Q6IA17 (SIGIR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SIGIRR
ORF Names:	UNQ301/PRO342

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	410 AA.
Sequence status	Complete.
Protein existence	Evidence 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.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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Signal-anchor Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	acute-phase response Inferred from sequence or structural similarity. Source: HGNC innate immune response Inferred from electronic annotation. Source: InterPro negative regulation of chemokine biosynthetic process Inferred from sequence or structural similarity. Source: HGNC negative regulation of cytokine-mediated signaling pathway Inferred from sequence or structural similarity. Source: HGNC negative regulation of lipopolysaccharide-mediated signaling pathway Traceable author statement Ref.9. Source: HGNC negative regulation of sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype Ref.8. Source: HGNC
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intracellular Inferred from electronic annotation. Source: InterPro
Molecular function	protein binding Inferred from physical interaction Ref.8Ref.11. Source: UniProtKB transmembrane signaling receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 410	410	Single Ig IL-1-related receptor		PRO_0000099065
Regions
	Topological domain	1 – 118	118	Extracellular Potential
	Transmembrane	119 – 139	21	Helical; Signal-anchor for type III membrane protein; Potential
	Topological domain	140 – 410	271	Cytoplasmic Potential
	Domain	9 – 109	101	Ig-like C2-type
	Domain	163 – 310	148	TIR
Amino acid modifications
	Modified residue	380	1	Phosphoserine By similarity
	Glycosylation	31	1	N-linked (GlcNAc...) Potential
	Glycosylation	73	1	N-linked (GlcNAc...) Potential
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	102	1	N-linked (GlcNAc...) Potential
	Disulfide bond	32 ↔ 98		By similarity
Natural variations
	Alternative sequence	358 – 410	53	VRGPV…SKDDM → MPAQPHSPTGEAQHRAEWGQ AQGTGPGGALGVEDSSRHRE PLHGLCPGGARPSVCLGTSW ASQAITAGGEQGQPLAVGLG QGCGWPPQASRSPHPRCPGA CFWRAISSTAHQWGLAGREP EQRSGRLGSRLAKLQCPHRL LLPGVQG in isoform 2.		VSP_015717
	Natural variant	312	1	Q → R. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs3210908 [ dbSNP | Ensembl ].		VAR_058702
Experimental info
	Sequence conflict	410	1	M → I in CAG33619. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: BA4564C2ABAB5104	FASTA	410	45,679
	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
	Isoform 2 [UniParc]. Checksum: 1DC974BAC4EC4D2A	FASTA	504	55,271
	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 DPEGDLGMPA 370 380 390 400 410 420 QPHSPTGEAQ HRAEWGQAQG TGPGGALGVE DSSRHREPLH GLCPGGARPS VCLGTSWASQ 430 440 450 460 470 480 AITAGGEQGQ PLAVGLGQGC GWPPQASRSP HPRCPGACFW RAISSTAHQW GLAGREPEQR 490 500 SGRLGSRLAK LQCPHRLLLP GVQG

References

	« Hide 'large scale' referencesShow '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. , 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: 12975309] [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. , 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: 14702039] [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. , 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: 16554811] [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: 15489334] [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: 10346978] [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: 14715412] [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: 12925853] [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: 15866876] [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: 21077278] [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: 21187075] [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.
IPI	IPI00029155. IPI00432567.
RefSeq	NP_001128525.1. NM_001135053.1. NP_001128526.1. NM_001135054.1. NP_068577.2. NM_021805.2.
UniGene	Hs.501624.
3D structure databases
ProteinModelPortal	Q6IA17.
SMR	Q6IA17. Positions 18-105, 163-309.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6IA17. 3 interactions.
MINT	MINT-1430901.
STRING	Q6IA17.
PTM databases
PhosphoSite	Q6IA17.
Polymorphism databases
DMDM	311033538.
Proteomic databases
PRIDE	Q6IA17.
Protocols and materials databases
DNASU	59307.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000332725; ENSP00000333656; ENSG00000185187. ENST00000397632; ENSP00000380756; ENSG00000185187. ENST00000431843; ENSP00000403104; ENSG00000185187.
GeneID	59307.
KEGG	hsa:59307.
UCSC	uc001lpd.2. human.
Organism-specific databases
CTD	59307.
GeneCards	GC11M000395.
H-InvDB	HIX0021476.
HGNC	HGNC:30575. SIGIRR.
HPA	HPA023188.
MIM	605478. gene.
neXtProt	NX_Q6IA17.
PharmGKB	PA142670915.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG39004.
GeneTree	ENSGT00630000089663.
HOGENOM	HOG000237348.
HOVERGEN	HBG080781.
KO	K05169.
OrthoDB	EOG4RR6HQ.
PhylomeDB	Q6IA17.
Gene expression databases
ArrayExpress	Q6IA17.
Bgee	Q6IA17.
CleanEx	HS_SIGIRR.
Genevestigator	Q6IA17.
GermOnline	ENSG00000185187. Homo sapiens.
Family and domain databases
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
InterPro	IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR015621. IL1-receptor. IPR004075. IL1_rcpt_1. IPR000157. TIR_dom. [Graphical view]
PANTHER	PTHR11890. IL1-receptor. 1 hit.
Pfam	PF01582. TIR. 1 hit. [Graphical view]
PRINTS	PR01537. INTRLKN1R1F.
SUPFAM	SSF52200. TIR. 1 hit.
PROSITE	PS50835. IG_LIKE. 1 hit. PS50104. TIR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	65192.
SOURCE	Search...

Entry information

Entry name

SIGIR_HUMAN

Accession

Primary (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 16, 2012
This is version 85 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.