ANXA1 (annexin A1)

2010-05-01   Flavia Cristina Rodrigues-Lisoni , Tiago Henrique , Eloiza Helena Tajara 

Department of Biology, Zootechny, Faculty of Engineering of Ilha Solteria (UNESP), Ilha Solteira, Brazil (FCRL); Department of Molecular Biology, School of Medicine (FAMERP), Sao Jose do Rio Preto, Brazil (TH, EHTDS)




Atlas Image
ANXA1 gene. The ANXA1 gene contains 13 exons, of which the first and last are uncoding 5 and 3 sequences (red regions), with the translation initiator codon (AUG) found near the beginning of the second exon (orange regions).


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.
Atlas Image
Schematic representation of annexin protein. N-terminal region with amino acids and four repetitions with 70-75 amino acids in C-terminal region.


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.

Implicated in

Entity name
Breast cancer
In breast cancer, ANXA1 is believed to function as a tumor suppressor. In study with a tissue microarray using 82 pairs of primary breast cancers and lymph node metastases from archival materials the results revealed that ANXA1 expression was lost in 79% of breast carcinomas, and there was no difference in ANXA1 expression between primary breast carcinoma and lymph node metastasis (Cao et al., 2008).
The suppressed ANXA1 expression in breast tissue is correlated with breast cancer development, progression and metastasis (Shen et al., 2006; Wang et al., 2010).
Entity name
Oral squamous cell carcinoma (OSCC)
ANXA1 expression could be used as a suitable biomarker for patients with oral cavity cancer and its adoption for complementary non-invasive diagnosis of oral squamous cell carcinoma is suggested. Beyond the anti-inflammatory function, annexin A1 may also play a tumor suppressor role in peripheral blood cells (Faria et al., 2010).
The nuclear localization of ANXA1 protein is a frequent event and could be used as a prognostic factor in OSCC (Lin et al., 2008).
Entity name
Laryngeal squamous cell carcinoma
In surgical tissue specimens from 20 patients with laryngeal squamous cell carcinoma, ultrastructural immunocytochemistry analysis showed in vivo down-regulation of ANXA1 expression in the tumor and increased in mast cells and laryngeal squamous carcinoma cell line treated with ANXA1 peptide. Combined in vivo and in vitro analysis demonstrated that ANXA1 plays a regulatory role in laryngeal cancer cell growth (Silistino-Souza et al., 2007).
ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms (Alves et al., 2008).
Entity name
Lung squamous cell carcinoma
The ANXA1 expression was identified by shot-gun proteomics strategy in lung squamous cell carcinoma.
The ANXA1 might play an important role in lung squamous cell carcinoma genesis, progression, recurrence, and metastasis and might be used as markers of this carcinoma (Nan et al., 2009).
Entity name
Prostate cancer
The reduction of ANXA1 expression, commonly associated with prostate cancer, could be due to elevated activity of histone deacetylases (DAcunto et al., 2010) and interleukin 6 expression (Inokuchi et al., 2009).
The ANXA1 expression is a contributing factor to the proapoptotic effects in prostate cancer (DAcunto et al., 2010) and enhancing tumor aggressiveness via the upregulation of interleukin 6 expression and activity (Inokuchi et al., 2009).
Entity name
Immunocytochemical detection of ANXA1 represents a simple, inexpensive, highly sensitive and specific (100%) assay for diagnosis of hairy cell leukaemia. This assay will be especially useful in distinguishing hairy cell leukaemia from splenic lymphoma with villous lymphocytes and variant hairy cell leukaemia, both of which usually respond poorly to treatments that are effective in hairy cell leukaemia (Falini et al., 2004).
The downregulated ANXA1 expression contributes considerably to the drug resistance in leukemia cell line (Zhu et al., 2009).
Entity name
Cervical cancer
A close association was observed between ANXA1 expression and tumour cell differentiation in invasive squamous cell carcinoma.
ANXA1 may be an effective candidate for detecting cervical intraephitelial neoplasia lesions and for evaluating tumour cell differentiation in squamous cell carcinoma of the cervix (Wang et al., 2008).
Entity name
Gastric cancer
Loss of ANXA1 expression was significantly associated with advanced T stage, lymph node metastasis, advanced disease stage, and poor histological differentiation.
ANXA1 expression decreased significantly as gastric cancer progressed and metastasized, suggesting the importance of ANXA1 as a negative biomarker for gastric cancer development and progression (Yu et al., 2008).
Entity name
Urinary bladder urothelial carcinoma
Comparative proteomics and immunohistochemistry demonstrated that ANXA1 is up-regulated in high grade urinary bladder urothelial carcinoma as compared to non-high grade carcinomas.
ANXA1 might be related to tumour progression. The ANXA1 overexpression and histological grade predicted disease-specific survival and metastasis-free survival (Li et al., 2010).
Entity name
Systemic lupus erythematosus
Auto-antibodies against annexin A1 have been detected in patients with auto-immune diseases such as systemic lupus erythematosus (Hirata et al., 1981; Goulding et al., 1989).
Entity name
Rheumatoid arthritis
ANXA1 has been recently shown to play a key role in T-cell activation and to be highly expressed in T cells from rheumatoid arthritis patients. Treatment of rheumatoid arthritis patients with steroid decreased ANXA1 expression in T cells.
Steroids regulate the adaptive immune response and suggest that ANXA1 may represent a target for the treatment of autoimmune diseases (DAcquisto et al., 2008).
Entity name
Crohns disease
Corticosteroids are widely used to treat patients with inflammatory bowel disease although the response is variable. Corticosteroids mediate some of their actions through ANXA1, and the induction of autoantibodies to ANXA1 has been proposed as a possible mechanism by which steroid efficacy is suboptimal in vivo (Beattie et al., 1995).
The high levels of IgM ANXA1 antibodies in patients with Crohns disease not taking corticosteroids provides further evidence of disturbed immunity in inflammatory bowel disease (Stevens et al., 1993).
Entity name
Cystic fibrosis
Downregulation and degradation of ANXA1 was found in the bronchoalveolar lavage fluid of patients with cystic fibrosis indicating the susceptibility of these patients to lung inflammation. ANXA1 may be a key protein involved in cystic fibrosis pathogenesis especially in relation to the not well defined field of inflammation in cystic fibrosis (Tsao et al., 1998).
Decreased expression of annexin A1 contributes to the worsening of the cystic fibrosis phenotype (Bensalem et al., 2005).
Entity name
Parkinsons disease
ANXA1 expression has been linked to Parkinsons disease. ANXA1 immunoreactivity has been found in ameboid microglia within the astrocytic envelope of neurons adjacent to or within glial scars in the parkinsonian substantia nigra (Knott et al., 2000).
Entity name
Multiple sclerosis
ANXA1 expression has been identified in the lesions of multiple sclerosis plaque and correlated with the degree of the disease (Probst-Cousin et al., 2002).
Strategies aiming at reducing ANXA1 functions or expression in T cells might represent a novel therapeutic approach for multiple sclerosis (Paschalidis et al., 2009).


