Annexin A1 (lipocortin 1) is a glucocorticoid-inducible member of the annexin family, built from a unique N-terminal domain and four calcium-binding annexin repeats. In the cytoplasm it binds calcium and, in a calcium-dependent manner, associates peripherally with anionic phospholipid membranes (plasma membrane, endosomes, secretory granules), can aggregate and fuse vesicles in vitro, and its N-terminus binds S100A11. ANXA1 lacks a signal peptide but is externalised to the cell surface and released (via gelatinase granules, extracellular vesicles and TMED10-dependent unconventional secretion). Extracellular ANXA1 and its N-terminal peptide Ac2-26 (released, for example, by cathepsin G) act as agonists of the formyl peptide receptors FPR1, FPR2/ALX and FPR3, limiting neutrophil transendothelial migration, promoting resolution of inflammation, efferocytosis and epithelial wound repair, inhibiting neuroendocrine hormone exocytosis and modulating T cell activation. It mediates part of the anti-inflammatory action of glucocorticoids. Its historically described phospholipase A2 inhibition reflects sequestration of phospholipid substrate. ANXA1 is also a substrate of EGFR, PKC and transglutaminase.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001533 cornified envelope | IDA PMID:10908733 Small proline-rich protein 1 is the major component of the c... | KEEP AS NON CORE | Summary: Annexin I was biochemically identified as a minor constituent of the cornified envelope of human oral keratinocytes. Reason: Direct biochemical evidence that ANXA1 is incorporated into the cross-linked cell envelope, consistent with it being a transglutaminase substrate. Correct location but a tissue-specific fate rather than a site of its core activity. Supporting Evidence: PMID:10908733 together with smaller amounts of involucrin, annexin I and several other known CE proteins. |
| GO:0001533 cornified envelope | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred cornified envelope location (mouse Anxa1). Reason: Supported by the human IDA (PMID:10908733); ANXA1 is a minor cross-linked envelope component. Non-core, tissue-specific. Supporting Evidence: PMID:10908733 together with smaller amounts of involucrin, annexin I and several other known CE proteins. |
| GO:0001780 neutrophil homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer of neutrophil homeostasis from the mouse knockout. Reason: Anxa1-null mice accumulate senescent neutrophils in bone marrow because resident macrophages fail to clear them. Real but a downstream organismal phenotype of the pro-resolving/clearance role; non-core. Supporting Evidence: PMID:21957127 AnxA1(-/-) mice have significantly increased neutrophil numbers in their bone marrow PMID:21957127 we conclude that expression of AnxA1 by resident macrophages is a critical determinant for neutrophil clearance in the bone marrow. |
| GO:0001780 neutrophil homeostasis | IMP PMID:21957127 Annexin A1 regulates neutrophil clearance by macrophages in ... | KEEP AS NON CORE | Summary: AnxA1-deficient mice have increased, more senescent bone-marrow neutrophils and defective macrophage clearance of neutrophils. Reason: Experimental (mouse knockout, with human apoptotic neutrophils and human recombinant AnxA1 used in assays). Accepted as a physiological consequence of ANXA1 pro-resolving activity, but a homeostatic outcome rather than the molecular role. Supporting Evidence: PMID:21957127 AnxA1(-/-) mice have significantly increased neutrophil numbers in their bone marrow PMID:21957127 we conclude that expression of AnxA1 by resident macrophages is a critical determinant for neutrophil clearance in the bone marrow. |
| GO:0001786 phosphatidylserine binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inherited phosphatidylserine binding, shared across the annexin family. Reason: ANXA1 binds PS-containing vesicles in a Ca2+-dependent manner; this is the defining membrane-recognition activity of annexins and directly measured for human ANXA1. IBA node placement at the annexin family root is consistent with the experimental data. Supporting Evidence: PMID:2532504 display Ca2+-dependent binding to phosphatidylserine-containing vesicles PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0001891 phagocytic cup | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping (by similarity to mouse) to phagocytic cup. Reason: Mouse Anxa1 colocalizes with actin at phagocytic cups; plausible for human phagocytes, consistent with macrophage phagocytosis defects in the knockout. Non-core localization. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt formation of phagocytic cups and phagosomes PMID:12475898 Anx-1-/- macrophages exhibited anomalies in phagocytosis |
| GO:0002548 monocyte chemotaxis | IDA PMID:15187149 An annexin 1 N-terminal peptide activates leukocytes by trig... | KEEP AS NON CORE | Summary: The ANXA1 N-terminal peptide (Ac2-26) induces chemotaxis of human monocytes via FPR family receptors. Reason: The experiment uses a synthetic N-terminal peptide acting as an extracellular FPR agonist; ANXA1 acts as a ligand that regulates monocyte chemotaxis rather than migrating itself. Physiologically, the dominant effect is desensitisation/inhibition of leukocyte emigration. Retained as non-core; the core process is regulation of leukocyte migration. Supporting Evidence: PMID:15187149 The annexin 1 peptide initiates chemotactic responses in human monocytes that express all three FPR family members and also desensitizes the cells toward subsequent stimulation with bacterial peptide agonists. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0002685 regulation of leukocyte migration | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based annotation: ANXA1 regulates leukocyte migration. Reason: Well supported: ANXA1/N-terminal peptides acting via FPRs inhibit neutrophil transendothelial migration, and knockout mice show increased leukocyte emigration. Appropriate level of specificity for a core anti-inflammatory process. Supporting Evidence: PMID:10882119 This causes a specific inhibition of the transendothelial migration of neutrophils and a desensitization of neutrophils toward a chemoattractant challenge. PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. |
| GO:0002685 regulation of leukocyte migration | ISS GO_REF:0000024 | ACCEPT | Summary: Curator ortholog transfer: regulation of leukocyte migration. Reason: As above; also supported by direct human data (PMID:10882119) and KO phenotype (PMID:12475898). Supporting Evidence: PMID:10882119 This causes a specific inhibition of the transendothelial migration of neutrophils and a desensitization of neutrophils toward a chemoattractant challenge. PMID:15187149 annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family. PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. |
| GO:0004859 phospholipase inhibitor activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO mapping of annexin domain to phospholipase inhibitor activity. Reason: Annexin-mediated PLA2 inhibition in vitro is explained by sequestration of the anionic phospholipid substrate interface rather than by binding to and inhibiting the enzyme, which is what the MF term asserts. The underlying activity is calcium-dependent phospholipid binding (already annotated). Supporting Evidence: PMID:9425121 a substrate depletion mechanism is now widely accepted as the explanation for most inhibitory studies. file:human/ANXA1/ANXA1-uniprot.txt Inhibition of phospholipase activity |
