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Q6SZW1 (SARM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length724 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 projectionaxon By similarity. Cell projectiondendrite By similarity. Cell junctionsynapse 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 processDifferentiation
Immunity
Innate immunity
Neurogenesis
   Cellular componentCell junction
Cell projection
Cytoplasm
Mitochondrion
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Transit peptide
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

regulation of dendrite morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of neuron death

Inferred from sequence or structural similarity. Source: UniProtKB

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentaxon

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2727Mitochondrion
Chain28 – 724697Sterile alpha and TIR motif-containing protein 1
PRO_0000097589

Regions

Domain412 – 47665SAM 1
Domain486 – 54863SAM 2
Domain559 – 65799TIR

Natural variations

Alternative sequence1 – 106106MVLTL…AWLLP → MGAVARAHGGLRVARARESV AGGRHRGAGRPGARAAGAAA GLVRAEAGGRRAGRGRRPGR GLPTGGGGLAAA in isoform 2.
VSP_013603
Natural variant231P → R.
Corresponds to variant rs7212814 [ dbSNP | Ensembl ].
VAR_061702

Experimental info

Mutagenesis111K → A: No effect on mitochondrial localization. Ref.10
Mutagenesis141R → A: Loss in ability to localize to mitochondria and reduction in apoptotic activity. Ref.10
Mutagenesis221R → A: No effect on mitochondrial localization. Ref.10
Mutagenesis271R → A: No effect on mitochondrial localization. Ref.10

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 6391EA4C31EF6604

FASTA72479,388
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 18E0005AF7A7B1C5
Show »

FASTA69075,337

References

« Hide '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 CLEAVAGE SITE, 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.
RefSeqNP_055892.2. NM_015077.3.
UniGeneHs.743510.

3D structure databases

ProteinModelPortalQ6SZW1.
SMRQ6SZW1. Positions 118-399, 406-536.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116726. 19 interactions.
STRING9606.ENSP00000368351.

PTM databases

PhosphoSiteQ6SZW1.

Polymorphism databases

DMDM83288284.

Proteomic databases

PaxDbQ6SZW1.
PRIDEQ6SZW1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID23098.
KEGGhsa:23098.
UCSCuc010crl.1. human. [Q6SZW1-1]

Organism-specific databases

CTD23098.
GeneCardsGC17P026698.
H-InvDBHIX0013645.
HGNCHGNC:17074. SARM1.
HPAHPA024359.
HPA024759.
MIM607732. gene.
neXtProtNX_Q6SZW1.
PharmGKBPA134971180.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG329244.
HOGENOMHOG000008460.
HOVERGENHBG079166.
InParanoidQ6SZW1.
PhylomeDBQ6SZW1.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

CleanExHS_SARM1.
GenevestigatorQ6SZW1.

Family and domain databases

Gene3D1.10.150.50. 2 hits.
1.25.10.10. 1 hit.
3.40.50.10140. 1 hit.
InterProIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
IPR000157. TIR_dom.
[Graphical view]
PfamPF07647. SAM_2. 2 hits.
PF13676. TIR_2. 1 hit.
[Graphical view]
SMARTSM00454. SAM. 2 hits.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 2 hits.
SSF48371. SSF48371. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEPS50105. SAM_DOMAIN. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSARM1. human.
GenomeRNAi23098.
NextBio44273.
PROQ6SZW1.
SOURCESearch...

Entry information

Entry nameSARM1_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM