IL1RL1: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Interleukin 1 receptor-like 1''', also known as '''IL1RL1''' and '''ST2''', is a [[protein]] that in humans is encoded by the ''IL1RL1'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: IL1RL1 interleukin 1 receptor-like 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9173| accessdate = }}</ref><ref name="pmid1482686">{{cite journal |vauthors=Tominaga S, Yokota T, Yanagisawa K, Tsukamoto T, Takagi T, Tetsuka T | title = Nucleotide sequence of a complementary DNA for human ST2 | journal = Biochim. Biophys. Acta | volume = 1171 | issue = 2 | pages = 215–8 |date=December 1992 | pmid = 1482686 | doi = 10.1016/0167-4781(92)90125-j| url = | issn = }}</ref><ref name="pmid10191101">{{cite journal |vauthors=Dale M, Nicklin MJ | title = Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q | journal = Genomics | volume = 57 | issue = 1 | pages = 177–9 |date=April 1999 | pmid = 10191101 | doi = 10.1006/geno.1999.5767 | url = | issn = }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Interleukin 1 receptor-like 1
| HGNCid = 5998
| Symbol = IL1RL1
| AltSymbols =; T1; ST2; DER4; FIT-1; MGC32623; ST2L; ST2V
| OMIM = 601203
| ECnumber = 
| Homologene = 2862
| MGIid = 98427
| GeneAtlas_image1 = PBB_GE_IL1RL1_207526_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004888 |text = transmembrane receptor activity}} {{GNF_GO|id=GO:0004908 |text = interleukin-1 receptor activity}} {{GNF_GO|id=GO:0005057 |text = receptor signaling protein activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005575 |text = cellular_component}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 9173
    | Hs_Ensembl = ENSG00000115602
    | Hs_RefseqProtein = NP_003847
    | Hs_RefseqmRNA = NM_003856
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 2
    | Hs_GenLoc_start = 102294394
    | Hs_GenLoc_end = 102334929
    | Hs_Uniprot = Q01638
    | Mm_EntrezGene = 17082
    | Mm_Ensembl = ENSMUSG00000026069
    | Mm_RefseqmRNA = NM_001025602
    | Mm_RefseqProtein = NP_001020773
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 1
    | Mm_GenLoc_start = 40374143
    | Mm_GenLoc_end = 40409958
    | Mm_Uniprot = Q3UM53
  }}
}}
'''Interleukin 1 receptor-like 1''', also known as '''IL1RL1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: IL1RL1 interleukin 1 receptor-like 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9173| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
IL1RL1 is a member of the [[Toll-like receptor]] superfamily based on the function of its intracelluar TIR domain, but its extracellular region is composed of immunoglobulin domains. Unlike other members of the family IL1RL1 does not induce an inflammatory response through activation of [[NF-κB]], although it does activate [[MAP kinase]]s.<ref name="pmid15004556">{{cite journal |last1=Brint|first1=Elizabeth K|last2=Xu|first2=Damo|last3=Liu|first3=Haiying|last4=Dunne|first4=Aisling|last5=McKenzie|first5=Andrew N J|authorlink5=Andrew N. J. McKenzie|last6=O'Neill|first6=Luke A J|authorlink6=Luke A. J. O'Neill|last7=Liew|first7=Foo Y | title = ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance | journal = [[Nature Immunology]] | volume = 5 | issue = 4 | pages = 373–9 |year=2004 | pmid = 15004556 | doi = 10.1038/ni1050 }}</ref>
{{PBB_Summary
 
| section_title =  
ST2 is a member of the interleukin 1 receptor family. The ST2 protein has two isoforms and is directly implicated in the progression of cardiac disease: a soluble form (referred to as soluble ST2 or sST2) and a membrane-bound receptor form (referred to as the ST2 receptor or ST2L). When the myocardium is stretched, the ST2 gene is upregulated, increasing the concentration of circulating soluble ST2.<ref>{{Cite journal|last=Braunwald|first=Eugene|title=Heart Failure|url=http://linkinghub.elsevier.com/retrieve/pii/S2213177912000078|journal=JACC: Heart Failure|volume=1|issue=1|pages=1–20|doi=10.1016/j.jchf.2012.10.002|year=2013}}</ref> The ligand for ST2 is the cytokine [[Interleukin-33]](IL-33). Binding of IL-33 to the ST2 receptor, in response to cardiac disease or injury, such as an ischemic event, elicits a cardioprotective effect resulting in preserved cardiac function.  This cardioprotective IL-33 signal is counterbalanced by the level of soluble ST2, which binds IL-33 and makes it unavailable to the ST2 receptor for cardioprotective signaling. As a result, the heart is subjected to greater stress in the presence of high levels of soluble ST2.
| summary_text = The protein encoded by this gene is a member of the interleukin 1 receptor family. Studies of the similar gene in mouse suggested that this receptor can be induced by proinflammatory stimuli, and may be involved in the function of helper T cells. This gene, interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2) and interleukin 1 receptor-like 2 (IL1RL2) form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. Alternative splicing of this gene results in multiple transcript variants.<ref name="entrez">{{cite web | title = Entrez Gene: IL1RL1 interleukin 1 receptor-like 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9173| accessdate = }}</ref>
 
