Full text data of IL1R1
IL1R1
(IL1R, IL1RA, IL1RT1)
[Confidence: high (a blood group or CD marker)]
Interleukin-1 receptor type 1; IL-1R-1; IL-1RT-1; IL-1RT1 (CD121 antigen-like family member A; Interleukin-1 receptor alpha; IL-1R-alpha; Interleukin-1 receptor type I; p80; CD121a; Interleukin-1 receptor type 1, membrane form; mIL-1R1; mIL-1RI; Interleukin-1 receptor type 1, soluble form; sIL-1R1; sIL-1RI; Flags: Precursor)
Interleukin-1 receptor type 1; IL-1R-1; IL-1RT-1; IL-1RT1 (CD121 antigen-like family member A; Interleukin-1 receptor alpha; IL-1R-alpha; Interleukin-1 receptor type I; p80; CD121a; Interleukin-1 receptor type 1, membrane form; mIL-1R1; mIL-1RI; Interleukin-1 receptor type 1, soluble form; sIL-1R1; sIL-1RI; Flags: Precursor)
UniProt
P14778
ID IL1R1_HUMAN Reviewed; 569 AA.
AC P14778; Q587I7;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-APR-1990, sequence version 1.
DT 22-JAN-2014, entry version 174.
DE RecName: Full=Interleukin-1 receptor type 1;
DE Short=IL-1R-1;
DE Short=IL-1RT-1;
DE Short=IL-1RT1;
DE AltName: Full=CD121 antigen-like family member A;
DE AltName: Full=Interleukin-1 receptor alpha;
DE Short=IL-1R-alpha;
DE AltName: Full=Interleukin-1 receptor type I;
DE AltName: Full=p80;
DE AltName: CD_antigen=CD121a;
DE Contains:
DE RecName: Full=Interleukin-1 receptor type 1, membrane form;
DE Short=mIL-1R1;
DE Short=mIL-1RI;
DE Contains:
DE RecName: Full=Interleukin-1 receptor type 1, soluble form;
DE Short=sIL-1R1;
DE Short=sIL-1RI;
DE Flags: Precursor;
GN Name=IL1R1; Synonyms=IL1R, IL1RA, IL1RT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2532321; DOI=10.1093/nar/17.23.10114;
RA Chua A.O., Gubler U.;
RT "Sequence of the cDNA for the human fibroblast type interleukin-1
RT receptor.";
RL Nucleic Acids Res. 17:10114-10114(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=T-cell;
RX PubMed=2530587; DOI=10.1073/pnas.86.22.8946;
RA Sims J.E., Acres R.B., Grubin C.E., McMahan C.J., Wignall J.M.,
RA March C.J., Dower S.K.;
RT "Cloning the interleukin 1 receptor from human T cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8946-8950(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-124.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUL-2002) 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.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA 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.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA 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.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=8142597; DOI=10.1016/1043-4666(93)90032-Z;
RA Svenson M., Hansen M.B., Heegaard P., Abell K., Bendtzen K.;
RT "Specific binding of interleukin 1 (IL-1) beta and IL-1 receptor
RT antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to
RT soluble IL-1 receptor type I.";
RL Cytokine 5:427-435(1993).
RN [8]
RP LIGAND-BINDING.
RX PubMed=7989776;
RA Giri J.G., Wells J., Dower S.K., McCall C.E., Guzman R.N., Slack J.,
RA Bird T.A., Shanebeck K., Grabstein K.H., Sims J.E., Alderson M.R.;
RT "Elevated levels of shed type II IL-1 receptor in sepsis. Potential
RT role for type II receptor in regulation of IL-1 responses.";
RL J. Immunol. 153:5802-5809(1994).
RN [9]
RP INTERACTION WITH IL1RAP AND IRAK1.
RC TISSUE=Placenta;
RX PubMed=9371760; DOI=10.1073/pnas.94.24.12829;
RA Huang J., Gao X., Li S., Cao Z.;
RT "Recruitment of IRAK to the interleukin 1 receptor complex requires
RT interleukin 1 receptor accessory protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:12829-12832(1997).
RN [10]
RP PHOSPHORYLATION AT TYR-496, AND INTERACTION WITH PIK3R1.
RX PubMed=9821957; DOI=10.1016/S0014-5793(98)01270-8;
RA Marmiroli S., Bavelloni A., Faenza I., Sirri A., Ognibene A.,
RA Cenni V., Tsukada J., Koyama Y., Ruzzene M., Ferri A., Auron P.E.,
RA Toker A., Maraldi N.M.;
RT "Phosphatidylinositol 3-kinase is recruited to a specific site in the
RT activated IL-1 receptor I.";
RL FEBS Lett. 438:49-54(1998).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF ASP-369 AND ARG-428.
RX PubMed=10671496; DOI=10.1074/jbc.275.7.4670;
RA Slack J.L., Schooley K., Bonnert T.P., Mitcham J.L., Qwarnstrom E.E.,
RA Sims J.E., Dower S.K.;
RT "Identification of two major sites in the type I interleukin-1
RT receptor cytoplasmic region responsible for coupling to pro-
RT inflammatory signaling pathways.";
RL J. Biol. Chem. 275:4670-4678(2000).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-332 IN COMPLEX WITH IL1B.
