IL1AP_HUMAN
ID IL1AP_HUMAN Reviewed; 570 AA.
AC Q9NPH3; B1NLD0; D3DNW0; O14915; Q86WJ7;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Interleukin-1 receptor accessory protein;
DE Short=IL-1 receptor accessory protein;
DE Short=IL-1RAcP;
DE EC=3.2.2.6 {ECO:0000255|PROSITE-ProRule:PRU00204};
DE AltName: Full=Interleukin-1 receptor 3;
DE Short=IL-1R-3;
DE Short=IL-1R3;
DE Flags: Precursor;
GN Name=IL1RAP; Synonyms=C3orf13, IL1R3;
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), FUNCTION, AND INTERACTION WITH
RP IL1R1 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Saito T., Seki N.;
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND
RP INDUCTION BY PHORBOL ESTERS.
RC TISSUE=Liver;
RX PubMed=10799889; DOI=10.4049/jimmunol.164.10.5277;
RA Jensen L.E., Muzio M., Mantovani A., Whitehead A.S.;
RT "IL-1 signaling cascade in liver cells and the involvement of a soluble
RT form of the IL-1 receptor accessory protein.";
RL J. Immunol. 164:5277-5286(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND INDUCTION BY PHORBOL
RP ESTERS.
RC TISSUE=Liver;
RX PubMed=12781872; DOI=10.1016/s0898-6568(03)00039-1;
RA Jensen L.E., Whitehead A.S.;
RT "Expression of alternatively spliced interleukin-1 receptor accessory
RT protein mRNAs is differentially regulated during inflammation and
RT apoptosis.";
RL Cell. Signal. 15:793-802(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RX PubMed=17949817; DOI=10.1016/j.molimm.2007.09.002;
RA Lu H.L., Yang C.Y., Chen H.C., Hung C.S., Chiang Y.C., Ting L.P.;
RT "A novel alternatively spliced interleukin-1 receptor accessory protein
RT mIL-1RAcP687.";
RL Mol. Immunol. 45:1374-1384(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION (ISOFORM 4), TISSUE
RP SPECIFICITY (ISOFORM 4), AND INTERACTION WITH IL1R1.
RX PubMed=19481478; DOI=10.1016/j.immuni.2009.03.020;
RA Smith D.E., Lipsky B.P., Russell C., Ketchem R.R., Kirchner J., Hensley K.,
RA Huang Y., Friedman W.J., Boissonneault V., Plante M.M., Rivest S.,
RA Sims J.E.;
RT "A central nervous system-restricted isoform of the interleukin-1 receptor
RT accessory protein modulates neuronal responses to interleukin-1.";
RL Immunity 30:817-831(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 118-179.
RX PubMed=9479509; DOI=10.1006/geno.1997.5113;
RA Dale M., Hammond D.W., Cox A., Nicklin M.J.H.;
RT "The human gene encoding the interleukin-1 receptor accessory protein
RT (IL1RAP) maps to chromosome 3q28 by fluorescence in situ hybridization and
RT radiation hybrid mapping.";
RL Genomics 47:325-326(1998).
RN [11]
RP INTERACTION WITH IL1R2.
RX PubMed=9862719;
RA Lang D., Knop J., Wesche H., Raffetseder U., Kurrle R., Boraschi D.,
RA Martin M.U.;
RT "The type II IL-1 receptor interacts with the IL-1 receptor accessory
RT protein: a novel mechanism of regulation of IL-1 responsiveness.";
RL J. Immunol. 161:6871-6877(1998).
RN [12]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=10653850; DOI=10.1093/intimm/12.2.151;
RA Tominaga K., Yoshimoto T., Torigoe K., Kurimoto M., Matsui K., Hada T.,
RA Okamura H., Nakanishi K.;
RT "IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from
RT human T cells.";
RL Int. Immunol. 12:151-160(2000).
RN [13]
RP INTERACTION WITH IRAK2.
RX PubMed=12659850; DOI=10.1016/s0006-291x(03)00385-1;
RA Boch J.A., Yoshida Y., Koyama Y., Wara-Aswapati N., Peng H., Unlu S.,
RA Auron P.E.;
RT "Characterization of a cascade of protein interactions initiated at the IL-
RT 1 receptor.";
RL Biochem. Biophys. Res. Commun. 303:525-531(2003).
RN [14]
RP FUNCTION (SECRETED FORMS), AND TISSUE SPECIFICITY.
RX PubMed=12530978; DOI=10.1016/s1074-7613(02)00514-9;
RA Smith D.E., Hanna R., Friend D., Moore H., Chen H., Farese A.M.,
RA MacVittie T.J., Virca G.D., Sims J.E.;
RT "The soluble form of IL-1 receptor accessory protein enhances the ability
RT of soluble type II IL-1 receptor to inhibit IL-1 action.";
RL Immunity 18:87-96(2003).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP FUNCTION, AND MODEL OF THE IL-33 SIGNALING COMPLEX.
RX PubMed=19836339; DOI=10.1016/j.str.2009.08.009;
RA Lingel A., Weiss T.M., Niebuhr M., Pan B., Appleton B.A., Wiesmann C.,
RA Bazan J.F., Fairbrother W.J.;
RT "Structure of IL-33 and its interaction with the ST2 and IL-1RAcP
RT receptors--insight into heterotrimeric IL-1 signaling complexes.";
RL Structure 17:1398-1410(2009).
RN [19]
RP TISSUE SPECIFICITY.
RX PubMed=20805474; DOI=10.1073/pnas.1004408107;
RA Jaeraas M., Johnels P., Hansen N., Agerstam H., Tsapogas P., Rissler M.,
RA Lassen C., Olofsson T., Bjerrum O.W., Richter J., Fioretos T.;
RT "Isolation and killing of candidate chronic myeloid leukemia stem cells by
RT antibody targeting of IL-1 receptor accessory protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:16280-16285(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP TISSUE SPECIFICITY.
RX PubMed=22723552; DOI=10.1182/blood-2012-01-404699;
RA Barreyro L., Will B., Bartholdy B., Zhou L., Todorova T.I., Stanley R.F.,
RA Ben-Neriah S., Montagna C., Parekh S., Pellagatti A., Boultwood J.,
RA Paietta E., Ketterling R.P., Cripe L., Fernandez H.F., Greenberg P.L.,
RA Tallman M.S., Steidl C., Mitsiades C.S., Verma A., Steidl U.;
RT "Overexpression of IL-1 receptor accessory protein in stem and progenitor
RT cells and outcome correlation in AML and MDS.";
RL Blood 120:1290-1298(2012).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=23479569; DOI=10.1182/blood-2012-09-458935;
RA Askmyr M., Aagerstam H., Hansen N., Gordon S., Arvanitakis A., Rissler M.,
RA Juliusson G., Richter J., Jaeraas M., Fioretos T.;
RT "Selective killing of candidate AML stem cells by antibody targeting of
RT IL1RAP.";
RL Blood 121:3709-3713(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP TISSUE SPECIFICITY.
RX PubMed=25595648; DOI=10.1152/ajplung.00305.2014;
RA Xia J., Zhao J., Shang J., Li M., Zeng Z., Zhao J., Wang J., Xu Y., Xie J.;
RT "Increased IL-33 expression in chronic obstructive pulmonary disease.";
RL Am. J. Physiol. 308:L27-L27(2015).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 21-350 IN COMPLEX WITH IL1R2 AND
RP IL1B, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-107; ASN-111;
RP ASN-118 AND ASN-209.
RX PubMed=20802483; DOI=10.1038/ni.1925;
RA Wang D., Zhang S., Li L., Liu X., Mei K., Wang X.;
RT "Structural insights into the assembly and activation of IL-1beta with its
RT receptors.";
RL Nat. Immunol. 11:905-911(2010).
CC -!- FUNCTION: Coreceptor for IL1RL2 in the IL-36 signaling system (By
CC similarity). Coreceptor with IL1R1 in the IL-1 signaling system.
