| Identification |
|---|
| HMDB Protein ID
| HMDBP12393 |
| Secondary Accession Numbers
| None |
| Name
| NAD(+) hydrolase tir-1 |
| Synonyms
|
- NADase tir-1
- Neuronal symmetry protein 2
- SARM1 homolog
- Sterile alpha and TIR motif-containing protein tir-1
|
| Gene Name
| TIR-1 |
| Protein Type
| Unknown |
| Biological Properties |
|---|
| General Function
| Not Available |
| Specific Function
| NAD(+) hydrolase, which plays a key role in non-apoptotic cell death by regulating NAD(+) metabolism (PubMed:27671644). In response to stress, homooligomerizes and catalyzes cleavage of NAD(+) into ADP-D-ribose (ADPR) and nicotinamide; NAD(+) cleavage promoting non-apoptotic neuronal cell death (PubMed:31439792). In males, involved in non-apoptotic death of the linker cell which guides gonad elongation during larval development (PubMed:22363008). Required for both innate immune response and specification of AWC(OFF) neuron (PubMed:15048112, PubMed:15123841, PubMed:15625192). During late embryogenesis, it acts downstream of CAMKII (unc-43) to regulate specification of asymmetric odorant receptors in AWC(OFF) neuron via the nsy-1/ASK1 pmk-1/p38 MAP kinase signaling cascade. Required to localize nsy-1 to postsynaptic regions of AWC neuron, suggesting that it may act by assembling a signaling complex that regulate odorant receptor expression (PubMed:15625192). Also plays a central role in resistance to infection to a broad range of bacterial and fungi pathogens, possibly by activating pmk-1, independently of the NF-kappa-B pathway. Required for expression of antimicrobial peptides nlp-29 and nlp-31 (PubMed:15048112, PubMed:15123841). Its role in immune response and neuron specification may be mediated by the same nsy-1/ASK1 pmk-1/p38 MAP kinase cascade signaling pathway (PubMed:15048112, PubMed:15123841, PubMed:15625192). Involved in the response to anoxic conditions probably by activating the p38 pathway composed of nsy-1/sek-1/pmk-1 (PubMed:21212236). Involved in regulation of the serotonergic response of ADF neurons to pathogenic food (PubMed:23505381). In addition, plays a role in the up-regulation of gcs-1 upon arsenite treatment, most likely through activation of pmk-1, to confer protection against toxicity induced by heavy metals (PubMed:25204677).Regulates expression of antimicrobial peptide nlp-29 in response to fungal infection or physical injury. |
| Pathways
|
Not Available
|
| Reactions
| Not Available |
| GO Classification
|
| Biological Process |
| defense response to bacterium |
| positive regulation of transcription from RNA polymerase II promoter involved in defense response to Gram-negative bacterium |
| cell-cell signaling involved in cell fate commitment |
| positive regulation of neuron death |
| negative regulation of MyD88-independent toll-like receptor signaling pathway |
| defense response to fungus |
| NAD catabolic process |
| negative regulation of gene expression |
| innate immune response |
| regulation of neuron death |
| protein localization |
| activation of MAPK activity |
| positive regulation of transcription from RNA polymerase II promoter |
| signal transduction |
| response to axon injury |
| nervous system development |
| positive regulation of gene expression |
| Cellular Component |
| axon cytoplasm |
| dendrite |
| Molecular Function |
| NAD+ nucleosidase activity |
| NAD(P)+ nucleosidase activity |
| NAD+ nucleotidase, cyclic ADP-ribose generating |
| signaling adaptor activity |
| protein kinase binding |
