P46193 · ANXA1_BOVIN
- ProteinAnnexin A1
- GeneANXA1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids346 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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. Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response. 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. Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (By similarity).
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 Ca2+ and can bind up to eight Ca2+ ions (By similarity).
Displays Ca2+-dependent binding to phospholipid membranes (By similarity).
Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca2+-dependent interaction between phagosomes and the actin cytoskeleton (By similarity).
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 Ca2+ and can bind up to eight Ca2+ ions (By similarity).
Displays Ca2+-dependent binding to phospholipid membranes (By similarity).
Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca2+-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. 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.
Miscellaneous
Was originally identified as calcium and phospholipid binding protein that displays Ca2+-dependent binding to phospholipid membranes and can promote membrane aggregation in vitro. Was initially identified as inhibitor of phospholipase A2 activity (in vitro). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates.
Features
Showing features for site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 26-27 | Cleavage; by CTSG | ||||
Sequence: KG | ||||||
Binding site | 59 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 60 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 62 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 97 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 100 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 105 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 127 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 129 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 131 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 132 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 134 | Ca2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 171 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 210 | Ca2+ 5 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 213 | Ca2+ 5 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 215 | Ca2+ 5 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 253 | Ca2+ 6 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 255 | Ca2+ 5 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 256 | Ca2+ 6 (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 261 | Ca2+ 6 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 286 | Ca2+ 7 (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 288 | Ca2+ 7 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 290 | Ca2+ 7 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 328 | Ca2+ 8 (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 330 | Ca2+ 7 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 331 | Ca2+ 8 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 336 | Ca2+ 8 (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameAnnexin A1
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionP46193
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Membrane ; Peripheral membrane protein
Endosome membrane ; Peripheral membrane protein
Cell membrane ; Peripheral membrane protein
Cytoplasmic vesicle membrane ; Peripheral membrane protein
Note: Colocalizes with actin fibers at phagocytic cups. Secreted, at least in part via exosomes and other secretory vesicles. Detected in exosomes and other extracellular vesicles. Secretion is increased in response to wounding and inflammation (By similarity).
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 (By similarity).
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).
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 (By similarity).
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).
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, modified residue, peptide, chain, cross-link, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Peptide | PRO_0000454553 | 2-26 | Annexin Ac2-26 | |||
Sequence: AMVSEFLKQAWFIENEEQEYIKTVK | ||||||
Chain | PRO_0000067457 | 2-346 | Annexin A1 | |||
Sequence: AMVSEFLKQAWFIENEEQEYIKTVKGSKGGPGSAVSPYPTFNPSSDVEALHKAITVKGVDEATIIEILTKRNNAQRQQIKAAYLQEKGKPLDEVLKKALLGHLEEVVLALLKTPAQFDAEELRAAMKGLGTDEDTLNEILASRTNREIREINRVYREELKRDLAKDIASDTSGDYEKALLSLAKGDRSEELAVNDDLADSDARALYEAGERRKGTDVNVFITILTTRSYPHLRRVFQKYSKYSKHDMNKVLDLELKGDIEKCLTVIVKCATSQPMFFAEKLHQAMKGIGTRHKTLIRIMVSRSEIDMNDIKACYQKLYGISLCQAILDETKGDYEKILVALCGRD | ||||||
Modified residue | 5 | Phosphoserine; by TRPM7 | ||||
Sequence: S | ||||||
Cross-link | 19 | Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?) | ||||
Sequence: Q | ||||||
Modified residue | 21 | Phosphotyrosine; by EGFR | ||||
Sequence: Y | ||||||
Modified residue | 34 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 37 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 41 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 58 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 136 | Phosphothreonine | ||||
Sequence: T | ||||||
Cross-link | 214 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate | ||||
Sequence: K | ||||||
Cross-link | 214 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Modified residue | 239 | N6-acetyllysine | ||||
Sequence: K | ||||||
Cross-link | 257 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K | ||||||
Modified residue | 312 | N6-acetyllysine | ||||
Sequence: K | ||||||
Disulfide bond | 324↔343 | |||||
Sequence: CQAILDETKGDYEKILVALC | ||||||
Cross-link | 332 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K |
Post-translational modification
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected on surface epithelia and mucosal glands in nasal cavity, trachea, bronchi and bronchioles. Detected in blood vessel endothelial cells. Detected in neutrophils (at protein level).
Interaction
Subunit
Homodimer; non-covalently linked (By similarity).
Homodimer; linked by transglutamylation. Homodimers linked by transglutamylation are observed in placenta, but not in other tissues. Interacts with S100A11. Heterotetramer, formed by two molecules each of S100A11 and ANXA1 (By similarity).
Interacts with DYSF (By similarity).
Interacts with EGFR (By similarity).
Homodimer; linked by transglutamylation. Homodimers linked by transglutamylation are observed in placenta, but not in other tissues. Interacts with S100A11. Heterotetramer, formed by two molecules each of S100A11 and ANXA1 (By similarity).
Interacts with DYSF (By similarity).
Interacts with EGFR (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 42-113 | Annexin 1 | ||||
Sequence: FNPSSDVEALHKAITVKGVDEATIIEILTKRNNAQRQQIKAAYLQEKGKPLDEVLKKALLGHLEEVVLALLK | ||||||
Repeat | 114-185 | Annexin 2 | ||||
Sequence: TPAQFDAEELRAAMKGLGTDEDTLNEILASRTNREIREINRVYREELKRDLAKDIASDTSGDYEKALLSLAK | ||||||
Repeat | 197-269 | Annexin 3 | ||||
Sequence: DLADSDARALYEAGERRKGTDVNVFITILTTRSYPHLRRVFQKYSKYSKHDMNKVLDLELKGDIEKCLTVIVK | ||||||
Repeat | 273-344 | Annexin 4 | ||||
Sequence: SQPMFFAEKLHQAMKGIGTRHKTLIRIMVSRSEIDMNDIKACYQKLYGISLCQAILDETKGDYEKILVALCG |
Domain
The full-length protein can bind eight Ca2+ 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 Ca2+, these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding.
Sequence similarities
Belongs to the annexin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length346
- Mass (Da)38,952
- Last updated2006-05-30 v2
- Checksum09FA6CEF5F1AD9FB
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 58 | in Ref. 2; AAX46348 | ||||
Sequence: K → R | ||||||
Sequence conflict | 156 | in Ref. 1; CAA39971 | ||||
Sequence: Y → H | ||||||
Sequence conflict | 182 | in Ref. 1; CAA39971 | ||||
Sequence: S → A | ||||||
Sequence conflict | 222 | in Ref. 1; CAA39971 | ||||
Sequence: I → T | ||||||
Sequence conflict | 265 | in Ref. 2; AAX46348 | ||||
Sequence: T → I |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X56649 EMBL· GenBank· DDBJ | CAA39971.1 EMBL· GenBank· DDBJ | mRNA | ||
BT021501 EMBL· GenBank· DDBJ | AAX46348.1 EMBL· GenBank· DDBJ | mRNA | ||
BC103375 EMBL· GenBank· DDBJ | AAI03376.1 EMBL· GenBank· DDBJ | mRNA |