| GO:0005102 signaling receptor binding | TAS PMID:10882119 A novel ligand of the formyl peptide receptor: annexin I reg... | MODIFY | Summary: ANXA1 N-terminal peptides are endogenous ligands of the formyl peptide receptor (FPR) on human neutrophils. Reason: "Signaling receptor binding" is correct but uninformative. ANXA1 (and its N-terminal Ac2-26 peptide) acts as an agonist of FPR1/FPR2/FPR3, activating and desensitising these GPCRs, which fits receptor ligand activity. Proposed replacements: receptor ligand activity Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005509 calcium ion binding | EXP PMID:11078886 Solution structure and membrane-binding property of the N-te... | ACCEPT | Summary: Calcium binding by human annexin I (N-terminal peptide CD/NMR; Ca2+ stabilises membrane-bound helix). Reason: Annexin repeats bind multiple Ca2+ ions; calcium binding is fundamental to ANXA1 membrane association. The cited experiment is indirect (N-terminal peptide), but the function is well established for the protein. Supporting Evidence: PMID:11078886 These results suggest that the N-terminal tail domain of human annexin I interacts with biological membranes in a partially calcium-dependent manner. PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based calcium ion binding (annexin repeat). Reason: Annexin repeats are type II Ca2+-binding sites; correct. Supporting Evidence: PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0005509 calcium ion binding | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-transferred calcium ion binding. Reason: Correct; consistent with Ca2+-dependent phospholipid binding of human ANXA1. Supporting Evidence: PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0005509 calcium ion binding | TAS PMID:2967291 Cloning and expression of cDNA for human endonexin II, a Ca2... | ACCEPT | Summary: Traceable author statement from the endonexin II (ANXA5) cloning paper, which compares annexin family members including lipocortin I. Reason: The abstract focuses on endonexin II, but describes the annexins (incl. lipocortin I) as Ca2+-dependent phospholipid binding proteins. Calcium binding by ANXA1 is clearly correct, so the curator is deferred to. Supporting Evidence: PMID:2967291 Endonexin II is a member of the family of Ca2+-dependent phospholipid binding proteins known as annexins. PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0005515 protein binding | IPI PMID:20029029 Regulation of epidermal growth factor receptor trafficking b... | REMOVE | Summary: Membrane yeast two-hybrid screen of ligand-unoccupied EGFR identified ANXA1 among candidate interactors. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. ANXA1 is a well-known EGFR kinase substrate; that relationship is captured on the kinase side, and no specific ANXA1 MF is established here. Supporting Evidence: PMID:20029029 We used a modified membrane yeast two-hybrid system together with bioinformatics to identify 87 candidate proteins interacting with the ligand-unoccupied EGFR. |
| GO:0005515 protein binding | IPI PMID:21383699 Annexin-1 interacts with NEMO and RIP1 to constitutively act... | REMOVE | Summary: Co-immunoprecipitation of ANXA1 with RIPK1 in metastatic breast cancer cells; ANXA1 required for RIP1 recruitment to NEMO. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. A scaffold/adaptor role in IKK activation is suggested but not established well enough to propose a specific MF term. Supporting Evidence: PMID:21383699 silencing of ANXA1 prevents the interaction of NEMO and RIP1, which indicates that ANXA1 is required for the recruitment of RIP1 to the IKK complex |
| GO:0005515 protein binding | IPI PMID:21383699 Annexin-1 interacts with NEMO and RIP1 to constitutively act... | REMOVE | Summary: Co-immunoprecipitation of ANXA1 with IKBKG/NEMO in breast cancer cells. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. Cancer-cell-line specific; a defined adaptor activity is not established. Supporting Evidence: PMID:21383699 immunoprecipitation confirmed that ANXA1 can bind to and interact with IKKΞ³ or NEMO, but not IKKΞ± or IKKΞ². |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | REMOVE | Summary: EGFR interactome mass spectrometry identifies ANXA1. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. Supporting Evidence: PMID:24189400 Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: EGFR network proteomics in KRAS(G13D) colorectal cancer cells identifies ANXA1. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D). |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary Y2H interaction with an LNPK isoform. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. High-throughput binary screen, no functional context. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput Y2H interactome screen of neurodegenerative disease proteins reports interaction with LEG1. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. High-throughput screen without functional follow-up for ANXA1. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput Y2H interactome screen of neurodegenerative disease proteins reports interaction with ZHX1-C8orf76. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. High-throughput screen without functional follow-up for ANXA1. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput Y2H interactome screen of neurodegenerative disease proteins reports interaction with EVA1B. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. High-throughput screen without functional follow-up for ANXA1. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:34237247 Global mapping of Salmonella enterica-host protein-protein i... | REMOVE | Summary: Host-pathogen interaction mapping detected ANXA1 binding to the Salmonella PipB effector. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. A host-pathogen effector interaction does not define a normal ANXA1 molecular function. Supporting Evidence: PMID:34237247 SteC-FMNL1, PipB2-ATP1A1, PipB2-ANXA1, SseJ-CD44, SseL-SACM1L or PipB-GroEL. |
| GO:0005515 protein binding | IPI PMID:34237247 Global mapping of Salmonella enterica-host protein-protein i... | REMOVE | Summary: Host-pathogen interaction mapping detected ANXA1 binding to the Salmonella SseJ effector. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. A host-pathogen effector interaction does not define a normal ANXA1 molecular function. Supporting Evidence: PMID:34237247 SteC-FMNL1, PipB2-ATP1A1, PipB2-ANXA1, SseJ-CD44, SseL-SACM1L or PipB-GroEL. |
| GO:0005515 protein binding | IPI PMID:34237247 Global mapping of Salmonella enterica-host protein-protein i... | REMOVE | Summary: Host-pathogen interaction mapping detected ANXA1 binding to the Salmonella PipB2 effector. Reason: Generic protein binding is uninformative about ANXA1 function. Per project policy this IPI row is removed; this does not dispute that the reported interaction occurs. A host-pathogen effector interaction does not define a normal ANXA1 molecular function. Supporting Evidence: PMID:34237247 SteC-FMNL1, PipB2-ATP1A1, PipB2-ANXA1, SseJ-CD44, SseL-SACM1L or PipB-GroEL. |
| GO:0005543 phospholipid binding | TAS PMID:2967291 Cloning and expression of cDNA for human endonexin II, a Ca2... | ACCEPT | Summary: Phospholipid binding (TAS) from the endonexin II cloning paper describing annexins as Ca2+/phospholipid binding proteins. Reason: Correct though general; the more precise calcium-dependent phospholipid binding is also annotated. Curator deferred to. Supporting Evidence: PMID:2967291 Endonexin II is a member of the family of Ca2+-dependent phospholipid binding proteins known as annexins. PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0005544 calcium-dependent phospholipid binding | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited calcium-dependent phospholipid binding (annexin family IBA; ANXA1 among the experimental sources). Reason: Core annexin activity with direct experimental support for human ANXA1; ANXA1 appearing in the WITH/FROM list reflects its own experimental grounding. Supporting Evidence: PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. PMID:2532504 display Ca2+-dependent binding to phosphatidylserine-containing vesicles |
| GO:0005544 calcium-dependent phospholipid binding | IDA PMID:2138016 Characterization of Ca2(+)-dependent phospholipid binding, v... | ACCEPT | Summary: Lipocortin I shows Ca2+-dependent binding to anionic phospholipid vesicles (PA > PS > PI; not PC). Reason: Direct biochemical evidence for the core membrane-binding activity of ANXA1. Supporting Evidence: PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0005544 calcium-dependent phospholipid binding | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation of calcium-dependent phospholipid binding. Reason: Correct, consistent with experimental data. Supporting Evidence: PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. PMID:2532504 display Ca2+-dependent binding to phosphatidylserine-containing vesicles |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | ACCEPT | Summary: ANXA1 detected in human tear fluid by proteomics. Reason: ANXA1 is secreted/externalised via unconventional routes; detection in tears is consistent. Supporting Evidence: PMID:22664934 Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach. |
| GO:0005576 extracellular region | HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter... | ACCEPT | Summary: ANXA1 detected in tears by shotgun proteomics. Reason: Consistent with known secretion of ANXA1. Supporting Evidence: PMID:23580065 Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naΓ―ve to therapy. |
