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Sterile alpha and TIR motif-containing protein tir-1 (Neuronal symmetry protein 2) (SARM1 homolog)

 SARM1_CAEEL             Reviewed;        1000 AA.
Q86DA5; O17801; O17802; Q19373; Q7JMF4; Q7JMF5;
10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
01-JUN-2003, sequence version 1.
05-JUL-2017, entry version 125.
RecName: Full=Sterile alpha and TIR motif-containing protein tir-1;
AltName: Full=Neuronal symmetry protein 2;
AltName: Full=SARM1 homolog;
Name=tir-1; Synonyms=nsy-2; ORFNames=F13B10.1;
Caenorhabditis elegans.
Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.
NCBI_TaxID=6239;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE
SPLICING.
STRAIN=Bristol N2;
PubMed=9851916; DOI=10.1126/science.282.5396.2012;
The C. elegans sequencing consortium;
"Genome sequence of the nematode C. elegans: a platform for
investigating biology.";
Science 282:2012-2018(1998).
[2]
FUNCTION, TISSUE SPECIFICITY, HOMODIMERIZATION, AND INTERACTION WITH
RAB-1 AND PAL-1.
PubMed=15048112; DOI=10.1038/ni1060;
Couillault C., Pujol N., Reboul J., Sabatier L., Guichou J.-F.,
Kohara Y., Ewbank J.J.;
"TLR-independent control of innate immunity in Caenorhabditis elegans
by the TIR domain adaptor protein TIR-1, an ortholog of human SARM.";
Nat. Immunol. 5:488-494(2004).
[3]
FUNCTION.
PubMed=15123841; DOI=10.1073/pnas.0308625101;
Liberati N.T., Fitzgerald K.A., Kim D.H., Feinbaum R., Golenbock D.T.,
Ausubel F.M.;
"Requirement for a conserved Toll/interleukin-1 resistance domain
protein in the Caenorhabditis elegans immune response.";
Proc. Natl. Acad. Sci. U.S.A. 101:6593-6598(2004).
[4]
FUNCTION, SUBCELLULAR LOCATION, DOMAIN, TISSUE SPECIFICITY, AND
INTERACTION WITH UNC-43.
PubMed=15625192; DOI=10.1101/gad.1276505;
Chuang C.-F., Bargmann C.I.;
"A Toll-interleukin 1 repeat protein at the synapse specifies
asymmetric odorant receptor expression via ASK1 MAPKKK signaling.";
Genes Dev. 19:270-281(2005).
[5]
REVIEW.
PubMed=18089857; DOI=10.1126/stke.4172007pe73;
Dalod M.;
"Studies of SARM1 uncover similarities between immune and neuronal
responses to danger.";
Sci. STKE 2007:PE73-PE73(2007).
[6]
FUNCTION.
PubMed=18394898; DOI=10.1016/j.cub.2008.02.079;
Pujol N., Cypowyj S., Ziegler K., Millet A., Astrain A., Goncharov A.,
Jin Y., Chisholm A.D., Ewbank J.J.;
"Distinct innate immune responses to infection and wounding in the C.
elegans epidermis.";
Curr. Biol. 18:481-489(2008).
[7]
FUNCTION.
PubMed=21212236; DOI=10.1534/genetics.110.124883;
Hayakawa T., Kato K., Hayakawa R., Hisamoto N., Matsumoto K.,
Takeda K., Ichijo H.;
"Regulation of anoxic death in Caenorhabditis elegans by mammalian
apoptosis signal-regulating kinase (ASK) family proteins.";
Genetics 187:785-792(2011).
[8]
FUNCTION.
PubMed=22363008; DOI=10.1126/science.1215156;
Blum E.S., Abraham M.C., Yoshimura S., Lu Y., Shaham S.;
"Control of nonapoptotic developmental cell death in Caenorhabditis
elegans by a polyglutamine-repeat protein.";
Science 335:970-973(2012).
-!- FUNCTION: Required for both innate immune response and
specification of AWC(OFF) neuron (PubMed:15048112,
PubMed:15123841, PubMed:15625192). During late embryogenesis, it.
acts downstream of CAMKII (unc-43) to regulate specification of
asymmetric odorant receptors in AWC(OFF) neuron via the nsy-1/ASK1
pmk-1/p38 MAP kinase signaling cascade. Required to localize nsy-1
to postsynaptic regions of AWC neuron, suggesting that it may act
by assembling a signaling complex that regulate odorant receptor
expression (PubMed:15625192). Also plays a central role in
resistance to infection to a broad range of bacterial and fungi
pathogens, possibly by activating pmk-1, independently of the NF-
kappa-B pathway. Required for expression of antimicrobial peptides
nlp-29 and nlp-31 (PubMed:15048112, PubMed:15123841). Its role in
immune response and neuron specification may be mediated by the
same nsy-1/ASK1 pmk-1/p38 MAP kinase cascade signaling pathway
(PubMed:15048112, PubMed:15123841, PubMed:15625192). Involved in
the response to anoxic conditions probably by activating the p38
pathway composed of nsy-1/sek-1/pmk-1 (PubMed:21212236). In males,
involved in non-apoptotic death of the linker cell which guides
gonad elongation during larval development (PubMed:22363008).
{ECO:0000269|PubMed:15048112, ECO:0000269|PubMed:15123841,
ECO:0000269|PubMed:15625192, ECO:0000269|PubMed:21212236,
ECO:0000269|PubMed:22363008}.
-!- FUNCTION: Isoform b: Regulates expression of antimicrobial peptide
nlp-29 in response to fungal infection or physical injury.
{ECO:0000269|PubMed:18394898}.
-!- SUBUNIT: Homodimer (Probable). Interacts with rab-1, pal-1 and
unc-43. {ECO:0000269|PubMed:15048112, ECO:0000269|PubMed:15625192,
ECO:0000305}.
-!- INTERACTION:
Self; NbExp=3; IntAct=EBI-319472, EBI-319472;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15625192}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=5;
Name=c;
IsoId=Q86DA5-1; Sequence=Displayed;
Note=No experimental confirmation available.;
Name=a;
IsoId=Q86DA5-2; Sequence=VSP_013608, VSP_013612;
Note=No experimental confirmation available.;
Name=b;
IsoId=Q86DA5-3; Sequence=VSP_013609, VSP_013610, VSP_013614;
Note=No experimental confirmation available.;
Name=d;
IsoId=Q86DA5-4; Sequence=VSP_013613, VSP_013614;
Note=No experimental confirmation available.;
Name=e;
IsoId=Q86DA5-5; Sequence=VSP_013611, VSP_013612;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Highly expressed in hypodermis. Localizes to
postsynaptic regions of axons. {ECO:0000269|PubMed:15048112,
ECO:0000269|PubMed:15625192}.
-!- DOMAIN: The TIR domain is required to activate signaling cascade,
possibly for activation of nsy-1. {ECO:0000269|PubMed:15625192}.
-!- DOMAIN: The SAM domains mediate the localization to postsynaptic
regions of neurons. {ECO:0000269|PubMed:15625192}.
-----------------------------------------------------------------------
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EMBL; Z49936; CAA90181.1; -; Genomic_DNA.
EMBL; Z49936; CAA90182.1; -; Genomic_DNA.
EMBL; Z49936; CAD90174.1; -; Genomic_DNA.
EMBL; Z49936; CAE47466.1; -; Genomic_DNA.
EMBL; Z49936; CAE47467.1; -; Genomic_DNA.
PIR; T20816; T20816.
PIR; T20817; T20817.
RefSeq; NP_001021251.2; NM_001026080.3.
RefSeq; NP_001021252.1; NM_001026081.2. [Q86DA5-4]
RefSeq; NP_001021253.1; NM_001026082.2. [Q86DA5-5]
RefSeq; NP_497784.1; NM_065383.1. [Q86DA5-2]
RefSeq; NP_497785.1; NM_065384.4. [Q86DA5-3]
UniGene; Cel.17227; -.
ProteinModelPortal; Q86DA5; -.
SMR; Q86DA5; -.
BioGrid; 40740; 13.
DIP; DIP-26569N; -.
IntAct; Q86DA5; 19.
MINT; MINT-1043860; -.
STRING; 6239.F13B10.1c; -.
iPTMnet; Q86DA5; -.
PaxDb; Q86DA5; -.
PeptideAtlas; Q86DA5; -.
GeneID; 175502; -.
UCSC; F13B10.1e.2; c. elegans. [Q86DA5-1]
CTD; 175502; -.
WormBase; F13B10.1a; CE20681; WBGene00006575; tir-1. [Q86DA5-2]
WormBase; F13B10.1b; CE15818; WBGene00006575; tir-1. [Q86DA5-3]
WormBase; F13B10.1c; CE50801; WBGene00006575; tir-1.
WormBase; F13B10.1d; CE35712; WBGene00006575; tir-1. [Q86DA5-4]
WormBase; F13B10.1e; CE35713; WBGene00006575; tir-1. [Q86DA5-5]
eggNOG; KOG3678; Eukaryota.
eggNOG; ENOG410XQ4A; LUCA.
HOGENOM; HOG000008460; -.
InParanoid; Q86DA5; -.
OrthoDB; EOG091G01TX; -.
PhylomeDB; Q86DA5; -.
PRO; PR:Q86DA5; -.
Proteomes; UP000001940; Chromosome III.
Bgee; WBGene00006575; -.
ExpressionAtlas; Q86DA5; baseline.
GO; GO:1904115; C:axon cytoplasm; IDA:WormBase.
GO; GO:0030425; C:dendrite; IBA:GO_Central.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0019901; F:protein kinase binding; IPI:WormBase.
GO; GO:0017137; F:Rab GTPase binding; IPI:WormBase.
GO; GO:0035591; F:signaling adaptor activity; IDA:WormBase.
GO; GO:0000187; P:activation of MAPK activity; IMP:WormBase.
GO; GO:0045168; P:cell-cell signaling involved in cell fate commitment; IMP:WormBase.
GO; GO:0042742; P:defense response to bacterium; IMP:WormBase.
GO; GO:0050832; P:defense response to fungus; IMP:UniProtKB.
GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:WormBase.
GO; GO:1902097; P:positive regulation of transcription from RNA polymerase II promoter involved in defense response to Gram-negative bacterium; IMP:WormBase.
GO; GO:0008104; P:protein localization; IMP:WormBase.
GO; GO:1901214; P:regulation of neuron death; IBA:GO_Central.
GO; GO:0007165; P:signal transduction; IEA:InterPro.
Gene3D; 1.25.10.10; -; 1.
Gene3D; 3.40.50.10140; -; 1.
InterPro; IPR011989; ARM-like.
InterPro; IPR016024; ARM-type_fold.
InterPro; IPR001660; SAM.
InterPro; IPR013761; SAM/pointed.
InterPro; IPR000157; TIR_dom.
Pfam; PF00536; SAM_1; 1.
Pfam; PF07647; SAM_2; 1.
Pfam; PF13676; TIR_2; 1.
SMART; SM00454; SAM; 2.
SMART; SM00255; TIR; 1.
SUPFAM; SSF47769; SSF47769; 2.
SUPFAM; SSF48371; SSF48371; 1.
SUPFAM; SSF52200; SSF52200; 1.
PROSITE; PS50105; SAM_DOMAIN; 1.
PROSITE; PS50104; TIR; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Cytoplasm;
Developmental protein; Differentiation; Immunity; Innate immunity;
Neurogenesis; Reference proteome; Repeat.
CHAIN 1 1000 Sterile alpha and TIR motif-containing
protein tir-1.
/FTId=PRO_0000097587.
DOMAIN 614 678 SAM 1. {ECO:0000255|PROSITE-
ProRule:PRU00184}.
DOMAIN 684 750 SAM 2. {ECO:0000255|PROSITE-
ProRule:PRU00184}.
DOMAIN 760 902 TIR. {ECO:0000255|PROSITE-
ProRule:PRU00204}.
COMPBIAS 100 130 Pro-rich.
VAR_SEQ 1 638 Missing (in isoform d). {ECO:0000305}.
/FTId=VSP_013613.
VAR_SEQ 1 414 Missing (in isoform b). {ECO:0000305}.
/FTId=VSP_013609.
VAR_SEQ 1 183 Missing (in isoform e). {ECO:0000305}.
/FTId=VSP_013611.
VAR_SEQ 1 83 MLPNRKPPRPSPSFQSLNNNNQRFPLRRSLKIAQAHSLPTV
PSEDAKDDDLITPELSTDFDFREIQHRYLMALQNEQDGETT
S -> MGEEILTERNQLSRQDASCFRSPRSPLGR (in
isoform a). {ECO:0000305}.
/FTId=VSP_013608.
VAR_SEQ 415 569 IILTFKRAPECPDILRHAALALANILLYTCFEGKKKIIQKK
IPEWLFFLASQADDVTRYYACIAVCTIVSVKEFEPLVRKSD
TMKLVEPFLQVHDPATFARDYHKYAQGNTKEWLERLLPMLQ
PSRRREARSVAAFHFTLEATIKKEQNKLDVFQ -> MCALV
SSPMVSLPFNENVAPECRRNLLPRFAAVSPRPKAAVTPFVS
TPSSSSITSFPYSLKLSNSNSNCSSLSRPSSLTDLPILLRD
VEDQMYDDDETPIIPCGSPSSSNSMLAQIQFHPPPTEMNSP
LKTSLKKLPMKTALVIRPQMFVKENSVQLERFRKSKTRRFF
HPYAK (in isoform b). {ECO:0000305}.
/FTId=VSP_013610.
VAR_SEQ 954 973 CKLLKHRHLVYYLIFLVFSV -> F (in isoform b
and isoform d). {ECO:0000305}.
/FTId=VSP_013614.
VAR_SEQ 954 970 CKLLKHRHLVYYLIFLV -> F (in isoform a and
isoform e). {ECO:0000305}.
/FTId=VSP_013612.
SEQUENCE 1000 AA; 112883 MW; 1436FFF7BA34EC6D CRC64;
MLPNRKPPRP SPSFQSLNNN NQRFPLRRSL KIAQAHSLPT VPSEDAKDDD LITPELSTDF
DFREIQHRYL MALQNEQDGE TTSTDDAFFE LDDDDDLSSP SVPGSPVDPP SISVPLPPKS
APPCPTQPAP LTNGDLYPTI LSNGTPIPNG RITPALSTVS VSLIHEARLQ QSLSTPCNGS
EEEMHNGQVR KESEYRRFKS EGSTAGASLP AAEKTHMDEL SPVDQRSTSG TARFLIQQDS
VVNPSTKMSN TEQVAMMHTL KTKLSKYQAM MDKAFEEIAK VEDANIIEGC TIVRKLMRKV
WNTPKVSADL ANALCDYLRD RDYFDKLIKM FISPNTAACD QVRMECGKVL EECTSSANLE
YIVNKSYTKK IMIVAMKLNK TPDQQRLSLS LIGNLFKHSN AVSLSLIETD VIDHIILTFK
RAPECPDILR HAALALANIL LYTCFEGKKK IIQKKIPEWL FFLASQADDV TRYYACIAVC
TIVSVKEFEP LVRKSDTMKL VEPFLQVHDP ATFARDYHKY AQGNTKEWLE RLLPMLQPSR
RREARSVAAF HFTLEATIKK EQNKLDVFQE IGAIQALKEV ASSPDEVAAK FASEALTVIG
EEVPYKLAQQ VPGWTCADVQ YWVKKIGFEE YVEKFAKQMV DGDLLLQLTE NDLKHDVGMI
SGLHRKRFLR ELQTLKVAAD YSSVDESNLD NFLMGLSPEL SVYTYQMLTN GVNRSLLSSL
TDEMMQNACG ITNPIHRLKL TQAFETAKHP DDVEVAMLSK QIDVFISYRR STGNQLASLI
KVLLQLRGYR VFIDVDKLYA GKFDSSLLKN IQAAKHFILV LTPNSLDRLL NDDNCEDWVH
KELKCAFEHQ KNIIPIFDTA FEFPTKEDQI PNDIRMITKY NGVKWVHDYQ DACMAKVVRF
ITGELNRTTP TTKEMPSISR KTTQQRWQTT NTVSRTGPSR SIGGPRMEPP TPTCKLLKHR
HLVYYLIFLV FSVTPTGSQE RATSTRRKIQ PSASTTSDRN


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