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FLASH GENE
Symbol ANXA1 contributors: mct - updated : 29-11-2017
HGNC name annexin A1
HGNC id 533
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvesselcapillary    Homo sapiens
Digestiveesophagus   moderately
 pharynx   highly
Hearing/Equilibriumear   moderately
Nervousbrain   highly Homo sapiens
Reproductivefemale systemplacenta  highly
Respiratoryrespiratory tractlarynx  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
Connectivebone  highly
Epithelialabsorptive excretorydigestive epithelium (mucosa)   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
Digestiveepithelial cell Homo sapiens
Nervousependymal cell Homo sapiens
Nervousglia Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • formyl peptide receptor ligand
  • a relatively short N terminus
  • a C terminal "core" region containing four annexin, functioning by increasing ICAM1 clustering around adherent neutrophils to anchor them to the endothelium and promote transmigration through the transcellular route
  • conjugated Other
    HOMOLOGY
    interspecies homolog to C.elegans ZC155.1
    homolog to rattus Anxa1 (89.02 pc)
    homolog to murine Anxa1 (87.28 pc)
    Homologene
    FAMILY
  • calcium dependent phospholipid binding proteins
  • annexin family
  • CATEGORY regulatory , transport
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text located on the cytosolic face of the plasma membrane
    basic FUNCTION
  • calcium dependent phospholipid binding protein, modulating antiinflammatory response (phospholipase A2 inhibitory activity)
  • involved in the regulation of early delayed glucocorticoid feadback action in the hypothalamo-hypophysial system
  • role of endogenous ANXA1 in the protective and reparative properties of the intestinal mucosal epithelium
  • mediating the glucocorticoid inhibition of cyclic adenosine 3', 5'-monophosphate-stimulated prolactin secretion
  • promoting membrane fusion
  • mediator of the anti-inflammatory actions of endogenous and exogenous glucocorticoids (GC)
  • regulating the MAPK/ERK pathway
  • potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner
  • fundamental for brain homeostasis
  • Ca(2+)-dependent membrane binding protein, which has been implicated in membrane trafficking and reorganization
  • important component of phagocytosis that appears to link actin accumulation to different steps of phagosome formation
  • multifunctional, calcium-dependent phospholipid binding protein involved in a host of processes including inflammation, regulation of neuroendocrine signaling, apoptosis, and membrane trafficking
  • may be required for the constitutive activity of IKBKB and NFKB in highly metatstatic breast cancer
  • required for the recruitment of RIPK1 to the IKK complex, which may be important for the activation of NFKB
  • critical for the constitutive activation of NFkB in breast cancer to promote metastasis
  • expressed in brain microvascular endothelial cells, where it regulates blood–brain barrier(BBB) integrity
  • is a stabilizer for fibrillar actin and consequently cell polarity
  • ANXA1 complex coordinates the actions of PRKCA and PRKCB to control the distribution of oxytocin vesicles between the axon and the cell body
  • ANXA1 expression is "tumor-specific" and might play a multifaceted role in cancer development and progression
  • contributes to the pathological consequence and sequelae of most serious human diseases including cardiovascular disease and cancer
  • role for ANXA1 in shaping the adaptive immunity against M. tuberculosis
  • endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits
  • is essential in cell differentiation and proliferation
  • potential role of ANXA1 in the regulation of bone marrow-derived mesenchymal stem cell (BM-MSC) proliferation and osteogenic differentiation
  • is a key modulator of mesenchymal stromal cell-mediated improvements in islet function
  • nuclear translocation of ANXA1 is involved in neuronal apoptosis after ischemic stroke
  • plays a pivotal role in APP clearance
  • promotes the proliferation of esophageal squamous cell carcinoma (ESCC) cells, and increases the expression of SNAI1, whereas it inhibits that of CDH1, thus enhancing the migration and invasion of ESCC cells
