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Protein

Single Ig IL-1-related receptor

Gene

SIGIRR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Enzyme and pathway databases

ReactomeiR-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-9008059 Interleukin-37 signaling

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

EuPathDBiHostDB:ENSG00000185187.12
HGNCiHGNC:30575 SIGIRR
MIMi605478 gene
neXtProtiNX_Q6IA17

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Disulfide bondi32 ↔ 98PROSITE-ProRule annotation
Glycosylationi73N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi86N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi102N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei383PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ6IA17
MaxQBiQ6IA17
PaxDbiQ6IA17
PeptideAtlasiQ6IA17
PRIDEiQ6IA17
ProteomicsDBi66356
66357 [Q6IA17-2]

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
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

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
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR015621 IL-1_rcpt_fam
IPR000157 TIR_dom
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR11890 PTHR11890, 1 hit
PfamiView protein in Pfam
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00255 TIR, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS50104 TIR, 1 hit

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 → Y1 PublicationCorresponds to variant dbSNP:rs117739035Ensembl.1
Natural variantiVAR_074165115P → R1 PublicationCorresponds to variant dbSNP:rs111819059Ensembl.1
Natural variantiVAR_058702312Q → R5 PublicationsCorresponds to variant dbSNP:rs3210908Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiSIGIR_HUMAN
AccessioniPrimary (citable) accession number: Q6IA17
Secondary accession number(s): Q3KQY2, Q6UXI3, Q9H733
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: November 2, 2010
Last modified: June 20, 2018
This is version 133 of the entry and version 3 of the sequence. See 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

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