Sarm1
entrez
287545
canonical
uniprot
D3ZUM2
canonical
ensembl
ENSRNOG00000010244
resolver
ensembl
ENSRNOG00055025827
resolver
ensembl
ENSRNOG00060019012
resolver
ensp
ENSRNOP00000013639
resolver
ensp
ENSRNOP00055036468
resolver
ensp
ENSRNOP00060026891
resolver
enst
ENSRNOT00000013639
resolver
enst
ENSRNOT00055044562
resolver
enst
ENSRNOT00060032893
resolver
genesymbol
Sarm1
resolver
uniprot_entry
SARM1_RAT
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
MVLTLLFSAYKLCRFFIMSGPRPGADRLTVPGPDRSGGTSPWWAAGGRGSREVSPGVGTEVQGALERSLPELQQALSELKQASAAQAVGAGLAEVFQLVEEAWLLPAVGREVAQGLCDAIRLDGGLDLLLRLLQAPELETRVQAARLLEQILVAENRDRVARIGLGVILNLSKEREPVELARSVAGILEHMFKHSEETCQRLVAAGGLDAVLYWCRRTDPALLRHCALALANCALHGGQTVQRCMVEKRAAEWLFPLAFSKEDELLRLHACLAVAVLATNKEVEREVEHSGTLALVEPLVASLDPGRFARCLVDASDTSQGRGPDDLQSLVLLLDSSRLEAQCIGAFYLCAEAAIKSLQGKTKVFSDIGAIQSLKRLVSYSTNGTTSTLAKRALRLLGEEVPRRILPCVASWKEAEVQTWLQQIGFSQYCENFRDQQVDGDLLLRLTDEELQTDLGMKSSITRKRFFRELTELKTFASYATCDRSNLADWLGSLDPRFRQYTYGLVSCGLDRSLLHRVSEQQLLEDCGIRLGVHRTRILSAAREMLHSPLPCTGGKPSGDTPDVFISYRRNSGSQLASLLKVHLQLHGFSVFIDVEKLEAGKFEDKLIQSVMAARNFVLVLSAGALDKCMQDHECKDWVHKEIVTALSCSKNIVPIIDGFEWPEPQALPEDMQAVLTFNGIKWSHEYQEATIEKIIRFLQGRPSQDSSAGSDTSLEGATSMGLP
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. 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. 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:Q6PDS3, ECO:0000250|UniProtKB:Q6SZW1}.
uniprot
proteins
mass_dalton
79688
uniprot
proteins
mutagenesis
MUTAGEN 548; /note="S->A: Reduced infarct size, neuronal death and neurobehavioral dysfunction in response to cerebral ischemia/reperfusion (I/R) injury."; /evidence="ECO:0000269|PubMed:32968873
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-548 by JNK kinases (MAPK8, MAPK9 and /or MAPK10) enhance the NAD(+) hydrolase (NADase) activity (PubMed:32968873). Phosphorylation at Ser-548 and subsequent activation takes place in response to oxidative stress conditions and inhibits mitochondrial respiration (By similarity). Phosphorylation at Ser-548 increases in response to cerebral ischemia/reperfusion (I/R) injury (PubMed:32968873). {ECO:0000250|UniProtKB:Q6SZW1, ECO:0000269|PubMed:32968873}.
uniprot
proteins
protein_family
SARM1 family
uniprot
proteins
pubmed
15057822
uniprot
proteins
pubmed
32968873
uniprot
proteins
sequence_length
724
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6SZW1}. Cell projection, axon {ECO:0000250|UniProtKB:Q6PDS3}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q6PDS3}. Synapse {ECO:0000250|UniProtKB:Q6PDS3}. Mitochondrion {ECO:0000250|UniProtKB:Q6SZW1}. Note=Associated with microtubules. {ECO:0000250|UniProtKB:Q6PDS3}.
uniprot
proteins