UniProt functional annotation for Q6IDD9



	UniProt functional annotation for Q6IDD9

UniProt code: Q6IDD9.

Organism: Drosophila melanogaster (Fruit fly).

Taxonomy: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora.

Function: NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism (PubMed:22678360, 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:22678360). Wallerian degeneration is triggered by NAD(+) depletion: in response to injury, it is activated and catalyzes cleavage of NAD(+) into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide; NAD(+) cleavage promoting axon destruction (PubMed:22678360, PubMed:28334607, PubMed:31439792). Involved in the down-regulation of the tracheal immune response to Gram-negative bacteria (PubMed:22022271). This is likely by mediating Tollo signaling in the tracheal epithelium (PubMed:22022271). {ECO:0000269|PubMed:22022271, ECO:0000269|PubMed:22678360, ECO:0000269|PubMed:28334607, ECO:0000269|PubMed:31439792}.

Catalytic activity: Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide; Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6; Evidence={ECO:0000269|PubMed:28334607, ECO:0000269|PubMed:31439792}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302; Evidence={ECO:0000269|PubMed:28334607, ECO:0000269|PubMed:31439792};

Catalytic activity: Reaction=NAD(+) = cyclic ADP-ribose + H(+) + nicotinamide; Xref=Rhea:RHEA:38611, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:73672; Evidence={ECO:0000269|PubMed:28334607}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38612; Evidence={ECO:0000269|PubMed:28334607};

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q6PDS3}. Cell projection, axon {ECO:0000269|PubMed:22678360}.

Tissue specificity: Widely expressed in larval brains and adult brains.

Domain: The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity. {ECO:0000250|UniProtKB:Q6SZW1}.

Disruption phenotype: Severed axons in wild-type flies disappear completely within a week of injury, whereas axons of neurons homozygous for any one of the three loss-of-function alleles: l(3)896, l(3)4621, and l(3)4705 persist for several weeks after severing (PubMed:22678360). After infection with Gram-negative bacteria, the respiratory epithelium displays an over-active immune response with a greater increase in expression of Drs compared to wild-type larvae (PubMed:22022271). {ECO:0000269|PubMed:22022271, ECO:0000269|PubMed:22678360}.

Similarity: Belongs to the SARM1 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Drosophila melanogaster (Fruit fly).
Taxonomy:		Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora.



Function:		NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism (PubMed:22678360, 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:22678360). Wallerian degeneration is triggered by NAD(+) depletion: in response to injury, it is activated and catalyzes cleavage of NAD(+) into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide; NAD(+) cleavage promoting axon destruction (PubMed:22678360, PubMed:28334607, PubMed:31439792). Involved in the down-regulation of the tracheal immune response to Gram-negative bacteria (PubMed:22022271). This is likely by mediating Tollo signaling in the tracheal epithelium (PubMed:22022271). {ECO:0000269\|PubMed:22022271, ECO:0000269\|PubMed:22678360, ECO:0000269\|PubMed:28334607, ECO:0000269\|PubMed:31439792}.


Catalytic activity:		Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide; Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6; Evidence={ECO:0000269\|PubMed:28334607, ECO:0000269\|PubMed:31439792}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302; Evidence={ECO:0000269\|PubMed:28334607, ECO:0000269\|PubMed:31439792};
Catalytic activity:		Reaction=NAD(+) = cyclic ADP-ribose + H(+) + nicotinamide; Xref=Rhea:RHEA:38611, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:73672; Evidence={ECO:0000269\|PubMed:28334607}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38612; Evidence={ECO:0000269\|PubMed:28334607};
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:Q6PDS3}. Cell projection, axon {ECO:0000269\|PubMed:22678360}.
Tissue specificity:		Widely expressed in larval brains and adult brains.
Domain:		The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity. {ECO:0000250\|UniProtKB:Q6SZW1}.
Disruption phenotype:		Severed axons in wild-type flies disappear completely within a week of injury, whereas axons of neurons homozygous for any one of the three loss-of-function alleles: l(3)896, l(3)4621, and l(3)4705 persist for several weeks after severing (PubMed:22678360). After infection with Gram-negative bacteria, the respiratory epithelium displays an over-active immune response with a greater increase in expression of Drs compared to wild-type larvae (PubMed:22022271). {ECO:0000269\|PubMed:22022271, ECO:0000269\|PubMed:22678360}.
Similarity:		Belongs to the SARM1 family. {ECO:0000305}.