id: P84077 gene_symbol: ARF1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: ARF1 encodes ADP-ribosylation factor 1, a myristoylated class I ARF-family small GTPase that cycles between cytosolic GDP-bound and membrane-associated GTP-bound states. Active ARF1 acts mainly on Golgi and trans-Golgi network membranes, where it recruits and regulates coat/adaptor and lipid-transfer machinery for vesicle budding, coat disassembly, intra-Golgi traffic, Golgi-to-ER retrograde transport, TGN-to-endosomal/plasma-membrane routes, and glycosphingolipid export. Its major cellular role is regulation of membrane trafficking through the secretory and endomembrane systems rather than serving as a structural coat subunit. existing_annotations: - term: id: GO:0006886 label: intracellular protein transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Intracellular protein transport is a valid broad process for ARF1-dependent Golgi/TGN and COPI-related trafficking. action: ACCEPT reason: This IBA term captures the conserved trafficking role of ARF1. It is broader than the PN retrograde-transport candidate but biologically sound. supported_by: - reference_id: Reactome:R-HSA-6811434 supporting_text: Retrograde traffic from the cis-Golgi to the ERGIC or the ER is mediated in part by microtubule-directed COPI-coated vesicles - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - term: id: GO:0005525 label: GTP binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: GTP binding is the nucleotide-binding state required for ARF1 activation and membrane-effector recruitment. action: ACCEPT reason: This is a core biochemical property of ARF1 and is directly tied to ARF1-dependent coat recruitment and vesicle budding. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - term: id: GO:0005886 label: plasma membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Plasma membrane association/activity is reported in signaling and PLD contexts but is not the primary ARF1 compartment. action: KEEP_AS_NON_CORE reason: ARF1 can participate in plasma-membrane-linked signaling or trafficking, but the dominant conserved role is Golgi/TGN membrane trafficking. supported_by: - reference_id: PMID:8529647 supporting_text: The results indicate that ARF proteins and their nucleotide-exchange factor are apparently involved in the signalling pathway leading from mAChR activation to PLD stimulation in human embryonic kidney cells. - term: id: GO:0000139 label: Golgi membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0003924 label: GTPase activity evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: ARF1 is a canonical small GTPase that binds guanine nucleotide and hydrolyzes GTP as part of its membrane-trafficking cycle. action: ACCEPT reason: The GTP/GDP cycle is the core molecular function of ARF1. GTP binding promotes membrane/effector engagement and GTP hydrolysis, stimulated by ARFGAPs and coatomer, drives coat disassembly. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:0003925 label: G protein activity evidence_type: IEA original_reference_id: GO_REF:0000003 qualifier: enables review: summary: ARF1 is an ADP-ribosylation factor family small G protein whose active GTP-bound state recruits trafficking effectors. action: ACCEPT reason: Although broader than GTPase activity, small G protein activity is an appropriate molecular-function description for ARF1. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - term: id: GO:0005525 label: GTP binding evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables review: summary: GTP binding is the nucleotide-binding state required for ARF1 activation and membrane-effector recruitment. action: ACCEPT reason: This is a core biochemical property of ARF1 and is directly tied to ARF1-dependent coat recruitment and vesicle budding. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - term: id: GO:0014069 label: postsynaptic density evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Synaptic and postsynaptic-density annotations reflect transferred neuronal ARF1/PICK1 biology rather than the core conserved Golgi trafficking function. action: KEEP_AS_NON_CORE reason: These annotations are plausible as specialized neuronal contexts, but they are not the main ARF1 function and are supported here by similarity rather than direct human ARF1 experiments. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Neuronal annotations transferred from orthology, including postsynaptic density, synapse, receptor internalization, Arp2/3 regulation, long-term synaptic depression, and dendritic spine organization, are retained only as non-core specialized contexts. - term: id: GO:0045202 label: synapse evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Synaptic and postsynaptic-density annotations reflect transferred neuronal ARF1/PICK1 biology rather than the core conserved Golgi trafficking function. action: KEEP_AS_NON_CORE reason: These annotations are plausible as specialized neuronal contexts, but they are not the main ARF1 function and are supported here by similarity rather than direct human ARF1 experiments. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Neuronal annotations transferred from orthology, including postsynaptic density, synapse, receptor internalization, Arp2/3 regulation, long-term synaptic depression, and dendritic spine organization, are retained only as non-core specialized contexts. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:10198630 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14654833 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17563369 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19644450 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22981988 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31467278 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:36396045 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0000287 label: magnesium ion binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: Magnesium binding is consistent with ARF1 nucleotide binding and GTPase chemistry. action: ACCEPT reason: Small GTPases require Mg2+-coordinated nucleotide binding/hydrolysis; this is a supporting biochemical property rather than a standalone biological role. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: The magnesium ion binding annotation is retained as a cofactor-level biochemical property of the nucleotide/GTPase mechanism, not as an independent biological role. - term: id: GO:0005794 label: Golgi apparatus evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Cytosolic localization is consistent with the soluble GDP-bound pool of ARF1 between membrane-recruitment cycles. action: ACCEPT reason: ARF1 is a peripheral, myristoylated small GTPase that cycles between cytosol and membranes; cytosol is therefore a real localization, though not the active membrane-bound state. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Cytosol and endomembrane annotations are accurate localization context for a cycling peripheral membrane GTPase, but the active functional emphasis remains Golgi/TGN membrane recruitment and coat/adaptor regulation. - term: id: GO:0012505 label: endomembrane system evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Endomembrane localization is broad but consistent with ARF1 function at Golgi/TGN and related trafficking membranes. action: ACCEPT reason: ARF1 acts on Golgi, TGN, and related endomembrane trafficking intermediates; this term is less specific than Golgi membrane but accurate. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Cytosol and endomembrane annotations are accurate localization context for a cycling peripheral membrane GTPase, but the active functional emphasis remains Golgi/TGN membrane recruitment and coat/adaptor regulation. - reference_id: Reactome:R-HSA-6811434 supporting_text: Retrograde traffic from the cis-Golgi to the ERGIC or the ER is mediated in part by microtubule-directed COPI-coated vesicles - term: id: GO:0030017 label: sarcomere evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Sarcomere localization is not supported by the reviewed ARF1 functional literature and is not part of the ARF1 trafficking model. action: REMOVE reason: This automatic transfer appears disconnected from ARF1 core Golgi/TGN trafficking and should not be retained without stronger direct evidence. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Sarcomere localization and mitotic cleavage furrow ingression are not supported as core ARF1 biology in this review; the curated evidence supports Golgi/TGN endomembrane trafficking instead. - term: id: GO:0032991 label: protein-containing complex evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: part_of review: summary: ARF1 forms transient regulatory complexes with effectors and regulators, but a generic protein-containing complex annotation is not informative. action: MARK_AS_OVER_ANNOTATED reason: This term loses the biology of an active small GTPase recruiting coat/adaptor machinery. It should not be treated as a core complex-membership assertion. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Generic protein-containing complex annotations are treated as over-annotated because ARF1 forms transient regulatory complexes with coat, adaptor, GEF, and GAP machinery rather than acting as a stable structural complex subunit. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:1990386 label: mitotic cleavage furrow ingression evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Mitotic cleavage furrow ingression is a possible specialized small-GTPase trafficking context but is not supported here by direct ARF1 evidence. action: MARK_AS_OVER_ANNOTATED reason: The annotation is too specific for the available electronically transferred evidence and should not be considered core ARF1 biology. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Sarcomere localization and mitotic cleavage furrow ingression are not supported as core ARF1 biology in this review; the curated evidence supports Golgi/TGN endomembrane trafficking instead. - term: id: GO:0003925 label: G protein activity evidence_type: IDA original_reference_id: PMID:17687330 qualifier: enables review: summary: ARF1 is an ADP-ribosylation factor family small G protein whose active GTP-bound state recruits trafficking effectors. action: ACCEPT reason: Although broader than GTPase activity, small G protein activity is an appropriate molecular-function description for ARF1. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - term: id: GO:0046836 label: glycolipid transport evidence_type: IDA original_reference_id: PMID:17687330 qualifier: involved_in review: summary: ARF1 regulates FAPP2-dependent glucosylceramide transfer and glycosphingolipid synthesis/export. action: KEEP_AS_NON_CORE reason: The process is experimentally supported, but it is a specialized lipid-trafficking context downstream of ARF1 effector recruitment rather than the broad conserved core role. supported_by: - reference_id: PMID:17687330 supporting_text: the whole glycosphingolipid synthetic pathway sensitive to regulation by phosphatidylinositol 4-phosphate and ARF1. - term: id: GO:1903292 label: protein localization to Golgi membrane evidence_type: IDA original_reference_id: PMID:17687330 qualifier: involved_in review: summary: ARF1 promotes Golgi/TGN localization