RX PubMed=9062193; DOI=10.1038/386190a0;
RA Vigers G.P.A., Anderson L.J., Caffes P., Brandhuber B.J.;
RT "Crystal structure of the type-I interleukin-1 receptor complexed with
RT interleukin-1beta.";
RL Nature 386:190-194(1997).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 21-331 IN COMPLEX WITH IL1RA.
RX PubMed=9062194; DOI=10.1038/386194a0;
RA Schreuder H., Tardif C., Trump-Kallmeyer S., Soffientini A.,
RA Sarubbi E., Akeson A., Bowlin T., Yanofsky S., Barrett R.W.;
RT "A new cytokine-receptor binding mode revealed by the crystal
RT structure of the IL-1 receptor with an antagonist.";
RL Nature 386:194-200(1997).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 4-315 IN COMPLEX WITH THE
RP ANTAGONIST PEPTIDE AF10847.
RX PubMed=10903327; DOI=10.1074/jbc.M006071200;
RA Vigers G.P.A., Dripps D.J., Edwards C.K. III, Brandhuber B.J.;
RT "X-ray crystal structure of a small antagonist peptide bound to
RT interleukin-1 receptor type 1.";
RL J. Biol. Chem. 275:36927-36933(2000).
CC -!- FUNCTION: Receptor for IL1A, IL1B and IL1RN. After binding to
CC interleukin-1 associates with the corecptor IL1RAP to form the
CC high affinity interleukin-1 receptor complex which mediates
CC interleukin-1-dependent activation of NF-kappa-B, MAPK and other
CC pathways. Signaling involves the recruitment of adapter molecules
CC such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR
CC domains of the receptor/coreceptor subunits. Binds ligands with
CC comparable affinity and binding of antagonist IL1RN prevents
CC association with IL1RAP to form a signaling complex.
CC -!- SUBUNIT: The interleukin-1 receptor complex is a heterodimer of
CC IL1R1 and IL1RAP. Interacts with PIK3R1.
CC -!- INTERACTION:
CC Q9Y4K3:TRAF6; NbExp=2; IntAct=EBI-525905, EBI-359276;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein. Cell membrane (Probable). Secreted.
CC -!- PTM: A soluble form (sIL1R1) is probably produced by proteolytic
CC cleavage at the cell surface (shedding).
CC -!- PTM: Rapidely phosphorylated on Tyr-496 in response to IL-1, which
CC creates a SH2 binding site for the PI 3-kinase regulatory subunit
CC PIK3R1.
CC -!- SIMILARITY: Belongs to the interleukin-1 receptor family.
CC -!- SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- SIMILARITY: Contains 1 TIR domain.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il1r1/";
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DR EMBL; X16896; CAA34773.1; -; mRNA.
DR EMBL; M27492; AAA59137.1; -; mRNA.
DR EMBL; AF531102; AAM88423.1; -; Genomic_DNA.
DR EMBL; AC007271; AAX81988.1; -; Genomic_DNA.
DR EMBL; CH471127; EAX01799.1; -; Genomic_DNA.
DR EMBL; BC067506; AAH67506.1; -; mRNA.
DR EMBL; BC075062; AAH75062.1; -; mRNA.
DR EMBL; BC075063; AAH75063.1; -; mRNA.
DR PIR; A36187; A36187.
DR RefSeq; NP_000868.1; NM_000877.2.
DR RefSeq; XP_005263985.1; XM_005263928.1.
DR RefSeq; XP_005263986.1; XM_005263929.1.
DR RefSeq; XP_005263987.1; XM_005263930.1.
DR RefSeq; XP_005263988.1; XM_005263931.1.
DR RefSeq; XP_005263989.1; XM_005263932.1.
DR RefSeq; XP_005263990.1; XM_005263933.1.
DR RefSeq; XP_005263991.1; XM_005263934.1.
DR UniGene; Hs.701982; -.
DR PDB; 1G0Y; X-ray; 3.00 A; R=21-332.
DR PDB; 1IRA; X-ray; 2.70 A; Y=18-336.
DR PDB; 1ITB; X-ray; 2.50 A; B=18-332.
DR PDB; 4DEP; X-ray; 3.10 A; B/E=18-336.
DR PDB; 4GAF; X-ray; 2.15 A; B=18-336.
DR PDBsum; 1G0Y; -.
DR PDBsum; 1IRA; -.
DR PDBsum; 1ITB; -.
DR PDBsum; 4DEP; -.
DR PDBsum; 4GAF; -.
DR ProteinModelPortal; P14778; -.
DR SMR; P14778; 23-332, 383-539.
DR DIP; DIP-93N; -.
DR IntAct; P14778; 6.
DR MINT; MINT-262640; -.
DR STRING; 9606.ENSP00000233946; -.
DR ChEMBL; CHEMBL1959; -.
DR DrugBank; DB00026; Anakinra.
DR PhosphoSite; P14778; -.
DR DMDM; 124308; -.
DR PaxDb; P14778; -.
DR PRIDE; P14778; -.
DR Ensembl; ENST00000233946; ENSP00000233946; ENSG00000115594.
DR Ensembl; ENST00000410023; ENSP00000386380; ENSG00000115594.
DR GeneID; 3554; -.
DR KEGG; hsa:3554; -.
DR UCSC; uc002tbq.3; human.
DR CTD; 3554; -.
