HEK293T/Human SARM1 Stable Cell Line

NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism. 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. 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. Also able to hydrolyze NADP(+), but not other NAD(+)-related molecules. Can activate neuronal cell death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. 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.

1. we identify a physical interaction between the autoinhibitory N terminus and the TIR domain of SARM1, revealing a previously unrecognized direct connection between these domains that we propose mediates autoinhibition and activation upon injury. PMID: 27671644
2. Active nerve degeneration requires SARM1 and MAP kinases, including DLK, while the NAD+ synthetic enzyme NMNAT2 prevents degeneration. PMID: 26844829
3. Data show that sterile alpha- and armadillo-motif-containing protein (SARM) modulates MyD88 protein-mediated Toll-like receptors (TLRs) activation through BB-loop dependent interleukin-1 receptor (TIR) TIR-TIR interactions. PMID: 26592460
4. These results indicate that association of PINK1 with SARM1 and TRAF6 is an important step for mitophagy. PMID: 23885119
5. The innate immunity adaptor SARM translocates to the nucleus to stabilize lamins and prevent DNA fragmentation in response to pro-apoptotic signaling. PMID: 23923041
6. Rapid Wallerian degeneration requires the pro-degenerative molecules SARM1. PMID: 24840802
7. Data found that the UXT isoforms elicit dual opposing regulatory effects on SARM-induced apoptosis. PMID: 24021647
8. SARM overexpression caused mitochondrial clustering which has also been observed in several cell death phenomenon. PMID: 23175186
9. The N-terminal 27 amino acids (S27) of SARM, which is hydrophobic and polybasic, acts as a mitochondria-targeting signal sequence, associating SARM to the mitochondria. The S27 peptide has an inherent ability to bind to lipids and mitochondria. PMID: 22145856
10. SARM-mediated inhibition may not be exclusively directed at TRIF or MyD88, but that SARM may also directly inhibit MAPK phosphorylation PMID: 20306472
11. Candidate gene in the onset of hereditary infectious/inflammatory diseases. PMID: 15893701
12. TIR adaptor SARM is a negative regulator of Toll-like receptor signaling. PMID: 16964262
13. confirmed the co-localization of retinoschisin with Na/K ATPase and SARM1 in photoreceptors and bipolar cells of retina tissue PMID: 17804407
14. SARM1 deficiencies may uncover unexpected similarities between the ways in which neurons and immune cells sense and respond to danger. PMID: 18089857

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Cytoplasm. Cell projection, axon. Cell projection, dendrite. Cell junction, synapse. Mitochondrion.

Predominantly expressed in brain, kidney and liver. Expressed at lower level in placenta.

HGNC: 17074

OMIM: 607732

KEGG: hsa:23098

STRING: 9606.ENSP00000406738

UniGene: Hs.743510