of PH-domain effectors such as FAPP proteins by cooperating with phosphatidylinositol 4-phosphate. action: ACCEPT reason: Effector recruitment to Golgi/TGN membranes is a central consequence of ARF1 activation and is directly supported by the FAPP studies. supported_by: - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - reference_id: PMID:17687330 supporting_text: the whole glycosphingolipid synthetic pathway sensitive to regulation by phosphatidylinositol 4-phosphate and ARF1. - term: id: GO:0005765 label: lysosomal membrane evidence_type: IDA original_reference_id: PMID:41293316 qualifier: located_in review: summary: ARF1 can relocalize to damaged lysosomal membranes in LLOME-treated cells. action: KEEP_AS_NON_CORE reason: The localization is experimentally observed, but the same study identifies ARF5, not ARF1, as the isoform required for lysosomal recovery, so this should not be treated as a core ARF1 function. supported_by: - reference_id: PMID:41293316 supporting_text: we found that ARF1, ARF5, and ARF6 localize to lysosomal membranes following L-leucyl-L-leucine methyl ester (LLOME)-induced permeabilization. - term: id: GO:0160281 label: cytoplasmic side of trans-Golgi network membrane evidence_type: IDA original_reference_id: PMID:17687330 qualifier: is_active_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: EXP original_reference_id: PMID:17555535 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0003924 label: GTPase activity evidence_type: EXP original_reference_id: PMID:10022920 qualifier: enables review: summary: This paper identifies a Golgi/plasma-membrane ARF-GAP with activity toward ARF1, supporting ARF1 as a regulated GTPase. action: ACCEPT reason: GTPase activity is the core ARF1 molecular function; the paper supports regulation of ARF1 GTPase cycling by ARF-GAPs. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:0003924 label: GTPase activity evidence_type: EXP original_reference_id: PMID:10102276 qualifier: enables review: summary: ARF1 is a canonical small GTPase that binds guanine nucleotide and hydrolyzes GTP as part of its membrane-trafficking cycle. action: ACCEPT reason: The GTP/GDP cycle is the core molecular function of ARF1. GTP binding promotes membrane/effector engagement and GTP hydrolysis, stimulated by ARFGAPs and coatomer, drives coat disassembly. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:0003924 label: GTPase activity evidence_type: EXP original_reference_id: PMID:15107860 qualifier: enables review: summary: ARF1 is a canonical small GTPase that binds guanine nucleotide and hydrolyzes GTP as part of its membrane-trafficking cycle. action: ACCEPT reason: The GTP/GDP cycle is the core molecular function of ARF1. GTP binding promotes membrane/effector engagement and GTP hydrolysis, stimulated by ARFGAPs and coatomer, drives coat disassembly. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:0003924 label: GTPase activity evidence_type: EXP original_reference_id: PMID:8253837 qualifier: enables review: summary: ARF1 is a canonical small GTPase that binds guanine nucleotide and hydrolyzes GTP as part of its membrane-trafficking cycle. action: ACCEPT reason: The GTP/GDP cycle is the core molecular function of ARF1. GTP binding promotes membrane/effector engagement and GTP hydrolysis, stimulated by ARFGAPs and coatomer, drives coat disassembly. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:0014069 label: postsynaptic density evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Synaptic and postsynaptic-density annotations reflect transferred neuronal ARF1/PICK1 biology rather than the core conserved Golgi trafficking function. action: KEEP_AS_NON_CORE reason: These annotations are plausible as specialized neuronal contexts, but they are not the main ARF1 function and are supported here by similarity rather than direct human ARF1 experiments. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Neuronal annotations transferred from orthology, including postsynaptic density, synapse, receptor internalization, Arp2/3 regulation, long-term synaptic depression, and dendritic spine organization, are retained only as non-core specialized contexts. - term: id: GO:0003924 label: GTPase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-8847883 qualifier: enables review: summary: ARF1 is a canonical small GTPase that binds guanine nucleotide and hydrolyzes GTP as part of its membrane-trafficking cycle. action: ACCEPT reason: The GTP/GDP cycle is the core molecular function of ARF1. GTP binding promotes membrane/effector engagement and GTP hydrolysis, stimulated by ARFGAPs and coatomer, drives coat disassembly. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12668765 qualifier: enables review: summary: ARF-dependent GGA localization is supported, but generic protein binding is too vague. action: MARK_AS_OVER_ANNOTATED reason: The GGA GAT-domain interaction is biologically real, but ARF1 should not be curated mainly as protein binding; its informative role is active small-GTPase recruitment of trafficking adaptors. supported_by: - reference_id: PMID:12668765 supporting_text: The ARF binding site is located in the N-terminal extension and is separate from the core three-helix bundle. - term: id: GO:0019904 label: protein domain specific binding evidence_type: IMP original_reference_id: PMID:12668765 qualifier: enables review: summary: ARF1 binding to the GGA1 GAT domain is a characterized adaptor-recruitment interaction, but it is not the core ARF1 molecular function. action: KEEP_AS_NON_CORE reason: The IMP-supported GGA1-GAT interaction is real and relevant to ARF-dependent adaptor recruitment, but GTPase activity and