ILRL2_HUMAN
ID ILRL2_HUMAN Reviewed; 575 AA.
AC Q9HB29; A4FU63; Q13525; Q45H74; Q53TU8; Q587I8;
DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 171.
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 Short=IL-36R;
DE AltName: Full=Interleukin-1 receptor-related protein 2;
DE Short=IL-1Rrp2;
DE Short=IL1R-rp2;
DE Flags: Precursor;
GN Name=IL1RL2; Synonyms=IL1RRP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8898719; DOI=10.1016/s0165-5728(96)00047-1;
RA Lovenberg T.W., Crowe P.D., Liu C., Chalmers D.T., Liu X.-J., Liaw C.,
RA Clevenger W., Oltersdorf T., De Souza E.B., Maki R.A.;
RT "Cloning of a cDNA encoding a novel interleukin-1 receptor related protein
RT (IL1R-rp2).";
RL J. Neuroimmunol. 70:113-122(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-352 AND PRO-550.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION AS RECEPTOR FOR IL36G.
RX PubMed=11466363; DOI=10.4049/jimmunol.167.3.1440;
RA Debets R., Timans J.C., Homey B., Zurawski S., Sana T.R., Lo S., Wagner J.,
RA Edwards G., Clifford T., Menon S., Bazan J.F., Kastelein R.A.;
RT "Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an
RT antagonist and agonist of NF-kappa B activation through the orphan IL-1
RT receptor-related protein 2.";
RL J. Immunol. 167:1440-1446(2001).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=16646978; DOI=10.1186/ar1946;
RA Magne D., Palmer G., Barton J.L., Mezin F., Talabot-Ayer D., Bas S.,
RA Duffy T., Noger M., Guerne P.A., Nicklin M.J., Gabay C.;
RT "The new IL-1 family member IL-1F8 stimulates production of inflammatory
RT mediators by synovial fibroblasts and articular chondrocytes.";
RL Arthritis Res. Ther. 8:R80-R80(2006).
RN [8]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=24829417; DOI=10.4049/jimmunol.1301481;
RA Foster A.M., Baliwag J., Chen C.S., Guzman A.M., Stoll S.W.,
RA Gudjonsson J.E., Ward N.L., Johnston A.;
RT "IL-36 promotes myeloid cell infiltration, activation, and inflammatory
RT activity in skin.";
RL J. Immunol. 192:6053-6061(2014).
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 (By
CC similarity). The IL-36 signaling system is thought to be present in
CC epithelial barriers and to take part in local inflammatory response; it
CC is similar to the IL-1 system. Seems to be involved in skin
CC inflammatory response by induction of the IL-23/IL-17/IL-22 pathway.
CC {ECO:0000250|UniProtKB:Q9ERS7, ECO:0000269|PubMed:11466363}.
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 (By similarity). {ECO:0000250|UniProtKB:Q9ERS7}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:24829417}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HB29-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HB29-2; Sequence=VSP_056292, VSP_056293, VSP_056294;
CC -!- TISSUE SPECIFICITY: Expressed in synovial fibroblasts and articular
CC chondrocytes. Expressed in keratinocytes and monocyte-derived dendritic
CC cells. Expressed in monocytes and myeloid dendritic cells; at protein
CC level. {ECO:0000269|PubMed:16646978, ECO:0000269|PubMed:24829417}.
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 -!- SIMILARITY: Belongs to the interleukin-1 receptor family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB53237.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il1rl2/";
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DR EMBL; AF284434; AAG21368.1; -; mRNA.
DR EMBL; U49065; AAB53237.1; ALT_FRAME; mRNA.
DR EMBL; DQ131903; AAZ38712.1; -; Genomic_DNA.
DR EMBL; AC007271; AAX81989.1; -; Genomic_DNA.
DR EMBL; AC007248; AAY15046.1; -; Genomic_DNA.
DR EMBL; BC107064; AAI07065.1; -; mRNA.
DR CCDS; CCDS2056.1; -. [Q9HB29-1]
DR CCDS; CCDS86867.1; -. [Q9HB29-2]
DR PIR; G02426; G02426.
