Q6SZW1 (SARM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sterile alpha and TIR motif-containing protein 1

Alternative name(s):
Sterile alpha and Armadillo repeat protein
Sterile alpha motif domain-containing protein 2
Short name=MyD88-5
Short name=SAM domain-containing protein 2
Tir-1 homolog

Gene names

Name:	SARM1
Synonyms:	KIAA0524, SAMD2, SARM

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	724 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal 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. Ref.4 Ref.5 Ref.6 Ref.9
Subunit structure	Interacts with TICAM1/TRIF and thereby interferes with TICAM1/TRIF function. Interacts with MAPK10/JNK3 and SDC2 (via cytoplasmic domain) By similarity. Ref.5
Subcellular location	Cytoplasm. Cell projection › axon By similarity. Cell projection › dendrite By similarity. Cell junction › synapse By similarity. Mitochondrion. Note: Associated with microtubules By similarity. Ref.9 Ref.10
Tissue specificity	Predominantly expressed in brain, kidney and liver. Expressed at lower level in placenta. Ref.1 Ref.7
Induction	Up-regulated by lipopolysaccharides (LPS). Ref.9
Sequence similarities	Contains 2 SAM (sterile alpha motif) domains. Contains 1 TIR domain.
Caution	Was initially (Ref.1) reported to contain ARM repeats. Such repeats are however not predicted by any detection method.

Ontologies

Keywords
Biological process	Differentiation Immunity Innate immunity Neurogenesis
Cellular component	Cell junction Cell projection Cytoplasm Mitochondrion Synapse
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Transit peptide
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	innate immune response Inferred from electronic annotation. Source: UniProtKB-KW regulation of dendrite morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB regulation of neuron death Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	axon Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-KW dendrite Inferred from sequence or structural similarity. Source: UniProtKB microtubule Inferred from sequence or structural similarity. Source: UniProtKB mitochondrion Inferred from direct assay Ref.10. Source: UniProtKB synapse Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6SZW1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6SZW1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: MVLTLLLSAY...QLVEEAWLLP → MGAVARAHGG...PTGGGGLAAA

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 27	27	Mitochondrion
	Chain	28 – 724	697	Sterile alpha and TIR motif-containing protein 1		PRO_0000097589
Regions
	Domain	412 – 476	65	SAM 1
	Domain	486 – 548	63	SAM 2
	Domain	559 – 657	99	TIR
Natural variations
	Alternative sequence	1 – 106	106	MVLTL…AWLLP → MGAVARAHGGLRVARARESV AGGRHRGAGRPGARAAGAAA GLVRAEAGGRRAGRGRRPGR GLPTGGGGLAAA in isoform 2.		VSP_013603
	Natural variant	23	1	P → R. Corresponds to variant rs7212814 [ dbSNP | Ensembl ].		VAR_061702
Experimental info
	Mutagenesis	11	1	K → A: No effect on mitochondrial localization. Ref.10
	Mutagenesis	14	1	R → A: Loss in ability to localize to mitochondria and reduction in apoptotic activity. Ref.10
	Mutagenesis	22	1	R → A: No effect on mitochondrial localization. Ref.10
	Mutagenesis	27	1	R → A: No effect on mitochondrial localization. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 6391EA4C31EF6604	FASTA	724	79,388
	10 20 30 40 50 60 MVLTLLLSAY KLCRFFAMSG PRPGAERLAV PGPDGGGGTG PWWAAGGRGP REVSPGAGTE 70 80 90 100 110 120 VQDALERALP ELQQALSALK QAGGARAVGA GLAEVFQLVE EAWLLPAVGR EVAQGLCDAI 130 140 150 160 170 180 RLDGGLDLLL RLLQAPELET RVQAARLLEQ ILVAENRDRV ARIGLGVILN LAKEREPVEL 190 200 210 220 230 240 ARSVAGILEH MFKHSEETCQ RLVAAGGLDA VLYWCRRTDP ALLRHCALAL GNCALHGGQA 250 260 270 280 290 300 VQRRMVEKRA AEWLFPLAFS KEDELLRLHA CLAVAVLATN KEVEREVERS GTLALVEPLV 310 320 330 340 350 360 ASLDPGRFAR CLVDASDTSQ GRGPDDLQRL VPLLDSNRLE AQCIGAFYLC AEAAIKSLQG 370 380 390 400 410 420 KTKVFSDIGA IQSLKRLVSY STNGTKSALA KRALRLLGEE VPRPILPSVP SWKEAEVQTW 430 440 450 460 470 480 LQQIGFSKYC ESFREQQVDG DLLLRLTEEE LQTDLGMKSG ITRKRFFREL TELKTFANYS 490 500 510 520 530 540 TCDRSNLADW LGSLDPRFRQ YTYGLVSCGL DRSLLHRVSE QQLLEDCGIH LGVHRARILT 550 560 570 580 590 600 AAREMLHSPL PCTGGKPSGD TPDVFISYRR NSGSQLASLL KVHLQLHGFS VFIDVEKLEA 610 620 630 640 650 660 GKFEDKLIQS VMGARNFVLV LSPGALDKCM QDHDCKDWVH KEIVTALSCG KNIVPIIDGF 670 680 690 700 710 720 EWPEPQVLPE DMQAVLTFNG IKWSHEYQEA TIEKIIRFLQ GRSSRDSSAG SDTSLEGAAP MGPT
	Isoform 2 [UniParc]. Checksum: 18E0005AF7A7B1C5	FASTA	690	75,337
	10 20 30 40 50 60 MGAVARAHGG LRVARARESV AGGRHRGAGR PGARAAGAAA GLVRAEAGGR RAGRGRRPGR 70 80 90 100 110 120 GLPTGGGGLA AAAVGREVAQ GLCDAIRLDG GLDLLLRLLQ APELETRVQA ARLLEQILVA 130 140 150 160 170 180 ENRDRVARIG LGVILNLAKE REPVELARSV AGILEHMFKH SEETCQRLVA AGGLDAVLYW 190 200 210 220 230 240 CRRTDPALLR HCALALGNCA LHGGQAVQRR MVEKRAAEWL FPLAFSKEDE LLRLHACLAV 250 260 270 280 290 300 AVLATNKEVE REVERSGTLA LVEPLVASLD PGRFARCLVD ASDTSQGRGP DDLQRLVPLL 310 320 330 340 350 360 DSNRLEAQCI GAFYLCAEAA IKSLQGKTKV FSDIGAIQSL KRLVSYSTNG TKSALAKRAL 370 380 390 400 410 420 RLLGEEVPRP ILPSVPSWKE AEVQTWLQQI GFSKYCESFR EQQVDGDLLL RLTEEELQTD 430 440 450 460 470 480 LGMKSGITRK RFFRELTELK TFANYSTCDR SNLADWLGSL DPRFRQYTYG LVSCGLDRSL 490 500 510 520 530 540 LHRVSEQQLL EDCGIHLGVH RARILTAARE MLHSPLPCTG GKPSGDTPDV FISYRRNSGS 550 560 570 580 590 600 QLASLLKVHL QLHGFSVFID VEKLEAGKFE DKLIQSVMGA RNFVLVLSPG ALDKCMQDHD 610 620 630 640 650 660 CKDWVHKEIV TALSCGKNIV PIIDGFEWPE PQVLPEDMQA VLTFNGIKWS HEYQEATIEK 670 680 690 IIRFLQGRSS RDSSAGSDTS LEGAAPMGPT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans." Mink M., Fogelgren B., Olszewski K., Maroy P., Csiszar K. Genomics 74:234-244(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Brain.
[2]	"SARM1 isoforms nucleotide sequence." Bousson J.-C., Casteran C., Tiraby G. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-724. Tissue: Brain.
[4]	"Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response." Liberati N.T., Fitzgerald K.A., Kim D.H., Feinbaum R., Golenbock D.T., Ausubel F.M. Proc. Natl. Acad. Sci. U.S.A. 101:6593-6598(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling." Carty M., Goodbody R., Schroeder M., Stack J., Moynagh P.N., Bowie A.G. Nat. Immunol. 7:1074-1081(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TICAM1.
[6]	"DisSARMing Toll-like receptor signaling." O'Neill L.A.J. Nat. Immunol. 7:1023-1025(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival." Kim Y., Zhou P., Qian L., Chuang J.Z., Lee J., Li C., Iadecola C., Nathan C., Ding A. J. Exp. Med. 204:2063-2074(2007) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Studies of SARM1 uncover similarities between immune and neuronal responses to danger." Dalod M. Sci. STKE 2007:PE73-PE73(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"SARM inhibits both TRIF- and MyD88-mediated AP-1 activation." Peng J., Yuan Q., Lin B., Panneerselvam P., Wang X., Luan X.L., Lim S.K., Leung B.P., Ho B., Ding J.L. Eur. J. Immunol. 40:1738-1747(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
[10]	"Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: definition of the critical region and residues in the signal sequence." Panneerselvam P., Singh L.P., Ho B., Chen J., Ding J.L. Biochem. J. 442:263-271(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MITOCHONDRIAL TRANSIT PEPTIDE, MUTAGENESIS OF LYS-11; ARG-14; ARG-22 AND ARG-27.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ290445 mRNA. Translation: CAB90355.1. AY444166 mRNA. Translation: AAR17520.1. AB011096 mRNA. Translation: BAA25450.1.
IPI	IPI00007919. IPI00448630.
RefSeq	NP_055892.2. NM_015077.2.
UniGene	Hs.446689.
3D structure databases
ProteinModelPortal	Q6SZW1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000368351.
PTM databases
PhosphoSite	Q6SZW1.
Polymorphism databases
DMDM	83288284.
Proteomic databases
PaxDb	Q6SZW1.
PRIDE	Q6SZW1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	23098.
KEGG	hsa:23098.
UCSC	uc010crl.1. human.
Organism-specific databases
CTD	23098.
GeneCards	GC17P026698.
H-InvDB	HIX0013645.
HGNC	HGNC:17074. SARM1.
HPA	HPA024359. HPA024759.
MIM	607732. gene.
neXtProt	NX_Q6SZW1.
PharmGKB	PA134971180.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG329244.
HOGENOM	HOG000008460.
HOVERGEN	HBG079166.
InParanoid	Q6SZW1.
OrthoDB	EOG46WZ7W.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
CleanEx	HS_SARM1.
Genevestigator	Q6SZW1.
GermOnline	ENSG00000004139. Homo sapiens.
Family and domain databases
Gene3D	1.10.150.50. 2 hits. 1.25.10.10. 1 hit.
InterPro	IPR011989. ARM-like. IPR016024. ARM-type_fold. IPR001660. SAM. IPR013761. SAM/pointed. IPR011510. SAM_2. IPR000157. TIR_dom. [Graphical view]
Pfam	PF07647. SAM_2. 2 hits. PF13676. TIR_2. 1 hit. [Graphical view]
SMART	SM00454. SAM. 2 hits. SM00255. TIR. 1 hit. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit. SSF47769. SAM_homology. 1 hit. SSF52200. TIR. 1 hit.
PROSITE	PS50105. SAM_DOMAIN. 2 hits. PS50104. TIR. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SARM1. human.
GenomeRNAi	23098.
NextBio	44273.
SOURCE	Search...

Entry information

Entry name

SARM1_HUMAN

Accession

Primary (citable) accession number: Q6SZW1
Secondary accession number(s): O60277, Q7LGG3, Q9NXY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.