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FLASH GENE

Symbol

SARM1

contributors: mct/pgu - updated : 28-01-2016

HGNC name	sterile alpha and TIR motif containing 1
HGNC id	17074

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015077 9 - 7001 76.7 724 - 2001 11386760 SARM-AS - - 400 - - liver, kidney, brain 2001 11386760 antisense transcript coordinately expressed with SARM in kidney, liver and independently in brain

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       highly Nervous brain         Urinary kidney

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal and sterile alpha motif domains important in the autoregulation of SARM1 activity
	HEAT/Armadillo motifs
	TIR domain (Toll interleukin 1 receptor)

HOMOLOGY

interspecies	ortholog to Drosophila sarm
	homolog to C.elegans SARM

Homologene

FAMILY	fifth member of the Toll-like receptor (TLR) adaptor family
	MyD88 (myeloid differentiation primary response gene 88) family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm

basic FUNCTION	probable mucin protein may be involved in protein-protein interactions promoting the formation of diverse protein complexes
	negative regulator of Toll-like receptor signaling
	negative regulator of TICAM1-dependent Toll-like receptor signaling
	function as a specific inhibitor of TRIF-dependent TLR signaling
	downregulates NF-kappaB and IRF3-mediated TLR3 and TLR4 signaling
	negative regulator of Toll-like receptor 3 (TLR3) in innate immunity signaling
	required for proper initiation and elongation of dendrites, axonal outgrowth, and neuronal polarization
	SARM1 is a member of an ancient axon death signaling pathway
	may be potentially broadly required to promote Wallerian degeneration in the nervous system
	regulates the innate immune responses of the central nervous system through regulating the inflammatory and anti-virus cytokines produced by neurons

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with RS1 (interaction may be part of a novel SARM1-mediated cell signaling pathway required for the maintenance of retinal cell organization and photoreceptor-bipolar synaptic structure)
	negative regulator of the TICAM1-dependent pathway via its interaction with TICAM1
	inhibits both TICAM1- and MYD88-mediated AP-1 activation
	interacts with and receives signal from SDC2 and controls dendritic arborization through the MKK4-JNK pathway
	is a negative regulator of Toll-like receptor 3 (TLR3) in innate immunity signaling
	association of PINK1 with SARM1 and TRAF6 is an important step for mitophagy
	absence of SARM1 rescues development and survival of NMNAT2-deficient axons
	SARM1, mediates TLR7/TLR9-induced apoptosis in neurons

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function exacerbates the progression of prion pathogenesis, by up-regulating XAF1, which promotes neuronal apoptosis, and accelerates prion disease

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology     pharmacological inhibition of SARM1 may represent a promising therapeutic avenue for patients with axonal loss

ANIMAL & CELL MODELS

Sarm1-deficient mice may uncover unexpected similarities between the ways in which neurons and immune cells sense and respond to danger