}}
== Molecular biology ==
 
The gene is found on the long arm of Chromosome 2 (2q12). It is 40,536 bases long and is located on the Watson (plus) strand. It encodes a protein of 556 amino acids (molecular weight 63,358 Da). Both membrane bound and soluble forms are known. The protein is known to interact with [[MyD88]], [[IRAK1]], [[IRAK4]] and [[TRAF6]]. It appears to be essential for the normal function of T helper cells type 2 (Th2 cells) .
 
==Clinical significance ==
 
Mutations in this gene have been linked to [[atopic dermatitis]] and [[asthma]].
 
The protein encoded by this gene serves as a [[ST2 cardiac biomarker|cardiac biomarker]].


==References==
==References==
{{reflist|2}}
{{reflist|colwidth=35em}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin|colwidth=35em}}
{{PBB_Further_reading
*{{cite journal   |vauthors=Tominaga S, Yokota T, Yanagisawa K, etal |title=Nucleotide sequence of a complementary DNA for human ST2. |journal=Biochim. Biophys. Acta |volume=1171 |issue= 2 |pages= 215–8 |year= 1993 |pmid= 1482686 |doi=  10.1016/0167-4781(92)90125-j}}
| citations =
*{{cite journal   |vauthors=Gayle MA, Slack JL, Bonnert TP, etal |title=Cloning of a putative ligand for the T1/ST2 receptor. |journal=J. Biol. Chem. |volume=271 |issue= 10 |pages= 5784–9 |year= 1996 |pmid= 8621446 |doi=10.1074/jbc.271.10.5784  }}
*{{cite journal | author=Tominaga S, Yokota T, Yanagisawa K, ''et al.'' |title=Nucleotide sequence of a complementary DNA for human ST2. |journal=Biochim. Biophys. Acta |volume=1171 |issue= 2 |pages= 215-8 |year= 1993 |pmid= 1482686 |doi=  }}
*{{cite journal   |vauthors=Yanagisawa K, Naito Y, Kuroiwa K, etal |title=The expression of ST2 gene in helper T cells and the binding of ST2 protein to myeloma-derived RPMI8226 cells. |journal=J. Biochem. |volume=121 |issue= 1 |pages= 95–103 |year= 1997 |pmid= 9058198 |doi=  10.1093/oxfordjournals.jbchem.a021577}}
*{{cite journal | author=Gayle MA, Slack JL, Bonnert TP, ''et al.'' |title=Cloning of a putative ligand for the T1/ST2 receptor. |journal=J. Biol. Chem. |volume=271 |issue= 10 |pages= 5784-9 |year= 1996 |pmid= 8621446 |doi= }}
*{{cite journal  |vauthors=Kumar S, Tzimas MN, Griswold DE, Young PR |title=Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli. |journal=Biochem. Biophys. Res. Commun. |volume=235 |issue= 3 |pages= 474–8 |year= 1997 |pmid= 9207179 |doi= 10.1006/bbrc.1997.6810 }}
*{{cite journal | author=Yanagisawa K, Naito Y, Kuroiwa K, ''et al.'' |title=The expression of ST2 gene in helper T cells and the binding of ST2 protein to myeloma-derived RPMI8226 cells. |journal=J. Biochem. |volume=121 |issue= 1 |pages= 95-103 |year= 1997 |pmid= 9058198 |doi=  }}
*{{cite journal   |vauthors=Löhning M, Stroehmann A, Coyle AJ, etal |title=T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 12 |pages= 6930–5 |year= 1998 |pmid= 9618516 |doi=10.1073/pnas.95.12.6930  | pmc=22690  |bibcode=1998PNAS...95.6930L }}
*{{cite journal  | author=Kumar S, Tzimas MN, Griswold DE, Young PR |title=Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli. |journal=Biochem. Biophys. Res. Commun. |volume=235 |issue= 3 |pages= 474-8 |year= 1997 |pmid= 9207179 |doi= 10.1006/bbrc.1997.6810 }}
*{{cite journal  |vauthors=Moritz DR, Rodewald HR, Gheyselinck J, Klemenz R |title=The IL-1 receptor-related T1 antigen is expressed on immature and mature mast cells and on fetal blood mast cell progenitors. |journal=J. Immunol. |volume=161 |issue= 9 |pages= 4866–74 |year= 1998 |pmid= 9794420 |doi=  }}
*{{cite journal | author=Löhning M, Stroehmann A, Coyle AJ, ''et al.'' |title=T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 12 |pages= 6930-5 |year= 1998 |pmid= 9618516 |doi= }}
*{{cite journal   |vauthors=Saccani S, Polentarutti N, Penton-Rol G, etal |title=Divergent effects of LPS on expression of IL-1 receptor family members in mononuclear phagocytes in vitro and in vivo. |journal=Cytokine |volume=10 |issue= 10 |pages= 773–80 |year= 1999 |pmid= 9811530 |doi= 10.1006/cyto.1998.0359 }}
*{{cite journal  | author=Moritz DR, Rodewald HR, Gheyselinck J, Klemenz R |title=The IL-1 receptor-related T1 antigen is expressed on immature and mature mast cells and on fetal blood mast cell progenitors. |journal=J. Immunol. |volume=161 |issue= 9 |pages= 4866-74 |year= 1998 |pmid= 9794420 |doi=  }}
*{{cite journal  |vauthors=Dale M, Nicklin MJ |title=Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q. |journal=Genomics |volume=57 |issue= 1 |pages= 177–9 |year= 1999 |pmid= 10191101 |doi= 10.1006/geno.1999.5767 }}
*{{cite journal | author=Saccani S, Polentarutti N, Penton-Rol G, ''et al.'' |title=Divergent effects of LPS on expression of IL-1 receptor family members in mononuclear phagocytes in vitro and in vivo. |journal=Cytokine |volume=10 |issue= 10 |pages= 773-80 |year= 1999 |pmid= 9811530 |doi= 10.1006/cyto.1998.0359 }}
*{{cite journal   |vauthors=Iwahana H, Yanagisawa K, Ito-Kosaka A, etal |title=Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells. |journal=Eur. J. Biochem. |volume=264 |issue= 2 |pages= 397–406 |year= 1999 |pmid= 10491084 |doi=10.1046/j.1432-1327.1999.00615.x }}
*{{cite journal  | author=Dale M, Nicklin MJ |title=Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q. |journal=Genomics |volume=57 |issue= 1 |pages= 177-9 |year= 1999 |pmid= 10191101 |doi= 10.1006/geno.1999.5767 }}
*{{cite journal   |vauthors=Tominaga S, Kuroiwa K, Tago K, etal |title=Presence and expression of a novel variant form of ST2 gene product in human leukemic cell line UT-7/GM. |journal=Biochem. Biophys. Res. Commun. |volume=264 |issue= 1 |pages= 14–8 |year= 1999 |pmid= 10527832 |doi= 10.1006/bbrc.1999.1469 }}
*{{cite journal | author=Iwahana H, Yanagisawa K, Ito-Kosaka A, ''et al.'' |title=Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells. |journal=Eur. J. Biochem. |volume=264 |issue= 2 |pages= 397-406 |year= 1999 |pmid= 10491084 |doi=  }}
*{{cite journal   |vauthors=Li H, Tago K, Io K, etal |title=The cloning and nucleotide sequence of human ST2L cDNA. |journal=Genomics |volume=67 |issue= 3 |pages= 284–90 |year= 2000 |pmid= 10936050 |doi= 10.1006/geno.2000.6269 }}
*{{cite journal | author=Tominaga S, Kuroiwa K, Tago K, ''et al.'' |title=Presence and expression of a novel variant form of ST2 gene product in human leukemic cell line UT-7/GM. |journal=Biochem. Biophys. Res. Commun. |volume=264 |issue= 1 |pages= 14-8 |year= 1999 |pmid= 10527832 |doi= 10.1006/bbrc.1999.1469 }}
*{{cite journal  |vauthors=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=10.1101/gr.143000  | pmc=310948 }}
*{{cite journal | author=Li H, Tago K, Io K, ''et al.'' |title=The cloning and nucleotide sequence of human ST2L cDNA. |journal=Genomics |volume=67 |issue= 3 |pages= 284-90 |year= 2000 |pmid= 10936050 |doi= 10.1006/geno.2000.6269 }}
*{{cite journal   |vauthors=Sweet MJ, Leung BP, Kang D, etal |title=A novel pathway regulating lipopolysaccharide-induced shock by ST2/T1 via inhibition of Toll-like receptor 4 expression. |journal=J. Immunol. |volume=166 |issue= 11 |pages= 6633–9 |year= 2001 |pmid= 11359817 |doi=  10.4049/jimmunol.166.11.6633}}
*{{cite journal  | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi=  }}
*{{cite journal   |vauthors=Tago K, Noda T, Hayakawa M, etal |title=Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V. |journal=Biochem. Biophys. Res. Commun. |volume=285 |issue= 5 |pages= 1377–83 |year= 2001 |pmid= 11478810 |doi= 10.1006/bbrc.2001.5306 }}
*{{cite journal | author=Sweet MJ, Leung BP, Kang D, ''et al.'' |title=A novel pathway regulating lipopolysaccharide-induced shock by ST2/T1 via inhibition of Toll-like receptor 4 expression. |journal=J. Immunol. |volume=166 |issue= 11 |pages= 6633-9 |year= 2001 |pmid= 11359817 |doi=  }}
*{{cite journal   |vauthors=Lécart S, Lecointe N, Subramaniam A, etal |title=Activated, but not resting human Th2 cells, in contrast to Th1 and T regulatory cells, produce soluble ST2 and express low levels of ST2L at the cell surface. |journal=Eur. J. Immunol. |volume=32 |issue= 10 |pages= 2979–87 |year= 2002 |pmid= 12355452 |doi= 10.1002/1521-4141(2002010)32:10<2979::AID-IMMU2979>3.0.CO;2-5 }}
*{{cite journal | author=Tago K, Noda T, Hayakawa M, ''et al.'' |title=Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V. |journal=Biochem. Biophys. Res. Commun. |volume=285 |issue= 5 |pages= 1377-83 |year= 2001 |pmid= 11478810 |doi= 10.1006/bbrc.2001.5306 }}
*{{cite journal   |vauthors=Brint EK, Fitzgerald KA, Smith P, etal |title=Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction. |journal=J. Biol. Chem. |volume=277 |issue= 51 |pages= 49205–11 |year= 2003 |pmid= 12368275 |doi= 10.1074/jbc.M209685200 }}
*{{cite journal | author=Lécart S, Lecointe N, Subramaniam A, ''et al.'' |title=Activated, but not resting human Th2 cells, in contrast to Th1 and T regulatory cells, produce soluble ST2 and express low levels of ST2L at the cell surface. |journal=Eur. J. Immunol. |volume=32 |issue= 10 |pages= 2979-87 |year= 2002 |pmid= 12355452 |doi= 10.1002/1521-4141(2002010)32:10<2979::AID-IMMU2979>3.0.CO;2-5 }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M }}
*{{cite journal | author=Brint EK, Fitzgerald KA, Smith P, ''et al.'' |title=Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction. |journal=J. Biol. Chem. |volume=277 |issue= 51 |pages= 49205-11 |year= 2003 |pmid= 12368275 |doi= 10.1074/jbc.M209685200 }}
*{{cite journal   |vauthors=Haga Y, Yanagisawa K, Ohto-Ozaki H, etal |title=The effect of ST2 gene product on anchorage-independent growth of a glioblastoma cell line, T98G. |journal=Eur. J. Biochem. |volume=270 |issue= 1 |pages= 163–70 |year= 2003 |pmid= 12492487 |doi=10.1046/j.1432-1033.2003.03377.x }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Weinberg EO, Shimpo M, Hurwitz S, etal |title=Identification of serum soluble ST2 receptor as a novel heart failure biomarker. |journal=Circulation |volume=107 |issue= 5 |pages= 721–6 |year= 2003 |pmid= 12578875 |doi=10.1161/01.CIR.0000047274.66749.FE }}
*{{cite journal | author=Haga Y, Yanagisawa K, Ohto-Ozaki H, ''et al.'' |title=The effect of ST2 gene product on anchorage-independent growth of a glioblastoma cell line, T98G. |journal=Eur. J. Biochem. |volume=270 |issue= 1 |pages= 163-70 |year= 2003 |pmid= 12492487 |doi=  }}
*{{cite journal   |vauthors=Gevaert K, Goethals M, Martens L, etal |title=Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. |journal=Nat. Biotechnol. |volume=21 |issue= 5 |pages= 566–9 |year= 2004 |pmid= 12665801 |doi= 10.1038/nbt810 }}
*{{cite journal | author=Weinberg EO, Shimpo M, Hurwitz S, ''et al.'' |title=Identification of serum soluble ST2 receptor as a novel heart failure biomarker. |journal=Circulation |volume=107 |issue= 5 |pages= 721-6 |year= 2003 |pmid= 12578875 |doi=  }}
*{{cite journal | author=Gevaert K, Goethals M, Martens L, ''et al.'' |title=Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. |journal=Nat. Biotechnol. |volume=21 |issue= 5 |pages= 566-9 |year= 2004 |pmid= 12665801 |doi= 10.1038/nbt810 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{Cytokine receptors}}
{{WikiDoc Sources}}
{{Interleukin receptor modulators}}
 
