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Protein

Single Ig IL-1-related receptor

Gene

SIGIRR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:SIGIRR
ORF Names:UNQ301/PRO342
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:30575. SIGIRR.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 118118ExtracellularSequence analysisAdd
BLAST
Transmembranei119 – 13921Helical; Signal-anchor for type III membrane proteinSequence analysisAdd
BLAST
Topological domaini140 – 410271CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142670915.

Polymorphism and mutation databases

BioMutaiSIGIRR.
DMDMi311033538.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 410410Single Ig IL-1-related receptorPRO_0000099065Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi31 – 311N-linked (GlcNAc...)Sequence analysis
Disulfide bondi32 ↔ 98PROSITE-ProRule annotation
Glycosylationi73 – 731N-linked (GlcNAc...)Sequence analysis
Glycosylationi86 – 861N-linked (GlcNAc...)Sequence analysis
Glycosylationi102 – 1021N-linked (GlcNAc...)Sequence analysis
Modified residuei383 – 3831PhosphoserineBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ6IA17.
MaxQBiQ6IA17.
PaxDbiQ6IA17.
PRIDEiQ6IA17.

PTM databases

iPTMnetiQ6IA17.
PhosphoSiteiQ6IA17.
SwissPalmiQ6IA17.

Expressioni

Tissue specificityi

Mainly expressed in epithelial tissues such as kidney, lung and gut.2 Publications

Inductioni

Down-regulated during inflammation by inhibition of an SP1-mediated pathway.1 Publication

Gene expression databases

BgeeiQ6IA17.
CleanExiHS_SIGIRR.
ExpressionAtlasiQ6IA17. baseline and differential.
GenevisibleiQ6IA17. HS.

Organism-specific databases

HPAiHPA023188.

Interactioni

Subunit structurei

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 PALM3.3 Publications

Protein-protein interaction databases

BioGridi121873. 7 interactions.
IntActiQ6IA17. 3 interactions.
MINTiMINT-1430901.
STRINGi9606.ENSP00000333656.

Structurei

3D structure databases

ProteinModelPortaliQ6IA17.
SMRiQ6IA17. Positions 163-308.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 109101Ig-like C2-typeAdd
BLAST
Domaini163 – 310148TIRPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the interleukin-1 receptor family.Curated
Contains 1 TIR domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEXB. Eukaryota.
ENOG410ZFDI. LUCA.
GeneTreeiENSGT00840000129987.
HOGENOMiHOG000237348.
HOVERGENiHBG080781.
InParanoidiQ6IA17.
KOiK05169.
PhylomeDBiQ6IA17.
TreeFamiTF325519.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.40.50.10140. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR015621. IL-1_rcpt_fam.
IPR000157. TIR_dom.
[Graphical view]
PANTHERiPTHR11890. PTHR11890. 1 hit.
PfamiPF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS50104. TIR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6IA17-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPGVCDRAPD FLSPSEDQVL RPALGSSVAL NCTAWVVSGP HCSLPSVQWL
60 70 80 90 100
KDGLPLGIGG HYSLHEYSWV KANLSEVLVS SVLGVNVTST EVYGAFTCSI
110 120 130 140 150
QNISFSSFTL QRAGPTSHVA AVLASLLVLL ALLLAALLYV KCRLNVLLWY
160 170 180 190 200
QDAYGEVEIN DGKLYDAYVS YSDCPEDRKF VNFILKPQLE RRRGYKLFLD
210 220 230 240 250
DRDLLPRAEP SADLLVNLSR CRRLIVVLSD AFLSRAWCSH SFREGLCRLL
260 270 280 290 300
ELTRRPIFIT FEGQRRDPAH PALRLLRQHR HLVTLLLWRP GSVTPSSDFW
310 320 330 340 350
KEVQLALPRK VQYRPVEGDP QTQLQDDKDP MLILRGRVPE GRALDSEVDP
360 370 380 390 400
DPEGDLGVRG PVFGEPSAPP HTSGVSLGES RSSEVDVSDL GSRNYSARTD
410
FYCLVSKDDM
Length:410
Mass (Da):45,679
Last modified:November 2, 2010 - v3
Checksum:iBA4564C2ABAB5104
GO
Isoform 2 (identifier: Q6IA17-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     358-410: VRGPVFGEPS...FYCLVSKDDM → MPAQPHSPTG...HRLLLPGVQG

Note: No experimental confirmation available.
Show »
Length:504
Mass (Da):55,271
Checksum:i1DC974BAC4EC4D2A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti410 – 4101M → I in CAG33619 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti80 – 801S → Y.1 Publication
VAR_074164
Natural varianti115 – 1151P → R.1 Publication
VAR_074165
Natural varianti312 – 3121Q → R.5 Publications
Corresponds to variant rs3210908 [ dbSNP | Ensembl ].
VAR_058702

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei358 – 41053VRGPV…SKDDM → MPAQPHSPTGEAQHRAEWGQ AQGTGPGGALGVEDSSRHRE PLHGLCPGGARPSVCLGTSW ASQAITAGGEQGQPLAVGLG QGCGWPPQASRSPHPRCPGA CFWRAISSTAHQWGLAGREP EQRSGRLGSRLAKLQCPHRL LLPGVQG in isoform 2. 1 PublicationVSP_015717Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31325.1. [Q6IA17-1]
RefSeqiNP_001128525.1. NM_001135053.1. [Q6IA17-1]
NP_001128526.1. NM_001135054.1. [Q6IA17-1]
NP_068577.2. NM_021805.2. [Q6IA17-1]
UniGeneiHs.501624.

Genome annotation databases

EnsembliENST00000332725; ENSP00000333656; ENSG00000185187. [Q6IA17-1]
ENST00000397632; ENSP00000380756; ENSG00000185187. [Q6IA17-1]
ENST00000431843; ENSP00000403104; ENSG00000185187. [Q6IA17-1]
GeneIDi59307.
KEGGihsa:59307.
UCSCiuc001lpd.3. human. [Q6IA17-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31325.1. [Q6IA17-1]
RefSeqiNP_001128525.1. NM_001135053.1. [Q6IA17-1]
NP_001128526.1. NM_001135054.1. [Q6IA17-1]
NP_068577.2. NM_021805.2. [Q6IA17-1]
UniGeneiHs.501624.

3D structure databases

ProteinModelPortaliQ6IA17.
SMRiQ6IA17. Positions 163-308.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121873. 7 interactions.
IntActiQ6IA17. 3 interactions.
MINTiMINT-1430901.
STRINGi9606.ENSP00000333656.

PTM databases

iPTMnetiQ6IA17.
PhosphoSiteiQ6IA17.
SwissPalmiQ6IA17.

Polymorphism and mutation databases

BioMutaiSIGIRR.
DMDMi311033538.

Proteomic databases

EPDiQ6IA17.
MaxQBiQ6IA17.
PaxDbiQ6IA17.
PRIDEiQ6IA17.

Protocols and materials databases

DNASUi59307.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332725; ENSP00000333656; ENSG00000185187. [Q6IA17-1]
ENST00000397632; ENSP00000380756; ENSG00000185187. [Q6IA17-1]
ENST00000431843; ENSP00000403104; ENSG00000185187. [Q6IA17-1]
GeneIDi59307.
KEGGihsa:59307.
UCSCiuc001lpd.3. human. [Q6IA17-1]

Organism-specific databases

CTDi59307.
GeneCardsiSIGIRR.
H-InvDBHIX0021476.
HGNCiHGNC:30575. SIGIRR.
HPAiHPA023188.
MIMi605478. gene.
neXtProtiNX_Q6IA17.
PharmGKBiPA142670915.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEXB. Eukaryota.
ENOG410ZFDI. LUCA.
GeneTreeiENSGT00840000129987.
HOGENOMiHOG000237348.
HOVERGENiHBG080781.
InParanoidiQ6IA17.
KOiK05169.
PhylomeDBiQ6IA17.
TreeFamiTF325519.

Enzyme and pathway databases

ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.

Miscellaneous databases

ChiTaRSiSIGIRR. human.
GeneWikiiSIGIRR.
GenomeRNAii59307.
NextBioi65192.
PROiQ6IA17.
SOURCEiSearch...

Gene expression databases

BgeeiQ6IA17.
CleanExiHS_SIGIRR.
ExpressionAtlasiQ6IA17. baseline and differential.
GenevisibleiQ6IA17. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.40.50.10140. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR015621. IL-1_rcpt_fam.
IPR000157. TIR_dom.
[Graphical view]
PANTHERiPTHR11890. PTHR11890. 1 hit.
PfamiPF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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. 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 IL1 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.
  12. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  13. "SIGIRR genetic variants in premature infants with necrotizing enterocolitis."
    Sampath V., Menden H., Helbling D., Li K., Gastonguay A., Ramchandran R., Dimmock D.P.
    Pediatrics 135:E1530-E1534(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TYR-80; ARG-115 AND ARG-312, FUNCTION.

Entry informationi

Entry nameiSIGIR_HUMAN
AccessioniPrimary (citable) accession number: Q6IA17
Secondary accession number(s): Q3KQY2, Q6UXI3, Q9H733
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: November 2, 2010
Last modified: May 11, 2016
This is version 121 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.