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Q6IA17 (SIGIR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
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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:
Single Ig IL-1-related receptor
Alternative name(s):
Single Ig IL-1R-related molecule
Single immunoglobulin domain-containing IL1R-related protein
Toll/interleukin-1 receptor 8
Short name=TIR8
Gene names
Name:SIGIRR
ORF Names:UNQ301/PRO342
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length410 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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. Ref.7 Ref.8 Ref.9

Subunit structure

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. Interacts with PALM3. Ref.8 Ref.9 Ref.11

Subcellular location

Membrane; Single-pass type III membrane protein Potential.

Tissue specificity

Mainly expressed in epithelial tissues such as kidney, lung and gut. Ref.7 Ref.10

Induction

Down-regulated during inflammation by inhibition of an SP1-mediated pathway. Ref.10

Sequence similarities

Belongs to the interleukin-1 receptor family.

Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Contains 1 TIR domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6IA17-1)

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: Q6IA17-2)

The sequence of this isoform differs from the canonical sequence as follows:
     358-410: VRGPVFGEPS...FYCLVSKDDM → MPAQPHSPTG...HRLLLPGVQG
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 410410Single Ig IL-1-related receptor
PRO_0000099065

Regions

Topological domain1 – 118118Extracellular Potential
Transmembrane119 – 13921Helical; Signal-anchor for type III membrane protein; Potential
Topological domain140 – 410271Cytoplasmic Potential
Domain9 – 109101Ig-like C2-type
Domain163 – 310148TIR

Amino acid modifications

Modified residue3801Phosphoserine By similarity
Glycosylation311N-linked (GlcNAc...) Potential
Glycosylation731N-linked (GlcNAc...) Potential
Glycosylation861N-linked (GlcNAc...) Potential
Glycosylation1021N-linked (GlcNAc...) Potential
Disulfide bond32 ↔ 98 By similarity

Natural variations

Alternative sequence358 – 41053VRGPV…SKDDM → MPAQPHSPTGEAQHRAEWGQ AQGTGPGGALGVEDSSRHRE PLHGLCPGGARPSVCLGTSW ASQAITAGGEQGQPLAVGLG QGCGWPPQASRSPHPRCPGA CFWRAISSTAHQWGLAGREP EQRSGRLGSRLAKLQCPHRL LLPGVQG in isoform 2.
VSP_015717
Natural variant3121Q → R. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs3210908 [ dbSNP | Ensembl ].
VAR_058702

Experimental info

Sequence conflict4101M → I in CAG33619. Ref.3

Sequences

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

Last modified November 2, 2010. Version 3.
Checksum: BA4564C2ABAB5104

FASTA41045,679
        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 VQYRPVEGDP QTQLQDDKDP MLILRGRVPE GRALDSEVDP DPEGDLGVRG 

       370        380        390        400        410 
PVFGEPSAPP HTSGVSLGES RSSEVDVSDL GSRNYSARTD FYCLVSKDDM

« Hide

Isoform 2 [UniParc].

Checksum: 1DC974BAC4EC4D2A
Show »

FASTA50455,271

References

« Hide 'large scale' references
[1]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
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. expand/collapse author list , 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.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ARG-312.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-312.
Tissue: Colon.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-312.
[4]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-312.
Tissue: Lung and Pancreas.
[6]"Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily."
Thomassen E., Renshaw B.R., Sims J.E.
Cytokine 11:389-399(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[7]"Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR."
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.
Eur. Cytokine Netw. 14:211-218(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]"SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling."
Wald D., Qin J., Zhao Z., Qian Y., Naramura M., Tian L., Towne J., Sims J.E., Stark G.R., Li X.
Nat. Immunol. 4:920-927(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IL1R1; TLR4; TLR5; TLR9; TRAF6 AND IRAK1.
[9]"SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated signaling through different mechanisms."
Qin J., Qian Y., Yao J., Grace C., Li X.
J. Biol. Chem. 280:25233-25241(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN IL-1 AND LPS RECEPTOR COMPLEXES.
[10]"Down-regulation of single immunoglobulin interleukin-1R-related molecule (SIGIRR)/TIR8 expression in intestinal epithelial cells during inflammation."
Kadota C., Ishihara S., Aziz M.M., Rumi M.A., Oshima N., Mishima Y., Moriyama I., Yuki T., Amano Y., Kinoshita Y.
Clin. Exp. Immunol. 162:348-361(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, TISSUE SPECIFICITY.
[11]"A novel binding protein of single immunoglobulin IL-1 receptor-related molecule: Paralemmin-3."
Chen X., Wu X., Zhao Y., Wang G., Feng J., Li Q., Qian G.
Biochem. Biophys. Res. Commun. 404:1029-1033(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PALM3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AY358342 mRNA. Translation: AAQ88708.1.
AK025099 mRNA. Translation: BAB15066.1.
CR457338 mRNA. Translation: CAG33619.1.
AC138230 Genomic DNA. No translation available.
BC003591 mRNA. Translation: AAH03591.1.
BC025953 mRNA. Translation: AAH25953.1.
BC106007 mRNA. Translation: AAI06008.1.
IPIIPI00029155.
IPI00432567.
RefSeqNP_001128525.1. NM_001135053.1.
NP_001128526.1. NM_001135054.1.
NP_068577.2. NM_021805.2.
UniGeneHs.501624.

3D structure databases

ProteinModelPortalQ6IA17.
SMRQ6IA17. Positions 19-103, 163-308.
ModBaseSearch...

Protein-protein interaction databases

IntActQ6IA17. 3 interactions.
MINTMINT-1430901.
STRING9606.ENSP00000333656.

PTM databases

PhosphoSiteQ6IA17.

Polymorphism databases

DMDM311033538.

Proteomic databases

PaxDbQ6IA17.
PRIDEQ6IA17.

Protocols and materials databases

DNASU59307.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332725; ENSP00000333656; ENSG00000185187.
ENST00000397632; ENSP00000380756; ENSG00000185187.
ENST00000431843; ENSP00000403104; ENSG00000185187.
GeneID59307.
KEGGhsa:59307.
UCSCuc001lpd.2. human.

Organism-specific databases

CTD59307.
GeneCardsGC11M000395.
H-InvDBHIX0021476.
HGNCHGNC:30575. SIGIRR.
HPAHPA023188.
MIM605478. gene.
neXtProtNX_Q6IA17.
PharmGKBPA142670915.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39004.
HOGENOMHOG000237348.
HOVERGENHBG080781.
KOK05169.
OrthoDBEOG4RR6HQ.
PhylomeDBQ6IA17.

Gene expression databases

ArrayExpressQ6IA17.
BgeeQ6IA17.
CleanExHS_SIGIRR.
GenevestigatorQ6IA17.
GermOnlineENSG00000185187. Homo sapiens.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR015621. IL1-receptor_fam.
IPR000157. TIR_dom.
[Graphical view]
PANTHERPTHR11890. PTHR11890. 1 hit.
PfamPF01582. TIR. 1 hit.
[Graphical view]
SUPFAMSSF52200. TIR. 1 hit.
PROSITEPS50835. IG_LIKE. 1 hit.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSIGIRR. human.
GenomeRNAi59307.
NextBio65192.
SOURCESearch...

Entry information

Entry nameSIGIR_HUMAN
AccessionPrimary (citable) accession number: Q6IA17
Secondary accession number(s): Q3KQY2, Q6UXI3, Q9H733
Entry history
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: November 2, 2010
Last modified: May 1, 2013
This is version 93 of the entry and version 3 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

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

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