Pubmed IDLast YearTitleAuthors
106088171999The annexin protein lipocortin 1 regulates the MAPK/ERK pathway.Alldridge LC et al
190766852008Annexin A1 subcellular expression in laryngeal squamous cell carcinoma.Alves VA et al
85802751995Lipocortin-1 autoantibody concentration in children with inflammatory bowel disease.Beattie RM et al
160144202005Down-regulation of the anti-inflammatory protein annexin A1 in cystic fibrosis knock-out mice and patients.Bensalem N et al
187768162008Loss of annexin A1 expression in breast cancer progression.Cao Y et al
183905872008Glucocorticoid treatment inhibits annexin-1 expression in rheumatoid arthritis CD4+ T cells.D'Acquisto F et al
202278222010Histone deacetylase inhibitor FR235222 sensitizes human prostate adenocarcinoma cells to apoptosis through up-regulation of Annexin A1.D'Acunto CW et al
91910441997Localization of five annexins in J774 macrophages and on isolated phagosomes.Diakonova M et al
151836262004Simple diagnostic assay for hairy cell leukaemia by immunocytochemical detection of annexin A1 (ANXA1).Falini B et al
198335462010Expression of annexin A1 mRNA in peripheral blood from oral squamous cell carcinoma patients.Faria PC et al
29747381988Eleventh Gaddum memorial lecture. Lipocortin and the mechanism of action of the glucocorticoids.Flower RJ et al
119170922002Annexins: from structure to function.Gerke V et al
25548261989Autoantibodies to recombinant lipocortin-1 in rheumatoid arthritis and systemic lupus erythematosus.Goulding NJ et al
62670231981The regulation of lipomodulin, a phospholipase inhibitory protein, in rabbit neutrophils by phosphorylation.Hirata F et al
16769801991Mouse lipocortin I gene structure and chromosomal assignment: gene duplication and the origins of a gene family.Horlick KR et al
193517892009Loss of annexin A1 disrupts normal prostate glandular structure by inducing autocrine IL-6 signaling.Inokuchi J et al
111248932000Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2.Knott C et al
18325541991Correlation of gene and protein structure of rat and human lipocortin I.Kovacic RT et al
200254792010Annexin-I overexpression is associated with tumour progression and independently predicts inferior disease-specific and metastasis-free survival in urinary bladder urothelial carcinoma.Li CF et al
182976882008Nuclear localization of annexin A1 is a prognostic factor in oral squamous cell carcinoma.Lin CY et al
115744262001Characterization of the annexin I gene and evaluation of its role in type 2 diabetes.Lindgren CM et al
189880002009Analysis of the expression protein profiles of lung squamous carcinoma cell using shot-gun proteomics strategy.Nan Y et al
199126482009Modulation of experimental autoimmune encephalomyelitis by endogenous annexin A1.Paschalidis N et al
126446212003Annexin 1: an endogenous anti-inflammatory protein.Perretti M et al
121753412002Expression of annexin-1 in multiple sclerosis plaques.Probst-Cousin S et al
81556921994Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins.Raynal P et al
169499102006Decreased expression of annexin A1 is correlated with breast cancer development and progression as determined by a tissue microarray analysis.Shen D et al
173406162007Annexin 1: differential expression in tumor and mast cells in human larynx cancer.Silistino-Souza R et al
128243022003A novel calcium-dependent proapoptotic effect of annexin 1 on human neutrophils.Solito E et al
113508572001Transfection of annexin 1 in monocytic cells produces a high degree of spontaneous and stimulated apoptosis associated with caspase-3 activation.Solito E et al
80976821993Antibodies to human recombinant lipocortin-I in inflammatory bowel disease.Stevens TR et al
94480531998Degradation of annexin I in bronchoalveolar lavage fluid from patients with cystic fibrosis.Tsao FH et al
21371291990Role of lipocortin I in the glucocorticoid induction of the terminal differentiation of a human squamous carcinoma.Violette SM et al
186527612008Decreased expression of annexin A1 during the progression of cervical neoplasia.Wang LD et al
203532772010Annexin A1 expression and its prognostic significance in human breast cancer.Wang LP et al
185359142008Tissue microarray analysis reveals strong clinical evidence for a close association between loss of annexin A1 expression and nodal metastasis in gastric cancer.Yu G et al
200018612009Involvement of annexin A1 in multidrug resistance of K562/ADR cells identified by the proteomic study.Zhu F et al
106552602000Annexin 1 expression and phosphorylation are upregulated during liver regeneration and transformation in antithrombin III SV40 T large antigen transgenic Coupade C et al

