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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

BioCyciZFISH:G66-31709-MONOMER.
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)DescriptionActionsGraphical viewLength
Topological domaini1 – 118ExtracellularSequence analysisAdd BLAST118
Transmembranei119 – 139Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST21
Topological domaini140 – 410CytoplasmicSequence analysisAdd BLAST271

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

DisGeNETi59307.
OpenTargetsiENSG00000185187.
PharmGKBiPA142670915.

Polymorphism and mutation databases

BioMutaiSIGIRR.
DMDMi311033538.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000990651 – 410Single Ig IL-1-related receptorAdd BLAST410

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi31N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi32 ↔ 98PROSITE-ProRule annotation
Glycosylationi73N-linked (GlcNAc...)Sequence analysis1
Glycosylationi86N-linked (GlcNAc...)Sequence analysis1
Glycosylationi102N-linked (GlcNAc...)Sequence analysis1
Modified residuei383PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ6IA17.
MaxQBiQ6IA17.
PaxDbiQ6IA17.
PeptideAtlasiQ6IA17.
PRIDEiQ6IA17.

PTM databases

iPTMnetiQ6IA17.
PhosphoSitePlusiQ6IA17.
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

BgeeiENSG00000185187.
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 interactors.
IntActiQ6IA17. 3 interactors.
MINTiMINT-1430901.
STRINGi9606.ENSP00000333656.

Structurei

3D structure databases

ProteinModelPortaliQ6IA17.
SMRiQ6IA17.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 109Ig-like C2-typeAdd BLAST101
Domaini163 – 310TIRPROSITE-ProRule annotationAdd BLAST148

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)DescriptionActionsGraphical viewLength
Sequence conflicti410M → I in CAG33619 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07416480S → Y.1 PublicationCorresponds to variant rs117739035dbSNPEnsembl.1
Natural variantiVAR_074165115P → R.1 PublicationCorresponds to variant rs111819059dbSNPEnsembl.1
Natural variantiVAR_058702312Q → R.5 PublicationsCorresponds to variant rs3210908dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015717358 – 410VRGPV…SKDDM → MPAQPHSPTGEAQHRAEWGQ AQGTGPGGALGVEDSSRHRE PLHGLCPGGARPSVCLGTSW ASQAITAGGEQGQPLAVGLG QGCGWPPQASRSPHPRCPGA CFWRAISSTAHQWGLAGREP EQRSGRLGSRLAKLQCPHRL LLPGVQG in isoform 2. 1 PublicationAdd BLAST53

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiQ6IA17.
PhosphoSitePlusiQ6IA17.
SwissPalmiQ6IA17.

Polymorphism and mutation databases

BioMutaiSIGIRR.
DMDMi311033538.

Proteomic databases

EPDiQ6IA17.
MaxQBiQ6IA17.
PaxDbiQ6IA17.
PeptideAtlasiQ6IA17.
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.
DisGeNETi59307.
GeneCardsiSIGIRR.
H-InvDBHIX0021476.
HGNCiHGNC:30575. SIGIRR.
HPAiHPA023188.
MIMi605478. gene.
neXtProtiNX_Q6IA17.
OpenTargetsiENSG00000185187.
PharmGKBiPA142670915.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:G66-31709-MONOMER.
ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000185187.
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...

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: November 2, 2016
This is version 126 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.