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:12475898). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (PubMed:12475898). 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:17948261). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17948261). Has no effect on unstimulated T-cells. Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (By similarity). 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 (By similarity). Plays a role in the formation of phagocytic cups and phagosomes (PubMed:21245195). Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (PubMed:21245195).
Annexin Ac2-26
Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades. Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors. Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration. Promotes resolution of inflammation and wound healing. Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2.
Post-translational modifications
Phosphorylated by protein kinase C, EGFR and TRPM7. Phosphorylated in response to EGF treatment.
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 lung (PubMed:12475898, PubMed:17384087). Detected at the apical membrane of airway epithelial cells (PubMed:17384087). Detected in intestinal epithelial cells (PubMed:18802107). Detected in skeletal muscle (PubMed:14506282). Detected in prostate (PubMed:23727357). Detected in thymus (at protein level) (PubMed:12475898). Detected in stomach, lung, spleen, ovary and uterus, and at lower levels in kidney, thymus and heart (PubMed:12475898).
Cellular localization
- Nucleus
- Cytoplasm
- Cell projection
- Cilium
- Basolateral cell membrane
- Lateral cell membrane
- Cell membrane
- Peripheral membrane protein
- Apical cell membrane
- Membrane
- Peripheral membrane protein
- Early endosome
- Cytoplasmic vesicle membrane
- Peripheral membrane protein
- Endosome membrane
- Peripheral membrane protein
- Secreted
- Secreted
- Extracellular space
- Cell membrane
- Peripheral membrane protein
- Extracellular side
- Secreted
- Extracellular exosome
- Cytoplasmic vesicle
- Secretory vesicle lumen
- Cell projection
- Phagocytic cup
- Colocalizes with actin fibers at phagocytic cups (PubMed:21245195). Secreted, at least in part via exosomes and other secretory vesicles. Detected in exosomes and other extracellular vesicles (PubMed:25664854). Secretion is increased in response to wounding and inflammation (PubMed:25664854). Detected in gelatinase granules in resting neutrophils. Neutrophil adhesion to endothelial cells stimulates secretion via gelatinase granules, but foreign particle phagocytosis has no effect. Displays calcium-dependent binding to phospholipid membranes (By similarity).
Alternative names
Anx1, Lpc-1, Lpc1, Anxa1, Annexin A1, Annexin I, Annexin-1, Calpactin II, Calpactin-2, Chromobindin-9, Lipocortin I, Phospholipase A2 inhibitory protein, p35