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Sterile alpha and TIR motif-containing protein 1 (Tir-1 homolog) (dSarm)

 SARM1_DROME             Reviewed;        1360 AA.
Q6IDD9; Q0E8H1; Q7KUA2; Q8SY48; Q9VSD2;
07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
05-JUL-2004, sequence version 1.
12-SEP-2018, entry version 118.
RecName: Full=Sterile alpha and TIR motif-containing protein 1;
AltName: Full=Tir-1 homolog;
Short=dSarm;
Name=Ect4; Synonyms=dsarm; ORFNames=CG43119;
Drosophila melanogaster (Fruit fly).
Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta;
Pterygota; Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha;
Ephydroidea; Drosophilidae; Drosophila; Sophophora.
NCBI_TaxID=7227;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Berkeley;
PubMed=10731132; DOI=10.1126/science.287.5461.2185;
Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X.,
Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D.,
Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G.,
Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D.,
Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M.,
Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S.,
Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P.,
Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I.,
Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P.,
de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M.,
Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P.,
Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W.,
Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K.,
Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J.,
Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C.,
Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A.,
Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z.,
Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X.,
Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D.,
Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A.,
Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L.,
Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M.,
Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G.,
Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H.,
Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
Spier E., Spradling A.C., Stapleton M., Strong R., Sun E.,
Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X.,
Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J.,
Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A.,
Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L.,
Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X.,
Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.;
"The genome sequence of Drosophila melanogaster.";
Science 287:2185-2195(2000).
[2]
GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
STRAIN=Berkeley;
PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q.,
Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M.,
Lewis S.E.;
"Annotation of the Drosophila melanogaster euchromatic genome: a
systematic review.";
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
STRAIN=Berkeley; TISSUE=Head;
PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M.,
George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H.,
Rubin G.M., Celniker S.E.;
"A Drosophila full-length cDNA resource.";
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
STRAIN=Berkeley; TISSUE=Head;
Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A.,
Pacleb J.M., Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
[5]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=22022271; DOI=10.1371/journal.ppat.1002319;
Akhouayri I., Turc C., Royet J., Charroux B.;
"Toll-8/Tollo negatively regulates antimicrobial response in the
Drosophila respiratory epithelium.";
PLoS Pathog. 7:E1002319-E1002319(2011).
[6]
REVIEW.
PubMed=22837513; DOI=10.1126/science.1226150;
Yu X.M., Luo L.;
"Neuroscience. dSarm-ing axon degeneration.";
Science 337:418-419(2012).
[7]
FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
PubMed=22678360; DOI=10.1126/science.1223899;
Osterloh J.M., Yang J., Rooney T.M., Fox A.N., Adalbert R.,
Powell E.H., Sheehan A.E., Avery M.A., Hackett R., Logan M.A.,
MacDonald J.M., Ziegenfuss J.S., Milde S., Hou Y.J., Nathan C.,
Ding A., Brown R.H. Jr., Conforti L., Coleman M., Tessier-Lavigne M.,
Zuechner S., Freeman M.R.;
"dSarm/Sarm1 is required for activation of an injury-induced axon
death pathway.";
Science 337:481-484(2012).
-!- FUNCTION: Negative regulator of MYD88- and TRIF-dependent toll-
like receptor signaling pathway which plays a pivotal role in
activating axonal degeneration following injury (PubMed:22678360).
Promotes Wallerian degeneration an injury-induced axonal death
pathway which involves degeneration of an axon distal to the
injury site (PubMed:22678360). Involved in the down-regulation of
the tracheal immune response to Gram-negative bacteria
(PubMed:22022271). This is likely by mediating Tollo signaling in
the tracheal epithelium (PubMed:22022271).
{ECO:0000269|PubMed:22022271, ECO:0000269|PubMed:22678360}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell projection,
axon {ECO:0000269|PubMed:22678360}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=C;
IsoId=Q6IDD9-1; Sequence=Displayed;
Note=No experimental confirmation available.;
Name=B;
IsoId=Q6IDD9-2; Sequence=VSP_013615, VSP_013616, VSP_013617;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Widely expressed in larval brains and adult
brains.
-!- DISRUPTION PHENOTYPE: Severed axons in wild-type flies disappear
completely within a week of injury, whereas axons of neurons
homozygous for any one of the three loss-of-function alleles:
l(3)896, l(3)4621, and l(3)4705 persist for several weeks after
severing (PubMed:22678360). After infection with Gram-negative
bacteria, the respiratory epithelium displays an over-active
immune response with a greater increase in expression of Drs
compared to wild-type larvae (PubMed:22022271).
{ECO:0000269|PubMed:22022271, ECO:0000269|PubMed:22678360}.
-----------------------------------------------------------------------
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EMBL; AE014296; AAN12011.1; -; Genomic_DNA.
EMBL; AE014296; ABI31243.1; -; Genomic_DNA.
EMBL; AY075346; AAL68207.1; -; mRNA.
EMBL; BT014666; AAT27290.1; -; mRNA.
RefSeq; NP_001036594.1; NM_001043129.3. [Q6IDD9-1]
RefSeq; NP_729327.1; NM_168254.2. [Q6IDD9-2]
UniGene; Dm.5517; -.
ProteinModelPortal; Q6IDD9; -.
BioGrid; 64320; 11.
STRING; 7227.FBpp0293535; -.
PaxDb; Q6IDD9; -.
PRIDE; Q6IDD9; -.
EnsemblMetazoa; FBtr0304994; FBpp0293531; FBgn0262579. [Q6IDD9-2]
EnsemblMetazoa; FBtr0304995; FBpp0293532; FBgn0262579. [Q6IDD9-1]
GeneID; 38895; -.
KEGG; dme:Dmel_CG43119; -.
UCSC; CG34373-RE; d. melanogaster. [Q6IDD9-1]
CTD; 38895; -.
FlyBase; FBgn0262579; Ect4.
eggNOG; KOG3678; Eukaryota.
eggNOG; ENOG410XQ4A; LUCA.
GeneTree; ENSGT00390000004155; -.
InParanoid; Q6IDD9; -.
OrthoDB; EOG091G01TX; -.
PhylomeDB; Q6IDD9; -.
GenomeRNAi; 38895; -.
PRO; PR:Q6IDD9; -.
Proteomes; UP000000803; Chromosome 3L.
Bgee; FBgn0262579; Expressed in 69 organ(s), highest expression level in adult hindgut (Drosophila).
ExpressionAtlas; Q6IDD9; differential.
Genevisible; Q6IDD9; DM.
GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0030425; C:dendrite; IBA:GO_Central.
GO; GO:0043005; C:neuron projection; IDA:FlyBase.
GO; GO:0043025; C:neuronal cell body; IDA:FlyBase.
GO; GO:0035591; F:signaling adaptor activity; IEA:InterPro.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0034128; P:negative regulation of MyD88-independent toll-like receptor signaling pathway; IEA:InterPro.
GO; GO:1901214; P:regulation of neuron death; IMP:FlyBase.
GO; GO:0048678; P:response to axon injury; IMP:FlyBase.
GO; GO:0007165; P:signal transduction; IBA:GO_Central.
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_sf.
InterPro; IPR039184; SARM1.
InterPro; IPR000157; TIR_dom.
InterPro; IPR035897; Toll_tir_struct_dom_sf.
PANTHER; PTHR22998; PTHR22998; 1.
Pfam; PF07647; SAM_2; 2.
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.
2: Evidence at transcript level;
Alternative splicing; Cell projection; Complete proteome; Cytoplasm;
Immunity; Innate immunity; Reference proteome; Repeat.
CHAIN 1 1360 Sterile alpha and TIR motif-containing
protein 1.
/FTId=PRO_0000097588.
DOMAIN 690 754 SAM 1. {ECO:0000255|PROSITE-
ProRule:PRU00184}.
DOMAIN 760 828 SAM 2. {ECO:0000255|PROSITE-
ProRule:PRU00184}.
DOMAIN 837 978 TIR.
VAR_SEQ 1 215 MKAAEIKRDLTNIQKSMSEINDLAKERITGGPGSISTTSAS
AITAPSTMSQTTTSRLAPKLTSAHPSIDDLRGLSRQDKITQ
LQKKIRASFENLVDHDDSNVIVTLPDDDDCPHNHFGSGLNL
THPTAAQLSASGLSGSSKTIDTIKFQEKSMKTESKTKVVTD
GFSSEQATSNSAEMKRLQAGDIDYQESKGASAMRNRLEVDG
VKTEENAAVI -> MSNQAPWPVRKGIFRSSGQSDFTPTRS
PSPIVEMPLSPPPVATPSNRFGINSPLSPPPQPIQVVAGST
TATTMSTASAARVSGAAASTSSSSSSSSSSQCSSQTSSSSS
SHTRVRKSSNPPPQPITSCPLSPPPPPPPQQQQQLPQQLPP
PTPINNTNHSAITTPNHNNNHNCNQMRNVREIPIEVEQS
(in isoform B).
{ECO:0000303|PubMed:12537569}.
/FTId=VSP_013615.
VAR_SEQ 1048 1078 ANHQANRYRQSPSPARQRGSTSQLSGYSRAP -> GGPTST
TSTTSSTPNSNSSSSSNQSPPAAPA (in isoform B).
{ECO:0000303|PubMed:12537569}.
/FTId=VSP_013616.
VAR_SEQ 1079 1360 Missing (in isoform B).
{ECO:0000303|PubMed:12537569}.
/FTId=VSP_013617.
SEQUENCE 1360 AA; 147884 MW; F3838F5AF4FE934D CRC64;
MKAAEIKRDL TNIQKSMSEI NDLAKERITG GPGSISTTSA SAITAPSTMS QTTTSRLAPK
LTSAHPSIDD LRGLSRQDKI TQLQKKIRAS FENLVDHDDS NVIVTLPDDD DCPHNHFGSG
LNLTHPTAAQ LSASGLSGSS KTIDTIKFQE KSMKTESKTK VVTDGFSSEQ ATSNSAEMKR
LQAGDIDYQE SKGASAMRNR LEVDGVKTEE NAAVIKEALS LRTGDITQQA SNNVAASSIT
VQSENFSADK KAISQSQQSQ TMTSNGIISQ EKHVSSASQA NYSMSHKGVS STGSSMITSS
SQMSAMNGQM LKLADLKLDD LKSLTAGSGQ QEIEQTINKY SNMLTSIVSS LQEDERGGSA
ITVHDVGGKK SQYLEKINEV IRRAWAVPTH GHELGYSLCN SLRQSGGLDL LMKNCVKPDL
QFSSAQLLEQ CLTTENRKHV VDNGLDKVVN VACVCTKNSN MEHSRVGTGI LEHLFKHSEG
TCSDVIRLGG LDAVLFECRT SDLETLRHCA SALANLSLYG GAENQEEMIL RKVPMWLFPL
AFHNDDNIKY YACLAIAVLV ANKEIEAEVL KSGCLDLVEP FVTSHDPSAF ARSNLAHAHG
QSKHWLKRLV PVLSSNREEA RNLAAFHFCM EAGIKREQGN TDIFREINAI EALKNVASCP
NAIASKFAAQ ALRLIGETVP HKLSQQVPLW SVEDVQEWVK QIGFNDYIDK FNESQVDGDL
LLKLNQDNLR ADIGIGNGIL LKRFERELQN LKRMADYSSK DTAKMHQFLS EIGTDYCTYT
YAMLNAGIDK CALPHVNEDM LMTECGIHNS IHRLRILNAV KNLENSLPSS SEENMAKTLD
VFVSYRRSNG SQLASLLKVH LQLRGFSVFI DVERLEAGKF DNGLLNSIRQ AKNFVLVLTP
DALHRCINDE DCKDWVHREI VAALNSNCNI IPIIDQQFDW PEVERLPEDM RSVAHFNGVN
WIHDYQDACI DKLERFLRGE KNIDRIAAMV PGTPGSVSYQ RMHSNDSDYQ SGGAGAGSGA
GTGGGGGGGV TGSVVDGLMV AANGSGQANH QANRYRQSPS PARQRGSTSQ LSGYSRAPSK
RSQILTPYRT QQAALLHKTG AGSASMQNMM PLAYLPPRRS SAAGLGHGSG SGMGSGYRSH
SVDGLLDQAG STPEQRIAAA AAKVTAGSTA LTNASSTSTL QPEEEVTDAA LNDSVTRRDK
HTLSPPGNVQ QHRKSRSLDH ILSKQTLAEL LPPSSELADG TQSMQNLAIP MTPQPQRRDT
SSSSKSPTPE RPPQPAMERV RERQSPEGVS ATESEREDQP EECLRHGNQQ RASASVHRGA
SLTSNKTSNS SLGSNFSAGG NNKTIFNRTM KKVRSLIKKP


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