ILRL2_MOUSE
ID ILRL2_MOUSE Reviewed; 574 AA.
AC Q9ERS7;
DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Interleukin-1 receptor-like 2;
DE EC=3.2.2.6 {ECO:0000255|PROSITE-ProRule:PRU00204};
DE AltName: Full=IL-36 receptor;
DE AltName: Full=Interleukin-1 receptor-related protein 2;
DE Short=IL-1Rrp2;
DE Short=IL1R-rp2;
DE Flags: Precursor;
GN Name=Il1rl2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10882729; DOI=10.1074/jbc.m004077200;
RA Born T.L., Smith D.E., Garka K.E., Renshaw B.R., Bertles J.S., Sims J.E.;
RT "Identification and characterization of two members of a novel class of the
RT interleukin-1 receptor (IL-1R) family. Delineation of a new class of IL-1R-
RT related proteins based on signaling.";
RL J. Biol. Chem. 275:29946-29954(2000).
RN [2]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21860022; DOI=10.1182/blood-2011-05-356873;
RA Vigne S., Palmer G., Lamacchia C., Martin P., Talabot-Ayer D.,
RA Rodriguez E., Ronchi F., Sallusto F., Dinh H., Sims J.E., Gabay C.;
RT "IL-36R ligands are potent regulators of dendritic and T cells.";
RL Blood 118:5813-5823(2011).
RN [3]
RP INTERACTION WITH IL1RAP.
RX PubMed=21965679; DOI=10.1074/jbc.m111.267922;
RA Towne J.E., Renshaw B.R., Douangpanya J., Lipsky B.P., Shen M., Gabel C.A.,
RA Sims J.E.;
RT "Interleukin-36 (IL-36) ligands require processing for full agonist (IL-
RT 36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity.";
RL J. Biol. Chem. 286:42594-42602(2011).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23064362; DOI=10.1172/jci63451;
RA Tortola L., Rosenwald E., Abel B., Blumberg H., Schafer M., Coyle A.J.,
RA Renauld J.C., Werner S., Kisielow J., Kopf M.;
RT "Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte
RT crosstalk.";
RL J. Clin. Invest. 122:3965-3976(2012).
CC -!- FUNCTION: Receptor for interleukin-36 (IL36A, IL36B and IL36G). After
CC binding to interleukin-36 associates with the coreceptor IL1RAP to form
CC the interleukin-36 receptor complex which mediates interleukin-36-
CC dependent activation of NF-kappa-B, MAPK and other pathways. The IL-36
CC signaling system is thought to be present in epithelial barriers and to
CC take part in local inflammatory response; it is similar to the IL-1
CC system. Seems to be involved in skin inflammatory response by induction
CC of the IL-23/IL-17/IL-22 pathway. {ECO:0000269|PubMed:21860022,
CC ECO:0000269|PubMed:23064362}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC -!- SUBUNIT: Interacts with IL1RAP; the association is enhanced by IL36B
CC indicative for an functional signaling complex and inhibited by IL36RN.
CC {ECO:0000269|PubMed:21965679}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow-derived dendritic cells,
CC splenic CD4(+) T-cells, bone marrow-derived macrophages and bone
CC marrow-derived neutrophils. {ECO:0000269|PubMed:21860022}.
CC -!- DOMAIN: The TIR domain mediates NAD(+) hydrolase (NADase) activity.
CC Self-association of TIR domains is required for NADase activity.
CC {ECO:0000255|PROSITE-ProRule:PRU00204}.
CC -!- DISRUPTION PHENOTYPE: Complete protection from imiquimodum (IMQ)-
CC induced skin pathology observed in wild-type mice, including
CC hyperkeratosis, acanthosis, neutrophil recruitment, and expansion of
CC IL-17-producing T-cells. {ECO:0000269|PubMed:23064362}.
CC -!- SIMILARITY: Belongs to the interleukin-1 receptor family.
CC {ECO:0000305}.
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DR EMBL; AF284433; AAG21367.1; -; mRNA.
DR CCDS; CCDS14910.1; -.
DR RefSeq; NP_573456.1; NM_133193.3.
DR RefSeq; XP_006495671.1; XM_006495608.3.
DR RefSeq; XP_006495672.1; XM_006495609.3.
DR RefSeq; XP_006495673.1; XM_006495610.3.
DR RefSeq; XP_006495674.1; XM_006495611.3.
DR AlphaFoldDB; Q9ERS7; -.
DR SMR; Q9ERS7; -.
DR STRING; 10090.ENSMUSP00000092630; -.
DR GlyGen; Q9ERS7; 9 sites.
DR iPTMnet; Q9ERS7; -.
DR PhosphoSitePlus; Q9ERS7; -.
DR PaxDb; Q9ERS7; -.
DR PRIDE; Q9ERS7; -.
DR ProteomicsDB; 267331; -.
DR Antibodypedia; 2361; 238 antibodies from 33 providers.
DR DNASU; 107527; -.
DR Ensembl; ENSMUST00000095020; ENSMUSP00000092630; ENSMUSG00000070942.
DR Ensembl; ENSMUST00000194296; ENSMUSP00000142248; ENSMUSG00000070942.
DR GeneID; 107527; -.
DR KEGG; mmu:107527; -.
DR UCSC; uc007atx.1; mouse.
DR CTD; 8808; -.
DR MGI; MGI:1913107; Il1rl2.
DR VEuPathDB; HostDB:ENSMUSG00000070942; -.
DR eggNOG; ENOG502QWEU; Eukaryota.
DR GeneTree; ENSGT01050000244846; -.
DR HOGENOM; CLU_025552_3_0_1; -.
DR InParanoid; Q9ERS7; -.
DR OMA; FEKQWCD; -.
DR OrthoDB; 1109920at2759; -.
DR PhylomeDB; Q9ERS7; -.
DR TreeFam; TF325519; -.
DR Reactome; R-MMU-9007892; Interleukin-38 signaling.
DR Reactome; R-MMU-9014826; Interleukin-36 pathway.
DR BioGRID-ORCS; 107527; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Il1rl2; mouse.
DR PRO; PR:Q9ERS7; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9ERS7; protein.
DR Bgee; ENSMUSG00000070942; Expressed in lip and 122 other tissues.
DR ExpressionAtlas; Q9ERS7; baseline and differential.
DR Genevisible; Q9ERS7; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004896; F:cytokine receptor activity; ISS:MGI.
DR GO; GO:0004909; F:interleukin-1, type I, activating receptor activity; IEA:InterPro.
DR GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IGI:MGI.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IMP:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:MGI.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.40.50.10140; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR015621; IL-1_rcpt_fam.
DR InterPro; IPR004076; IL-1_rcpt_I-typ.
DR InterPro; IPR004074; IL-1_rcpt_I/II-typ.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR11890; PTHR11890; 1.
DR Pfam; PF13895; Ig_2; 2.
DR Pfam; PF01582; TIR; 1.
DR PRINTS; PR01538; INTRLEUKN1R1.
DR PRINTS; PR01536; INTRLKN1R12F.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 2.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Hydrolase; Immunity; Immunoglobulin domain;
KW Inflammatory response; Innate immunity; Membrane; NAD; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..574
FT /note="Interleukin-1 receptor-like 2"
FT /id="PRO_0000015446"
FT TOPO_DOM 22..338
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 360..574
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..113
FT /note="Ig-like C2-type 1"
FT DOMAIN 132..215
FT /note="Ig-like C2-type 2"
FT DOMAIN 225..321
FT /note="Ig-like C2-type 3"
FT DOMAIN 384..539
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT ACT_SITE 470
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 269
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 149..199
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 252..319
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 574 AA; 65108 MW; A677A77BBFA50A76 CRC64;
MGVTSLLFCG VFFLLLLFVA ADTCEDIFMH NVIISEGQPF PFNCTYPPET NGAVNLTWYK
TPSKSPVSNN RHLRVHQDQT WILFLPLTLE DSGIYQCVIR NAHNCYQIAV NLTVLKNHWC
DSSMEGSPVN SPDVYQQILP IGKSGSLNCH LYFPESCALD SIKWYKGCEE IKAGKKYSPS
GAKLLVNNVA VEDGGSYACS ARLTHLGRHF TIRNYIAVNT KEVEYGRRIP NITYPKNNSI
EVPLGSTLIV NCNITDTKEN TNLRCWRVNN TLVDDYYKDS KRIQEGIETN VSLRDQIRYT
VNITFLKVKM EDYGRPFTCH AGVSAAYIIL IYPVPDFRAY LLGGLMAFLL LVVSVLFIYN
SFKIDIMLWY RSAFHTAQAP DDEKLYDAYV LYPKYPRGSQ GHDVDTLVLK ILPEVLEKQC
GYKLFIFGRD EFPGQAVASV IDENIKLCRR LMVFVAPESS SFGFLKNLSE EQIAVYNALI
QHGMKVILIE LEKVKDYSTM PESIQYIRQK HGAIQWDGDF TEQSQCAKTK FWKKVRYHMP
PRRYPASSPV QLLGHIPCNC KAGKCNAATG LITP
