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UniProtKB/Swiss-Prot entry Q6IA17


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name SIGIR_HUMAN
Primary accession number Q6IA17
Secondary accession numbers Q3KQY2 Q6UXI3 Q9H733
Integrated into Swiss-Prot on September 27, 2005
Sequence was last modified on September 27, 2005 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 57)
Name and origin of the protein
Protein name Single Ig IL-1-related receptor
Synonyms Single Ig IL-1R-related molecule
Single immunoglobulin domain-containing IL1R-related protein
Toll/interleukin-1 receptor 8
TIR8
Gene name
Name: SIGIRR
ORFNames: UNQ301/PRO342
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
DOI=10.1101/gr.1293003; PubMed=12975309 [NCBI, ExPASy, EBI, Israel, Japan]
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Colon;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Lung, and Pancreas;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
CHARACTERIZATION.
DOI=10.1006/cyto.1998.0452; PubMed=10346978 [NCBI, ExPASy, EBI, Israel, Japan]
Thomassen E., Renshaw B.R., Sims J.E.;
"Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily.";
Cytokine 11:389-399(1999).
[6]
FUNCTION, AND TISSUE SPECIFICITY.
PubMed=14715412 [NCBI, ExPASy, EBI, Israel, Japan]
Polentarutti N., Rol G.P., Muzio M., Bosisio D., Camnasio M., Riva F., Zoja C., Benigni A., Tomasoni S., Vecchi A., Garlanda C., Mantovani A.;
"Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR.";
Eur. Cytokine Netw. 14:211-218(2003).
[7]
FUNCTION, AND INTERACTION WITH IL1R1; TLR4; TLR5; TLR9; TRAF6 AND IRAK1.
DOI=10.1038/ni968; PubMed=12925853 [NCBI, ExPASy, EBI, Israel, Japan]
Wald D., Qin J., Zhao Z., Qian Y., Naramura M., Tian L., Towne J., Sims J.E., Stark G.R., Li X.;
"SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling.";
Nat. Immunol. 4:920-927(2003).
[8]
FUNCTION, AND IDENTIFICATION IN IL-1 AND LPS RECEPTOR COMPLEXES.
DOI=10.1074/jbc.M501363200; PubMed=15866876 [NCBI, ExPASy, EBI, Israel, Japan]
Qin J., Qian Y., Yao J., Grace C., Li X.;
"SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated signaling through different mechanisms.";
J. Biol. Chem. 280:25233-25241(2005).
Comments
  • FUNCTION: Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor-proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP.
  • SUBUNIT: Interacts with IL1R1, IRAK1, TLR4, TLR5, TLR9 and TRAF6. Upon IL-1 stimulation found in a complex at least composed of IL1R1, SIGIRR, MYD88, IRAK1 and TRAF6. Upon stimulation with LPC found in a complex at least composed of TLR4, SIG1IR, MYD88, IRAK1 and TRAF6.
  • SUBCELLULAR LOCATION: Membrane; Single-pass type III membrane protein (Potential).
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDQ6IA17-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDQ6IA17-2
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_015717.
  • TISSUE SPECIFICITY: Mainly expressed in epithelial tissues such as kidney, lung and gut.
  • SIMILARITY: Belongs to the interleukin-1 receptor family.
  • SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) domain.
  • SIMILARITY: Contains 1 TIR domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AY358342; AAQ88708.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK025099; BAB15066.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CR457338; CAG33619.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC003591; AAH03591.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC025953; AAH25953.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC106007; AAI06008.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00029155; -.
IPI00432567; -.
RefSeq NP_001128525.1; -.
NP_001128526.1; -.
NP_068577.2; -.
UniGene Hs.501624
3D structure databases
ModBase Q6IA17.
Protein-protein interaction databases
IntAct Q6IA17; 2.
PTM databases
PhosphoSite Q6IA17; -.
Organism-specific databases
GeneCards GC11M000395; -.
H-InvDB HIX0021476; -.
HGNC HGNC:30575; SIGIRR.
GenAtlas SIGIRR.
MIM 605478; gene. [NCBI / EBI]
PharmGKB PA142670915; -.
Gene expression databases
ArrayExpress Q6IA17; -.
Bgee Q6IA17; -.
CleanEx HS_SIGIRR; -.
GermOnline ENSG00000185187; Homo sapiens.