CC Associates with IL1R1 bound to IL1B to form the high affinity
CC interleukin-1 receptor complex which mediates interleukin-1-dependent
CC activation of NF-kappa-B and other pathways. Signaling involves the
CC recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or
CC IRAK2 via the respective TIR domains of the receptor/coreceptor
CC subunits. Recruits TOLLIP to the signaling complex. Does not bind to
CC interleukin-1 alone; binding of IL1RN to IL1R1, prevents its
CC association with IL1R1 to form a signaling complex. The cellular
CC response is modulated through a non-signaling association with the
CC membrane IL1R2 decoy receptor. Coreceptor for IL1RL1 in the IL-33
CC signaling system. Can bidirectionally induce pre- and postsynaptic
CC differentiation of neurons by trans-synaptically binding to PTPRD (By
CC similarity). May play a role in IL1B-mediated costimulation of IFNG
CC production from T-helper 1 (Th1) cells (Probable).
CC {ECO:0000250|UniProtKB:Q61730, ECO:0000269|PubMed:10799889,
CC ECO:0000269|PubMed:9371760, ECO:0000305|PubMed:10653850,
CC ECO:0000305|PubMed:19836339}.
CC -!- FUNCTION: [Isoform 2]: Associates with secreted ligand-bound IL1R2 and
CC increases the affinity of secreted IL1R2 for IL1B; this complex
CC formation may be the dominant mechanism for neutralization of IL1B by
CC secreted/soluble receptors (PubMed:12530978). Enhances the ability of
CC secreted IL1R1 to inhibit IL-33 signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q61730, ECO:0000269|PubMed:12530978}.
CC -!- FUNCTION: [Isoform 4]: Unable to mediate canonical IL-1 signaling
CC (PubMed:19481478). Required for Src phosphorylation by IL1B. May be
CC involved in IL1B-potentiated NMDA-induced calcium influx in neurons (By
CC similarity). {ECO:0000250|UniProtKB:Q61730,
CC ECO:0000269|PubMed:19481478}.
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: The interleukin-36 receptor complex is a heterodimer of IL1RL2
CC and IL1RAP; the association is inhibited by IL36RN (By similarity). The
CC interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP.
CC Associates with IL1R2 to form a non-signaling interleukin-1 receptor
CC complex. Isoform 4 interacts with IL1R1 in an interleukin-1-dependent
CC manner. Interacts with IL-33-bound IL1RL1 to form the minimal
CC interleukin-33 signaling complex with a 1:1:1 stoichiometry. Interacts
CC with KIT (independently of stimulation with KITLG/SCF). A mast cell-
CC specific KITLG/SCF-induced interleukin-33 signaling complex contains
CC IL1RL1, IL1RAP, KIT and MYD88 (By similarity). Interacts (via the first
CC immunoglobilin domain) with PTPRD (via the third immunoglobilin
CC domain); induces pre- and postsynaptic differentiation of neurons (By
CC similarity). {ECO:0000250|UniProtKB:Q61730,
CC ECO:0000269|PubMed:19481478, ECO:0000269|PubMed:20802483,
CC ECO:0000269|PubMed:9371760, ECO:0000269|PubMed:9862719,
CC ECO:0000305|PubMed:19836339}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Membrane-bound IL-1RAcP, mIL-1RAcP;
CC IsoId=Q9NPH3-1; Sequence=Displayed;
CC Name=2; Synonyms=Soluble IL-1RAcP, sIL-1RAcP;
CC IsoId=Q9NPH3-2; Sequence=VSP_008050, VSP_008051;
CC Name=3; Synonyms=Soluble IL-1RAcP-beta, sIL-1RAcP-beta;
CC IsoId=Q9NPH3-3; Sequence=VSP_008052;
CC Name=4; Synonyms=AcPb, mIL-1RAcP687;
CC IsoId=Q9NPH3-5; Sequence=VSP_041256;
CC -!- TISSUE SPECIFICITY: Detected in liver, skin, placenta, thymus and lung.
CC Isoform 4 is predominantly expressed in brain. Overexpressed on
CC candidate chronic myeloid leukemia (CML) stem cells, hematopoietic stem
CC cells and mononuclear cells of patients with acute myeloid leukemia
CC (AML). Overexpressed in patients with chronic obstructive pulmonary
CC disease (COPD). Expressed in T-helper 1 (Th1) and T-helper 2 (Th2) cell
CC subsets (PubMed:10653850). {ECO:0000269|PubMed:10653850,
CC ECO:0000269|PubMed:12530978, ECO:0000269|PubMed:19481478,
CC ECO:0000269|PubMed:20805474, ECO:0000269|PubMed:22723552,
CC ECO:0000269|PubMed:23479569, ECO:0000269|PubMed:25595648}.
CC -!- INDUCTION: Isoform 1 is down-regulated by phorbol ester treatment.
CC Isoform 2 is induced by phorbol ester treatment.
CC {ECO:0000269|PubMed:10799889, ECO:0000269|PubMed:12781872}.
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 -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the interleukin-1 receptor family.
CC {ECO:0000305}.
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DR EMBL; AF029213; AAB84059.1; -; mRNA.
DR EMBL; AB006537; BAA25421.1; -; mRNA.
DR EMBL; AF167343; AAF71687.1; -; mRNA.
DR EMBL; AF167340; AAF71688.1; -; Genomic_DNA.
DR EMBL; AF167335; AAF71688.1; JOINED; Genomic_DNA.
DR EMBL; AF167336; AAF71688.1; JOINED; Genomic_DNA.
DR EMBL; AF167337; AAF71688.1; JOINED; Genomic_DNA.
DR EMBL; AF167338; AAF71688.1; JOINED; Genomic_DNA.
DR EMBL; AF167339; AAF71688.1; JOINED; Genomic_DNA.
DR EMBL; AF167342; AAF71689.1; -; Genomic_DNA.
DR EMBL; AF167335; AAF71689.1; JOINED; Genomic_DNA.
DR EMBL; AF167336; AAF71689.1; JOINED; Genomic_DNA.
DR EMBL; AF167337; AAF71689.1; JOINED; Genomic_DNA.
DR EMBL; AF167338; AAF71689.1; JOINED; Genomic_DNA.
DR EMBL; AF167339; AAF71689.1; JOINED; Genomic_DNA.
DR EMBL; AF167340; AAF71689.1; JOINED; Genomic_DNA.
DR EMBL; AF167341; AAF71689.1; JOINED; Genomic_DNA.
DR EMBL; AF538730; AAQ01755.1; -; mRNA.
DR EMBL; AF538731; AAQ01756.1; -; mRNA.
DR EMBL; AF538732; AAQ01757.1; -; mRNA.
DR EMBL; AF538733; AAQ01758.1; -; mRNA.
DR EMBL; AF538734; AAQ01759.1; -; mRNA.
DR EMBL; AF487335; AAO49451.1; -; mRNA.
DR EMBL; EF591790; ABU90811.1; -; mRNA.
DR EMBL; FJ998418; ACR82488.1; -; mRNA.
DR EMBL; AC008249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78100.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78102.1; -; Genomic_DNA.
DR EMBL; BC053621; AAH53621.1; -; mRNA.
DR EMBL; AF016261; AAC39609.1; -; Genomic_DNA.
DR CCDS; CCDS3298.1; -. [Q9NPH3-1]
DR CCDS; CCDS46982.1; -. [Q9NPH3-2]
DR CCDS; CCDS54696.1; -. [Q9NPH3-5]
DR RefSeq; NP_001161400.1; NM_001167928.1. [Q9NPH3-1]
DR RefSeq; NP_001161401.1; NM_001167929.1. [Q9NPH3-1]
DR RefSeq; NP_001161402.1; NM_001167930.1. [Q9NPH3-2]
DR RefSeq; NP_001161403.1; NM_001167931.1. [Q9NPH3-5]
DR RefSeq; NP_002173.1; NM_002182.3. [Q9NPH3-1]
DR RefSeq; NP_608273.1; NM_134470.3. [Q9NPH3-2]
DR PDB; 3O4O; X-ray; 3.30 A; B=21-350.
DR PDB; 4DEP; X-ray; 3.10 A; C/F=21-367.
DR PDBsum; 3O4O; -.
DR PDBsum; 4DEP; -.
DR AlphaFoldDB; Q9NPH3; -.
DR SASBDB; Q9NPH3; -.
DR SMR; Q9NPH3; -.
DR BioGRID; 109771; 36.
DR CORUM; Q9NPH3; -.
DR DIP; DIP-33487N; -.
DR IntAct; Q9NPH3; 17.
DR MINT; Q9NPH3; -.
DR ChEMBL; CHEMBL4665591; -.
DR DrugCentral; Q9NPH3; -.
DR GuidetoPHARMACOLOGY; 1897; -.
DR GlyConnect; 1425; 13 N-Linked glycans (3 sites).
DR GlyGen; Q9NPH3; 9 sites, 13 N-linked glycans (3 sites).
DR iPTMnet; Q9NPH3; -.
DR PhosphoSitePlus; Q9NPH3; -.
DR BioMuta; IL1RAP; -.
DR DMDM; 34222652; -.
DR CPTAC; CPTAC-2221; -.
DR EPD; Q9NPH3; -.
DR jPOST; Q9NPH3; -.
DR MassIVE; Q9NPH3; -.
DR MaxQB; Q9NPH3; -.
DR PeptideAtlas; Q9NPH3; -.
DR PRIDE; Q9NPH3; -.
DR ProteomicsDB; 81999; -. [Q9NPH3-1]
DR ProteomicsDB; 82000; -. [Q9NPH3-2]
DR ProteomicsDB; 82001; -. [Q9NPH3-3]
DR ProteomicsDB; 82002; -. [Q9NPH3-5]
DR ABCD; Q9NPH3; 15 sequenced antibodies.
DR Antibodypedia; 19361; 386 antibodies from 38 providers.
DR DNASU; 3556; -.
DR Ensembl; ENST00000072516.7; ENSP00000072516.3; ENSG00000196083.10. [Q9NPH3-1]
DR Ensembl; ENST00000317757.7; ENSP00000314807.3; ENSG00000196083.10. [Q9NPH3-5]
DR Ensembl; ENST00000342550.6; ENSP00000345829.2; ENSG00000196083.10. [Q9NPH3-3]
DR Ensembl; ENST00000412504.6; ENSP00000412053.2; ENSG00000196083.10. [Q9NPH3-1]
DR Ensembl; ENST00000413869.5; ENSP00000416296.1; ENSG00000196083.10. [Q9NPH3-3]
DR Ensembl; ENST00000422485.5; ENSP00000409352.1; ENSG00000196083.10. [Q9NPH3-2]
DR Ensembl; ENST00000422940.5; ENSP00000387371.1; ENSG00000196083.10. [Q9NPH3-2]
DR Ensembl; ENST00000439062.6; ENSP00000401132.1; ENSG00000196083.10. [Q9NPH3-1]
DR Ensembl; ENST00000443369.6; ENSP00000408893.2; ENSG00000196083.10. [Q9NPH3-5]
DR Ensembl; ENST00000447382.6; ENSP00000390541.1; ENSG00000196083.10. [Q9NPH3-1]
DR GeneID; 3556; -.
DR KEGG; hsa:3556; -.
DR MANE-Select; ENST00000447382.6; ENSP00000390541.1; NM_002182.4; NP_002173.1.
DR UCSC; uc003fsk.4; human. [Q9NPH3-1]
DR CTD; 3556; -.
DR DisGeNET; 3556; -.
DR GeneCards; IL1RAP; -.
DR HGNC; HGNC:5995; IL1RAP.
DR HPA; ENSG00000196083; Tissue enriched (liver).
DR MIM; 602626; gene.
DR neXtProt; NX_Q9NPH3; -.
DR OpenTargets; ENSG00000196083; -.
DR PharmGKB; PA29811; -.
