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Symbol ANXA2 contributors: mct - updated : 15-06-2016
HGNC name annexin A2
HGNC id 537
  • 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
    interspecies homolog to murine Anxa2
    homolog to C.elegans Zc155.1
  • annexin family
  • calcium dependent phospholipid binding protein family
  • CATEGORY regulatory , signaling , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
  • 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
    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)
    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
    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
    Variant & Polymorphism
    Candidate gene
  • 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
    inhibition of annexin A2 expression in glioma cells could become a new target for glioma therapy
    targeting ANXA2-mediated signaling may provide a novel therapeutic approach to the treatment of airway inflammation in diseases such as chronic asthma
    may be new and prognostic marker of metastatic pancreatic ductal adenocarcinoma (PDA)