ANXA1
Domain
The full-length protein can bind eight Ca(2+) ions via the annexin repeats. Calcium binding causes a major conformation change that modifies dimer contacts and leads to surface exposure of the N-terminal phosphorylation sites; in the absence of Ca(2+), these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding.
Function
Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity).
Annexin Ac2-26
Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:22879591, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Promotes resolution of inflammation and wound healing (PubMed:25664854). Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2 (PubMed:22879591).
Post-translational modifications
Phosphorylated by protein kinase C, EGFR and TRPM7 (PubMed:15485879, PubMed:2457390). Phosphorylated in response to EGF treatment (PubMed:2532504).
Sumoylated.
Proteolytically cleaved by cathepsin CTSG to release the active N-terminal peptide Ac2-26.
Sequence Similarities
Belongs to the annexin family.
Tissue Specificity
Detected in resting neutrophils (PubMed:10772777). Detected in peripheral blood T-cells (PubMed:17008549). Detected in extracellular vesicles in blood serum from patients with inflammatory bowel disease, but not in serum from healthy donors (PubMed:25664854). Detected in placenta (at protein level) (PubMed:2532504). Detected in liver.
Cellular localization
- Nucleus
- Cytoplasm
- Cell projection
- Cilium
- Cell membrane
- Membrane
- Peripheral membrane protein
- Endosome membrane
- Peripheral membrane protein
- Basolateral cell membrane
- Apical cell membrane
- Lateral cell membrane
- Secreted
- Secreted
- Extracellular space
- Cell membrane
- Peripheral membrane protein
- Extracellular side
- Secreted
- Extracellular exosome
- Cytoplasmic vesicle
- Secretory vesicle lumen
- Cell projection
- Phagocytic cup
- Early endosome
- Cytoplasmic vesicle membrane
- Peripheral membrane protein
- Secreted, at least in part via exosomes and other secretory vesicles. Detected in exosomes and other extracellular vesicles (PubMed:25664854). Alternatively, the secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in the protein translocation from the cytoplasm into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059). Detected in gelatinase granules in resting neutrophils (PubMed:10772777). Secretion is increased in response to wounding and inflammation (PubMed:25664854). Secretion is increased upon T-cell activation (PubMed:17008549). Neutrophil adhesion to endothelial cells stimulates secretion via gelatinase granules, but foreign particle phagocytosis has no effect (PubMed:10772777). Colocalizes with actin fibers at phagocytic cups (By similarity). Displays calcium-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678).
Alternative names
ANX1, LPC1, ANXA1, Annexin A1, Annexin I, Annexin-1, Calpactin II, Calpactin-2, Chromobindin-9, Lipocortin I, Phospholipase A2 inhibitory protein, p35