SIGIR_MOUSE
ID SIGIR_MOUSE Reviewed; 409 AA.
AC Q9JLZ8; Q52L48;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Single Ig IL-1-related receptor;
DE AltName: Full=Single Ig IL-1R-related molecule;
DE AltName: Full=Single immunoglobulin domain-containing IL1R-related protein;
DE AltName: Full=Toll/interleukin-1 receptor 8;
DE Short=TIR8;
GN Name=Sigirr; Synonyms=Tir8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=14993616; DOI=10.1073/pnas.0308680101;
RA Garlanda C., Riva F., Polentarutti N., Buracchi C., Sironi M.,
RA De Bortoli M., Muzio M., Bergottini R., Scanziani E., Vecchi A., Hirsch E.,
RA Mantovani A.;
RT "Intestinal inflammation in mice deficient in Tir8, an inhibitory member of
RT the IL-1 receptor family.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:3522-3526(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP CHARACTERIZATION.
RX PubMed=10346978; DOI=10.1006/cyto.1998.0452;
RA Thomassen E., Renshaw B.R., Sims J.E.;
RT "Identification and characterization of SIGIRR, a molecule representing a
RT novel subtype of the IL-1R superfamily.";
RL Cytokine 11:389-399(1999).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=12925853; DOI=10.1038/ni968;
RA Wald D., Qin J., Zhao Z., Qian Y., Naramura M., Tian L., Towne J.,
RA Sims J.E., Stark G.R., Li X.;
RT "SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor
RT signaling.";
RL Nat. Immunol. 4:920-927(2003).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=21077278; DOI=10.1111/j.1365-2249.2010.04254.x;
RA Kadota C., Ishihara S., Aziz M.M., Rumi M.A., Oshima N., Mishima Y.,
RA Moriyama I., Yuki T., Amano Y., Kinoshita Y.;
RT "Down-regulation of single immunoglobulin interleukin-1R-related molecule
RT (SIGIRR)/TIR8 expression in intestinal epithelial cells during
RT inflammation.";
RL Clin. Exp. Immunol. 162:348-361(2010).
CC -!- FUNCTION: Acts as a negative regulator of the Toll-like and IL-1R
CC receptor signaling pathways. Attenuates the recruitment of receptor-
CC proximal signaling components to the TLR4 receptor, probably through an
CC TIR-TIR domain interaction with TLR4. Through its extracellular domain
CC interferes with the heterodimerization of Il1R1 and IL1RAP (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:12925853}.
CC -!- SUBUNIT: Interacts with IL1R1, IRAK1, TLR4, TLR5, TLR9 and TRAF6. Upon
CC IL-1 stimulation found in a complex at least composed of IL1R1, SIGIRR,
CC MYD88, IRAK1 and TRAF6. Upon stimulation with LPC found in a complex at
CC least composed of TLR4, SIG1IR, MYD88, IRAK1 and TRAF6. Interacts with
CC PALM3 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type III
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JLZ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JLZ8-2; Sequence=VSP_015718;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in kidney, and at moderate
CC levels in colon, small intestine, lung, spleen and liver. Not expressed
CC in brain and muscle. Expressed at high levels in epithelial cells, at
CC moderate levels in splenocytes, and at low or undetectable levels in
CC fibroblasts or endothelial cells. Expressed in mucosal and dendritic
CC cells. {ECO:0000269|PubMed:12925853, ECO:0000269|PubMed:14993616,
CC ECO:0000269|PubMed:21077278}.
CC -!- INDUCTION: Down-regulated by LPS. Down-regulated during inflammation by
CC inhibition of an SP1-mediated pathway. {ECO:0000269|PubMed:12925853,
CC ECO:0000269|PubMed:21077278}.
CC -!- SIMILARITY: Belongs to the interleukin-1 receptor family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF26200.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF113795; AAF26200.1; ALT_FRAME; mRNA.
DR EMBL; BC010806; AAH10806.1; -; mRNA.
DR EMBL; BC094069; AAH94069.1; -; mRNA.
DR CCDS; CCDS40179.1; -. [Q9JLZ8-1]
DR RefSeq; NP_075546.2; NM_023059.3. [Q9JLZ8-1]
DR RefSeq; XP_006536239.1; XM_006536176.2.
DR RefSeq; XP_006536240.1; XM_006536177.3. [Q9JLZ8-1]
DR RefSeq; XP_006536241.1; XM_006536178.3. [Q9JLZ8-1]
DR RefSeq; XP_006536242.1; XM_006536179.3. [Q9JLZ8-1]
DR RefSeq; XP_006536243.1; XM_006536180.2. [Q9JLZ8-1]
DR AlphaFoldDB; Q9JLZ8; -.
DR SMR; Q9JLZ8; -.
DR STRING; 10090.ENSMUSP00000095571; -.
