations.
    supporting_text: Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks.
- id: PMID:34524948
  title: Global Proximity Interactome of the Human Macroautophagy Pathway.
  findings:
  - statement: BioID mapping places core macroautophagy proteins in a proximity-interaction network and supports cautious interpretation of high-throughput interaction annotations.
    supporting_text: Here, we applied BioID to the study of macroautophagy in human cells, generating a proximity interaction map of 39 core macroautophagy proteins.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings:
  - statement: OpenCell provides endogenous tagging, localization, and interactome measurements for human cellular organization.
    supporting_text: well-curated localization and interactome measurements
- id: PMID:32009292
  title: A conserved ATG2-GABARAP family interaction is critical for phagophore formation.
  full_text_unavailable: true
  findings:
  - statement: A conserved ATG2 LIR mediates binding of ATG2A/ATG2B to GABARAP-subfamily ATG8 proteins; this interaction is required for phagophore formation and closure, whereas the ATG2-WIPI4 interaction is dispensable for autophagy flux.
  - statement: Endogenous ATG2B co-localizes with ATG2A on early autophagic membranes positive for WIPI2 and ATG16L1, providing direct ATG2B localization evidence at phagophore assembly sites.
- id: PMID:30952800
  title: ATG2 transports lipids to promote autophagosome biogenesis.
  findings:
  - statement: ATG2 is a lipid-transfer protein operating at the ER-autophagosome interface; lipid transfer is the major autophagy-dependent activity, since a lipid-transfer-competent ATG2 N-terminal fragment rescues autophagosome biogenesis in ATG2A/ATG2B double-knockout cells whereas lipid-transport-defective mutants do not.
- id: PMID:38622126
  title: ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores.
  findings:
  - statement: The endosomal PI3P-binding protein ANKFY1 binds ATG2A and enhances ATG2-mediated lipid transfer, identifying PI3P-enriched endosomes as an additional lipid source for ATG2-mediated phagophore expansion; ANKFY1 depletion impairs autophagosome growth and largely phenocopies ATG2A/ATG2B depletion.
- id: PMID:26280900
  title: Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies.
  full_text_unavailable: true
  findings:
  - statement: An autosomal-dominant germline 14q32 duplication spanning ATG2B and GSKIP predisposes to familial myeloid malignancies, and overexpression of ATG2B/GSKIP enhances hematopoietic progenitor differentiation and cooperates with JAK2/MPL/CALR driver mutations; the disease effect is a dosage-sensitive locus-level property shared with GSKIP rather than an ATG2B-specific molecular function.
core_functions:
- description: >-
    ATG2B is a WDR45/WIPI4-associated lipid-transfer and membrane-tethering
    protein that transfers lipids between ER-derived membrane sources and the
    growing isolation membrane/phagophore during autophagosome assembly.
  molecular_function:
    id: GO:0120013
    label: lipid transfer activity
  directly_involved_in:
  - id: GO:0120009
    label: intermembrane lipid transfer
  - id: GO:0000045
    label: autophagosome assembly
  locations:
  - id: GO:0034045
    label: phagophore assembly site membrane
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  - id: GO:0061908
    label: phagophore
  in_complex:
    id: GO:0062079
    label: ATG2-ATG18 complex
  supported_by:
  - reference_id: PMID:31721365
    supporting_text: ATG2B possesses the membrane tethering (MT) and LT activity
  - reference_id: PMID:28820312
    supporting_text: We also purified the ATG2B-WDR45 complex and then performed 3-dimensional reconstruction of the complex
  - reference_id: PMID:22219374
    supporting_text: these results suggest that Atg2A/B play an essential role, probably at a late step of autophagosome formation
proposed_new_terms: []
suggested_questions:
- question: >-
    Does ATG2B directly associate with lipid droplets at endogenous expression
    levels, or is the lipid-droplet phenotype secondary to altered ER/phagophore
    lipid handling?
  experts:
  - Noboru Mizushima
  - Noriyuki Noda
  - Li Yu
- question: >-
    Is ATG2B's GABARAP/ATG8-family interaction via the conserved ATG2 LIR
    individually required for ATG2B function at the phagophore (as shown for the
    ATG2 family), and does it represent a distinct ATG8-binding molecular
    function separable from WIPI4 binding in mammalian cells?
  experts:
  - David G. McEwan
  - Noboru Mizushima
suggested_experiments:
- hypothesis: >-
    ATG2B-WDR45 complex formation is required for efficient ATG2B recruitment to
    PI3P-positive phagophore membranes and for autophagosome membrane expansion.
  description: >-
    Use endogenous ATG2B knockout/rescue cells expressing wild-type ATG2B or
    WDR45-binding motif mutants, then measure ATG2B-WDR45 colocalization,
    autophagic flux, and phagophore closure under starvation.
  experiment_type: genome editing, rescue, live-cell imaging, and autophagy flux assay
- hypothesis: >-
    ATG2B, like ATG2A, can transfer lipids from PI3P-enriched endosomes (via
    ANKFY1) in addition to the ER, contributing endosome-derived lipid to
    phagophore expansion.
  description: >-
    In ATG2A/ATG2B double-knockout cells reconstituted with ATG2B, test whether
    ANKFY1 depletion reduces ATG2B-dependent autophagosome growth and PI3P
    distribution on phagophores, and assay ANKFY1-ATG2B binding and ATG2B-mediated
    lipid transfer between PI3P-containing liposomes in vitro.
  experiment_type: knockout/rescue, proximity imaging, in vitro lipid-transfer assay

