SARM1

SARM1 (Sterile Alpha And TIR Motif Containing 1) is a Protein Coding gene. Diseases associated with SARM1 include Wallerian Degeneration. Among its related pathways are Innate Immune System and Activated TLR4 signalling. Gene Ontology (GO) annotations related to this gene include binding.

Full Name

Sterile Alpha And TIR Motif Containing 1

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).