Sarm1
entrez
237868
canonical
uniprot
Q6PDS3
canonical
ensembl
ENSMUSG00000050132
resolver
ensp
ENSMUSP00000051059
resolver
ensp
ENSMUSP00000103922
resolver
genesymbol
Sarm1
resolver
genesymbol_syn
Kiaa0524
resolver
uniprot
Q5SYG5
resolver
uniprot
Q5SYG6
resolver
uniprot
Q6A054
resolver
uniprot
Q6SZW0
resolver
uniprot
Q8BRI9
resolver
uniprot_entry
SARM1_MOUSE
resolver
uniprot_sec
Q5SYG5
resolver
uniprot_sec
Q5SYG6
resolver
uniprot_sec
Q6A054
resolver
uniprot_sec
Q6SZW0
resolver
uniprot_sec
Q8BRI9
resolver
activity_regulation
ACTIVITY REGULATION: Autoinhibited: in the inactive state, the enzymatic TIR domain is held apart by the autoinhibiting ARM repeats. NAD(+)-binding to ARM repeats maintains an inactive state by promoting interaction between ARM repeats and the TIR domain, thereby facilitating inhibition of the enzymatic TIR domain. Following activation, possibly by nicotinamide mononucleotide (NMN), auto-inhibitory interactions are released, allowing self-association of the TIR domains and subsequent activation of the NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is facilitated by the octamer of SAM domains. {ECO:0000250|UniProtKB:Q6SZW1}.
uniprot
proteins
amino_acid_sequence
MVLTLLFSAYKLCRFFTMSGPRPGADRLTVPGPDRSGGASPWWAAGGRGSREVSPGVGTEVQGALERSLPELQQALSELKQASAARAVGAGLAEVFQLVEEAWLLPAVGREVAQGLCDAIRLDGGLDLLLRLLQAPELETRVQAARLLEQILVAENRDRVARIGLGVILNLAKEREPVELARSVAGILEHMFKHSEETCQRLVAAGGLDAVLYWCRRTDPALLRHCALALANCALHGGQTVQRCMVEKRAAEWLFPLAFSKEDELLRLHACLAVAVLATNKEVEREVEHSGTLALVEPLVASLDPGRFARCLVDASDTSQGRGPDDLQSLVLLLDSSRLEAQCIGAFYLCAEAAIKSLQGKTKVFSDIGAIQSLKRLVSYSTNGTTSALAKRALRLLGEEVPRRILPCVASWKEAEVQTWLQQIGFSQYCENFREQQVDGDLLLRLTDEELQTDLGMKSSITRKRFFRELTELKTFASYATCDRSNLADWLGSLDPRFRQYTYGLVSCGLDRSLLHRVSEQQLLEDCGIRLGVHRTRILSAAREMLHSPLPCTGGKLSGDTPDVFISYRRNSGSQLASLLKVHLQLHGFSVFIDVEKLEAGKFEDKLIQSVIAARNFVLVLSAGALDKCMQDHDCKDWVHKEIVTALSCGKNIVPIIDGFEWPEPQALPEDMQAVLTFNGIKWSHEYQEATIEKIIRFLQGRPSQDSSAGSDTSLEGATPMGLP
uniprot
proteins
ec_number
3.2.2.-
uniprot
proteins
ec_number
3.2.2.6
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q6SZW1, ECO:0000269|PubMed:17724133, ECO:0000269|PubMed:19587044, ECO:0000269|PubMed:21555464, ECO:0000269|PubMed:22678360, ECO:0000269|PubMed:25818290, ECO:0000269|PubMed:26423149, ECO:0000269|PubMed:26686637, ECO:0000269|PubMed:27735788, ECO:0000269|PubMed:28334607, ECO:0000269|PubMed:32312889}.
uniprot
proteins
mass_dalton
79606
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-548 by JNK kinases (MAPK8, MAPK9 and /or MAPK10) enhance the NAD(+) hydrolase (NADase) activity. Phosphorylation at Ser-548 and subsequent activation takes place in response to oxidative stress conditions and inhibits mitochondrial respiration. {ECO:0000250|UniProtKB:Q6SZW1}.
uniprot
proteins
protein_family
SARM1 family
uniprot
proteins
pubmed
15368895
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17724133
uniprot
proteins
pubmed
18089857
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19587044
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21555464
uniprot
proteins
pubmed
22678360
uniprot
proteins
pubmed
22837513
uniprot
proteins
pubmed
25818290
uniprot
proteins
pubmed
26423149
uniprot
proteins
pubmed
26686637
uniprot
proteins
pubmed
26912636
uniprot
proteins
pubmed
27735788
uniprot
proteins
pubmed
27797810
uniprot
proteins
pubmed
28334607
uniprot
proteins
pubmed
28978465
uniprot
proteins
pubmed
31439642
uniprot
proteins
pubmed
32312889
uniprot
proteins
pubmed
32584865
uniprot
proteins
sequence_length
724
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17724133}. Cell projection, axon {ECO:0000269|PubMed:22678360}. Cell projection, dendrite {ECO:0000269|PubMed:21555464}. Synapse {ECO:0000269|PubMed:22678360}. Mitochondrion {ECO:0000269|PubMed:17724133, ECO:0000269|PubMed:26423149}. Note=Associated with microtubules. {ECO:0000269|PubMed:17724133}.
uniprot
proteins