| GO:0005576 extracellular region | IDA PMID:17008549 Annexin-1 modulates T-cell activation and differentiation. | ACCEPT | Summary: ANXA1 is externalised/released upon T cell activation. Reason: Experimental support for secretion of ANXA1, which acts on FPR in an autocrine/paracrine manner. Supporting Evidence: PMID:17008549 the protein, initially localized in the cytoplasm of resting cells, is rapidly externalized on the cell surface or released into the extracellular milieu upon cell activation |
| GO:0005576 extracellular region | IDA PMID:19625660 Annexin A1 regulates hormone exocytosis through a mechanism ... | ACCEPT | Summary: ANXA1 acts in a paracrine/juxtacrine manner to inhibit hormone exocytosis. Reason: Supports extracellular presence of ANXA1 as a secreted mediator. Supporting Evidence: PMID:19625660 The glucocorticoid-regulated protein annexin A1 is a potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner. |
| GO:0005576 extracellular region | IDA PMID:25664854 Annexin A1-containing extracellular vesicles and polymeric n... | ACCEPT | Summary: ANXA1 released in extracellular vesicles from intestinal epithelial cells. Reason: Direct evidence for extracellular ANXA1. Supporting Evidence: PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (Secreted). Reason: Correct; ANXA1 is secreted by unconventional (EV and TMED10-dependent) routes. Supporting Evidence: PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. PMID:32272059 We identify TMED10 as a protein channel for the vesicle entry and secretion of many leaderless cargoes. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-379048 | ACCEPT | Summary: Reactome places ANXA1 as an extracellular FPR ligand in the reaction "Liganded Gq/11-activating GPCRs act as GEFs for Gq/11". Reason: ANXA1 is an extracellular agonist of FPR1/FPR2/FPR3; extracellular region is the correct location for the ligand role. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-380073 | ACCEPT | Summary: Reactome places ANXA1 as an extracellular FPR ligand in the reaction "Liganded Gi-activating GPCR acts as a GEF for Gi". Reason: ANXA1 is an extracellular agonist of FPR1/FPR2/FPR3; extracellular region is the correct location for the ligand role. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-391913 | ACCEPT | Summary: Reactome places ANXA1 as an extracellular FPR ligand in the reaction "FPR2 binds FPR2 ligands". Reason: ANXA1 is an extracellular agonist of FPR1/FPR2/FPR3; extracellular region is the correct location for the ligand role. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-444476 | ACCEPT | Summary: Reactome places ANXA1 as an extracellular FPR ligand in the reaction "FPRL2 receptor binds a wide range of ligands". Reason: ANXA1 is an extracellular agonist of FPR1/FPR2/FPR3; extracellular region is the correct location for the ligand role. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6785895 | ACCEPT | Summary: Reactome: ANXA1 among IL4/IL13-upregulated extracellular proteins. Reason: Extracellular location is correct; ANXA1 is secreted. Supporting Evidence: PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749448 | ACCEPT | Summary: Reactome places ANXA1 as an extracellular FPR ligand in the reaction "Liganded Gq-activating GPCRs bind inactive heterotrimeric Gq". Reason: ANXA1 is an extracellular agonist of FPR1/FPR2/FPR3; extracellular region is the correct location for the ligand role. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749452 | ACCEPT | Summary: Reactome places ANXA1 as an extracellular FPR ligand in the reaction "The Ligand:GPCR:Gq complex dissociates". Reason: ANXA1 is an extracellular agonist of FPR1/FPR2/FPR3; extracellular region is the correct location for the ligand role. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749454 | ACCEPT | Summary: Reactome places ANXA1 as an extracellular FPR ligand in the reaction "The Ligand:GPCR:Gi complex dissociates". Reason: ANXA1 is an extracellular agonist of FPR1/FPR2/FPR3; extracellular region is the correct location for the ligand role. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749456 | ACCEPT | Summary: Reactome places ANXA1 as an extracellular FPR ligand in the reaction "Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi". Reason: ANXA1 is an extracellular agonist of FPR1/FPR2/FPR3; extracellular region is the correct location for the ligand role. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0005634 nucleus | EXP PMID:19625660 Annexin A1 regulates hormone exocytosis through a mechanism ... | KEEP AS NON CORE | Summary: ANXA1 detected in nucleus of AtT20 cells. Reason: A minor nuclear pool is reported in several cell types; no nuclear function is established. Supporting Evidence: PMID:19625660 we show a critical involvement of phosphorylation on serine 27 and 45 in the translocation of the protein to the membrane and its inhibitory action on exocytosis. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Annexin-family IBA for nuclear localization. Reason: Some ANXA1 is nuclear, but the protein functions predominantly at membranes, cytoplasm and extracellularly. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005634 nucleus | IDA PMID:10772777 Annexin I is stored within gelatinase granules of human neut... | KEEP AS NON CORE | Summary: Small amounts of annexin I in neutrophil nuclei. Reason: Correct but minor pool. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005634 nucleus | IDA PMID:22056994 Suppression of MIP-2 or IL-8 production by annexins A1 and A... | KEEP AS NON CORE | Summary: Nuclear ANXA1 observed in human cells (apoptotic neutrophil/HeLa study). Reason: Minor pool; non-core. Supporting Evidence: PMID:22056994 Annexin A4 (ANXA4) is also recruited from the nucleus to the cytoplasm in apoptotic cells |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular location mapping to nucleus. Reason: Minor pool, non-core. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence in nucleoplasm. Reason: Minor pool; no nuclear function established. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Annexin-family IBA: active in cytoplasm. Reason: Cytoplasm is the predominant intracellular pool from which ANXA1 translocates to membranes in a Ca2+-dependent manner. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005737 cytoplasm | IDA PMID:10772777 Annexin I is stored within gelatinase granules of human neut... | ACCEPT | Summary: Cytoplasmic pool predominant in resting neutrophils. Reason: Direct evidence. Supporting Evidence: PMID:10772777 The cytoplasmic pool of annexin I was predominant |
| GO:0005737 cytoplasm | IDA PMID:17008549 Annexin-1 modulates T-cell activation and differentiation. | ACCEPT | Summary: ANXA1 localized in cytoplasm of resting T cells. Reason: Direct evidence. Supporting Evidence: PMID:17008549 the protein, initially localized in the cytoplasm of resting cells, is rapidly externalized on the cell surface or released into the extracellular milieu upon cell activation |
| GO:0005737 cytoplasm | IDA PMID:19625660 Annexin A1 regulates hormone exocytosis through a mechanism ... | ACCEPT | Summary: ANXA1 in cytoplasm of AtT20 cells. Reason: Correct. Supporting Evidence: PMID:19625660 we show a critical involvement of phosphorylation on serine 27 and 45 in the translocation of the protein to the membrane and its inhibitory action on exocytosis. |
| GO:0005737 cytoplasm | IDA PMID:22056994 Suppression of MIP-2 or IL-8 production by annexins A1 and A... | ACCEPT | Summary: ANXA1 cytoplasmic in human cells. Reason: Correct. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation: cytoplasm. Reason: Correct. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005737 cytoplasm | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | ACCEPT | Summary: HUVEC proteome includes ANXA1 (TAS). Reason: Cytoplasmic location is correct, although this proteomics paper is weak support. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005768 endosome | IDA PMID:18767904 Hrs and SNX3 functions in sorting and membrane invagination ... | ACCEPT | Summary: Endogenous ANXA1 colocalizes with SNX3 and ANXA2 on endosomes in HeLa cells. Reason: Direct imaging evidence; ANXA1 has a documented role on EGF-receptor-containing multivesicular endosomes. Supporting Evidence: PMID:18767904 These observations show that SNX3 is present on endosomes that contain both annexin A1 and annexin A2. |
| GO:0005769 early endosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt mapping to early endosome (by similarity). Reason: Consistent with ANXA1 on early/multivesicular endosomes. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Early endosome PMID:18767904 These observations show that SNX3 is present on endosomes that contain both annexin A1 and annexin A2. |