DR GeneCards; GC02P102681; -.
DR HGNC; HGNC:5993; IL1R1.
DR HPA; CAB007779; -.
DR MIM; 147810; gene.
DR neXtProt; NX_P14778; -.
DR PharmGKB; PA29809; -.
DR eggNOG; NOG40914; -.
DR HOGENOM; HOG000253916; -.
DR HOVERGEN; HBG052103; -.
DR InParanoid; P14778; -.
DR KO; K04386; -.
DR OMA; IQDYEKM; -.
DR OrthoDB; EOG7H1JK3; -.
DR PhylomeDB; P14778; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P14778; -.
DR ChiTaRS; IL1R1; human.
DR EvolutionaryTrace; P14778; -.
DR GeneWiki; Interleukin_1_receptor,_type_I; -.
DR GenomeRNAi; 3554; -.
DR NextBio; 13876; -.
DR PRO; PR:P14778; -.
DR ArrayExpress; P14778; -.
DR Bgee; P14778; -.
DR CleanEx; HS_IL1R1; -.
DR Genevestigator; P14778; -.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0004909; F:interleukin-1, Type I, activating receptor activity; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
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; IPR000157; TIR_dom.
DR PANTHER; PTHR11890; PTHR11890; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF01582; TIR; 1.
DR PRINTS; PR01538; INTRLEUKN1R1.
DR PRINTS; PR01536; INTRLKN1R12F.
DR SMART; SM00409; IG; 2.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Complete proteome; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 17
FT CHAIN 18 569 Interleukin-1 receptor type 1, membrane
FT form.
FT /FTId=PRO_0000015435.
FT CHAIN 18 ? Interleukin-1 receptor type 1, soluble
FT form.
FT /FTId=PRO_0000415344.
FT TOPO_DOM 18 336 Extracellular (Potential).
FT TRANSMEM 337 356 Helical; (Potential).
FT TOPO_DOM 357 569 Cytoplasmic (Potential).
FT DOMAIN 23 110 Ig-like C2-type 1.
FT DOMAIN 118 210 Ig-like C2-type 2.
FT DOMAIN 226 328 Ig-like C2-type 3.
FT DOMAIN 383 541 TIR.
FT MOD_RES 496 496 Phosphotyrosine.
FT CARBOHYD 100 100 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 193 193 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 233 233 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 249 249 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 263 263 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 297 297 N-linked (GlcNAc...) (Potential).
FT DISULFID 23 104
FT DISULFID 44 96
FT DISULFID 121 164
FT DISULFID 142 196
FT DISULFID 248 312
FT VARIANT 124 124 A -> G (in dbSNP:rs2228139).
FT /FTId=VAR_019131.
FT VARIANT 344 344 T -> M (in dbSNP:rs28362304).
FT /FTId=VAR_029189.
FT MUTAGEN 369 369 D->A: Reduces NF-kappa-B activation.
FT MUTAGEN 428 428 R->A: Reduces NF-kappa-B activation and
FT receptor-associated kinase activation.
FT STRAND 24 27
FT STRAND 32 35
FT STRAND 40 43
FT HELIX 48 50
FT STRAND 56 59
FT STRAND 72 77
FT STRAND 80 83
FT HELIX 88 90
FT STRAND 92 97
FT STRAND 100 102
FT STRAND 105 114
FT STRAND 120 122
FT HELIX 124 126
FT STRAND 127 133
FT STRAND 135 137
FT STRAND 138 141
FT HELIX 146 148
FT TURN 151 153
FT STRAND 159 162
FT STRAND 171 177
FT STRAND 180 183
FT HELIX 188 190
FT STRAND 192 202
FT STRAND 205 218
FT STRAND 227 230
FT STRAND 233 237
FT STRAND 240 242
FT STRAND 244 252
FT STRAND 256 262
FT STRAND 272 281
FT HELIX 287 289
FT STRAND 290 300
FT HELIX 303 306
FT STRAND 310 316
FT STRAND 319 328
SQ SEQUENCE 569 AA; 65402 MW; 5BAA83F8F0225C25 CRC64;
MKVLLRLICF IALLISSLEA DKCKEREEKI ILVSSANEID VRPCPLNPNE HKGTITWYKD
DSKTPVSTEQ ASRIHQHKEK LWFVPAKVED SGHYYCVVRN SSYCLRIKIS AKFVENEPNL
CYNAQAIFKQ KLPVAGDGGL VCPYMEFFKN ENNELPKLQW YKDCKPLLLD NIHFSGVKDR
LIVMNVAEKH RGNYTCHASY TYLGKQYPIT RVIEFITLEE NKPTRPVIVS PANETMEVDL
GSQIQLICNV TGQLSDIAYW KWNGSVIDED DPVLGEDYYS VENPANKRRS TLITVLNISE
IESRFYKHPF TCFAKNTHGI DAAYIQLIYP VTNFQKHMIG ICVTLTVIIV CSVFIYKIFK
IDIVLWYRDS CYDFLPIKAS DGKTYDAYIL YPKTVGEGST SDCDIFVFKV LPEVLEKQCG
YKLFIYGRDD YVGEDIVEVI NENVKKSRRL IIILVRETSG FSWLGGSSEE QIAMYNALVQ
DGIKVVLLEL EKIQDYEKMP ESIKFIKQKH GAIRWSGDFT QGPQSAKTRF WKNVRYHMPV
QRRSPSSKHQ LLSPATKEKL QREAHVPLG
//
ID IL1R1_HUMAN Reviewed; 569 AA.
AC P14778; Q587I7;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-APR-1990, sequence version 1.
DT 22-JAN-2014, entry version 174.
DE RecName: Full=Interleukin-1 receptor type 1;
DE Short=IL-1R-1;
DE Short=IL-1RT-1;
DE Short=IL-1RT1;
DE AltName: Full=CD121 antigen-like family member A;
DE AltName: Full=Interleukin-1 receptor alpha;
DE Short=IL-1R-alpha;
DE AltName: Full=Interleukin-1 receptor type I;
DE AltName: Full=p80;
DE AltName: CD_antigen=CD121a;
DE Contains:
DE RecName: Full=Interleukin-1 receptor type 1, membrane form;
DE Short=mIL-1R1;
DE Short=mIL-1RI;
DE Contains:
DE RecName: Full=Interleukin-1 receptor type 1, soluble form;
DE Short=sIL-1R1;
DE Short=sIL-1RI;
DE Flags: Precursor;
GN Name=IL1R1; Synonyms=IL1R, IL1RA, IL1RT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2532321; DOI=10.1093/nar/17.23.10114;
RA Chua A.O., Gubler U.;
RT "Sequence of the cDNA for the human fibroblast type interleukin-1
RT receptor.";
RL Nucleic Acids Res. 17:10114-10114(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=T-cell;
RX PubMed=2530587; DOI=10.1073/pnas.86.22.8946;
RA Sims J.E., Acres R.B., Grubin C.E., McMahan C.J., Wignall J.M.,
RA March C.J., Dower S.K.;
RT "Cloning the interleukin 1 receptor from human T cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8946-8950(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-124.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUL-2002) 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.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA 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.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA 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.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=8142597; DOI=10.1016/1043-4666(93)90032-Z;
RA Svenson M., Hansen M.B., Heegaard P., Abell K., Bendtzen K.;
RT "Specific binding of interleukin 1 (IL-1) beta and IL-1 receptor
RT antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to
RT soluble IL-1 receptor type I.";
RL Cytokine 5:427-435(1993).
RN [8]
RP LIGAND-BINDING.
RX PubMed=7989776;
RA Giri J.G., Wells J., Dower S.K., McCall C.E., Guzman R.N., Slack J.,
RA Bird T.A., Shanebeck K., Grabstein K.H., Sims J.E., Alderson M.R.;
RT "Elevated levels of shed type II IL-1 receptor in sepsis. Potential
RT role for type II receptor in regulation of IL-1 responses.";
RL J. Immunol. 153:5802-5809(1994).
RN [9]
RP INTERACTION WITH IL1RAP AND IRAK1.
RC TISSUE=Placenta;
RX PubMed=9371760; DOI=10.1073/pnas.94.24.12829;
RA Huang J., Gao X., Li S., Cao Z.;
RT "Recruitment of IRAK to the interleukin 1 receptor complex requires
RT interleukin 1 receptor accessory protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:12829-12832(1997).
RN [10]
RP PHOSPHORYLATION AT TYR-496, AND INTERACTION WITH PIK3R1.
RX PubMed=9821957; DOI=10.1016/S0014-5793(98)01270-8;
RA Marmiroli S., Bavelloni A., Faenza I., Sirri A., Ognibene A.,
RA Cenni V., Tsukada J., Koyama Y., Ruzzene M., Ferri A., Auron P.E.,
RA Toker A., Maraldi N.M.;
RT "Phosphatidylinositol 3-kinase is recruited to a specific site in the
RT activated IL-1 receptor I.";
RL FEBS Lett. 438:49-54(1998).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF ASP-369 AND ARG-428.
RX PubMed=10671496; DOI=10.1074/jbc.275.7.4670;
RA Slack J.L., Schooley K., Bonnert T.P., Mitcham J.L., Qwarnstrom E.E.,
RA Sims J.E., Dower S.K.;
RT "Identification of two major sites in the type I interleukin-1
RT receptor cytoplasmic region responsible for coupling to pro-
RT inflammatory signaling pathways.";
RL J. Biol. Chem. 275:4670-4678(2000).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-332 IN COMPLEX WITH IL1B.
RX PubMed=9062193; DOI=10.1038/386190a0;
RA Vigers G.P.A., Anderson L.J., Caffes P., Brandhuber B.J.;
RT "Crystal structure of the type-I interleukin-1 receptor complexed with
RT interleukin-1beta.";
RL Nature 386:190-194(1997).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 21-331 IN COMPLEX WITH IL1RA.
RX PubMed=9062194; DOI=10.1038/386194a0;
RA Schreuder H., Tardif C., Trump-Kallmeyer S., Soffientini A.,
RA Sarubbi E., Akeson A., Bowlin T., Yanofsky S., Barrett R.W.;
RT "A new cytokine-receptor binding mode revealed by the crystal
RT structure of the IL-1 receptor with an antagonist.";
RL Nature 386:194-200(1997).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 4-315 IN COMPLEX WITH THE
RP ANTAGONIST PEPTIDE AF10847.
