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    SIGIRR single Ig and TIR domain containing [ Homo sapiens (human) ]

    Gene ID: 59307, updated on 28-Oct-2024

    Summary

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    Official Symbol
    SIGIRRprovided by HGNC
    Official Full Name
    single Ig and TIR domain containingprovided by HGNC
    Primary source
    HGNC:HGNC:30575
    See related
    Ensembl:ENSG00000185187 MIM:605478; AllianceGenome:HGNC:30575
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TIR8; IL-1R8
    Summary
    Involved in negative regulation of Toll signaling pathway. Located in membrane. [provided by Alliance of Genome Resources, Oct 2024]
    Expression
    Ubiquitous expression in spleen (RPKM 19.3), kidney (RPKM 16.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SIGIRR in Genome Data Viewer
    Location:
    11p15.5
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (405716..417397, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (451081..462850, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (405716..417397, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene beta-1,4-N-acetyl-galactosaminyltransferase 4 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:380111-380268 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:393662-394424 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:396383-396912 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:405522-406215 Neighboring gene plakophilin 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2998 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2999 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3000 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:415472-416091 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3001 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3002 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3003 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3004 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:420870-421731 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:428546-429745 Neighboring gene anoctamin 9 Neighboring gene uncharacterized LOC105376506 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:434102-434620 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3005 Neighboring gene Sharpr-MPRA regulatory region 223 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:442612-443409 Neighboring gene RNA, 7SL, cytoplasmic 838, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4275 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3006 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3007 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:449779-450465 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3009 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3010 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:454927-455648 Neighboring gene phosphatidylserine synthase 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:460662-460845 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:467161-467660 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:471334-471857 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:471858-472380 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:476893-477888 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:484337-484858 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:487868-488008

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. SIGIRR genetic variants in premature infants with necrotizing enterocolitis. Sampath V, et al. Pediatrics, 2015 Jun. PMID 25963006, Free PMC Article
    2. Characterization of a long isoform of IL-1R8 (TIR8/SIGIRR). Vilia MG, et al. Eur Cytokine Netw, 2017 Jun 1. PMID 28840837
    3. SIGIRR/TIR-8 is an inhibitor of Toll-like receptor signaling in primary human cells and regulates inflammation in models of rheumatoid arthritis. Drexler SK, et al. Arthritis Rheum, 2010 Aug. PMID 20506350
    4. High IL-1R8 expression in breast tumors promotes tumor growth and contributes to impaired antitumor immunity. Campesato LF, et al. Oncotarget, 2017 Jul 25. PMID 28533483, Free PMC Article
    5. SIGIRR participates in negative regulation of LPS response and tolerance in human bladder epithelial cells. Li D, et al. BMC Immunol, 2015 Dec 3. PMID 26634342, Free PMC Article

    See all (55) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. IL-1R8: A molecular brake of anti-tumor and anti-viral activity of NK cells and ILC.
      Title: IL-1R8: A molecular brake of anti-tumor and anti-viral activity of NK cells and ILC.
    2. SIGIRR Mutation in Human Necrotizing Enterocolitis (NEC) Disrupts STAT3-Dependent microRNA Expression in Neonatal Gut.
      Title: SIGIRR Mutation in Human Necrotizing Enterocolitis (NEC) Disrupts STAT3-Dependent microRNA Expression in Neonatal Gut.
    3. IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway.
      Title: IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway.
    4. Single Immunoglobulin IL-1-Related Receptor (SIGIRR) Gene rs7396562 Polymorphism and Expression Level in Rheumatoid Arthritis.
      Title: Single Immunoglobulin IL-1-Related Receptor (SIGIRR) Gene rs7396562 Polymorphism and Expression Level in Rheumatoid Arthritis.
    5. IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8.
      Title: IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8.
    6. Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro.
      Title: Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro.
    7. MiR-340 suppresses CCl4-induced acute liver injury through exerting anti-inflammation targeting Sigirr.
      Title: MiR-340 suppresses CCl4-induced acute liver injury through exerting anti-inflammation targeting Sigirr.
    8. Single immunoglobulin and Tollinterleukin1 receptor domain containing molecule protects against severe acute pancreatitis in vitro by negatively regulating the Tolllike receptor4 signaling pathway: A clinical and experimental study.
      Title: Single immunoglobulin and Toll‑interleukin‑1 receptor domain containing molecule protects against severe acute pancreatitis in vitro by negatively regulating the Toll‑like receptor‑4 signaling pathway: A clinical and experimental study.
    9. The anti-inflammatory IL-37/SIGIRR axis is functionally compromised in HIV infection.
      Title: The anti-inflammatory IL-37/SIGIRR axis is functionally compromised in HIV infection.
    10. Immune response against Chlamydia trachomatis via toll-like receptors is negatively regulated by SIGIRR
      Title: Immune response against Chlamydia trachomatis via toll-like receptors is negatively regulated by SIGIRR.
    Submit: New GeneRIF Correction See all GeneRIFs (36)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC110992