| GO:0005769 early endosome | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog transfer of early endosome location. Reason: Consistent with human imaging data. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Early endosome PMID:18767904 These observations show that SNX3 is present on endosomes that contain both annexin A1 and annexin A2. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence: cytosol. Reason: Correct; cytosolic soluble pool. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005884 actin filament | IDA PMID:22773844 Annexin-1-mediated endothelial cell migration and angiogenes... | KEEP AS NON CORE | Summary: ANXA1 colocalizes with F-actin in endothelial lamellipodia. Reason: Colocalization with actin filaments is reported, consistent with its role in VEGF-driven migration; non-core. Supporting Evidence: PMID:22773844 ANXA1, both in basal and VEGF-induced conditions, colocalizes with F-actin in the lamellipodia of endothelial cells |
| GO:0005886 plasma membrane | EXP PMID:19625660 Annexin A1 regulates hormone exocytosis through a mechanism ... | ACCEPT | Summary: ANXA1 translocates to the plasma membrane in AtT20 cells. Reason: Correct; Ca2+/phosphorylation-dependent membrane translocation. Supporting Evidence: PMID:19625660 we show a critical involvement of phosphorylation on serine 27 and 45 in the translocation of the protein to the membrane and its inhibitory action on exocytosis. |
| GO:0005886 plasma membrane | EXP PMID:25664854 Annexin A1-containing extracellular vesicles and polymeric n... | ACCEPT | Summary: ANXA1 on the (outer) cell membrane/EVs of epithelial cells. Reason: Correct. Supporting Evidence: PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Annexin-family IBA: plasma membrane. Reason: Core membrane location of annexins; supported experimentally for ANXA1. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. PMID:10772777 provoked an intense mobilization of annexin I, with a marked externalization on the outer leaflet of the plasma membrane. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence: plasma membrane. Reason: Correct. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005886 plasma membrane | IDA PMID:10772777 Annexin I is stored within gelatinase granules of human neut... | ACCEPT | Summary: Annexin I at plasma membrane and externalised on outer leaflet of adherent neutrophils. Reason: Direct evidence. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. PMID:10772777 provoked an intense mobilization of annexin I, with a marked externalization on the outer leaflet of the plasma membrane. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation: plasma membrane. Reason: Correct. Supporting Evidence: PMID:10772777 In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. |
| GO:0005912 adherens junction | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | KEEP AS NON CORE | Summary: ANXA1 detected in the E-cadherin interactome by proteomics. Reason: High-throughput proximity/co-purification; plausible cortical membrane location but no functional role at adherens junctions established. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: ANXA1 identified in focal adhesion proteome. Reason: High-throughput; non-core. Supporting Evidence: PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for Ξ²-Pix in negative regulation of focal adhesion maturation. |
| GO:0005929 cilium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt mapping (by similarity) to cilium. Reason: Bovine ANXA1 cilium localization; human ANXA1 detected in exosome-like vesicles from ciliated airway epithelium. Plausible but non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Cell projection, cilium |
| GO:0006909 phagocytosis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phagocytosis (IBA, ANXA1 subfamily node). Reason: Anxa1-null macrophages show phagocytosis anomalies and defective clearance of apoptotic neutrophils; ANXA1 supports Ca2+-dependent phagosome-actin interactions. Supported but secondary to the anti-inflammatory ligand role. Supporting Evidence: PMID:12475898 Anx-1-/- macrophages exhibited anomalies in phagocytosis PMID:21957127 we conclude that expression of AnxA1 by resident macrophages is a critical determinant for neutrophil clearance in the bone marrow. |
| GO:0006909 phagocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer: phagocytosis. Reason: As for the IBA. Supporting Evidence: PMID:12475898 Anx-1-/- macrophages exhibited anomalies in phagocytosis file:human/ANXA1/ANXA1-uniprot.txt formation of phagocytic cups and phagosomes |
| GO:0006909 phagocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator ortholog transfer: phagocytosis. Reason: As for the IBA. Supporting Evidence: PMID:12475898 Anx-1-/- macrophages exhibited anomalies in phagocytosis file:human/ANXA1/ANXA1-uniprot.txt formation of phagocytic cups and phagosomes |
| GO:0006954 inflammatory response | IEA GO_REF:0000107 | MODIFY | Summary: Ortholog transfer of inflammatory response. Reason: ANXA1 is an anti-inflammatory, pro-resolving mediator; it limits rather than drives the inflammatory response (knockout mice show exaggerated inflammation). The parent term "inflammatory response" is better replaced by negative regulation of inflammatory response. Proposed replacements: negative regulation of inflammatory response Supporting Evidence: PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. PMID:19104500 we propose a model in which glucocorticoids regulate the expression and function of annexin A1 in opposing ways in innate and adaptive immune cells to mediate the resolution of inflammation. |
| GO:0006954 inflammatory response | ISS GO_REF:0000024 | MODIFY | Summary: Curator ortholog transfer of inflammatory response. Reason: ANXA1 is an anti-inflammatory, pro-resolving mediator; it limits rather than drives the inflammatory response (knockout mice show exaggerated inflammation). The parent term "inflammatory response" is better replaced by negative regulation of inflammatory response. Proposed replacements: negative regulation of inflammatory response Supporting Evidence: PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. PMID:19104500 we propose a model in which glucocorticoids regulate the expression and function of annexin A1 in opposing ways in innate and adaptive immune cells to mediate the resolution of inflammation. |
| GO:0006954 inflammatory response | TAS PMID:10882119 A novel ligand of the formyl peptide receptor: annexin I reg... | MODIFY | Summary: Annexin I regulates neutrophil extravasation through FPR; mediates anti-inflammatory glucocorticoid actions. Reason: ANXA1 is an anti-inflammatory, pro-resolving mediator; it limits rather than drives the inflammatory response (knockout mice show exaggerated inflammation). The parent term "inflammatory response" is better replaced by negative regulation of inflammatory response. Proposed replacements: negative regulation of inflammatory response Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. PMID:10882119 This causes a specific inhibition of the transendothelial migration of neutrophils and a desensitization of neutrophils toward a chemoattractant challenge. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Signal transduction (IBA, ANXA1-subfamily node). Reason: Broad but correct: extracellular ANXA1 initiates FPR-mediated signalling. The more specific GPCR signalling pathway term is preferable as core. Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. |
| GO:0007165 signal transduction | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | KEEP AS NON CORE | Summary: Signal transduction (TAS) from a HUVEC proteomics paper. Reason: Signal transduction is broadly correct for ANXA1 as an FPR ligand, but the cited HUVEC proteomics study only lists ANXA1 among identified proteins in broad functional categories and provides no specific evidence. Kept as non-core, consistent with the IBA row; the GPCR signalling term is preferred. Supporting Evidence: PMID:16130169 illustrates various cellular functions more related to cell motility and angiogenesis, protein folding, anti-oxidant defenses, signal transduction, proteasome pathway and resistance to apoptosis. |
| GO:0007166 cell surface receptor signaling pathway | TAS PMID:10882119 A novel ligand of the formyl peptide receptor: annexin I reg... | MODIFY | Summary: Annexin I peptides act as FPR ligands to trigger signalling. Reason: Correct but the receptor class is known: FPRs are GPCRs, so G protein-coupled receptor signaling pathway is more informative. Proposed replacements: G protein-coupled receptor signaling pathway Supporting Evidence: PMID:10882119 Peptides derived from the unique N-terminal domain of annexin I serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. |
| GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | IDA PMID:25664854 Annexin A1-containing extracellular vesicles and polymeric n... | MODIFY | Summary: Ac2-26 acting via FPRs promotes epithelial wound repair. Reason: ANXA1/Ac2-26 activates formyl peptide receptors (Gi-coupled GPCRs), eliciting Ca2+ transients, MAPK, and Rho kinase signalling; coupling to a cyclic nucleotide second messenger is not the defining feature. Generalise to G protein-coupled receptor signaling pathway. Proposed replacements: G protein-coupled receptor signaling pathway Supporting Evidence: PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | IMP PMID:15187149 An annexin 1 N-terminal peptide activates leukocytes by trig... | MODIFY | Summary: ANXA1 N-terminal peptide activates and desensitizes FPR family receptors in monocytes and transfected HEK293 cells. Reason: ANXA1/Ac2-26 activates formyl peptide receptors (Gi-coupled GPCRs), eliciting Ca2+ transients, MAPK, and Rho kinase signalling; coupling to a cyclic nucleotide second messenger is not the defining feature. Generalise to G protein-coupled receptor signaling pathway. Proposed replacements: G protein-coupled receptor signaling pathway Supporting Evidence: PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0008289 lipid binding | EXP PMID:8756690 Folding properties of an annexin I domain: a 1H-15N NMR and ... | ACCEPT | Summary: Lipid (micelle) interactions of an isolated annexin I repeat domain. Reason: The experiment shows detergent micelles structuring an isolated domain, which is weak evidence; however lipid binding is clearly correct for ANXA1 (Ca2+-dependent anionic phospholipid binding). Accepted as a general parent of the core activity. Supporting Evidence: PMID:8756690 Dodecylphosphocholine (DPC) micelles were used to provide the annexin domain with non-specific hydrophobic interactions. PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0008360 regulation of cell shape | IDA PMID:15187149 An annexin 1 N-terminal peptide activates leukocytes by trig... | KEEP AS NON CORE | Summary: Ac2-26 peptide induces cell shape changes/polarisation of FPR-expressing leukocytes. Reason: Downstream of FPR activation; non-core. Supporting Evidence: PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0009986 cell surface | IDA PMID:22056994 Suppression of MIP-2 or IL-8 production by annexins A1 and A... | ACCEPT | Summary: ANXA1 detected on the surface of apoptotic neutrophils and late apoptotic HeLa cells. Reason: Cell-surface exposure of ANXA1 is a key feature of its extracellular signalling and eat-me roles. Supporting Evidence: PMID:22056994 ANXA1 and a small amount of ANXA4 were detected on both early and late apoptotic human neutrophils. |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt mapping to endosome membrane (peripheral). Reason: Consistent with ANXA1 on endosomes. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Endosome membrane PMID:18767904 These observations show that SNX3 is present on endosomes that contain both annexin A1 and annexin A2. |
| GO:0010008 endosome membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog transfer: endosome membrane. Reason: Consistent with human imaging data. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Endosome membrane PMID:18767904 These observations show that SNX3 is present on endosomes that contain both annexin A1 and annexin A2. |
| GO:0012506 vesicle membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Annexin-family IBA: vesicle membrane. Reason: Consistent with Ca2+-dependent binding to vesicle/endosomal membranes and gelatinase granule association. Supporting Evidence: PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. PMID:18767904 These observations show that SNX3 is present on endosomes that contain both annexin A1 and annexin A2. |
| GO:0014839 myoblast migration involved in skeletal muscle regeneration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer of myoblast migration in skeletal muscle regeneration (mouse). Reason: Plausible from mouse studies; tissue-specific, non-core. Supporting Evidence: PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. |
| GO:0016020 membrane | EXP PMID:17008549 Annexin-1 modulates T-cell activation and differentiation. | ACCEPT | Summary: ANXA1 membrane association in T cells. Reason: Correct. Supporting Evidence: PMID:17008549 the protein, initially localized in the cytoplasm of resting cells, is rapidly externalized on the cell surface or released into the extracellular milieu upon cell activation |
| GO:0016020 membrane | EXP PMID:2532504 A dimeric form of lipocortin-1 in human placenta. | ACCEPT | Summary: Placental lipocortin-1 dimer binds PS-containing membranes. Reason: Correct; peripheral membrane protein. Supporting Evidence: PMID:2532504 display Ca2+-dependent binding to phosphatidylserine-containing vesicles |
| GO:0016020 membrane | EXP PMID:8557678 Calcium-dependent binding of S100C to the N-terminal domain ... | ACCEPT | Summary: Annexin I/S100C study; Ca2+-dependent membrane binding. Reason: Correct. Supporting Evidence: PMID:8557678 The annexin family of proteins is characterized by a conserved core domain that binds to phospholipids in a Ca(2+)-dependent manner. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation: membrane. Reason: Correct. Supporting Evidence: PMID:2138016 The Ca2+ requirement for all of the proteins was lowest for binding to vesicles composed of phosphatidic acid, followed by phosphatidylserine and then phosphatidylinositol. |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt mapping (by similarity) to basolateral cell membrane. Reason: Polarised-epithelium localization from ortholog data; plausible, non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Basolateral cell membrane |
| GO:0016323 basolateral plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog transfer: basolateral plasma membrane. Reason: Plausible, non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Basolateral cell membrane |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Combined automated annotation: apical plasma membrane. Reason: Plausible, non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Apical cell membrane |
| GO:0016324 apical plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog transfer: apical plasma membrane. Reason: Plausible, non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Apical cell membrane |
| GO:0016328 lateral plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Combined automated annotation: lateral plasma membrane. Reason: Plausible, non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Lateral cell membrane |
| GO:0016328 lateral plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog transfer: lateral plasma membrane. Reason: Plausible, non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Lateral cell membrane |
| GO:0018149 peptide cross-linking | IDA PMID:10908733 Small proline-rich protein 1 is the major component of the c... | MARK AS OVER ANNOTATED | Summary: Annexin I is a minor component of the transglutaminase cross-linked cornified envelope. Reason: ANXA1 is a substrate that becomes cross-linked; the cross-linking step is performed by transglutaminases. Being incorporated into a cross-linked structure is not participation in the peptide cross-linking process, so the term over-states ANXA1 involvement. Supporting Evidence: PMID:10908733 together with smaller amounts of involucrin, annexin I and several other known CE proteins. PMID:2532504 suggesting that the cross-link may be generated by a transglutaminase. |
| GO:0019834 phospholipase A2 inhibitor activity | IDA PMID:2936963 Cloning and expression of human lipocortin, a phospholipase ... | MARK AS OVER ANNOTATED | Summary: Recombinant human lipocortin inhibits PLA2 activity in vitro. Reason: The in vitro observation is real, but subsequent work showed annexin inhibition of PLA2 is mostly due to sequestration of the phospholipid substrate (interfacial competition), not enzyme binding. Kept as historical, non-core; not used as a core function. Marked as over-annotation (not removed): the experimental observation stands, but the MF term asserts binding to and inhibition of the enzyme, which the substrate-sequestration mechanism does not satisfy. Supporting Evidence: PMID:2936963 Our studies confirm that lipocortin is a potent inhibitor of phospholipase A2 activity. PMID:9425121 a substrate depletion mechanism is now widely accepted as the explanation for most inhibitory studies. |