RX PubMed=10903327; DOI=10.1074/jbc.M006071200;
RA Vigers G.P.A., Dripps D.J., Edwards C.K. III, Brandhuber B.J.;
RT "X-ray crystal structure of a small antagonist peptide bound to
RT interleukin-1 receptor type 1.";
RL J. Biol. Chem. 275:36927-36933(2000).
CC -!- FUNCTION: Receptor for IL1A, IL1B and IL1RN. After binding to
CC interleukin-1 associates with the corecptor IL1RAP to form the
CC high affinity interleukin-1 receptor complex which mediates
CC interleukin-1-dependent activation of NF-kappa-B, MAPK and other
CC pathways. Signaling involves the recruitment of adapter molecules
CC such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR
CC domains of the receptor/coreceptor subunits. Binds ligands with
CC comparable affinity and binding of antagonist IL1RN prevents
CC association with IL1RAP to form a signaling complex.
CC -!- SUBUNIT: The interleukin-1 receptor complex is a heterodimer of
CC IL1R1 and IL1RAP. Interacts with PIK3R1.
CC -!- INTERACTION:
CC Q9Y4K3:TRAF6; NbExp=2; IntAct=EBI-525905, EBI-359276;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein. Cell membrane (Probable). Secreted.
CC -!- PTM: A soluble form (sIL1R1) is probably produced by proteolytic
CC cleavage at the cell surface (shedding).
CC -!- PTM: Rapidely phosphorylated on Tyr-496 in response to IL-1, which
CC creates a SH2 binding site for the PI 3-kinase regulatory subunit
CC PIK3R1.
CC -!- SIMILARITY: Belongs to the interleukin-1 receptor family.
CC -!- SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- SIMILARITY: Contains 1 TIR domain.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il1r1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; X16896; CAA34773.1; -; mRNA.
DR EMBL; M27492; AAA59137.1; -; mRNA.
DR EMBL; AF531102; AAM88423.1; -; Genomic_DNA.
DR EMBL; AC007271; AAX81988.1; -; Genomic_DNA.
DR EMBL; CH471127; EAX01799.1; -; Genomic_DNA.
DR EMBL; BC067506; AAH67506.1; -; mRNA.
DR EMBL; BC075062; AAH75062.1; -; mRNA.
DR EMBL; BC075063; AAH75063.1; -; mRNA.
DR PIR; A36187; A36187.
DR RefSeq; NP_000868.1; NM_000877.2.
DR RefSeq; XP_005263985.1; XM_005263928.1.
DR RefSeq; XP_005263986.1; XM_005263929.1.
DR RefSeq; XP_005263987.1; XM_005263930.1.
DR RefSeq; XP_005263988.1; XM_005263931.1.
DR RefSeq; XP_005263989.1; XM_005263932.1.
DR RefSeq; XP_005263990.1; XM_005263933.1.
DR RefSeq; XP_005263991.1; XM_005263934.1.
DR UniGene; Hs.701982; -.
DR PDB; 1G0Y; X-ray; 3.00 A; R=21-332.
DR PDB; 1IRA; X-ray; 2.70 A; Y=18-336.
DR PDB; 1ITB; X-ray; 2.50 A; B=18-332.
DR PDB; 4DEP; X-ray; 3.10 A; B/E=18-336.
DR PDB; 4GAF; X-ray; 2.15 A; B=18-336.
DR PDBsum; 1G0Y; -.
DR PDBsum; 1IRA; -.
DR PDBsum; 1ITB; -.
DR PDBsum; 4DEP; -.
DR PDBsum; 4GAF; -.
DR ProteinModelPortal; P14778; -.
DR SMR; P14778; 23-332, 383-539.
DR DIP; DIP-93N; -.
DR IntAct; P14778; 6.
DR MINT; MINT-262640; -.
DR STRING; 9606.ENSP00000233946; -.
DR ChEMBL; CHEMBL1959; -.
DR DrugBank; DB00026; Anakinra.
DR PhosphoSite; P14778; -.
DR DMDM; 124308; -.
DR PaxDb; P14778; -.
DR PRIDE; P14778; -.
DR Ensembl; ENST00000233946; ENSP00000233946; ENSG00000115594.
DR Ensembl; ENST00000410023; ENSP00000386380; ENSG00000115594.
DR GeneID; 3554; -.
DR KEGG; hsa:3554; -.
DR UCSC; uc002tbq.3; human.
DR CTD; 3554; -.
DR GeneCards; GC02P102681; -.
DR HGNC; HGNC:5993; IL1R1.
DR HPA; CAB007779; -.
DR MIM; 147810; gene.
DR neXtProt; NX_P14778; -.
DR PharmGKB; PA29809; -.
DR eggNOG; NOG40914; -.
DR HOGENOM; HOG000253916; -.
DR HOVERGEN; HBG052103; -.
DR InParanoid; P14778; -.
DR KO; K04386; -.
DR OMA; IQDYEKM; -.
DR OrthoDB; EOG7H1JK3; -.
DR PhylomeDB; P14778; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P14778; -.
DR ChiTaRS; IL1R1; human.
DR EvolutionaryTrace; P14778; -.
DR GeneWiki; Interleukin_1_receptor,_type_I; -.
DR GenomeRNAi; 3554; -.
DR NextBio; 13876; -.
DR PRO; PR:P14778; -.