| small GTPase binding |
| identical protein binding |
|
| Cellular Location
|
Not Available
|
| Gene Properties |
|---|
| Chromosome Location
| Not Available |
| Locus
| Not Available |
| SNPs
| Not Available |
| Gene Sequence
|
Not Available
|
| Protein Properties |
|---|
| Number of Residues
| Not Available |
| Molecular Weight
| 110555.14 |
| Theoretical pI
| Not Available |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
Not Available
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| Q86DA5 |
| UniProtKB/Swiss-Prot Entry Name
| SARM1_CAEEL |
| PDB IDs
|
Not Available |
| GenBank Gene ID
| Not Available |
| GeneCard ID
| Not Available |
| GenAtlas ID
| Not Available |
| HGNC ID
| Not Available |
| References |
|---|
| General References
| - Liberati NT, Fitzgerald KA, Kim DH, Feinbaum R, Golenbock DT, Ausubel FM: Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6593-8. doi: 10.1073/pnas.0308625101. [PubMed:15123841 ]
- Summers DW, Gibson DA, DiAntonio A, Milbrandt J: SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation. Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6271-E6280. doi: 10.1073/pnas.1601506113. Epub 2016 Sep 26. [PubMed:27671644 ]
- Horsefield S, Burdett H, Zhang X, Manik MK, Shi Y, Chen J, Qi T, Gilley J, Lai JS, Rank MX, Casey LW, Gu W, Ericsson DJ, Foley G, Hughes RO, Bosanac T, von Itzstein M, Rathjen JP, Nanson JD, Boden M, Dry IB, Williams SJ, Staskawicz BJ, Coleman MP, Ve T, Dodds PN, Kobe B: NAD(+) cleavage activity by animal and plant TIR domains in cell death pathways. Science. 2019 Aug 23;365(6455):793-799. doi: 10.1126/science.aax1911. [PubMed:31439792 ]
- Authors unspecified: Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012-8. doi: 10.1126/science.282.5396.2012. [PubMed:9851916 ]
- Couillault C, Pujol N, Reboul J, Sabatier L, Guichou JF, Kohara Y, Ewbank JJ: TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nat Immunol. 2004 May;5(5):488-94. doi: 10.1038/ni1060. Epub 2004 Mar 28. [PubMed:15048112 ]
- Chuang CF, Bargmann CI: A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes Dev. 2005 Jan 15;19(2):270-81. doi: 10.1101/gad.1276505. Epub 2004 Dec 29. [PubMed:15625192 ]
- Pujol N, Cypowyj S, Ziegler K, Millet A, Astrain A, Goncharov A, Jin Y, Chisholm AD, Ewbank JJ: Distinct innate immune responses to infection and wounding in the C. elegans epidermis. Curr Biol. 2008 Apr 8;18(7):481-9. doi: 10.1016/j.cub.2008.02.079. [PubMed:18394898 ]
- Hayakawa T, Kato K, Hayakawa R, Hisamoto N, Matsumoto K, Takeda K, Ichijo H: Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins. Genetics. 2011 Mar;187(3):785-92. doi: 10.1534/genetics.110.124883. Epub 2011 Jan 6. [PubMed:21212236 ]
- Blum ES, Abraham MC, Yoshimura S, Lu Y, Shaham S: Control of nonapoptotic developmental cell death in Caenorhabditis elegans by a polyglutamine-repeat protein. Science. 2012 Feb 24;335(6071):970-3. doi: 10.1126/science.1215156. [PubMed:22363008 ]
- Xie Y, Moussaif M, Choi S, Xu L, Sze JY: RFX transcription factor DAF-19 regulates 5-HT and innate immune responses to pathogenic bacteria in Caenorhabditis elegans. PLoS Genet. 2013;9(3):e1003324. doi: 10.1371/journal.pgen.1003324. Epub 2013 Mar 7. [PubMed:23505381 ]
- Crook-McMahon HM, Olahova M, Button EL, Winter JJ, Veal EA: Genome-wide screening identifies new genes required for stress-induced phase 2 detoxification gene expression in animals. BMC Biol. 2014 Aug 14;12:64. doi: 10.1186/s12915-014-0064-6. [PubMed:25204677 ]
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