trafficking-process annotations better capture ARF1 core function. supported_by: - reference_id: PMID:12668765 supporting_text: The ARF binding site is located in the N-terminal extension and is separate from the core three-helix bundle. - term: id: GO:0003924 label: GTPase activity evidence_type: IDA original_reference_id: PMID:12771146 qualifier: enables review: summary: ASAP1 phosphorylation modulates GAP activity and hence ARF1 activity. action: ACCEPT reason: This directly supports ARF1 as a regulated GTPase in signaling/trafficking pathways. supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:0098586 label: cellular response to virus evidence_type: IMP original_reference_id: PMID:28389568 qualifier: involved_in review: summary: The viral-response annotation reflects HCV-induced Golgi remodeling through IRGM/GBF1/ARF-GTPase circuitry. action: KEEP_AS_NON_CORE reason: This is a real infection-specific context but not the conserved core function of ARF1. supported_by: - reference_id: PMID:28389568 supporting_text: which normally operates in Golgi membrane dynamics and vesicle coating in resting cells. - term: id: GO:0032991 label: protein-containing complex evidence_type: IMP original_reference_id: PMID:12668765 qualifier: part_of review: summary: ARF1 forms transient regulatory complexes with effectors and regulators, but a generic protein-containing complex annotation is not informative. action: MARK_AS_OVER_ANNOTATED reason: This term loses the biology of an active small GTPase recruiting coat/adaptor machinery. It should not be treated as a core complex-membership assertion. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Generic protein-containing complex annotations are treated as over-annotated because ARF1 forms transient regulatory complexes with coat, adaptor, GEF, and GAP machinery rather than acting as a stable structural complex subunit. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17956946 qualifier: enables review: summary: The physical interaction is real or plausible, but generic protein binding does not describe ARF1 molecular function. action: MARK_AS_OVER_ANNOTATED reason: Protein binding is non-informative for this gene. ARF1 should be represented by GTP binding/GTPase activity and by specific trafficking processes rather than generic interaction terms. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: 'Generic protein binding annotations are treated as over-annotated because ARF1 has many real effectors and regulators, but the term does not capture the informative activity: regulated small-GTPase recruitment of trafficking machinery.' - term: id: GO:0031252 label: cell leading edge evidence_type: IDA original_reference_id: PMID:22573891 qualifier: located_in review: summary: Cell-leading-edge localization is plausible in chemotactic signaling contexts involving PI3K/GBF1/ARF1 activation. action: KEEP_AS_NON_CORE reason: This is a specialized signaling/localization context, not the central Golgi/TGN ARF1 role. supported_by: - reference_id: PMID:22573891 supporting_text: is primarily responsible for Arf1 activation upon GPCR stimulation and is important for neutrophil chemotaxis and superoxide production. - term: id: GO:0005925 label: focal adhesion evidence_type: HDA original_reference_id: PMID:21423176 qualifier: located_in review: summary: This high-throughput localization is compatible with broad trafficking biology but does not define ARF1 core function. action: MARK_AS_OVER_ANNOTATED reason: High-throughput compartment detections should not outweigh the well-supported Golgi/TGN trafficking model for ARF1. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: High-throughput-only focal adhesion, extracellular exosome, and RNA-binding annotations are treated as over-annotated because they do not define the established ARF1 Golgi/TGN trafficking function. - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:23533145 qualifier: located_in review: summary: This high-throughput localization is compatible with broad trafficking biology but does not define ARF1 core function. action: MARK_AS_OVER_ANNOTATED reason: High-throughput compartment detections should not outweigh the well-supported Golgi/TGN trafficking model for ARF1. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: High-throughput-only focal adhesion, extracellular exosome, and RNA-binding annotations are treated as over-annotated because they do not define the established ARF1 Golgi/TGN trafficking function. - term: id: GO:0003723 label: RNA binding evidence_type: HDA original_reference_id: PMID:22681889 qualifier: enables review: summary: RNA binding is from a high-throughput mRNA-bound proteome study and is not a known ARF1 biochemical function. action: MARK_AS_OVER_ANNOTATED reason: The canonical ARF1 function is guanine nucleotide binding/hydrolysis and membrane trafficking; RNA binding should not be promoted without targeted validation. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: High-throughput-only focal adhesion, extracellular exosome, and RNA-binding annotations are treated as over-annotated because they do not define the established ARF1 Golgi/TGN trafficking function. - term: id: GO:0002090 label: regulation of receptor internalization evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: regulation of receptor internalization reflects transferred neuronal PICK1/AMPAR-related ARF1 biology. action: KEEP_AS_NON_CORE reason: These neuronal terms are plausible specialized contexts but are not the conserved core function of ARF1 and are supported by similarity transfer in this GOA set. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Neuronal annotations transferred from orthology, including postsynaptic density, synapse, receptor internalization, Arp2/3 regulation, long-term synaptic depression, and dendritic spine organization, are retained only as non-core specialized contexts. - term: id: GO:0034315 label: regulation of Arp2/3 complex-mediated actin nucleation evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: regulation of Arp2/3 complex-mediated actin nucleation reflects transferred neuronal PICK1/AMPAR-related ARF1 biology. action: KEEP_AS_NON_CORE reason: These neuronal terms are plausible specialized contexts but are not the conserved core function of ARF1 and are supported by similarity transfer in this GOA set. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Neuronal annotations transferred from orthology, including postsynaptic density, synapse, receptor internalization, Arp2/3 regulation, long-term synaptic depression, and dendritic spine organization, are retained only as non-core specialized contexts. - term: id: GO:0060292 label: long-term synaptic depression evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: long-term synaptic depression reflects transferred neuronal PICK1/AMPAR-related ARF1 biology. action: KEEP_AS_NON_CORE reason: These neuronal terms are plausible specialized contexts but are not the conserved core function of ARF1 and are supported by similarity transfer in this GOA set. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Neuronal annotations transferred from orthology, including postsynaptic density, synapse, receptor internalization, Arp2/3 regulation, long-term synaptic depression, and dendritic spine organization, are retained only as non-core specialized contexts. - term: id: GO:0097061 label: dendritic spine organization evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: dendritic spine organization reflects transferred neuronal PICK1/AMPAR-related ARF1 biology. action: KEEP_AS_NON_CORE reason: These neuronal terms are plausible specialized contexts but are not the conserved core function of ARF1 and are supported by similarity transfer in this GOA set. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Neuronal annotations transferred from orthology, including postsynaptic density, synapse, receptor internalization, Arp2/3 regulation, long-term synaptic depression, and dendritic spine organization, are retained only as non-core specialized contexts. - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19199708 qualifier: located_in review: summary: This high-throughput localization is compatible with broad trafficking biology but does not define ARF1 core function. action: MARK_AS_OVER_ANNOTATED reason: High-throughput compartment detections should not outweigh the well-supported Golgi/TGN trafficking model for ARF1. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: High-throughput-only focal adhesion, extracellular exosome, and RNA-binding annotations are treated as over-annotated because they do not define the established ARF1 Golgi/TGN trafficking function. - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:20458337 qualifier: located_in review: summary: This high-throughput localization is compatible with broad trafficking biology but does not define ARF1 core function. action: MARK_AS_OVER_ANNOTATED reason: High-throughput compartment detections should not outweigh the well-supported Golgi/TGN trafficking model for ARF1. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: High-throughput-only focal adhesion, extracellular exosome, and RNA-binding annotations are treated as over-annotated because they do not define the established ARF1 Golgi/TGN trafficking function. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-1675883 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-1676152 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-2130619 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-350769 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-421831 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-421833 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-432706 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-432712 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-8847875 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-8847880 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-8847883 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-8870499 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-8951498 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0000139 label: Golgi membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9845055 qualifier: located_in review: summary: Golgi membrane localization is central to ARF1 function in coat recruitment and Golgi/TGN trafficking. action: ACCEPT reason: ARF1 cycles between cytosol and Golgi/TGN membranes, where the active GTP-bound form recruits coat and lipid-metabolism effectors. supported_by: - reference_id: PMID:17555535 supporting_text: ARF1 but not ARF5 or 6 enhanced the stimulatory effect of PI4Kbeta on regulated exocytosis. - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-200879 qualifier: located_in review: summary: Cytosolic localization is consistent with the soluble GDP-bound pool of ARF1 between membrane-recruitment cycles. action: ACCEPT reason: ARF1 is a peripheral, myristoylated small GTPase that cycles between cytosol and membranes; cytosol is therefore a real localization, though not the active membrane-bound state. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Cytosol and endomembrane annotations are accurate localization context for a cycling peripheral membrane GTPase, but the active functional emphasis remains Golgi/TGN membrane recruitment and coat/adaptor regulation. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-350769 qualifier: located_in review: summary: Cytosolic localization is consistent with the soluble GDP-bound pool of ARF1 between membrane-recruitment cycles. action: ACCEPT reason: ARF1 is a peripheral, myristoylated small GTPase that cycles between cytosol and membranes; cytosol is therefore a real localization, though not the active membrane-bound state. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Cytosol and endomembrane annotations are accurate localization context for a cycling peripheral membrane GTPase, but the active functional emphasis remains Golgi/TGN membrane recruitment and coat/adaptor regulation. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-421831 qualifier: located_in review: summary: Cytosolic localization is consistent with the soluble GDP-bound pool of ARF1 between membrane-recruitment cycles. action: ACCEPT reason: ARF1 is a peripheral, myristoylated small GTPase that cycles between cytosol and membranes; cytosol is therefore a real localization, though not the active membrane-bound state. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Cytosol and endomembrane annotations are accurate localization context for a cycling peripheral membrane GTPase, but the active functional emphasis remains Golgi/TGN membrane recruitment and coat/adaptor regulation. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-432706 qualifier: located_in review: summary: Cytosolic localization is consistent with the soluble GDP-bound pool of ARF1 between membrane-recruitment cycles. action: ACCEPT reason: ARF1 is a peripheral, myristoylated small GTPase that cycles between cytosol and membranes; cytosol is therefore a real localization, though not the active membrane-bound state. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Cytosol and endomembrane annotations are accurate localization context for a cycling peripheral membrane GTPase, but the active functional emphasis remains Golgi/TGN membrane recruitment and coat/adaptor regulation. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8950173 qualifier: located_in review: summary: Cytosolic localization is consistent with the soluble GDP-bound pool of ARF1 between membrane-recruitment cycles. action: ACCEPT reason: ARF1 is a peripheral, myristoylated small GTPase that cycles between cytosol and membranes; cytosol is therefore a real localization, though not the active membrane-bound state. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Cytosol and endomembrane annotations are accurate localization context for a cycling peripheral membrane GTPase, but the active functional emphasis remains Golgi/TGN membrane recruitment and coat/adaptor regulation. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8951498 qualifier: located_in review: summary: Cytosolic localization is consistent with the soluble GDP-bound pool of ARF1 between membrane-recruitment cycles. action: ACCEPT reason: ARF1 is a peripheral, myristoylated small GTPase that cycles between cytosol and membranes; cytosol is therefore a real localization, though not the active membrane-bound state. supported_by: - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: Cytosol and endomembrane annotations are accurate localization context for a cycling peripheral membrane GTPase, but the active functional emphasis remains Golgi/TGN membrane recruitment and coat/adaptor regulation. - term: id: GO:0006878 label: intracellular copper ion homeostasis evidence_type: IMP original_reference_id: PMID:21034850 qualifier: involved_in review: summary: ARF1-dependent trafficking affects copper uptake and CTR1 distribution. action: KEEP_AS_NON_CORE reason: This is experimentally supported but appears to be a cargo/trafficking consequence rather than ARF1's primary molecular role. supported_by: - reference_id: PMID:21034850 supporting_text: Arf1-dependent trafficking pathways are therefore required for optimal copper uptake efficiency. - term: id: GO:0005886 label: plasma membrane evidence_type: TAS original_reference_id: PMID:8529647 qualifier: located_in review: summary: Plasma membrane association/activity is reported in signaling and PLD contexts but is not the primary ARF1 compartment. action: KEEP_AS_NON_CORE reason: ARF1 can participate in plasma-membrane-linked signaling or trafficking, but the dominant conserved role is Golgi/TGN membrane trafficking. supported_by: - reference_id: PMID:8529647 supporting_text: The results indicate that ARF proteins and their nucleotide-exchange factor are apparently involved in the signalling pathway leading from mAChR activation to PLD stimulation in human embryonic kidney cells. - term: id: GO:0006890 label: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum evidence_type: TAS original_reference_id: Reactome:R-HSA-6811434 qualifier: involved_in review: summary: PN projection and Reactome support adding the specific Golgi-to-ER retrograde transport process for ARF1. action: NEW reason: ARF1 is the regulatory small GTPase that promotes coat recruitment and controls COPI coat cycling. This supports a process-level retrograde transport annotation, while the projected COPI vesicle coat component term should not be added because ARF1 is not a coatomer subunit. additional_reference_ids: - Reactome:R-HSA-6811434 - file:human/ARF1/ARF1-notes.md supported_by: - reference_id: Reactome:R-HSA-6811434 supporting_text: Retrograde traffic from the cis-Golgi to the ERGIC or the ER is mediated in part by microtubule-directed COPI-coated vesicles - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - reference_id: file:human/ARF1/ARF1-notes.md supporting_text: The projected `GO:0030126 COPI vesicle coat` should not be added for ARF1. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000003 title: Gene Ontology annotation based on Enzyme Commission mapping 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:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:10022920 title: Identification of a new Pyk2 target protein with Arf-GAP activity. findings: [] - id: PMID:10102276 title: Structural and functional analysis of the ARF1-ARFGAP complex reveals a role for coatomer in GTP hydrolysis. findings: [] - id: PMID:10198630 title: 'Brefeldin A acts to stabilize an abortive ARF-GDP-Sec7 domain protein complex: involvement of specific residues of the Sec7 domain.' findings: [] - id: PMID:12668765 title: 'Structure of the GAT domain of human GGA1: a syntaxin amino-terminal domain fold in an endosomal trafficking adaptor.' findings: [] - id: PMID:12771146 title: The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. findings: [] - id: PMID:14654833 title: Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor. findings: [] - id: PMID:15107860 title: FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P. findings: [] - id: PMID:17555535 title: Specificity, promiscuity and localization of ARF protein interactions with NCS-1 and phosphatidylinositol-4 kinase-III beta. findings: [] - id: PMID:17563369 title: Structure-based discovery of an inhibitor of Arf activation by Sec7 domains through targeting of protein-protein complexes. findings: [] - id: PMID:17687330 title: Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide. findings: [] - id: PMID:17956946 title: Dissecting the role of the ARF guanine nucleotide exchange factor GBF1 in Golgi biogenesis and protein trafficking. findings: [] - id: PMID:19199708 title: Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). findings: [] - id: PMID:19644450 title: 'The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4.' findings: [] - id: PMID:20458337 title: MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. findings: [] - id: PMID:21034850 title: The ADP-ribosylation factor 1 (Arf1) is involved in regulating copper uptake. findings: [] - id: PMID:21423176 title: "Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for \u03B2-Pix in negative regulation of focal adhesion maturation." findings: [] - id: PMID:22573891 title: "GBF1 bears a novel phosphatidylinositol-phosphate binding module, BP3K, to link PI3K\u03B3 activity with Arf1 activation involved in GPCR-mediated neutrophil chemotaxis and superoxide production." findings: [] - id: PMID:22681889 title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. findings: [] - id: PMID:22981988 title: The BAR domain protein Arfaptin-1 controls secretory granule biogenesis at the trans-Golgi network. findings: [] - id: PMID:23533145 title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. findings: [] - id: PMID:28389568 title: Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M. findings: [] - id: PMID:31467278 title: Maximizing binary interactome mapping with a minimal number of assays. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:36396045 title: Targeting ARF1-IQGAP1 interaction to suppress colorectal cancer metastasis and vemurafenib resistance. findings: [] - id: PMID:41293316 title: Loss of ARF5 impairs recovery after lysosomal damage. findings: [] - id: PMID:8253837 title: Hydrolysis of bound GTP by ARF protein triggers uncoating of Golgi-derived COP-coated vesicles. findings: [] - id: PMID:8529647 title: Evidence for ADP-ribosylation-factor-mediated activation of phospholipase D by m3 muscarinic acetylcholine receptor. findings: [] - id: PMID:37914730 title: ARF1 prevents aberrant type I interferon induction by regulating STING activation and recycling. full_text_unavailable: true findings: - statement: ARF1 is a negative regulator of cGAS-STING type I interferon signaling; GTPase-defective heterozygous ARF1 missense mutations (e.g. R99C/R99H) cause a type I interferonopathy, with mutant ARF1 perturbing mitochondrial integrity (driving mtDNA release and cGAS activation) and causing accumulation of active STING at the Golgi/ERGIC due to defective retrograde transport. - id: PMID:37400497 title: Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis. full_text_unavailable: true findings: - statement: Arf1 integrates cellular metabolism with energy production by regulating fatty-acid storage and utilization; a hyperactive Arf1 mutant causes fatty-acid accumulation in lipid droplets, mitochondrial fragmentation, and decreased ATP synthesis, with the role in fatty-acid metabolism conserved in mammals and proposed to act via organelle contact sites. - id: PMID:36269825 title: 'Self-assembly and structure of a clathrin-independent AP-1:Arf1 tubular membrane coat.' findings: - statement: Myristoylated GTP-bound Arf1 recruits AP-1 and stabilizes it in an active conformation, and AP-1:Arf1 self-assembles into a clathrin-independent tubular membrane coat via Arf1 dimer interfaces; HIV-1 Nef hijacks this AP-1:Arf1 coat to sequester MHC-I, and coat-contact residues are conserved across Arf isoforms and AP-1/AP-3/AP-4. - id: Reactome:R-HSA-1675883 title: PI is phosphorylated to PI4P by PI4KB at the Golgi membrane findings: [] - id: Reactome:R-HSA-1676152 title: PI4KB binds to ARF1/3:GTP at the Golgi membrane findings: [] - id: Reactome:R-HSA-200879 title: Formation of a Nef:ARF1:CD4 complex findings: [] - id: Reactome:R-HSA-2130619 title: TGN-lysosomal vesicle coat assembly findings: [] - id: Reactome:R-HSA-350769 title: trans-Golgi Network Coat Activation findings: [] - id: Reactome:R-HSA-421831 title: trans-Golgi Network Coat