Ontologies
GO
GO:0016021; Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0004888; Molecular function: transmembrane receptor activity (inferred from electronic annotation from InterPro).
GO:0006953; Biological process: acute-phase response (inferred from sequence or structural similarity from HGNC).
GO:0045087; Biological process: innate immune response (inferred from electronic annotation from InterPro).
GO:0045079; Biological process: negative regulation of chemokine biosynthetic process (inferred from sequence or structural similarity from HGNC).
GO:0001960; Biological process: negative regulation of cytokine-mediated signaling pathway (inferred from sequence or structural similarity from HGNC).
GO:0031665; Biological process: negative regulation of lipopolysaccharide-mediated signaling pathway (traceable author statement from HGNC).
GO:0043433; Biological process: negative regulation of transcription factor activity (inferred from mutant phenotype from HGNC).
GO:0007165; Biological process: signal transduction (inferred from electronic annotation from InterPro).
QuickGo view.
Family and domain databases
InterPro IPR007110; Ig-like.
IPR015621; IL1-receptor.
IPR004075; IL1_rcpt_1.
IPR000157; Toll-Interleukin_rcpt.
Graphical view of domain structure.
PANTHER PTHR11890; IL1-receptor; 1.
Pfam PF01582; TIR; 1.
Pfam graphical view of domain structure.
PRINTS PR01537; INTRLKN1R1F.
PROSITE PS50835; IG_LIKE; 1.
PS50104; TIR; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE Q6IA17; -.
Genome annotation databases
Ensembl ENSG00000185187; Homo sapiens. [Contig view]
GeneID 59307; -.
Phylogenomic databases
HOVERGEN Q6IA17; -.
Other
NextBio 65192; -.
SOURCE SIGIRR; Homo sapiens.
ProtoNet Q6IA17.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Alternative splicing; Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane; Phosphoprotein; Signal-anchor; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   410  410     Single Ig IL-1-related receptor. PRO_0000099065
TOPO_DOM   1   118  118     Extracellular (Potential). 
TRANSMEM   119   139  21     Signal-anchor for type III membrane protein (Potential). 
TOPO_DOM   140   410  271     Cytoplasmic (Potential). 
DOMAIN   9   109  101     Ig-like C2-type. 
DOMAIN   163   310  148     TIR. 
MOD_RES   380   380        Phosphoserine (By similarity). 
CARBOHYD   31    31        N-linked (GlcNAc...) (Potential). 
CARBOHYD   73    73        N-linked (GlcNAc...) (Potential). 
CARBOHYD   86    86        N-linked (GlcNAc...) (Potential). 
CARBOHYD   102   102        N-linked (GlcNAc...) (Potential). 
DISULFID   32    98        By similarity. 
VAR_SEQ   358   410        VRGPVFGEPSAPPHTSGVSLGESRSSEVDVSDLGSRNYSA RTDFYCLVSKDDM -> MPAQPHSPTGEAQHRAEWGQAQGTGPGGALGVEDSSRHRE PLHGLCPGGARPSVCLGTSWASQAITAGGEQGQPLAVGLG QGCGWPPQASRSPHPRCPGACFWRAISSTAHQWGLAGREP EQRSGRLGSRLAKLQCPHRLLLPGVQG (in isoform 2). VSP_015717
CONFLICT   410   410        M -> I (in Ref. 3; CAG33619). 
Sequence information
Length: 410 AA [This is the length of the unprocessed precursor] Molecular weight: 45707 Da [This is the MW of the unprocessed precursor] CRC64: 2A7A663D79567ED6 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MPGVCDRAPD FLSPSEDQVL RPALGSSVAL NCTAWVVSGP HCSLPSVQWL KDGLPLGIGG 

        70         80         90        100        110        120 
HYSLHEYSWV KANLSEVLVS SVLGVNVTST EVYGAFTCSI QNISFSSFTL QRAGPTSHVA 

       130        140        150        160        170        180 
AVLASLLVLL ALLLAALLYV KCRLNVLLWY QDAYGEVEIN DGKLYDAYVS YSDCPEDRKF 

       190        200        210        220        230        240 
VNFILKPQLE RRRGYKLFLD DRDLLPRAEP SADLLVNLSR CRRLIVVLSD AFLSRAWCSH 

       250        260        270        280        290        300 
SFREGLCRLL ELTRRPIFIT FEGQRRDPAH PALRLLRQHR HLVTLLLWRP GSVTPSSDFW 

       310        320        330        340        350        360 
KEVQLALPRK VRYRPVEGDP QTQLQDDKDP MLILRGRVPE GRALDSEVDP DPEGDLGVRG 

       370        380        390        400        410 
PVFGEPSAPP HTSGVSLGES RSSEVDVSDL GSRNYSARTD FYCLVSKDDM 

Q6IA17 in FASTA format

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