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in acute-phase response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cell surface receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of Toll signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of chemokine production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of cytokine-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of interleukin-1-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of lipopolysaccharide-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cell surface IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    single Ig IL-1-related receptor
    Names
    single Ig IL-1R-related molecule
    single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
    single immunoglobulin domain IL1R1 related
    single immunoglobulin domain-containing IL1R-related protein
    toll/interleukin-1 receptor 8

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001135053.2 → NP_001128525.1  single Ig IL-1-related receptor

      See identical proteins and their annotated locations for NP_001128525.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. All three variants encode the same protein.
      Source sequence(s)
      AK025099, AK172830, BX369506, DA963481
      Consensus CDS
      CCDS31325.1
      UniProtKB/Swiss-Prot
      Q3KQY2, Q6IA17, Q6UXI3, Q9H733
      UniProtKB/TrEMBL
      E9PK23
      Related
      ENSP00000380756.3, ENST00000397632.7
      Conserved Domains (2) summary
      pfam01582
      Location:165 → 311
      TIR; TIR domain
      cl11960
      Location:8 → 111
      Ig; Immunoglobulin domain

    2. NM_001135054.2 → NP_001128526.1  single Ig IL-1-related receptor

      See identical proteins and their annotated locations for NP_001128526.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. All three variants encode the same protein.
      Source sequence(s)
      AK025099, AK172830, BX369506, DB112269
      Consensus CDS
      CCDS31325.1
      UniProtKB/Swiss-Prot
      Q3KQY2, Q6IA17, Q6UXI3, Q9H733
      UniProtKB/TrEMBL
      E9PK23
      Related
      ENSP00000403104.2, ENST00000431843.7
      Conserved Domains (2) summary
      pfam01582
      Location:165 → 311
      TIR; TIR domain
      cl11960
      Location:8 → 111
      Ig; Immunoglobulin domain

    3. NM_021805.3 → NP_068577.2  single Ig IL-1-related receptor

      See identical proteins and their annotated locations for NP_068577.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. All three variants encode the same protein.
      Source sequence(s)
      AK025099, AK172830, BX369506
      Consensus CDS
      CCDS31325.1
      UniProtKB/Swiss-Prot
      Q3KQY2, Q6IA17, Q6UXI3, Q9H733
      UniProtKB/TrEMBL
      E9PK23
      Related
      ENSP00000333656.3, ENST00000332725.7
      Conserved Domains (2) summary
      pfam01582
      Location:165 → 311
      TIR; TIR domain
      cl11960
      Location:8 → 111
      Ig; Immunoglobulin domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      405716..417397 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047427388.1 → XP_047283344.1  single Ig IL-1-related receptor isoform X2

      UniProtKB/TrEMBL
      H0YDR5
      Related
      ENSP00000434164.2, ENST00000528845.6

    2. XM_005253045.1 → XP_005253102.1  single Ig IL-1-related receptor isoform X1

      See identical proteins and their annotated locations for XP_005253102.1

      UniProtKB/TrEMBL
      A0A291NLA3, C9JFX4
      Related
      ENSP00000433022.1, ENST00000531205.5
      Conserved Domains (2) summary
      pfam01582
      Location:165 → 311
      TIR; TIR domain
      cl11960
      Location:8 → 111
      Ig; Immunoglobulin domain

    3. XM_047427387.1 → XP_047283343.1  single Ig IL-1-related receptor isoform X2

      UniProtKB/TrEMBL
      H0YDR5

    4. XM_005253046.2 → XP_005253103.1  single Ig IL-1-related receptor isoform X1

      See identical proteins and their annotated locations for XP_005253103.1

      UniProtKB/TrEMBL
      A0A291NLA3, C9JFX4
      Conserved Domains (2) summary
      pfam01582
      Location:165 → 311
      TIR; TIR domain
      cl11960
      Location:8 → 111
      Ig; Immunoglobulin domain

    5. XM_047427389.1 → XP_047283345.1  single Ig IL-1-related receptor isoform X3

      UniProtKB/TrEMBL
      H0YDF8
      Related
      ENSP00000433530.2, ENST00000526395.6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      451081..462850 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369598.1 → XP_054225573.1  single Ig IL-1-related receptor isoform X2

      UniProtKB/TrEMBL
      H0YDR5

    2. XM_054369596.1 → XP_054225571.1  single Ig IL-1-related receptor isoform X1

      UniProtKB/TrEMBL
      C9JFX4

    3. XM_054369597.1 → XP_054225572.1  single Ig IL-1-related receptor isoform X2

      UniProtKB/TrEMBL
      H0YDR5

    4. XM_054369595.1 → XP_054225570.1  single Ig IL-1-related receptor isoform X1

      UniProtKB/TrEMBL
      C9JFX4

    5. XM_054369599.1 → XP_054225574.1  single Ig IL-1-related receptor isoform X3

      UniProtKB/TrEMBL
      H0YDF8
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6IA17.3 GenPept UniProtKB/Swiss-Prot:Q6IA17

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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