SARM1, FLAG-Tag Recombinant
Recombinant human SARM1 (sterile alpha and TIR motif containing 1), encompassing amino acids 28-724 (end). This construct contains an N-terminal FLAG tag. The protein was affinity purified.
40 mM Tris-HCI, pH 8.0, 110 mM NaCl, 2.2 mM KCl, 20% glycerol, 3 mM DTT, 100 µg/ml FLAG peptide.
SARM1 (Sterile alpha and TIR motif containing 1) is a member of the Toll/Interleukin receptor-1 (TIR1) family of enzymes. It functions as an ADP-ribosyl cyclase and nicotinamide adenine dinucleotide (NAD) glycohydrolase. SARM1-TIR domains have intrinsic NADase activity, cleaving NAD+ into ADP Ribose (ADPR), cyclic ADPR, and Nicotinamide. Often associated with mitochondria, the protein functions as a sensor of metabolic stress. It is highly expressed in neurons, where it causes the depletion of axonal NAD+ and pathological axon loss. SARM1 functions downstream of NMNAT2 (nicotinamide nucleotide adenylyltransferase 2) to promote the active process of injury-induced neuronal degeneration known as Wallerian degeneration. Constitutive NADase activity resulting from mutation in the human SARM1 gene has been observed in neurodegenerative disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). Alternatively, loss of SARM1 activity protects neurons in models of brain injury or drug-induced neuron damage. Therefore, inhibition of SARM1 NAD+ cleavage activity may potentially reduce axonal degeneration.
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