  • is a glucocorticoid-regulated protein known for its anti-inflammatory and pro-resolving effects
  • is at least one of the endogenous determinants mediating the pro-resolving properties of cAMP-elevating agents and cAMP-mimetic drugs
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS inflammation , exocytosis transport
    text anti-inflammatory response
    PATHWAY
    metabolism lipid/lipoprotein
    signaling signal transduction
    lipid metabolism
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • calcium Ca2+ (2 to 4 ions with high affinity)
  • calcium- and phospholipid-binding protein
  • protein
  • formyl peptide receptor (FPR)
  • interacting with TSC22D3 (TSC22D3 is a previously unrecognized mechanism of the anti-inflammatory effects of ANXA1)
  • N-terminal tail of ANXA1 can interact with either membranes or S100A11 protein, and it adopts the conformation of an amphipathic alpha-helix upon these interactions
  • binding of annexin A1 to heparin/heparan sulfate is calcium- but not magnesium-dependent
  • can bind to and interact with IKBKG or NEMO, but not IKBKA or IKBKB
  • ANXA1/FPR2 system has an important role in effecting the resolution of cerebral inflammation in sepsis
  • exogenous ANXA1 acts through FPR2, inhibits the activity of RHOA, promoting cytoskeletal stability and enhancing tight junction formation, hence contributing to BBB integrity 6)
  • during neutrophil activation, CTSG regulates the secretion/release of multiple peptide modulators of neutrophil functions, including ANXA1 and CAMP
  • overexpression of CRISP3 in prostate tumor may maintain higher KLK3 expression and lower ANXA1 expression
  • ANXA1 interacted with the BID (BH3-interacting-domain death agonist) promoter directly
  • ANXA1 interacts with TP53 and promotes TP53 transcriptional activity, which in turn regulates BID expression
  • ANXA1-regulated contacts function in the transfer of ER-derived cholesterol to the multivesicular endosomes/bodies (MVBs) when low-density lipoprotein-cholesterol in endosomes is low
  • cell & other
    REGULATION
    induced by 17 beta-estradiol in CCRF-CEM cells (synthesis and secretion)
    inhibited by exogenous glucorticoids in brain
    phosphorylated by protein kinase C and epidermal growth factor receptor/kinase
    cleavage by the proteinase 3
    Other Ubiquitination of annexin A1 may play an important role in mutagenesis, an initial step of cell transformation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal cancers, correlated with KRAS mutation and may be involved in invasive tumor growth and metastasis
    tumoral     --over  
    in lung cancer
    constitutional     --low  
    in the plasma and cerebrovascular endothelium of patients with multiple sclerosis (MS) (pMID: 23277546)
    constitutional     --over  
    in the brains of AD patients
    constitutional        
    silencing ANXA1 decreases the expression of BID and suppresses CASP3 pathway activation, thus improving cell survival after oxygen-glucose deprivation-reoxygenation (OGD/R)
    constitutional     --over  
    were associated with a systemic inflammatory phenotype in Preeclampsia (PE) suggesting ANXA1 deregulation in PE pathogenesis
    Susceptibility fragile X syndrome: over or low expression in FMR1
    Variant & Polymorphism
    Candidate gene
    Marker
  • could be considered as a biomarker of clinical prognostic prediction and targeted therapy of gastric adenocarcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    modulating ANXA1 levels has therapeutic potential to suppress breast cancer metastasis
    cancerdigestivecolon
    could be of potential use as a predictive marker for guiding targeted therapy for colorectal cancer
    neurologyacquired 
    therapeutic target for pathologic processes characterized by compromised BBB function, such as multiple sclerosis (MS)
    neurologyneurodegenerativealzheimer
    potential pharmacological tool for AD therapeutics
    ANIMAL & CELL MODELS
  • Anxa1-/- mice exhibit significantly increased BBB permeability as a result of disrupted interendothelial cell tight junctions
  • Anxa1(-/-) mice are more susceptible to M. tuberculosis infection, as evidenced by a transient increase in the pulmonary bacterial burden, and exacerbated and disorganized granulomatous inflammation