DR ArrayExpress; P14778; -.
DR Bgee; P14778; -.
DR CleanEx; HS_IL1R1; -.
DR Genevestigator; P14778; -.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0004909; F:interleukin-1, Type I, activating receptor activity; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
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; IPR000157; TIR_dom.
DR PANTHER; PTHR11890; PTHR11890; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF01582; TIR; 1.
DR PRINTS; PR01538; INTRLEUKN1R1.
DR PRINTS; PR01536; INTRLKN1R12F.
DR SMART; SM00409; IG; 2.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Complete proteome; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 17
FT CHAIN 18 569 Interleukin-1 receptor type 1, membrane
FT form.
FT /FTId=PRO_0000015435.
FT CHAIN 18 ? Interleukin-1 receptor type 1, soluble
FT form.
FT /FTId=PRO_0000415344.
FT TOPO_DOM 18 336 Extracellular (Potential).
FT TRANSMEM 337 356 Helical; (Potential).
FT TOPO_DOM 357 569 Cytoplasmic (Potential).
FT DOMAIN 23 110 Ig-like C2-type 1.
FT DOMAIN 118 210 Ig-like C2-type 2.
FT DOMAIN 226 328 Ig-like C2-type 3.
FT DOMAIN 383 541 TIR.
FT MOD_RES 496 496 Phosphotyrosine.
FT CARBOHYD 100 100 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 193 193 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 233 233 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 249 249 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 263 263 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 297 297 N-linked (GlcNAc...) (Potential).
FT DISULFID 23 104
FT DISULFID 44 96
FT DISULFID 121 164
FT DISULFID 142 196
FT DISULFID 248 312
FT VARIANT 124 124 A -> G (in dbSNP:rs2228139).
FT /FTId=VAR_019131.
FT VARIANT 344 344 T -> M (in dbSNP:rs28362304).
FT /FTId=VAR_029189.
FT MUTAGEN 369 369 D->A: Reduces NF-kappa-B activation.
FT MUTAGEN 428 428 R->A: Reduces NF-kappa-B activation and
FT receptor-associated kinase activation.
FT STRAND 24 27
FT STRAND 32 35
FT STRAND 40 43
FT HELIX 48 50
FT STRAND 56 59
FT STRAND 72 77
FT STRAND 80 83
FT HELIX 88 90
FT STRAND 92 97
FT STRAND 100 102
FT STRAND 105 114
FT STRAND 120 122
FT HELIX 124 126
FT STRAND 127 133
FT STRAND 135 137
FT STRAND 138 141
FT HELIX 146 148
FT TURN 151 153
FT STRAND 159 162
FT STRAND 171 177
FT STRAND 180 183
FT HELIX 188 190
FT STRAND 192 202
FT STRAND 205 218
FT STRAND 227 230
FT STRAND 233 237
FT STRAND 240 242
FT STRAND 244 252
FT STRAND 256 262
FT STRAND 272 281
FT HELIX 287 289
FT STRAND 290 300
FT HELIX 303 306
FT STRAND 310 316
FT STRAND 319 328
SQ SEQUENCE 569 AA; 65402 MW; 5BAA83F8F0225C25 CRC64;
MKVLLRLICF IALLISSLEA DKCKEREEKI ILVSSANEID VRPCPLNPNE HKGTITWYKD
DSKTPVSTEQ ASRIHQHKEK LWFVPAKVED SGHYYCVVRN SSYCLRIKIS AKFVENEPNL
CYNAQAIFKQ KLPVAGDGGL VCPYMEFFKN ENNELPKLQW YKDCKPLLLD NIHFSGVKDR
LIVMNVAEKH RGNYTCHASY TYLGKQYPIT RVIEFITLEE NKPTRPVIVS PANETMEVDL
GSQIQLICNV TGQLSDIAYW KWNGSVIDED DPVLGEDYYS VENPANKRRS TLITVLNISE
IESRFYKHPF TCFAKNTHGI DAAYIQLIYP VTNFQKHMIG ICVTLTVIIV CSVFIYKIFK
IDIVLWYRDS CYDFLPIKAS DGKTYDAYIL YPKTVGEGST SDCDIFVFKV LPEVLEKQCG
YKLFIYGRDD YVGEDIVEVI NENVKKSRRL IIILVRETSG FSWLGGSSEE QIAMYNALVQ
DGIKVVLLEL EKIQDYEKMP ESIKFIKQKH GAIRWSGDFT QGPQSAKTRF WKNVRYHMPV
QRRSPSSKHQ LLSPATKEKL QREAHVPLG
//
MIM
147810
*RECORD*
*FIELD* NO
147810
*FIELD* TI
*147810 INTERLEUKIN 1 RECEPTOR, TYPE I; IL1R1
;;INTERLEUKIN 1 RECEPTOR, ALPHA, TYPE I; IL1RA;;
read moreINTERLEUKIN 1 RECEPTOR; IL1R
*FIELD* TX
CLONING
Interleukin-1, which has a role as a mediator in inflammation, consists
of 2 separate but related proteins, IL1-alpha (147720) and IL1-beta
(147760). Dower et al. (1986) showed that the cell surface receptors for
the 2 forms of interleukin-1 are identical. Sims et al. (1989) cloned
the human IL1R gene and compared it with the mouse gene. Both encode
proteins containing a single membrane-spanning segment, a large
cytoplasmic region, and an extracellular, IL1-binding portion composed
of 3 immunoglobulin-like domains. The IL1R gene expressed in human
dermal fibroblasts was found to be identical to that expressed in T
cells.