 
{{gene-2-stub}}

Latest revision as of 23:48, 31 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Interleukin 1 receptor-like 1, also known as IL1RL1 and ST2, is a protein that in humans is encoded by the IL1RL1 gene.[1][2][3]

Function

IL1RL1 is a member of the Toll-like receptor superfamily based on the function of its intracelluar TIR domain, but its extracellular region is composed of immunoglobulin domains. Unlike other members of the family IL1RL1 does not induce an inflammatory response through activation of NF-κB, although it does activate MAP kinases.[4]

ST2 is a member of the interleukin 1 receptor family. The ST2 protein has two isoforms and is directly implicated in the progression of cardiac disease: a soluble form (referred to as soluble ST2 or sST2) and a membrane-bound receptor form (referred to as the ST2 receptor or ST2L). When the myocardium is stretched, the ST2 gene is upregulated, increasing the concentration of circulating soluble ST2.[5] The ligand for ST2 is the cytokine Interleukin-33(IL-33). Binding of IL-33 to the ST2 receptor, in response to cardiac disease or injury, such as an ischemic event, elicits a cardioprotective effect resulting in preserved cardiac function. This cardioprotective IL-33 signal is counterbalanced by the level of soluble ST2, which binds IL-33 and makes it unavailable to the ST2 receptor for cardioprotective signaling. As a result, the heart is subjected to greater stress in the presence of high levels of soluble ST2.

Molecular biology

The gene is found on the long arm of Chromosome 2 (2q12). It is 40,536 bases long and is located on the Watson (plus) strand. It encodes a protein of 556 amino acids (molecular weight 63,358 Da). Both membrane bound and soluble forms are known. The protein is known to interact with MyD88, IRAK1, IRAK4 and TRAF6. It appears to be essential for the normal function of T helper cells type 2 (Th2 cells) .

Clinical significance

Mutations in this gene have been linked to atopic dermatitis and asthma.

The protein encoded by this gene serves as a cardiac biomarker.

References

  1. ↑ "Entrez Gene: IL1RL1 interleukin 1 receptor-like 1".
  2. ↑ Tominaga S, Yokota T, Yanagisawa K, Tsukamoto T, Takagi T, Tetsuka T (December 1992). "Nucleotide sequence of a complementary DNA for human ST2". Biochim. Biophys. Acta. 1171 (2): 215–8. doi:10.1016/0167-4781(92)90125-j. PMID 1482686.
  3. ↑ Dale M, Nicklin MJ (April 1999). "Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q". Genomics. 57 (1): 177–9. doi:10.1006/geno.1999.5767. PMID 10191101.
  4. ↑ Brint, Elizabeth K; Xu, Damo; Liu, Haiying; Dunne, Aisling; McKenzie, Andrew N J; O'Neill, Luke A J; Liew, Foo Y (2004). "ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance". Nature Immunology. 5 (4): 373–9. doi:10.1038/ni1050. PMID 15004556.
  5. ↑ Braunwald, Eugene (2013). "Heart Failure". JACC: Heart Failure. 1 (1): 1–20. doi:10.1016/j.jchf.2012.10.002.

Further reading


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