ATG2B

Gene Description

Existing Annotations Review

Core Functions

ATG2B is a WDR45/WIPI4-associated lipid-transfer and membrane-tethering protein that transfers lipids between ER-derived membrane sources and the growing isolation membrane/phagophore during autophagosome assembly.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research report: Human ATG2B (UniProt: Q96BY7; gene: ATG2B/C14orf103) — functional annotation and current evidence

0) Scope, gene/protein identity verification, and ambiguity checks

1) Key concepts and definitions (current understanding)

1.1 Macroautophagy, phagophore expansion, and membrane contact sites

1.2 ATG2-family proteins as bulk lipid transfer “bridges”

2) Molecular function of ATG2B: what does it do?

2.1 Primary function: non-vesicular lipid transfer that enables phagophore expansion

2.2 ATG2B is not an enzyme catalyzing a classical reaction

3) Subcellular localization: where does ATG2B act?

3.1 ER–phagophore contact sites and early autophagy membranes

3.2 Direct ATG2B localization evidence

4) Interaction partners and pathway placement

4.1 WIPI4/WDR45 (Atg18 family)

4.2 ATG8-family proteins (GABARAP subfamily) via an ATG2 LIR

4.3 ATG9A and lipid scrambling

5) Recent developments and latest research (prioritizing 2023–2024)

5.1 2023: Noncanonical ATG2 engagement after lysosome damage

5.2 2024: Endosomes as an additional lipid source for ATG2-mediated phagophore growth (ANKFY1)

5.3 2023: Updated expert synthesis of phagophore–ER contact site organization

6) Current applications and real-world implementations

6.1 Clinical genetics: germline 14q32 duplication involving ATG2B and GSKIP

6.2 Hypothesis-generating disease associations from Open Targets

7) Relevant statistics and data points from recent/authoritative studies

8) Expert opinions and analysis (authoritative syntheses)

9) Summary table of evidence

10) Conclusions (functional annotation)

Artifacts

Citations

📚 Additional Documentation

Notes

ATG2B notes

Deep research provenance

Evidence synthesis

Falcon deep research findings (2026-06-07)

Pn Notes

ATG2B PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Regulation of autophagophore membrane composition | ATG2-WIPI complex component

Projected GO annotations (1)

Note

📄 View Raw YAML