GENE FUNCTION
Chen et al. (2007) found that the acute neutrophilic inflammatory
response to cell injury requires the signaling protein Myd88 (602170).
Analysis of the contribution of Myd88-dependent receptors to this
response revealed only a minor reduction in mice doubly deficient in
Toll-like receptor-2 (Tlr2; 603028) and Tlr4 (603030) and normal
responses in mice lacking Tlr1 (601194), Tlr3 (603029), Tlr6 (605403),
Tlr7 (300365), Tlr9 (605474), or Tlr11 (606270) or the IL18 receptor
(IL18R; 604494). However, mice lacking IL1R showed a markedly reduced
neutrophilic inflammatory response to dead cells and tissue injury in
vivo as well as greatly decreased collateral damage from inflammation.
This inflammatory response required IL1-alpha, and IL1R function was
required on non-bone-marrow-derived cells. Notably, the acute monocyte
response to cell death, which is thought to be important for tissue
repair, was much less dependent on the IL1R-Myd88 pathway. Also, this
pathway was not required for the neutrophil response to a microbial
stimulus. These findings suggested that inhibiting the IL1R-MYD88
pathway in vivo could block the damage from acute inflammation that
occurs in response to sterile cell death, and do so in a way that might
not compromise tissue repair or host defense against pathogens.
MAPPING
By a combination of somatic cell hybrid analysis and chromosomal in situ
hybridization, Copeland et al. (1991) mapped the IL1R gene to human
chromosome 2q12. By RFLP analysis in interspecific backcrosses, Copeland
et al. (1991) mapped the corresponding mouse gene at the centromeric end
of chromosome 1, a region homologous to a portion of human chromosome 2.
Dale and Nicklin (1999) showed by radiation hybrid mapping that IL1R1,
IL1R2 (147811), IL1RL2 (604512), IL1RL1 (601203), and IL18R1 (604494)
map to 2q12 and are transcribed in the same direction, with IL1R2 being
transcribed towards the cluster.
ANIMAL MODEL
Using microcomputed tomography, Bajayo et al. (2005) found that mice
lacking Il1r1 had decreased trabecular thickness and number, as well as
decreased skeletal growth. Transgenic mice overexpressing Il1 receptor
antagonist (IL1RA, or IL1RN; 147679) in the central nervous system also
had low bone mass, suggesting that silencing of central Il1r1 signaling
leads to progressive impairment of accrual and maintenance of bone mass.
Both mouse models exhibited increased bone resorption, and the
Il1ra-transgenic mice also showed an increase in bone formation, as
observed in human osteoporosis. Hormone levels in the mutant mice did
not differ from wildtype. Bajayo et al. (2005) concluded that pathways
other than the hypothalamic-pituitary-adrenal and
hypothalamic-pituitary-gonadal axes communicate the central IL1 signal
to bone.
*FIELD* RF
1. Bajayo, A.; Goshen, I.; Feldman, S.; Csernus, V.; Iverfeldt, K.;
Shohami, E.; Yirmiya, R.; Bab, I.: Central IL-1 receptor signaling
regulates bone growth and mass. Proc. Nat. Acad. Sci. 102: 12956-12961,
2005.
2. Chen, C.-J.; Kono, H.; Golenbock, D.; Reed, G.; Akira, G.; Rock,
K. L.: Identification of a key pathway required for the sterile inflammatory
response triggered by dying cells. Nature Med. 13: 851-856, 2007.
3. Copeland, N. G.; Silan, C. M.; Kingsley, D. M.; Jenkins, N. A.;
Cannizzaro, L. A.; Croce, C. M.; Huebner, K.; Sims, J. E.: Chromosomal
location of murine and human IL-1 receptor genes. Genomics 9: 44-50,
1991.
4. Dale, M.; Nicklin, M. J.: 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: 177-179,
1999.
5. Dower, S. K.; Kronheim, S. R.; Hopp, T. P.; Cantrell, M.; Deeley,
M.; Gillis, S.; Henney, C. S.; Urdal, D. L.: The cell surface receptors
for interleukin-1(alpha) and interleukin-1(beta) are identical. Nature 324:
266-268, 1986.
6. Sims, J. E.; Acres, R. B.; Grubin, C. E.; McMahan, C. J.; Wignall,
J. M.; March, C. J.; Dower, S. K.: Cloning the interleukin 1 receptor
from human T cells. Proc. Nat. Acad. Sci. 86: 8946-8950, 1989.
