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FLASH GENE
Symbol HSPB6 contributors: mct/pgu - updated : 08-09-2014
HGNC name heat shock protein, alpha-crystallin-related, B6
HGNC id 26511
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a unique N terminus
  • a consensus motif (RRAS) for protein kinase A(PKA)/protein kinase G-dependent phosphorylation at Ser16
  • a conserved alpha-crystallin domain at the C terminus, which facilitates the chaperone activity
  • mono polymer monomer , dimer
    HOMOLOGY
    Homologene
    FAMILY small heat shock protein (HSP20) family
    CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • secreted through exosomes, independent of the endoplasmic reticulum-Golgi pathway
  • basic FUNCTION
  • protects cardiomyocytes against apoptosis (Nicolaou 2008)
  • increases in HSPB6 levels can protect against LPS-induced cardiac apoptosis and dysfunction, associated with inhibition of NF-kappaB activity
  • bind to unfolded or misfolded proteins and protect them from aggregation
  • in the heart, the small HSPB6 has emerged as a key mediator of protection against apoptosis, remodeling, and ischemia/reperfusion injury
  • novel regulator of sarcoplasmic reticulum Ca cycling by targeting the PPP1CC-PLN axis
  • its acetylation regulates human myometrial activity
  • serves as a novel cardiokine in regulating myocardial angiogenesis through activation of the KDR signaling cascade
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component may exist as disulfide-linked dimer and monomer
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with HSP22
  • binds to BAG3 through the hydrophobic groove formed by its strands beta4 and beta8, a region previously known to be responsible for the formation and stability of higher-order oligomers of many sHsps (small Hsps)
  • HDAC8 is a non-nuclear lysine deacetylase (KDAC) that can interact with HSPB6 to affect its acetylation
  • YWHAZ monomeric form interacts with MAPT and with the HSPB6 protein
  • interaction between HSPB6 and KDR
  • interacton with cofilin (might affect potentially interaction of 14-3-3 with protein phosphatases and/or protein kinases involved in dephosphorylation or phosphorylation of cofilin and by this means regulate cofilin-dependent reorganization of cytoskeleton)
  • AKAP13 may serve an ancillary cardioprotective role by favouring the association of PRKACA with HSPB6
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism other mutation P20L is associated with structural alterations, diminished phosphorylation at Ser16, and loss of the cardioprotective effects under stress conditions
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascular  
    dual benefit of targeting HSPB6 in heart disease
    cardiovascularatheromacardiac
    phosphorylation of HSPB6 at serine 16 may represent a potential therapeutic target in ischemic heart disease
    immunologyinfectious 
    may be a new therapeutic agent for the treatment of sepsis
    ANIMAL & CELL MODELS