DR GlyGen; Q9JLZ8; 5 sites.
DR iPTMnet; Q9JLZ8; -.
DR PhosphoSitePlus; Q9JLZ8; -.
DR EPD; Q9JLZ8; -.
DR jPOST; Q9JLZ8; -.
DR MaxQB; Q9JLZ8; -.
DR PaxDb; Q9JLZ8; -.
DR PRIDE; Q9JLZ8; -.
DR ProteomicsDB; 257246; -. [Q9JLZ8-1]
DR ProteomicsDB; 257247; -. [Q9JLZ8-2]
DR Antibodypedia; 9633; 313 antibodies from 29 providers.
DR DNASU; 24058; -.
DR Ensembl; ENSMUST00000097958; ENSMUSP00000095571; ENSMUSG00000025494. [Q9JLZ8-1]
DR Ensembl; ENSMUST00000209294; ENSMUSP00000147541; ENSMUSG00000025494. [Q9JLZ8-1]
DR Ensembl; ENSMUST00000210167; ENSMUSP00000147280; ENSMUSG00000025494. [Q9JLZ8-2]
DR GeneID; 24058; -.
DR KEGG; mmu:24058; -.
DR UCSC; uc009kjk.1; mouse. [Q9JLZ8-1]
DR UCSC; uc009kjm.1; mouse. [Q9JLZ8-2]
DR CTD; 59307; -.
DR MGI; MGI:1344402; Sigirr.
DR VEuPathDB; HostDB:ENSMUSG00000025494; -.
DR eggNOG; ENOG502QVF7; Eukaryota.
DR GeneTree; ENSGT01050000244846; -.
DR HOGENOM; CLU_040046_0_0_1; -.
DR InParanoid; Q9JLZ8; -.
DR OMA; LEQDWCT; -.
DR OrthoDB; 735868at2759; -.
DR PhylomeDB; Q9JLZ8; -.
DR TreeFam; TF325519; -.
DR BioGRID-ORCS; 24058; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q9JLZ8; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9JLZ8; protein.
DR Bgee; ENSMUSG00000025494; Expressed in yolk sac and 150 other tissues.
DR ExpressionAtlas; Q9JLZ8; baseline and differential.
DR Genevisible; Q9JLZ8; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:HGNC-UCL.
DR GO; GO:0006953; P:acute-phase response; IMP:HGNC-UCL.
DR GO; GO:0032682; P:negative regulation of chemokine production; IMP:HGNC-UCL.
DR GO; GO:0001960; P:negative regulation of cytokine-mediated signaling pathway; IMP:HGNC-UCL.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:HGNC-UCL.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.40.50.10140; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR015621; IL-1_rcpt_fam.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR11890; PTHR11890; 1.
DR Pfam; PF13895; Ig_2; 1.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Membrane; Phosphoprotein; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..409
FT /note="Single Ig IL-1-related receptor"
FT /id="PRO_0000099066"
FT TOPO_DOM 1..117
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..138
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 139..409
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 9..108
FT /note="Ig-like C2-type"
FT DOMAIN 162..306
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT MOD_RES 382
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 357..409
FT /note="VRGPVFGEPPTPLQETRICIGESHGSEMDVSDLGSRNYSARTDFYCLVSEDD
FT V -> MLTADQGVKHSSSVLERTQAWRTLASRDPVS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015718"
FT CONFLICT 154
FT /note="G -> R (in Ref. 1; AAF26200)"
FT /evidence="ECO:0000305"
FT CONFLICT 208..209
FT /note="EP -> DA (in Ref. 1; AAF26200)"
FT /evidence="ECO:0000305"
FT CONFLICT 277..278
FT /note="QH -> HD (in Ref. 1; AAF26200)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 409 AA; 46159 MW; 9D175DC27AAFBE18 CRC64;
MAGVCDMAPN FLSPSEDQAL GLALGREVAL NCTAWVFSRP QCPQPSVQWL KDGLALGNGS
HFSLHEDFWV SANFSEIVSS VLVLNLTNAE DYGTFTCSVW NVSSHSFTLW RAGPAGHVAA
VLASLLVLVV LLLVALLYVK CRLNMLLWYQ DTYGEVEMND GKLYDAYVSY SDCPEDRKFV
NFILKPQLER RRGYKLFLED RDLLPRAEPS ADLLVNLSRC RRLIVVLSDA FLSRPWCSQS
FREGLCRLLE LTRRPIFITF EGQRREPIHP ALRLLRQHRH LVTLVLWKPG SVTPSSDFWK
ELQLALPRKV QYRPVEGDPQ TRLQDDKDPM LIVRGRAAQG RGMESELDPD PEGDLGVRGP
VFGEPPTPLQ ETRICIGESH GSEMDVSDLG SRNYSARTDF YCLVSEDDV
