P46193 · ANXA1_BOVIN

  • Protein
    Annexin A1
  • Gene
    ANXA1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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.

TypeIDPosition(s)Description
Site26-27Cleavage; by CTSG
Binding site59Ca2+ 1 (UniProtKB | ChEBI)
Binding site60Ca2+ 1 (UniProtKB | ChEBI)
Binding site62Ca2+ 1 (UniProtKB | ChEBI)
Binding site97Ca2+ 2 (UniProtKB | ChEBI)
Binding site100Ca2+ 2 (UniProtKB | ChEBI)
Binding site105Ca2+ 2 (UniProtKB | ChEBI)
Binding site127Ca2+ 3 (UniProtKB | ChEBI)
Binding site129Ca2+ 3 (UniProtKB | ChEBI)
Binding site131Ca2+ 3 (UniProtKB | ChEBI)
Binding site132Ca2+ 4 (UniProtKB | ChEBI)
Binding site134Ca2+ 4 (UniProtKB | ChEBI)
Binding site171Ca2+ 3 (UniProtKB | ChEBI)
Binding site210Ca2+ 5 (UniProtKB | ChEBI)
Binding site213Ca2+ 5 (UniProtKB | ChEBI)
Binding site215Ca2+ 5 (UniProtKB | ChEBI)
Binding site253Ca2+ 6 (UniProtKB | ChEBI)
Binding site255Ca2+ 5 (UniProtKB | ChEBI)
Binding site256Ca2+ 6 (UniProtKB | ChEBI)
Binding site261Ca2+ 6 (UniProtKB | ChEBI)
Binding site286Ca2+ 7 (UniProtKB | ChEBI)
Binding site288Ca2+ 7 (UniProtKB | ChEBI)
Binding site290Ca2+ 7 (UniProtKB | ChEBI)
Binding site328Ca2+ 8 (UniProtKB | ChEBI)
Binding site330Ca2+ 7 (UniProtKB | ChEBI)
Binding site331Ca2+ 8 (UniProtKB | ChEBI)
Binding site336Ca2+ 8 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentearly endosome membrane
Cellular Componentextracellular exosome
Cellular Componentextracellular space
Cellular Componentlateral plasma membrane
Cellular Componentmembrane
Cellular Componentmotile cilium
Cellular Componentnucleus
Cellular Componentphagocytic cup
Cellular Componentplasma membrane
Cellular Componentvesicle membrane
Molecular Functioncalcium ion binding
Molecular Functioncalcium-dependent phospholipid binding
Molecular Functionphosphatidylserine binding
Molecular Functionphospholipase A2 inhibitor activity
Biological Processactin cytoskeleton organization
Biological Processadaptive immune response
Biological Processcalcium ion transmembrane transport
Biological Processcellular response to glucocorticoid stimulus
Biological ProcessG protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
Biological Processgranulocyte chemotaxis
Biological Processinflammatory response
Biological Processinnate immune response
Biological Processmonocyte chemotaxis
Biological Processnegative regulation of exocytosis
Biological Processnegative regulation of T-helper 2 cell differentiation
Biological Processneutrophil activation
Biological Processphagocytosis
Biological Processpositive regulation of interleukin-2 production
Biological Processpositive regulation of T cell proliferation
Biological Processpositive regulation of T-helper 1 cell differentiation
Biological Processpositive regulation of wound healing
Biological Processregulation of cell shape
Biological Processregulation of hormone secretion
Biological Processregulation of inflammatory response
Biological Processregulation of interleukin-1 production
Biological Processregulation of leukocyte migration
Biological Processsignal transduction

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Annexin A1
  • Alternative names
    • Annexin I
    • Annexin-1
    • Calpactin II
    • Calpactin-2
    • Chromobindin-9
  • Cleaved into 1 chains

Gene names

    • Name
      ANXA1
    • Synonyms
      ANX1

Organism names

  • Taxonomic identifier
  • Strain
    • Crossbred X Angus
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos

Accessions

  • Primary accession
    P46193
  • Secondary accessions
    • Q3ZBF5
    • Q58DU6

Proteomes

Subcellular Location

Nucleus
Cytoplasm
Lateral cell membrane
Cell membrane
; Peripheral membrane protein
Apical cell membrane
Membrane
; Peripheral membrane protein
Endosome membrane
; Peripheral membrane protein
Secreted
Cell membrane
; Peripheral membrane protein
Early endosome
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).

Keywords

Phenotypes & Variants

PTM/Processing

Features

Showing features for initiator methionine, modified residue, peptide, chain, cross-link, disulfide bond.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
PeptidePRO_00004545532-26Annexin Ac2-26
ChainPRO_00000674572-346Annexin A1
Modified residue5Phosphoserine; by TRPM7
Cross-link19Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)
Modified residue21Phosphotyrosine; by EGFR
Modified residue34Phosphoserine
Modified residue37Phosphoserine
Modified residue41Phosphothreonine
Modified residue58N6-acetyllysine
Modified residue136Phosphothreonine
Cross-link214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate
Cross-link214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Modified residue239N6-acetyllysine
Cross-link257Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)
Modified residue312N6-acetyllysine
Disulfide bond324↔343
Cross-link332Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)

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

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).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for repeat.

TypeIDPosition(s)Description
Repeat42-113Annexin 1
Repeat114-185Annexin 2
Repeat197-269Annexin 3
Repeat273-344Annexin 4

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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    346
  • Mass (Da)
    38,952
  • Last updated
    2006-05-30 v2
  • Checksum
    09FA6CEF5F1AD9FB
MAMVSEFLKQAWFIENEEQEYIKTVKGSKGGPGSAVSPYPTFNPSSDVEALHKAITVKGVDEATIIEILTKRNNAQRQQIKAAYLQEKGKPLDEVLKKALLGHLEEVVLALLKTPAQFDAEELRAAMKGLGTDEDTLNEILASRTNREIREINRVYREELKRDLAKDIASDTSGDYEKALLSLAKGDRSEELAVNDDLADSDARALYEAGERRKGTDVNVFITILTTRSYPHLRRVFQKYSKYSKHDMNKVLDLELKGDIEKCLTVIVKCATSQPMFFAEKLHQAMKGIGTRHKTLIRIMVSRSEIDMNDIKACYQKLYGISLCQAILDETKGDYEKILVALCGRD

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict58in Ref. 2; AAX46348
Sequence conflict156in Ref. 1; CAA39971
Sequence conflict182in Ref. 1; CAA39971
Sequence conflict222in Ref. 1; CAA39971
Sequence conflict265in Ref. 2; AAX46348

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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