DR RefSeq; NP_003845.2; NM_003854.2. [Q9HB29-1]
DR RefSeq; XP_005264093.1; XM_005264036.1.
DR PDB; 6U6U; X-ray; 2.31 A; R=21-215.
DR PDBsum; 6U6U; -.
DR AlphaFoldDB; Q9HB29; -.
DR SMR; Q9HB29; -.
DR BioGRID; 114336; 24.
DR IntAct; Q9HB29; 6.
DR STRING; 9606.ENSP00000264257; -.
DR ChEMBL; CHEMBL4665591; -.
DR GuidetoPHARMACOLOGY; 1736; -.
DR GlyGen; Q9HB29; 9 sites.
DR iPTMnet; Q9HB29; -.
DR PhosphoSitePlus; Q9HB29; -.
DR BioMuta; IL1RL2; -.
DR DMDM; 90110768; -.
DR MassIVE; Q9HB29; -.
DR PaxDb; Q9HB29; -.
DR PeptideAtlas; Q9HB29; -.
DR PRIDE; Q9HB29; -.
DR ABCD; Q9HB29; 19 sequenced antibodies.
DR Antibodypedia; 2361; 238 antibodies from 33 providers.
DR DNASU; 8808; -.
DR Ensembl; ENST00000264257.7; ENSP00000264257.2; ENSG00000115598.10. [Q9HB29-1]
DR Ensembl; ENST00000441515.3; ENSP00000413348.2; ENSG00000115598.10. [Q9HB29-2]
DR GeneID; 8808; -.
DR KEGG; hsa:8808; -.
DR MANE-Select; ENST00000264257.7; ENSP00000264257.2; NM_003854.4; NP_003845.2.
DR UCSC; uc002tbs.4; human. [Q9HB29-1]
DR CTD; 8808; -.
DR DisGeNET; 8808; -.
DR GeneCards; IL1RL2; -.
DR HGNC; HGNC:5999; IL1RL2.
DR HPA; ENSG00000115598; Tissue enhanced (skin).
DR MIM; 604512; gene.
DR neXtProt; NX_Q9HB29; -.
DR OpenTargets; ENSG00000115598; -.
DR PharmGKB; PA29815; -.
DR VEuPathDB; HostDB:ENSG00000115598; -.
DR eggNOG; ENOG502QWEU; Eukaryota.
DR GeneTree; ENSGT01050000244846; -.
DR HOGENOM; CLU_025552_3_0_1; -.
DR InParanoid; Q9HB29; -.
DR OMA; FEKQWCD; -.
DR OrthoDB; 1109920at2759; -.
DR PhylomeDB; Q9HB29; -.
DR TreeFam; TF325519; -.
DR PathwayCommons; Q9HB29; -.
DR Reactome; R-HSA-9007892; Interleukin-38 signaling.
DR Reactome; R-HSA-9014826; Interleukin-36 pathway.
DR SignaLink; Q9HB29; -.
DR BioGRID-ORCS; 8808; 16 hits in 1061 CRISPR screens.
DR ChiTaRS; IL1RL2; human.
DR GeneWiki; IL1RL2; -.
DR GenomeRNAi; 8808; -.
DR Pharos; Q9HB29; Tbio.
DR PRO; PR:Q9HB29; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HB29; protein.
DR Bgee; ENSG00000115598; Expressed in skin of abdomen and 91 other tissues.
DR ExpressionAtlas; Q9HB29; baseline and differential.
DR Genevisible; Q9HB29; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004908; F:interleukin-1 receptor activity; TAS:ProtInc.
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:0006968; P:cellular defense response; TAS:ProtInc.
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; IEA:Ensembl.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IEA:Ensembl.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; IPR015621; IL-1_rcpt_fam.
DR InterPro; IPR004076; IL-1_rcpt_I-typ.
DR InterPro; IPR004074; IL-1_rcpt_I/II-typ.
DR InterPro; IPR041416; IL-1RAcP-like_ig.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR11890; PTHR11890; 1.