| GO:0019834 phospholipase A2 inhibitor activity | IDA PMID:3013422 Two human 35 kd inhibitors of phospholipase A2 are related t... | MARK AS OVER ANNOTATED | Summary: Lipocortin I purified from placenta as a PLA2 inhibitor. Reason: Same caveat as above: substrate-depletion mechanism. Marked as over-annotation (not removed): the experimental observation stands, but the MF term asserts binding to and inhibition of the enzyme, which the substrate-sequestration mechanism does not satisfy. Supporting Evidence: PMID:3013422 We have purified two 35 kd phospholipase A2 inhibitors from human placenta, which we refer to as lipocortin I and II. PMID:9425121 a substrate depletion mechanism is now widely accepted as the explanation for most inhibitory studies. |
| GO:0019834 phospholipase A2 inhibitor activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA prediction of phospholipase A2 inhibitor activity. Reason: Electronic propagation of a historically defined activity whose mechanism is substrate sequestration; overstates a direct enzyme-inhibitor function. Supporting Evidence: PMID:9425121 a substrate depletion mechanism is now widely accepted as the explanation for most inhibitory studies. file:human/ANXA1/ANXA1-uniprot.txt Inhibition of phospholipase activity |
| GO:0030036 actin cytoskeleton organization | IDA PMID:15187149 An annexin 1 N-terminal peptide activates leukocytes by trig... | KEEP AS NON CORE | Summary: Ac2-26 triggers actin cytoskeleton rearrangement in FPR-expressing cells. Reason: Downstream effect of FPR signalling; non-core. Consistent with actin-dependent inhibition of exocytosis. Supporting Evidence: PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. PMID:19625660 annexin A1-dependent inhibition of adrenocorticotrophin release involves the enhancement of actin polymerization to prevent exocytosis via formyl peptide receptor and Rho kinase signaling pathways. |
| GO:0030216 keratinocyte differentiation | IDA PMID:10908733 Small proline-rich protein 1 is the major component of the c... | MARK AS OVER ANNOTATED | Summary: Annexin I found among oral keratinocyte cell envelope proteins. Reason: Detection as a minor cornified envelope component does not show that ANXA1 contributes to keratinocyte differentiation; the paper attributes the specialised barrier role to SPR1. Supporting Evidence: PMID:10908733 together with smaller amounts of involucrin, annexin I and several other known CE proteins. |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt mapping (by similarity) to cytoplasmic vesicle membrane. Reason: Consistent with Ca2+-dependent peripheral association with vesicle membranes. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Cytoplasmic vesicle membrane |
| GO:0030659 cytoplasmic vesicle membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog transfer: cytoplasmic vesicle membrane. Reason: Consistent. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Cytoplasmic vesicle membrane |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | KEEP AS NON CORE | Summary: ANXA1 detected in ECM-enriched proteomic fractions. Reason: High-throughput detection; ANXA1 is abundant and secreted, so ECM-fraction detection is plausible but not indicative of an ECM structural role. Supporting Evidence: PMID:25037231 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | KEEP AS NON CORE | Summary: ANXA1 detected in ECM-enriched proteomic fractions. Reason: High-throughput detection; ANXA1 is abundant and secreted, so ECM-fraction detection is plausible but not indicative of an ECM structural role. Supporting Evidence: PMID:28344315 Proteomic characterization of human multiple myeloma bone marrow extracellular matrix. |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | KEEP AS NON CORE | Summary: ANXA1 detected in ECM-enriched proteomic fractions. Reason: High-throughput detection; ANXA1 is abundant and secreted, so ECM-fraction detection is plausible but not indicative of an ECM structural role. Supporting Evidence: PMID:28675934 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics. |
| GO:0031340 positive regulation of vesicle fusion | IDA PMID:2138016 Characterization of Ca2(+)-dependent phospholipid binding, v... | KEEP AS NON CORE | Summary: Lipocortin I lowers the Ca2+ threshold for liposome fusion in vitro. Reason: In vitro liposome assay; cellular relevance to membrane fusion events (e.g. endosome fusion) plausible but not core. Supporting Evidence: PMID:2138016 Lipocortin I promoted fusion of liposome membranes by lowering threshold Ca2+ concentrations. |
| GO:0031340 positive regulation of vesicle fusion | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction: positive regulation of vesicle fusion. Reason: Supported by in vitro data; non-core. Supporting Evidence: PMID:2138016 Lipocortin I promoted fusion of liposome membranes by lowering threshold Ca2+ concentrations. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt mapping: cytoplasmic vesicle (secretory vesicle lumen/gelatinase granules). Reason: ANXA1 stored in neutrophil gelatinase granules. Supporting Evidence: PMID:10772777 Electron microscopy showed the presence of annexin I inside the gelatinase granules. |
| GO:0031514 motile cilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer: motile cilium. Reason: Plausible from ortholog data; non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Cell projection, cilium |
| GO:0031514 motile cilium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator ortholog transfer: motile cilium. Reason: Plausible; non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Cell projection, cilium |
| GO:0031901 early endosome membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog transfer: early endosome membrane. Reason: Consistent with ANXA1 endosome association. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Early endosome PMID:18767904 These observations show that SNX3 is present on endosomes that contain both annexin A1 and annexin A2. |
| GO:0031982 vesicle | HDA PMID:19190083 Characterization of exosome-like vesicles released from huma... | ACCEPT | Summary: ANXA1 in exosome-like vesicles from human tracheobronchial ciliated epithelium. Reason: Consistent with EV release of ANXA1. Supporting Evidence: PMID:19190083 Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense. |
| GO:0032652 regulation of interleukin-1 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer: regulation of IL-1 production. Reason: Anxa1-null mice show increased IL-1beta generation in inflammation; secondary to anti-inflammatory role. Supporting Evidence: PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. |
| GO:0032652 regulation of interleukin-1 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator ortholog transfer: regulation of IL-1 production. Reason: As above. Supporting Evidence: PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. |
| GO:0032717 negative regulation of interleukin-8 production | IMP PMID:22056994 Suppression of MIP-2 or IL-8 production by annexins A1 and A... | KEEP AS NON CORE | Summary: Blocking ANXA1 on apoptotic neutrophils increases macrophage IL-8/MIP-2 production. Reason: Antibody-blocking evidence that surface ANXA1 on apoptotic cells dampens macrophage chemokine output; consistent with pro-resolving role; non-core. Supporting Evidence: PMID:22056994 suggesting that ANXA1 and ANXA4 suppress MIP-2 or IL-8 production by macrophages in response to late apoptotic human neutrophils. |
| GO:0032743 positive regulation of interleukin-2 production | IDA PMID:17008549 Annexin-1 modulates T-cell activation and differentiation. | KEEP AS NON CORE | Summary: Recombinant ANXA1 increases IL-2 production by anti-CD3/CD28 stimulated T cells. Reason: Experimental; context-specific modulation of T cell activation. Supporting Evidence: PMID:17008549 induced a concentration-dependent increase in cell proliferation and IL-2 production |
| GO:0033031 positive regulation of neutrophil apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer: positive regulation of neutrophil apoptotic process. Reason: Exogenous AnxA1 accelerates neutrophil apoptosis (pro-resolving); non-core. Supporting Evidence: PMID:21957127 Thus, exogenous administration of AnxA1 accelerates neutrophil apoptosis (32, 35) |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | IDA PMID:22773844 Annexin-1-mediated endothelial cell migration and angiogenes... | KEEP AS NON CORE | Summary: ANXA1 mediates VEGF-induced endothelial cell migration; VEGF increases ANXA1 by repressing miR-196a. Reason: Experimental; context-specific downstream role. Supporting Evidence: PMID:22773844 This finding highlights the fact that ANXA1 is a required mediator of VEGF-induced cell migration. |
| GO:0042102 positive regulation of T cell proliferation | IDA PMID:17008549 Annexin-1 modulates T-cell activation and differentiation. | KEEP AS NON CORE | Summary: ANXA1 augments proliferation of TCR-stimulated T cells. Reason: Experimental, context-specific. Supporting Evidence: PMID:17008549 addition of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69 expression and cell proliferation. |
| GO:0042119 neutrophil activation | IDA PMID:22879591 Cathepsin G-regulated release of formyl peptide receptor ago... | KEEP AS NON CORE | Summary: Ac2-26 enhances CXCL2 release by immune-complex stimulated neutrophils via FPR. Reason: Experimental (mouse neutrophils, cathepsin G-released Ac2-26). Shows ANXA1 peptides can activate neutrophils; non-core relative to the predominant anti-inflammatory role. Supporting Evidence: PMID:22879591 Extracellular AnxA1 N-terminal peptide Ac2-26 and CRAMP peptide induced CXCL2 release by IC-stimulated CG/NE neutrophils via activation of formyl peptide receptors. |
| GO:0042383 sarcolemma | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer: sarcolemma. Reason: Plausible (dysferlin-associated membrane repair in muscle); non-core. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Interacts with EGFR (By similarity). |
| GO:0043066 negative regulation of apoptotic process | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | MARK AS OVER ANNOTATED | Summary: Negative regulation of apoptotic process (TAS) from HUVEC proteomics. Reason: The proteomics paper does not test ANXA1 in apoptosis; ANXA1 rather promotes neutrophil apoptosis in other studies. Weak/unsupported generalisation. Supporting Evidence: PMID:16130169 illustrates various cellular functions more related to cell motility and angiogenesis, protein folding, anti-oxidant defenses, signal transduction, proteasome pathway and resistance to apoptosis. PMID:21957127 Thus, exogenous administration of AnxA1 accelerates neutrophil apoptosis (32, 35) |
| GO:0045627 positive regulation of T-helper 1 cell differentiation | IDA PMID:17008549 Annexin-1 modulates T-cell activation and differentiation. | KEEP AS NON CORE | Summary: ANXA1 skews naive T cell differentiation toward Th1. Reason: Experimental; adaptive immune modulation is secondary. Supporting Evidence: PMID:17008549 differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells |
| GO:0045629 negative regulation of T-helper 2 cell differentiation | IDA PMID:17008549 Annexin-1 modulates T-cell activation and differentiation. | KEEP AS NON CORE | Summary: ANXA1 reduces Th2 differentiation (reciprocal of Th1 skewing). Reason: Experimental; non-core. Supporting Evidence: PMID:17008549 differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells |
| GO:0045920 negative regulation of exocytosis | IMP PMID:19625660 Annexin A1 regulates hormone exocytosis through a mechanism ... | KEEP AS NON CORE | Summary: ANXA1 inhibits ACTH exocytosis from AtT20 cells via FPR/Rho kinase-dependent actin polymerisation. Reason: Experimental, well-established neuroendocrine glucocorticoid effector role; secondary to the core FPR ligand activity. Supporting Evidence: PMID:19625660 The glucocorticoid-regulated protein annexin A1 is a potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner. PMID:19625660 annexin A1-dependent inhibition of adrenocorticotrophin release involves the enhancement of actin polymerization to prevent exocytosis via formyl peptide receptor and Rho kinase signaling pathways. |
| GO:0046632 alpha-beta T cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer: alpha-beta T cell differentiation. Reason: Consistent with T cell differentiation effects; non-core. Supporting Evidence: PMID:17008549 differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells |
| GO:0046632 alpha-beta T cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator ortholog transfer: alpha-beta T cell differentiation. Reason: Non-core. Supporting Evidence: PMID:17008549 differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells |
| GO:0046883 regulation of hormone secretion | IMP PMID:19625660 Annexin A1 regulates hormone exocytosis through a mechanism ... | KEEP AS NON CORE | Summary: ANXA1 regulates ACTH (hormone) release. Reason: Experimental; non-core. Supporting Evidence: PMID:19625660 The glucocorticoid-regulated protein annexin A1 is a potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner. |
| GO:0048306 calcium-dependent protein binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction: calcium-dependent protein binding. Reason: ANXA1 binds S100A11 in a Ca2+-dependent manner, so the term is correct, although S100 protein binding is more informative. Supporting Evidence: PMID:8557678 In cellular extracts, endogenous annexin I and the 10-kDa protein associated in a reversible Ca(2+)-dependent manner. |
| GO:0048306 calcium-dependent protein binding | IPI PMID:15226301 Identification and characterization of the acidic pH binding... | UNDECIDED | Summary: IPI with alpha-2-macroglobulin from a study of LRP-1 acidic pH binding sites. Reason: The cached abstract identifies annexin VI (bovine liver) as the alpha2M*-binding protein and does not mention annexin I; the full text is not available, so the curator may have seen ANXA1 data. Cannot verify. Supporting Evidence: PMID:15226301 Annexin VI has been identified as a major membrane-associated protein capable of directly binding alpha(2)M(*) at acidic pH. |
| GO:0050727 regulation of inflammatory response | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog transfer: regulation of inflammatory response. Reason: Core process: ANXA1 is a glucocorticoid-induced endogenous anti-inflammatory/pro-resolving mediator. Supporting Evidence: PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. PMID:19104500 we propose a model in which glucocorticoids regulate the expression and function of annexin A1 in opposing ways in innate and adaptive immune cells to mediate the resolution of inflammation. |
| GO:0050727 regulation of inflammatory response | ISS GO_REF:0000024 | ACCEPT | Summary: Curator ortholog transfer: regulation of inflammatory response. Reason: As above. Supporting Evidence: PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. PMID:19104500 we propose a model in which glucocorticoids regulate the expression and function of annexin A1 in opposing ways in innate and adaptive immune cells to mediate the resolution of inflammation. |
| GO:0051051 negative regulation of transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction: negative regulation of transport. Reason: Very general; reflects inhibition of hormone exocytosis and leukocyte transmigration. Not wrong but uninformative. Supporting Evidence: PMID:19625660 The glucocorticoid-regulated protein annexin A1 is a potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | ACCEPT | Summary: ANXA1 identified in exosome proteomes. Reason: Consistent with experimental evidence that ANXA1 is released in EVs/exosomes. Supporting Evidence: PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes. PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | ACCEPT | Summary: ANXA1 identified in exosome proteomes. Reason: Consistent with experimental evidence that ANXA1 is released in EVs/exosomes. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0070062 extracellular exosome | HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells. | ACCEPT | Summary: ANXA1 identified in exosome proteomes. Reason: Consistent with experimental evidence that ANXA1 is released in EVs/exosomes. Supporting Evidence: PMID:21362503 Protein profile of exosomes from trabecular meshwork cells. PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | ACCEPT | Summary: ANXA1 identified in exosome proteomes. Reason: Consistent with experimental evidence that ANXA1 is released in EVs/exosomes. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0070062 extracellular exosome | IDA PMID:25664854 Annexin A1-containing extracellular vesicles and polymeric n... | ACCEPT | Summary: ANXA1 released in extracellular vesicles from intestinal epithelial cells. Reason: Direct experimental support. Supporting Evidence: PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0070062 extracellular exosome | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction: extracellular exosome. Reason: Correct. Supporting Evidence: file:human/ANXA1/ANXA1-uniprot.txt Secreted, extracellular exosome PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0071385 cellular response to glucocorticoid stimulus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cellular response to glucocorticoid stimulus (ANXA1 subfamily node). Reason: ANXA1 is glucocorticoid-induced and mediates part of glucocorticoid anti-inflammatory action; Anxa1-null mice are partly resistant to glucocorticoids. ANXA1 therefore acts within the glucocorticoid response as an effector, not merely as a responding transcript. Supporting Evidence: PMID:19104500 we propose a model in which glucocorticoids regulate the expression and function of annexin A1 in opposing ways in innate and adaptive immune cells to mediate the resolution of inflammation. PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. |
