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FLASH GENE
Symbol ANXA2 contributors: mct - updated : 15-06-2016
HGNC name annexin A2
HGNC id 537
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivesalivary gland   highly
Urinarybladder   highly
Visualeyeanterior segmentcornea  
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly
cells
SystemCellPubmedSpeciesStageRna symbol
not specificchondrocyte Homo sapiens
Skeletonosteoblast Homo sapiens
Skin/Tegumentkeratinocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES Hydrophilic
STRUCTURE
motifs/domains
  • a relatively short N-terminal tail domain able to undergo Ca(2+)-independent membrane-binding, and having different roles in the H+- and Ca2+-mediated membrane bridging mechanisms, with S100A10 binding motif is located in the first 12 AAs of the N-terminal domain, but conflicting reports exist as to the importance of N-terminal ANXA2 acetylation with regard to S100A10 binding
  • a C terminal "core" region made of four repeats homolog to the endonexin fold
  • hydrophilic pore
  • secondary structure four compact domains consisting of five alpha-helices each
    conjugated Other
    mono polymer heteromer , tetramer
    HOMOLOGY
    interspecies homolog to murine Anxa2
    homolog to C.elegans Zc155.1
    Homologene
    FAMILY
  • annexin family
  • calcium dependent phospholipid binding protein family
  • CATEGORY regulatory , signaling , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,nucleus
    text
  • in the lamina beneath the plasma membrane
  • S100A10 and ANXA2 were also found to localize in the nucleus
  • basic FUNCTION
  • phospholipase A2 inhibitor, involved in an H+-mediated mechanism leading to a novel AnxA2-membrane complex structure
  • playing a role in the regulation of cellular growth and in signal transduction
  • functioning as an autocrine factor which heighten osteoclast formation and bone resorption
  • regulating the production and autoproteolysis of plasmin at the cell surface (prossessing an intrinsic plasmin reductase activity)
  • stimulating both the proliferation and differentiation of osteoclasts precursors through production of GM-CSF(granulocyte-macrophage colony-stimulating factor) and TNFSF11 respectively
  • annexin A2 and SNAP23 are involved in the same pathway in the regulation of lung surfactant secretion
  • able to bridge membranes either as a dimer or as a monomer, respectively
  • regulate F10 signaling specifically in the absence of cell surface tissue factor and may thus play physiological or pathological roles when factor Xa is generated in a tissue factor-depleted environment
  • plays an essential role inMultidrug resistance-induced tumor invasion
  • calcium-dependent phospholipid binding protein has been implicated in VEGF-mediated retinal neovascularization and is upregulated by VEGF in choroid retinal endothelial cells
  • its expression in osteoblasts is under the control of VEGF, which may have implications for both angiogenesis and bone mineralization under low oxygen conditions
  • regulates endothelial morphogenesis through an adherens junction-mediated pathway upstream of AKT1
  • plays an important role in hematopoietic stem cell (HSC) localization to the endosteal/osteoblastic marrow niche
  • may serves as an anchor for CXCL12 to help in the localization of HSCs to the niche
  • participate in processes localized to the cell surface including extracellular protease regulation and cell-cell interactions
  • is a critical regulator in infection-initiated inflammation, which protects the host from excessive inflammatory damage
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS development , exocytosis transport
    text skeletal development
    PATHWAY
    metabolism
    signaling signal transduction
  • S100A10/ANXA2/HLTF pathway mediates both neurogenic and behavioral responses to selective serotonin reuptake inhibitors (SSRIs)
  • a component
  • tetramer of 2 light chains (p10 proteins) and 2 heavy chains (p36 proteins)
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • calcium Ca2+ (2 ions with high affinity)
  • phospholipid
  • beta(2)GPI
  • protein
  • binds negatively charged phospholipid membranes through either Ca2+-dependent or Ca2+-independent/H+-dependent mechanisms
  • ANXA2, ANXA8, and ANXA9 interacted with proAREG and ADAM17 on the cell surface
  • ANXA2, ANXA8, ANXA9, play an essential role in the ADAM17-mediated ectodomain shedding of EGFR ligands
  • HLTF, chromatin-remodeling factor, is a target for the S100A10/ANXA2 heterotetrameric complex
  • ANXA2 is a well-characterized binding partner for S100A10
  • S100A10/ANXA2 not only increases the DNA-binding affinity of HLTF but also anchors HLTF to the nuclear matrix presumably via the interaction of ANXA2 with actin and PIP2
  • PLG stimulates airway smooth muscle (ASM) cytokine production in a manner regulated by ANXA2
  • ANXA2-S100A10 molecular bridge participates in cell-cell interactions, revealing a hitherto unexplored function of this protein interaction
  • is a lipid raft-associated trafficking factor for SLC12A1
  • plausible new role of ANXA2 in the reduction of PCSK9 protein levels via a translational mechanism
  • S100A10, and not ANXA2, is the primary plasminogen receptor within the ANXA2-S100A10 complex and contributes to the plasmin-mediated effects that were originally ascribed to ANXA2b
  • ANXA2 directly exerted negative regulation of inflammatory responses through TLR4-initiated TICAM2-TICAM1 pathway occurring on endosomes
  • KRT8 binds to ANXA2, a protein known to mediate apoptosis as well as the redox pathway
  • TRIM65 has an essential oncogenic role via ubiquitination of ANXA2 in urothelial carcinoma of the bladder (UCB) pathogenesis
  • cell & other
  • mediating the binding of beta(2) GPI to endothelial cells
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in small cell lung carcinoma
    tumoral     --over  
    in the clear-cell renal cell carcinoma, significant associations with a higher stage, a higher nuclear grade
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • MYH7, IGFBP7, ANXA2, and DES are all excellent candidate plasma biomarkers of heart failure
  • may be new prognostic marker of metastatic pancreatic ductal adenocarcinoma (PDA)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    inhibition of annexin A2 expression in glioma cells could become a new target for glioma therapy
    allergyasthm 
    targeting ANXA2-mediated signaling may provide a novel therapeutic approach to the treatment of airway inflammation in diseases such as chronic asthma
    cancerendocrinepancreas
    may be new and prognostic marker of metastatic pancreatic ductal adenocarcinoma (PDA)
    ANIMAL & CELL MODELS