The exon-intron organization of ANXA1 genes in vertebrates have been described and are highly conserved, each gene consisting of 13 exons of which the first and last are uncoding 5 and 3 sequences, with the translation initiator codon (AUG) found near the beginning of the second exon (Kovacic et al., 1991).

Transcription produces 9 different mRNAs to this gene. The ANXA1 gene is expressed in the tissues: bone, bone marrow, brain, cartilage, cerebellum, cerebrum, cervix, colon, ear, embryonic tissue, endocrine, esophagus, eye, fetus, gastrointestinal tract, heart, kidney, liver, lung, lymph node, lymphoreticular, mammary gland, muscle, nervous, ovary, pancreas, pancreatic islet, parathyroid, peripheral nervous system, pituitary gland, placenta, pooled tissue, prostate, salivary gland, skin, soft tissue, spleen, stem cell, stomach, synovium, t-cell, testis, thymus, thyroid, uncharacterized tissue, uterus, vascular.

No known pseudogenes.

Belongs to the annexin family. Contains 4 annexin repeats.

The ANXA1 gene encodes a 38.71 kDa protein. Similarly to other annexins, annexin A1 is characterized by a C-terminal homologous domain with 4 to 8 repeats of 70-75 aminoacids, responsible for calcium and phospholipid binding properties. The variable N-terminal region is unique in length and sequence and includes potential sites of phosphorylation, glycosylation and peptidase action (Gerke and Moss, 2002).

The human ANXA1 gene promoter contains consensus sequences for: glucocorticoids, AP-1 and NFIL-6. However the regulation from glucocorticoid (GC) appear to be dependent upon an activation involving NFIL-6 or AP1 (Solito et al., 1998a; Solito et al., 1998b). The GC mediated regulations confirm the original studies which proposed ANXA1 as mediator of the glucocorticoid action (Flower, 1988). In mouse, in contrast, GC regulation is mediated through two consensus sequences present in the upstream region of TATA box (Horlick et al., 1991). However the data of Antonicelli et al. 2001 regarding sequences of the mouse Anxa1 promoter brought evidence of the involvement of the CREB transcription factor (the cyclic AMP-responding element-binding protein) in the activation of this gene by cyclic AMP and glucocorticoids.

ANXA1 is preferentially localized in the cytoplasm and associated with the plasma membrane or cytoskeleton, but it has also been localized outside the plasma membrane.

The function of the annexin A1 is far to be clear, it has been involved in signal transduction (Alldridge et al., 1999; de Coupade et al., 2000), vesicle transport (Diakonova et al., 1997), cell transformation (Violette et al., 1990; Solito et al., 1998a), inflammation (Perretti and Gavins, 2003), cell matrix interaction and apoptosis (Raynal and Pollard, 1994; Solito et al., 2001; Solito et al., 2003).

The comparison of conserved and variable residues between human annexin 1 protein and annexin protein from different vertebrates shows amino acid identities of 100% (Pan troglodytes), 91% (Canis familiars), 87% (Mus musculus), 89% (Rattus norvegicus) and 77% (Gallus gallus) (Rodrigues-Lisoni et al., 2006).

Reduced expression of ANXA1 could be explain by some mechanisms include gene deletions and mutations, hyper-methylation of the promoter with subsequent loss of transcription, and alterations in the post-translation processing (e.g. phosphorylation) of the protein involved in annexins regulation (de Coupade et al., 2000; Rodrigues-Lisoni et al., 2006; Alves et al., 2008).
Lindgren et al. (2001) studied subjects with type 2 diabetes and find a G instead of T at nucleotide position 362 from the transcription start site (exon 5) of ANXA1 gene in all individuals sequenced.