Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol ANXA6 contributors: shn/npt - updated : 04-03-2020
HGNC name annexin A6
HGNC id 544
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a relatively short N terminus
  • a C terminal "core" region containing four repeats homolog to the endonexin fold
  • contains 8 annexin repeats
    • conjugated PhosphoP , Other
    HOMOLOGY
    interspecies ortholog to anxa6, Danio rerio
    ortholog to ANXA6, Pan troglodytes
    ortholog to Anxa6, Rattus norvegicus
    ortholog to Anxa6, Mus musculus
    Homologene
    FAMILY
  • calcium-dependent membrane and phospholipid binding protein
  • annexin family
    • CATEGORY regulatory , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis
  • regulating the release of calcium Ca2+ from intracellular strores
  • a retinoid binding activity
  • putative roles in adhesion-related cellular processes that contribute to breast cancer progression
  • may play a particular role in the organization of lipid microdomains in Niemann-Pick disease
  • in the presence of calcium, ANXA6 re-located to the fractions enriched in detergent-resistant microdomains only in the Niemann-Pick disease cells, suggestive of ANXA6 participation in organization of these microdomains
  • ANXA6 via its stimulatory actions on PRKCA and its role in mediating Ca(2+) flux across membranes regulates terminal differentiation and mineralization events of chondrocytes
  • ANXA6-induced plasma membrane remodelling indicated that elevated ANXA6 expression decreased membrane order through the regulation of cellular cholesterol homeostasis and the actin cytoskeleton
  • ANXA6 protein in adipocytes was upregulated by oxidative stress which might trigger ANXA6 induction in adipose tissues and contribute to impaired fat storage and adiponectin release
  • implicated in many biological processes, including cell proliferation, survival, differentiation, inflammation, but also membrane repair and viral infection
  • novel role for ANXA6 in articular chondrocytes via its modulation of WNT/CTNNB1 and NFKB1 signaling activities and the cross-talk between these two signaling pathways
  • controls cholesterol and membrane transport in endo- and exocytosis, and modulates triglyceride accumulation and storage
  • acts as a scaffolding protein for negative regulators of growth factor receptors and their effector pathways in many different cell types
  • is a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a RAB7-GAP and membrane contact sites (MCS) formation
  • stabilize and establish the formation of multifactorial signaling complexes
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS exocytosis transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • calcium Ca2+
  • phospholipid
  • vitamin A (all-trans retinol)
    • protein
  • CD21
  • Ras p21 regulatory protein p120GAP
  • Ca(2+)-regulated EF-hand proteins S100A1 and S100B
  • EBV/C3d receptor (CR2)
  • active H-Ras (HRasG12V)
  • ANXA6 inhibits DNM1L activity, and Ca2+-binding to ANXA6 relieves this inhibition to permit DNM1L-mediated mitochondrial fission
  • cooperative mechanism where ANXA6 potentiates NPPA-dependent counterhypertrophic responses in cardiomyocytes by facilitating regulated traffic of pro-NPPA
  • elevated ANXA6 levels cause late endosome (LE) cholesterol accumulation, ANXA6 and blockage of LE cholesterol transport are critical for endosomal function required for STX6-mediated recycling of integrins in cell migration
  • PLA2G4A -dependent pathways contribute to the novel regulatory role of hepatic ANXA6 in lipid droplet (LD) formation
  • ANXA6 acts as a scaffold for RASGRF2 and RAS proteins and its interaction with RASGRF2 is modulated by GTP and/or activation of Ras proteins
    • cell & other
  • cytoskeleton in a calcium-dependent manner
  • interacts with membranes in a Ca2+-dependent manner
    • REGULATION
    induced by EBV
    Other phosphorylated in response to growth factor stimulation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation
    tumoral     --low  
    is specifically reduced in human hepatocellular carcinoma suggesting a role of this protein in hepatocarcinogenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    annexin A6 can be exploited to inhibit chronic mechanical pain
    ANIMAL & CELL MODELS
  • Annexin A6-deficient mice showed increased sensitivity to mechanical stimuli