Annexin A1 (ANXA1)

The protein contains 346 amino acids for an estimated molecular weight of 38714 Da.

 

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 p (updated: Jan. 31, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 0
No model available.

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Biological Process

Actin cytoskeleton reorganization GO Logo
Adaptive immune response GO Logo
Alpha-beta T cell differentiation GO Logo
Arachidonic acid secretion GO Logo
Cell surface receptor signaling pathway GO Logo
Cellular response to glucocorticoid stimulus GO Logo
Cellular response to hydrogen peroxide GO Logo
Cellular response to vascular endothelial growth factor stimulus GO Logo
Cytokine-mediated signaling pathway GO Logo
DNA duplex unwinding GO Logo
DNA rewinding GO Logo
Endocrine pancreas development GO Logo
Estrous cycle GO Logo
G protein-coupled receptor signaling pathway GO Logo
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger GO Logo
Gliogenesis GO Logo
Granulocyte chemotaxis GO Logo
Hepatocyte differentiation GO Logo
Inflammatory response GO Logo
Innate immune response GO Logo
Insulin secretion GO Logo
Keratinocyte differentiation GO Logo
Monocyte chemotaxis GO Logo
Movement of cell or subcellular component GO Logo
Myoblast migration involved in skeletal muscle regeneration GO Logo
Negative regulation of apoptotic process GO Logo
Negative regulation of exocytosis GO Logo
Negative regulation of interleukin-8 production GO Logo
Negative regulation of interleukin-8 secretion GO Logo
Negative regulation of phospholipase A2 activity GO Logo
Negative regulation of protein secretion GO Logo
Negative regulation of T-helper 2 cell differentiation GO Logo
Neutrophil clearance GO Logo
Neutrophil homeostasis GO Logo
Peptide cross-linking GO Logo
Phagocytosis GO Logo
Positive regulation of cell migration involved in sprouting angiogenesis GO Logo
Positive regulation of G1/S transition of mitotic cell cycle GO Logo
Positive regulation of interleukin-2 production GO Logo
Positive regulation of neutrophil apoptotic process GO Logo
Positive regulation of prostaglandin biosynthetic process GO Logo
Positive regulation of T cell proliferation GO Logo
Positive regulation of T-helper 1 cell differentiation GO Logo
Positive regulation of vesicle fusion GO Logo
Positive regulation of wound healing GO Logo
Prolactin secretion GO Logo
Prostate gland development GO Logo
Regulation of cell population proliferation GO Logo
Regulation of cell shape GO Logo
Regulation of hormone secretion GO Logo
Regulation of inflammatory response GO Logo
Regulation of interleukin-1 production GO Logo
Regulation of leukocyte migration GO Logo
Response to drug GO Logo
Response to estradiol GO Logo
Response to interleukin-1 GO Logo
Response to peptide hormone GO Logo
Response to X-ray GO Logo
Signal transduction GO Logo

The reference OMIM entry for this protein is 151690

Annexin a1; anxa1
Annexin i; anx1
Lipocortin i; lpc1
Calpactin ii

CLONING

The antiinflammatory action of glucocorticoids has been attributed to the induction of a group of proteins, collectively called lipocortin, that inhibit phospholipase A2. These proteins are thought to control the biosynthesis of potent mediators of inflammation, prostaglandins and leukotrienes, by inhibiting release of their common precursor, arachidonic acid, a process that requires hydrolysis of phospholipids by phospholipase A2. Lipocortin-like proteins have been isolated from monocytes, neutrophils, renal medullary cells, and other cell types. The predominant active form has an apparent relative molecular mass of 40,000. Partially purified lipocortin mimics the effect of steroids and mediates antiinflammatory activity in various in vivo model systems. Using amino acid sequence information from purified rat lipocortin, Wallner et al. (1986) cloned cDNA for human lipocortin and expressed the gene in E. coli. They confirmed that LPC is a potent inhibitor of phospholipase A2. Lipocortin I belongs to the family of annexins, which are structurally related proteins that have a molecular mass of approximately 35,000 to 40,000. They undergo Ca(2+)-dependent binding to phospholipids that are preferentially located on the cytosolic face of the plasma membrane. The individual proteins in this family have been discovered by investigators with various goals in mind and have been given a variety of names (Kaplan et al., 1988). Horlick et al. (1991) isolated overlapping mouse genomic clones for Lipo1. The gene in the mouse encodes a protein of 346 amino acid residues.

GENE STRUCTURE

Horlick et al. (1991) demonstrated that the mouse Lipo1 gene spans about 17 kb and is divided into 13 exons. Horlick et al. (1991) pointed out a similarity in gene structure between mouse Lipo1 and Lipo2 (151740), suggesting that they have a recent evolutionary ancestor.

GENE FAMILY

Crompton et al. (1988) reviewed the lipocortin/calpactin family of proteins. Pepinsky et al. (1988) described the characteristics of 3 proteins they called lipocortin III, lipocortin V, and lipocortin VI. Lipocortins III and IV are apparently identical. Shohat et al. (1989) advanced the hypothesis that familial Mediterranean fever (FMF; 249100) patients are homozygous for a mutant allele for one of the lipocortin genes.

MAPPING

Huebner et al. (1987, 1988) mapped the ANXA1 gene to 9q11-q22 by chromosomal in situ hybridization and segregation analysis in somatic cell hybrids using a cDNA clone. By analysis of recombinant inbred strains, Horlick et al. (1991) showed that the Lipo1 gene is located on mouse chromosome 19.

GENE FUNCTION

Walther et al. (2000) showed that ANXA1 acts through the formyl peptide receptor (FPR; 136537) on human neutrophils. Peptides derived from the unique N-terminal domain of ANXA1 serve as FPR ligands and trigger different signaling pathways in a dose-dependent manner. Lower peptide concentrations possibly found in inflammatory situations elicit Ca(2+) transients without fully activating the mitogen-activated protein kinase pathway. This causes a specific inhibition of the transendothelial migration of neutrophils and a desensitization of neutrophils toward a chemoattractant challenge. These findings identified ANXA1 peptides as novel, endogenous FPR ligands and established a mechanistic basis of ANXA1-mediated antiinflammatory effects. Perretti et al. (2002) reported that inhibition of polymorphonuclear n ... More on the omim web site

Subscribe to this protein entry history

Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 151690 was added.

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed