UniProt functional annotation for P04083

UniProt code: P04083.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
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). Promotes resolution of inflammation and wound healing (PubMed:25664854). Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). 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). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). 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). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:25664854, ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}.
Subunit: Homodimer; non-covalently linked (By similarity). Homodimer; linked by transglutamylation (PubMed:2532504). Homodimers linked by transglutamylation are observed in placenta, but not in other tissues (PubMed:2532504). Interacts with S100A11 (PubMed:8557678, PubMed:10673436). Heterotetramer, formed by two molecules each of S100A11 and ANXA1 (PubMed:10673436). Interacts with DYSF (By similarity). Interacts with EGFR (By similarity). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:10673436, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:8557678}.
Subcellular location: Nucleus {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:19625660}. Cytoplasm {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660}. Cell projection, cilium {ECO:0000250|UniProtKB:P46193}. Cell membrane {ECO:0000269|PubMed:10772777}. Membrane {ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:8557678}; Peripheral membrane protein {ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:8557678}. Endosome membrane {ECO:0000250|UniProtKB:P07150}; Peripheral membrane protein {ECO:0000250|UniProtKB:P07150}. Basolateral cell membrane {ECO:0000250|UniProtKB:P51662}. Apical cell membrane {ECO:0000250|UniProtKB:P10107}. Lateral cell membrane {ECO:0000250|UniProtKB:P10107}. Secreted {ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:25664854}. Secreted, extracellular space {ECO:0000269|PubMed:25664854}. Cell membrane {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:25664854}; Peripheral membrane protein {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:25664854}; Extracellular side {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:25664854}. Secreted, exosome {ECO:0000269|PubMed:25664854}. Cytoplasmic vesicle, secretory vesicle lumen {ECO:0000269|PubMed:10772777}. Cell projection, phagocytic cup {ECO:0000250|UniProtKB:P10107}. Early endosome {ECO:0000250|UniProtKB:P19619}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P19619}; Peripheral membrane protein {ECO:0000250|UniProtKB:P19619}. Note=Secreted, at least in part via exosomes and other secretory vesicles. Detected in exosomes and other extracellular vesicles (PubMed:25664854). 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). {ECO:0000250|UniProtKB:P10107, ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:25664854, ECO:0000269|PubMed:8557678}.
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. {ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:2936963}.
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. {ECO:0000250|UniProtKB:P19619}.
Domain: The N-terminal 26 amino acids are sufficient for its extracellular functions in the regulation of inflammation and wound healing (PubMed:25664854). Acylated peptides that contain the first 26 amino acids of the mature protein can activate signaling via the formyl peptide receptors (PubMed:15187149, PubMed:25664854). {ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:25664854}.
Ptm: Phosphorylated by protein kinase C, EGFR and TRPM7 (PubMed:2457390, PubMed:15485879). Phosphorylated in response to EGF treatment (PubMed:2532504). {ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:2457390, ECO:0000269|PubMed:2532504}.
Ptm: Sumoylated. {ECO:0000250|UniProtKB:P10107}.
Pharmaceutical: Peptides based on the N-terminal sequence might be used for the treatment of inflammation, e.g. in chronic bowel diseases and in rheumatoid arthritis. {ECO:0000305}.
Miscellaneous: Was originally identified as calcium and phospholipid binding protein that displays Ca(2+)-dependent binding to phospholipid membranes and can promote membrane aggregation in vitro. Was initially identified as inhibitor of phospholipase A2 activity (in vitro) (PubMed:2936963, PubMed:8425544). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates. {ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000305}.
Similarity: Belongs to the annexin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.