Other Information

Locus ID:

NCBI: 301
MIM: 151690
HGNC: 533
Ensembl: ENSG00000135046


dbSNP: 301
ClinVar: 301
TCGA: ENSG00000135046


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class A/1 (Rhodopsin-like receptors)REACTOMER-HSA-373076
Peptide ligand-binding receptorsREACTOMER-HSA-375276
Formyl peptide receptors bind formyl peptides and many other ligandsREACTOMER-HSA-444473
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (i) signalling eventsREACTOMER-HSA-418594
G alpha (q) signalling eventsREACTOMER-HSA-416476
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Muscle contractionREACTOMER-HSA-397014
Smooth Muscle ContractionREACTOMER-HSA-445355
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
191045002009Annexin A1 and glucocorticoids as effectors of the resolution of inflammation.247
232419622013Annexin A1, formyl peptide receptor, and NOX1 orchestrate epithelial repair.106
172154812007Annexin 1: the new face of an old molecule.101
169849152006Requirement for annexin A1 in plasma membrane repair.91
185940252008Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles.90
173720182007Annexin-1 and peptide derivatives are released by apoptotic cells and stimulate phagocytosis of apoptotic neutrophils by macrophages.85
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
186633552008MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers.84
256648542015Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair.83
203085422010Annexin A1 regulates TGF-beta signaling and promotes metastasis formation of basal-like breast cancer cells.73


Flavia Cristina Rodrigues-Lisoni ; Tiago Henrique ; Eloiza Helena Tajara

ANXA1 (annexin A1)

Atlas Genet Cytogenet Oncol Haematol. 2010-05-01

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