DR Pfam; PF13895; Ig_2; 1.
DR Pfam; PF18452; Ig_6; 1.
DR Pfam; PF01582; TIR; 1.
DR PRINTS; PR01538; INTRLEUKN1R1.
DR PRINTS; PR01536; INTRLKN1R12F.
DR SMART; SM00409; IG; 3.
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 3D-structure; Alternative splicing; Disulfide bond; Glycoprotein;
KW Hydrolase; Immunity; Immunoglobulin domain; Inflammatory response;
KW Innate immunity; Membrane; NAD; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..575
FT /note="Interleukin-1 receptor-like 2"
FT /id="PRO_0000015445"
FT TOPO_DOM 20..335
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 357..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 20..111
FT /note="Ig-like C2-type 1"
FT DOMAIN 126..211
FT /note="Ig-like C2-type 2"
FT DOMAIN 222..318
FT /note="Ig-like C2-type 3"
FT DOMAIN 381..536
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT ACT_SITE 467
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..95
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 146..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 249..316
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..46
FT /note="MWSLLLCGLSIALPLSVTADGCKDIFMKNEILSASQPFAFNCTFPP -> MT
FT GLVSLSYFPLSTRSCALQSCSPVWGCGPCCSAGCPSPFHCLSQQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056292"
FT VAR_SEQ 47..163
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056293"
FT VAR_SEQ 217..218
FT /note="TE -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056294"
FT VARIANT 237
FT /note="I -> T (in dbSNP:rs13405631)"
FT /id="VAR_053378"
FT VARIANT 352
FT /note="V -> I (in dbSNP:rs33946385)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025259"
FT VARIANT 550
FT /note="L -> P (in dbSNP:rs2302612)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025260"
FT CONFLICT 486
FT /note="I -> V (in Ref. 1; AAG21368)"
FT /evidence="ECO:0000305"
FT CONFLICT 545..556
FT /note="PPVQLLQHTPCY -> LRSTCRSTHLCTA (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 556
FT /note="Y -> C (in Ref. 1; AAG21368)"
FT /evidence="ECO:0000305"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:6U6U"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 53..59
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 91..98
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 103..113
FT /evidence="ECO:0007829|PDB:6U6U"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:6U6U"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 154..163
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 179..184
FT /evidence="ECO:0007829|PDB:6U6U"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 191..201
FT /evidence="ECO:0007829|PDB:6U6U"
FT STRAND 204..215
FT /evidence="ECO:0007829|PDB:6U6U"
SQ SEQUENCE 575 AA; 65405 MW; 7AC0FCAB43A2A6CD CRC64;
MWSLLLCGLS IALPLSVTAD GCKDIFMKNE ILSASQPFAF NCTFPPITSG EVSVTWYKNS
SKIPVSKIIQ SRIHQDETWI LFLPMEWGDS GVYQCVIKGR DSCHRIHVNL TVFEKHWCDT
SIGGLPNLSD EYKQILHLGK DDSLTCHLHF PKSCVLGPIK WYKDCNEIKG ERFTVLETRL
LVSNVSAEDR GNYACQAILT HSGKQYEVLN GITVSITERA GYGGSVPKII YPKNHSIEVQ
LGTTLIVDCN VTDTKDNTNL RCWRVNNTLV DDYYDESKRI REGVETHVSF REHNLYTVNI
TFLEVKMEDY GLPFMCHAGV STAYIILQLP APDFRAYLIG GLIALVAVAV SVVYIYNIFK
IDIVLWYRSA FHSTETIVDG KLYDAYVLYP KPHKESQRHA VDALVLNILP EVLERQCGYK
LFIFGRDEFP GQAVANVIDE NVKLCRRLIV IVVPESLGFG LLKNLSEEQI AVYSALIQDG
MKVILIELEK IEDYTVMPES IQYIKQKHGA IRWHGDFTEQ SQCMKTKFWK TVRYHMPPRR
CRPFPPVQLL QHTPCYRTAG PELGSRRKKC TLTTG