*FIELD* CN
Ada Hamosh - updated: 2/25/2008
Paul J. Converse - updated: 5/17/2007
Paul J. Converse - updated: 2/4/2000
*FIELD* CD
Victor A. McKusick: 1/7/1987
*FIELD* ED
alopez: 03/03/2008
terry: 2/25/2008
mgross: 5/18/2007
terry: 5/17/2007
carol: 2/4/2000
psherman: 11/20/1998
carol: 8/18/1998
dkim: 7/23/1998
dkim: 7/2/1998
mark: 4/10/1996
carol: 5/14/1993
supermim: 3/16/1992
carol: 1/16/1991
supermim: 3/20/1990
carol: 12/19/1989
ddp: 10/27/1989
*RECORD*
*FIELD* NO
147810
*FIELD* TI
*147810 INTERLEUKIN 1 RECEPTOR, TYPE I; IL1R1
;;INTERLEUKIN 1 RECEPTOR, ALPHA, TYPE I; IL1RA;;
read moreINTERLEUKIN 1 RECEPTOR; IL1R
*FIELD* TX
CLONING
Interleukin-1, which has a role as a mediator in inflammation, consists
of 2 separate but related proteins, IL1-alpha (147720) and IL1-beta
(147760). Dower et al. (1986) showed that the cell surface receptors for
the 2 forms of interleukin-1 are identical. Sims et al. (1989) cloned
the human IL1R gene and compared it with the mouse gene. Both encode
proteins containing a single membrane-spanning segment, a large
cytoplasmic region, and an extracellular, IL1-binding portion composed
of 3 immunoglobulin-like domains. The IL1R gene expressed in human
dermal fibroblasts was found to be identical to that expressed in T
cells.
GENE FUNCTION
Chen et al. (2007) found that the acute neutrophilic inflammatory
response to cell injury requires the signaling protein Myd88 (602170).
Analysis of the contribution of Myd88-dependent receptors to this
response revealed only a minor reduction in mice doubly deficient in
Toll-like receptor-2 (Tlr2; 603028) and Tlr4 (603030) and normal
responses in mice lacking Tlr1 (601194), Tlr3 (603029), Tlr6 (605403),
Tlr7 (300365), Tlr9 (605474), or Tlr11 (606270) or the IL18 receptor
(IL18R; 604494). However, mice lacking IL1R showed a markedly reduced
neutrophilic inflammatory response to dead cells and tissue injury in
vivo as well as greatly decreased collateral damage from inflammation.
This inflammatory response required IL1-alpha, and IL1R function was
required on non-bone-marrow-derived cells. Notably, the acute monocyte
response to cell death, which is thought to be important for tissue
repair, was much less dependent on the IL1R-Myd88 pathway. Also, this
pathway was not required for the neutrophil response to a microbial
stimulus. These findings suggested that inhibiting the IL1R-MYD88
pathway in vivo could block the damage from acute inflammation that
occurs in response to sterile cell death, and do so in a way that might
not compromise tissue repair or host defense against pathogens.
MAPPING
By a combination of somatic cell hybrid analysis and chromosomal in situ
hybridization, Copeland et al. (1991) mapped the IL1R gene to human
chromosome 2q12. By RFLP analysis in interspecific backcrosses, Copeland
et al. (1991) mapped the corresponding mouse gene at the centromeric end
of chromosome 1, a region homologous to a portion of human chromosome 2.
Dale and Nicklin (1999) showed by radiation hybrid mapping that IL1R1,
IL1R2 (147811), IL1RL2 (604512), IL1RL1 (601203), and IL18R1 (604494)
map to 2q12 and are transcribed in the same direction, with IL1R2 being
transcribed towards the cluster.
ANIMAL MODEL
Using microcomputed tomography, Bajayo et al. (2005) found that mice
lacking Il1r1 had decreased trabecular thickness and number, as well as
decreased skeletal growth. Transgenic mice overexpressing Il1 receptor
antagonist (IL1RA, or IL1RN; 147679) in the central nervous system also
had low bone mass, suggesting that silencing of central Il1r1 signaling
leads to progressive impairment of accrual and maintenance of bone mass.
Both mouse models exhibited increased bone resorption, and the
Il1ra-transgenic mice also showed an increase in bone formation, as
observed in human osteoporosis. Hormone levels in the mutant mice did
not differ from wildtype. Bajayo et al. (2005) concluded that pathways
other than the hypothalamic-pituitary-adrenal and
hypothalamic-pituitary-gonadal axes communicate the central IL1 signal
to bone.
*FIELD* RF
1. Bajayo, A.; Goshen, I.; Feldman, S.; Csernus, V.; Iverfeldt, K.;
Shohami, E.; Yirmiya, R.; Bab, I.: Central IL-1 receptor signaling
regulates bone growth and mass. Proc. Nat. Acad. Sci. 102: 12956-12961,
2005.
2. Chen, C.-J.; Kono, H.; Golenbock, D.; Reed, G.; Akira, G.; Rock,
K. L.: Identification of a key pathway required for the sterile inflammatory
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Cannizzaro, L. A.; Croce, C. M.; Huebner, K.; Sims, J. E.: Chromosomal
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*FIELD* CN
Ada Hamosh - updated: 2/25/2008
Paul J. Converse - updated: 5/17/2007
Paul J. Converse - updated: 2/4/2000
*FIELD* CD
Victor A. McKusick: 1/7/1987
*FIELD* ED
alopez: 03/03/2008
terry: 2/25/2008
mgross: 5/18/2007
terry: 5/17/2007
carol: 2/4/2000
psherman: 11/20/1998
carol: 8/18/1998
dkim: 7/23/1998
dkim: 7/2/1998
mark: 4/10/1996
carol: 5/14/1993
supermim: 3/16/1992
carol: 1/16/1991
supermim: 3/20/1990
carol: 12/19/1989
ddp: 10/27/1989