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FLASH GENE
Symbol SARM1 contributors: mct/pgu - updated : 28-01-2016
HGNC name sterile alpha and TIR motif containing 1
HGNC id 17074
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal and sterile alpha motif domains important in the autoregulation of SARM1 activity
  • HEAT/Armadillo motifs
  • TIR domain (Toll interleukin 1 receptor)
    • HOMOLOGY
    interspecies ortholog to Drosophila sarm
    homolog to C.elegans SARM
    Homologene
    FAMILY
  • fifth member of the Toll-like receptor (TLR) adaptor family
  • MyD88 (myeloid differentiation primary response gene 88) family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • probable mucin protein may be involved in protein-protein interactions promoting the formation of diverse protein complexes
  • negative regulator of Toll-like receptor signaling
  • negative regulator of TICAM1-dependent Toll-like receptor signaling
  • function as a specific inhibitor of TRIF-dependent TLR signaling
  • downregulates NF-kappaB and IRF3-mediated TLR3 and TLR4 signaling
  • negative regulator of Toll-like receptor 3 (TLR3) in innate immunity signaling
  • required for proper initiation and elongation of dendrites, axonal outgrowth, and neuronal polarization
  • SARM1 is a member of an ancient axon death signaling pathway
  • may be potentially broadly required to promote Wallerian degeneration in the nervous system
  • regulates the innate immune responses of the central nervous system through regulating the inflammatory and anti-virus cytokines produced by neurons
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with RS1 (interaction may be part of a novel SARM1-mediated cell signaling pathway required for the maintenance of retinal cell organization and photoreceptor-bipolar synaptic structure)
  • negative regulator of the TICAM1-dependent pathway via its interaction with TICAM1
  • inhibits both TICAM1- and MYD88-mediated AP-1 activation
  • interacts with and receives signal from SDC2 and controls dendritic arborization through the MKK4-JNK pathway
  • is a negative regulator of Toll-like receptor 3 (TLR3) in innate immunity signaling
  • association of PINK1 with SARM1 and TRAF6 is an important step for mitophagy
  • absence of SARM1 rescues development and survival of NMNAT2-deficient axons
  • SARM1, mediates TLR7/TLR9-induced apoptosis in neurons
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    exacerbates the progression of prion pathogenesis, by up-regulating XAF1, which promotes neuronal apoptosis, and accelerates prion disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurology  
    pharmacological inhibition of SARM1 may represent a promising therapeutic avenue for patients with axonal loss
    ANIMAL & CELL MODELS
    Sarm1-deficient mice may uncover unexpected similarities between the ways in which neurons and immune cells sense and respond to danger