Assembly findings: [] - id: Reactome:R-HSA-421833 title: Vamp And trans-Golgi Network AP-1 Binding Coupled With Cargo Capture findings: [] - id: Reactome:R-HSA-432706 title: trans-Golgi Network Lysosome Vesicle Destined Membrane Coat Assembly findings: [] - id: Reactome:R-HSA-432712 title: Vamp And trans-Golgi Network AP-1 Binding Coupled With Cargo Capture On Lysosome Vesicle Destined Golgi Membrane findings: [] - id: Reactome:R-HSA-8847875 title: ARF1:GTP binds Golgin TRIP11 findings: [] - id: Reactome:R-HSA-8847880 title: CYTH proteins bind ARF1:GTP findings: [] - id: Reactome:R-HSA-8847883 title: CYTH proteins stimulate ARF1 GTPase activity findings: [] - id: Reactome:R-HSA-8870499 title: PLEKHA3,8 bind PI4P, ARF1 findings: [] - id: Reactome:R-HSA-8950173 title: Expression of ADP-ribosylation factor 1 findings: [] - id: Reactome:R-HSA-8951498 title: Dissociation of Arf1:GDP, AP-1 Clathrin coated nonameric complex findings: [] - id: Reactome:R-HSA-9845055 title: PLEKHA8 catalyzes transport of GlcCer to plasma membrane findings: [] - id: file:human/ARF1/ARF1-notes.md title: ARF1 PN review notes findings: - statement: ARF1 is a regulatory ARF-family GTPase for Golgi/TGN trafficking; PN retrograde transport propagation is supported, but COPI vesicle coat component propagation is rejected. - id: Reactome:R-HSA-6811434 title: COPI-dependent Golgi-to-ER retrograde traffic findings: - statement: Reactome pathway supporting ARF1 participation in COPI-dependent Golgi-to-ER retrograde traffic. - id: Reactome:R-HSA-6807878 title: COPI-mediated anterograde transport findings: [] - id: Reactome:R-HSA-6811438 title: Intra-Golgi traffic findings: [] - id: Reactome:R-HSA-432720 title: Lysosome Vesicle Biogenesis findings: [] - id: Reactome:R-HSA-432722 title: Golgi Associated Vesicle Biogenesis findings: [] - id: Reactome:R-HSA-9845576 title: Glycosphingolipid transport findings: [] core_functions: - description: ARF1 functions as a guanine-nucleotide-regulated membrane-trafficking switch at Golgi and TGN membranes. In its GTP-bound state it recruits coat/adaptor and lipid-metabolism effectors, including machinery for COPI-dependent Golgi-to-ER and intra-Golgi trafficking; GTP hydrolysis stimulated by ARFGAPs and coatomer promotes coat disassembly and recycling of the trafficking machinery. ARF1 is therefore best represented as a regulatory small GTPase in vesicle-mediated intracellular transport, not as a structural COPI coat subunit. molecular_function: id: GO:0003924 label: GTPase activity directly_involved_in: - id: GO:0006886 label: intracellular protein transport - id: GO:0006890 label: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum - id: GO:1903292 label: protein localization to Golgi membrane locations: - id: GO:0000139 label: Golgi membrane - id: GO:0160281 label: cytoplasmic side of trans-Golgi network membrane - id: GO:0005829 label: cytosol supported_by: - reference_id: PMID:8253837 supporting_text: The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein, ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle transport. - reference_id: PMID:10102276 supporting_text: a tripartite complex controls the GTP hydrolysis reaction triggering disassembly of COPI vesicle coats. - reference_id: Reactome:R-HSA-6811434 supporting_text: Retrograde traffic from the cis-Golgi to the ERGIC or the ER is mediated in part by microtubule-directed COPI-coated vesicles - reference_id: PMID:15107860 supporting_text: FAPPs are essential components of a PtdIns(4)P- and ARF-regulated machinery. proposed_new_terms: [] suggested_questions: - question: Should PN-to-GO propagation for `COPI coating and uncoating` distinguish structural coatomer subunits from regulatory GTPases such as ARF1 so that `GO:0030126 COPI vesicle coat` is not projected to ARF1? - question: Would a process term for ARF-dependent COPI coat assembly/disassembly better capture ARF1 than the cellular-component term `COPI vesicle coat`? - question: Should ARF1's role in terminating cGAS-STING signaling via retrograde Golgi-to-ER recycling of STING be captured as a distinct negative-regulation-of-type-I-interferon process annotation, or does it remain a downstream consequence of the core retrograde-transport function? suggested_experiments: - description: Use acute endogenous ARF1 depletion or rapid ARF1 inactivation together with rescue by GTPase-cycle mutants, then quantify KDEL receptor/chaperone retrieval from Golgi to ER and COPI coat recruitment/uncoating kinetics. hypothesis: ARF1 GTPase cycling is required for efficient Golgi-to-ER retrieval of escaped ER proteins, supporting the retrograde-transport annotation without implying ARF1 is a structural COPI coat component. experiment_type: cell biology - description: Perform proximity labeling of endogenous ARF1 during synchronized COPI budding/uncoating and compare enrichment of coatomer subunits, ARFGAPs, KDEL receptors, and cargo proteins across GTP-locked and GDP-locked ARF1 states. hypothesis: ARF1 associates transiently with COPI coat-cycle machinery as a regulatory GTPase rather than as a stable COPI coat constituent. experiment_type: proteomics - description: Express disease-associated GTPase-defective ARF1 variants (e.g. R99C/R99H) in ARF1-edited cells and quantify STING retrograde Golgi-to-ER recycling, mitochondrial morphology and mtDNA release, and interferon-stimulated gene induction relative to wild-type ARF1 rescue. hypothesis: Loss of ARF1 GTPase cycling impairs STING retrograde transport and mitochondrial integrity, causing cGAS-STING-dependent type I interferon hyperactivation, distinct from ARF1's bulk Golgi/TGN coat-recruitment role. experiment_type: cell biology