Recombinant Mouse NAD (+) hydrolase SARM1 (Sarm1), partial

Function

NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism (PubMed:25818290, PubMed:26686637, PubMed:27735788, PubMed:32312889). 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:21555464, PubMed:22678360, PubMed:25818290, PubMed:26423149, PubMed:26686637). 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:28334607). Also able to hydrolyze NADP(+), but not other NAD(+)-related molecules (By similarity). Can activate neuronal cell death in response to stress (PubMed:19587044). Regulates dendritic arborization through the MAPK4-JNK pathway (PubMed:17724133, PubMed:21555464). 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:21555464). Acts as a non-self dsDNA sensor in a sequence-independent manner to elicit NAD(+) degradation and thus to promote programmed cell death (By similarity)

Subcellular Location

Cytoplasm; Cell projection, axon; Cell projection, dendrite; Synapse; Mitochondrion

Tissue Specificity

Widely expressed in the brain and neurons (at protein level) (PubMed:21555464). Expressed in photoreceptor cells of the neural retina (PubMed:32312889)

Subunit

Homooctamer; forms an octameric ring via SAM domains (By similarity). Interacts with TICAM1/TRIF and thereby interferes with TICAM1/TRIF function (By similarity). Interacts with SDC2 (via cytoplasmic domain) and MAPK10/JNK3 (PubMed:17724133, PubMed:21555464)

• Bousson J.-C. et al. SARM1 isoforms nucleotide sequence. (OCT-)
• Okazaki N. et al. Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries. — DNA Res. (2004)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• Church D.M. et al. Lineage-specific biology revealed by a finished genome assembly of the mouse. — PLoS Biol. (2009)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Kim Y. et al. MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival. — J. Exp. Med. (2007)
• Dalod M. et al. Studies of SARM1 uncover similarities between immune and neuronal responses to danger. — Sci. STKE (2007)
• Szretter K.J. et al. The immune adaptor molecule SARM modulates tumor necrosis factor alpha production and microglia activation in the brainstem and restricts West Nile virus pathogenesis. — J. Virol. (2009)