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FLASH GENE
Symbol S100A6 contributors: mct/npt - updated : 24-12-2012
HGNC name S100 calcium binding protein A6
HGNC id 10496
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two calcium binding domains with an EF-hand motif
  • one S100 specific N-terminus
  • one classical C-terminus
  • ICaBP type calcium binding domain
  • HOMOLOGY
    Homologene
    FAMILY
  • S100 family of EF-hand, calcium-binding proteins
  • CATEGORY signaling cytokine , receptor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nuclear envelope,ext
    text
  • in primary human endothelial cells, S100A6 was present in both the nucleus and the cytoplasm
  • basic FUNCTION
  • may be playing a role in stimulation of Ca2+-dependent insulin release,stimulation of prolactin secretion and exocytosis
  • growth-regulated gene inducible by growth factors, having a functional role in tumor necrosis factor-alpha-induced myocyte apoptosis
  • linked with cell cycle progression, cytoskeleton rearrangement, exocytosis, and cell survival
  • may be involved in cell proliferation, cytoskeletal dynamics and tumorigenesis
  • regulates a spectrum of growth and differentiation properties in cardiac muscle, in keeping with its role in cell cycle progression in proliferating cell lineages
  • involvement of this protein in intra- and extra-cellular signalling pathways in the umbilical cord
  • small EF-hand calcium- and zinc-binding protein involved in the regulation of cell proliferation and cytoskeletal dynamics
  • has an important role in regulating endothelial commitment to, and progression through, the cell cycle
  • CELLULAR PROCESS cell cycle
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    component of the pro-survival pathway activated by TNF- alpha and provides a homeostatic mechanism to limit TNF-alpha-induced myocyte apoptosis by interfering with TP53 phosphorylation
    a component
  • constituent of epidermal differentiation complex
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • increase in intracellular concentration of Ca(2+), transduced by S100A6, is necessary for nuclear translocation of the SUGT1 protein
  • with S100A2, S100A4 and S100A1, interacting with MDM2, making the binding to MDM2 a general feature of S100 proteins
  • S100A6-SUGT1 dephosphorylation promotes its nuclear translocation, most likely due to disruption of the SUGT1-HSP90AA1 complex
  • S100A1, S100A2, S100A6, and S100B proteins specifically interact with PPP5C-tetratricopeptide repeat (TPR) domain
  • cell & other
    REGULATION
    activated by TNFalpha- signaling via NF-kB
    induced by tumor necrosis factor-alpha via an NF-kB-dependent mechanism, serving a role in homeostasis to limit tumor necrosis factor-alpha-induced apoptosis by regulating TP53 phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in primary colorectal adenocarcinomas with liver metastases
    tumoral     --over  
    in osteosarcoma cells loss of its expression correlates with a metastatic phenotype
    constitutional     --over  
    overexpressed in neurodegenerative disorders and a proposed marker for Amyotrophic Lateral Sclerosis (ALS)
    constitutional       gain of function
    upregulation of astrocytic S100A6 in response to extracellular glutamate may be involved in neuronal damage under pathophysiological conditions
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • proposed marker for Amyotrophic Lateral Sclerosis (ALS)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    with SPP1, may be promising diagnostic markers and therapeutic targets for hepatocellular carcinoma
    ANIMAL & CELL MODELS