| GO:0071385 cellular response to glucocorticoid stimulus | IDA PMID:2936963 Cloning and expression of human lipocortin, a phospholipase ... | ACCEPT | Summary: Lipocortin is a glucocorticoid-induced PLA2-inhibitory protein mediating steroid anti-inflammatory effects. Reason: ANXA1 is glucocorticoid-induced and mediates part of glucocorticoid anti-inflammatory action; Anxa1-null mice are partly resistant to glucocorticoids. ANXA1 therefore acts within the glucocorticoid response as an effector, not merely as a responding transcript. Supporting Evidence: PMID:2936963 The anti-inflammatory action of glucocorticoids has been attributed to the induction of a group of phospholipase A2 inhibitory proteins, collectively called lipocortin. PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. |
| GO:0071385 cellular response to glucocorticoid stimulus | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog transfer: cellular response to glucocorticoid stimulus. Reason: ANXA1 is glucocorticoid-induced and mediates part of glucocorticoid anti-inflammatory action; Anxa1-null mice are partly resistant to glucocorticoids. ANXA1 therefore acts within the glucocorticoid response as an effector, not merely as a responding transcript. Supporting Evidence: PMID:19104500 we propose a model in which glucocorticoids regulate the expression and function of annexin A1 in opposing ways in innate and adaptive immune cells to mediate the resolution of inflammation. PMID:12475898 Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. |
| GO:0071621 granulocyte chemotaxis | IDA PMID:15187149 An annexin 1 N-terminal peptide activates leukocytes by trig... | KEEP AS NON CORE | Summary: Ac2-26 induces chemotaxis of granulocytes via FPR. Reason: As for monocyte chemotaxis: ANXA1 peptide acts as an FPR agonist (chemotaxis followed by desensitisation); non-core. Supporting Evidence: PMID:15187149 a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. PMID:15187149 annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family. |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | IDA PMID:22773844 Annexin-1-mediated endothelial cell migration and angiogenes... | KEEP AS NON CORE | Summary: ANXA1 promotes VEGF-driven endothelial migration and angiogenesis. Reason: Experimental; context-specific. Supporting Evidence: PMID:22773844 This finding highlights the fact that ANXA1 is a required mediator of VEGF-induced cell migration. |
| GO:0090303 positive regulation of wound healing | IDA PMID:25664854 Annexin A1-containing extracellular vesicles and polymeric n... | KEEP AS NON CORE | Summary: ANXA1-containing EVs and Ac2-26 nanoparticles promote intestinal epithelial wound repair via FPR. Reason: Experimental; tissue-specific consequence of FPR ligand activity. Supporting Evidence: PMID:25664854 endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. |
| GO:0097350 neutrophil clearance | IMP PMID:21957127 Annexin A1 regulates neutrophil clearance by macrophages in ... | KEEP AS NON CORE | Summary: ANXA1 required for bone-marrow macrophage clearance of apoptotic neutrophils. Reason: Experimental (mouse knockout); supports a pro-resolving, efferocytosis-promoting role. Non-core physiological outcome. Supporting Evidence: PMID:21957127 we conclude that expression of AnxA1 by resident macrophages is a critical determinant for neutrophil clearance in the bone marrow. |
| GO:0098609 cell-cell adhesion | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Inter-ontology inference of cell-cell adhesion from cadherin binding HDA. Reason: Derived solely from E-cadherin interactome proteomics; no evidence ANXA1 mediates cell-cell adhesion. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. |
| GO:0098641 cadherin binding involved in cell-cell adhesion | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: ANXA1 co-purifies with E-cadherin in interactome proteomics. Reason: High-throughput co-purification does not establish direct cadherin binding nor a role in adhesion; likely indirect association via cortical membrane. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. |
| GO:0044548 S100 protein binding | IDA PMID:8557678 Calcium-dependent binding of S100C to the N-terminal domain ... | NEW | Summary: The ANXA1 N-terminus (residues 1-12/14) binds S100A11 in a Ca2+-dependent manner; crystal structure of the S100A11-ANXA1 peptide complex. Reason: Replaces uninformative protein binding with the specific, structurally validated S100A11 interaction, which forms an ANXA1-S100A11 heterotetramer proposed to bridge membranes. Binding term, no process asserted. Supporting Evidence: PMID:8557678 the 10-kDa protein bound specifically to a site within the first 12 amino acids of annexin I. PMID:8557678 In cellular extracts, endogenous annexin I and the 10-kDa protein associated in a reversible Ca(2+)-dependent manner. PMID:10673436 We have solved the crystal structure of a complex of calcium-loaded S100C with a synthetic peptide that corresponds to the first 14 residues of the annexin I N terminus at 2.3 A resolution. |
| GO:0140284 endoplasmic reticulum-endosome membrane contact site | IDA PMID:27270042 Annexin A1 Tethers Membrane Contact Sites that Mediate ER to... | NEW | Summary: Immuno-EM (pre-embedding and cryo-immunoEM) places ANXA1 at membrane contact sites between the ER and EGFR-positive multivesicular bodies in HeLa cells; ANXA1 depletion markedly reduces these contacts. Reason: Not in GOA. Direct EM localization plus loss-of-function in a full-text primary paper (Eden et al. 2016) supports this location; ANXA1 with ER-associated S100A11 tethers ER-MVB contacts used for PTP1B access to endosomal EGFR and for ORP1L/VAP-dependent cholesterol delivery. Location term only; ANXA1 is not itself the sterol transporter (ORP1L/VAP perform that step). Identified during reconciliation with the falcon deep research. Supporting Evidence: PMID:27270042 showed that annexin A1 was present at MCSs between the ER and EGFR-MVBs PMID:27270042 Here we show that these contacts are tethered by annexin A1 and its Ca(2+)-dependent ligand, S100A11, and form a subpopulation of differentially regulated contact sites between the ER and endocytic organelles. file:human/ANXA1/ANXA1-deep-research-falcon.md There, endosomal ANXA1 and ER-associated **S100A11** help tether the two membranes. |
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Download this section (compressed HTML)Q: Does full-length secreted ANXA1, as opposed to the Ac2-26 peptide, activate FPR1 and FPR3 in vivo, or is FPR2/ALX the principal physiological receptor?
Q: Is ANXA1-mediated inhibition of phospholipase A2 ever physiologically relevant in cells, or is it entirely explained by substrate sequestration in vitro?
Q: Should the alpha-2-macroglobulin calcium-dependent protein binding IPI (PMID:15226301) be attributed to ANXA1, given the abstract identifies annexin VI as the binder?
Q: What is the relative contribution of EV-mediated versus TMED10-dependent unconventional secretion to extracellular ANXA1 pools in neutrophils and epithelia?
Experiment: Compare wild-type versus cathepsin G/proteinase 3-resistant ANXA1 N-terminal mutants for FPR1/FPR2/FPR3 activation (BRET G protein and beta-arrestin assays) and for inhibition of neutrophil transendothelial migration in Fpr1/Fpr2 knockout backgrounds.
Hypothesis: Physiological anti-inflammatory effects of ANXA1 require FPR2/ALX engagement by full-length protein rather than proteolytically released Ac2-26.
Type: receptor pharmacology
Experiment: Measure direct ANXA1-PLA2 (cPLA2alpha, sPLA2-IIA) binding by SPR in the absence of lipid, and test inhibition at varying substrate interface concentrations to distinguish enzyme inhibition from interfacial competition.
Hypothesis: ANXA1 does not directly bind and inhibit phospholipase A2 enzymes.
Type: biochemical assay
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