Function
NAD+ hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD+ metabolism (PubMed:25908823, PubMed:27671644, PubMed:28334607).
Acts as a negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway by promoting Wallerian degeneration, an injury-induced form of programmed subcellular death which involves degeneration of an axon distal to the injury site (PubMed:15123841, PubMed:16964262, PubMed:20306472, PubMed:25908823).
Wallerian degeneration is triggered by NAD+ depletion: in response to injury, SARM1 is activated and catalyzes cleavage of NAD+ into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide; NAD+ cleavage promoting cytoskeletal degradation and axon destruction (PubMed:25908823, PubMed:28334607, PubMed:30333228, PubMed:31128467, PubMed:31439793, PubMed:32049506, PubMed:32828421, PubMed:31439792, PubMed:33053563).
Also able to hydrolyze NADP+, but not other NAD+-related molecules (PubMed:29395922).
Can activate neuronal cell death in response to stress (PubMed:20306472).
Regulates dendritic arborization through the MAPK4-JNK pathway (By similarity).
Involved in innate immune response: inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38 (PubMed:16964262).
Biological Process
Biological Process cell differentiationIEA:UniProtKB-KW
Biological Process innate immune responseIEA:UniProtKB-KW
Biological Process NAD catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of MyD88-independent toll-like receptor signaling pathwayIEA:InterPro
Biological Process nervous system developmentIEA:UniProtKB-KW
Biological Process positive regulation of neuron deathManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of dendrite morphogenesisISS:UniProtKB
Biological Process regulation of neuron apoptotic processIEA:Ensembl
Biological Process regulation of neuron deathISS:UniProtKB
Biological Process response to axon injuryManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process response to glucoseIEA:Ensembl
Biological Process signal transductionIEA:InterPro
Cellular Location
Cytoplasm
Cell projection, axon
Cell projection, dendrite
Synapse
Mitochondrion
Associated with microtubules.
PTM
Phosphorylation at Ser-548 by JNK kinases (MAPK8, MAPK9 and /or MAPK10) enhance the NAD+ hydrolase (NADase) activity (PubMed:30333228).
Phosphorylation at Ser-548 and subsequent activation takes place in response to oxidative stress conditions and inhibits mitochondrial respiration (PubMed:30333228).