DR VEuPathDB; HostDB:ENSG00000196083; -.
DR GeneTree; ENSGT01050000244913; -.
DR HOGENOM; CLU_025552_1_0_1; -.
DR InParanoid; Q9NPH3; -.
DR OMA; KRSHRWS; -.
DR OrthoDB; 985064at2759; -.
DR PhylomeDB; Q9NPH3; -.
DR TreeFam; TF325519; -.
DR PathwayCommons; Q9NPH3; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. [Q9NPH3-1]
DR Reactome; R-HSA-388844; Receptor-type tyrosine-protein phosphatases. [Q9NPH3-1]
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [Q9NPH3-1]
DR Reactome; R-HSA-9014826; Interleukin-36 pathway. [Q9NPH3-1]
DR Reactome; R-HSA-9014843; Interleukin-33 signaling. [Q9NPH3-1]
DR Reactome; R-HSA-9020702; Interleukin-1 signaling. [Q9NPH3-1]
DR SignaLink; Q9NPH3; -.
DR SIGNOR; Q9NPH3; -.
DR BioGRID-ORCS; 3556; 15 hits in 1069 CRISPR screens.
DR ChiTaRS; IL1RAP; human.
DR EvolutionaryTrace; Q9NPH3; -.
DR GeneWiki; IL1RAP; -.
DR GenomeRNAi; 3556; -.
DR Pharos; Q9NPH3; Tclin.
DR PRO; PR:Q9NPH3; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NPH3; protein.
DR Bgee; ENSG00000196083; Expressed in right lobe of liver and 149 other tissues.
DR ExpressionAtlas; Q9NPH3; baseline and differential.
DR Genevisible; Q9NPH3; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004908; F:interleukin-1 receptor activity; IBA:GO_Central.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IBA:GO_Central.
DR GO; GO:0002114; F:interleukin-33 receptor activity; IEA:Ensembl.
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:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; IEA:Ensembl.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IEA:Ensembl.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IBA:GO_Central.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0099151; P:regulation of postsynaptic density assembly; IEA:Ensembl.
DR GO; GO:1905606; P:regulation of presynapse assembly; IEA:Ensembl.
DR GO; GO:0099560; P:synaptic membrane adhesion; IEA:Ensembl.
DR GO; GO:0099545; P:trans-synaptic signaling by trans-synaptic complex; IEA:Ensembl.
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; 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; PF18452; Ig_6; 1.
DR Pfam; PF01582; TIR; 1.
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; Cell membrane; Disulfide bond;
KW Glycoprotein; Hydrolase; Immunity; Immunoglobulin domain;
KW Inflammatory response; Innate immunity; Membrane; NAD; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..570
FT /note="Interleukin-1 receptor accessory protein"
FT /id="PRO_0000015450"
FT TOPO_DOM 21..367
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 368..388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 389..570
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..128
FT /note="Ig-like C2-type 1"
FT DOMAIN 141..230
FT /note="Ig-like C2-type 2"
FT DOMAIN 242..348
FT /note="Ig-like C2-type 3"
FT DOMAIN 403..546
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 69..85
FT /note="Essential for interaction with PTPRD"
FT /evidence="ECO:0000250|UniProtKB:Q61730"
FT REGION 549..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 482
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20802483"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20802483"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20802483"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20802483"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 24..122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:20802483"
FT DISULFID 47..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:20802483"
FT DISULFID 137..181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:20802483"
FT DISULFID 160..212
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:20802483"
FT DISULFID 266..332
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:20802483"
FT VAR_SEQ 302..570
FT /note="ISHSRTEDETRTQILSIKKVTSEDLKRSYVCHARSAKGEVAKAAKVKQKVPA
FT PRYTVELACGFGATVLLVVILIVVYHVYWLEMVLFYRAHFGTDETILDGKEYDIYVSYA
FT RNAEEEEFVLLTLRGVLENEFGYKLCIFDRDSLPGGIVTDETLSFIQKSRRLLVVLSPN
FT YVLQGTQALLELKAGLENMASRGNINVILVQYKAVKETKVKELKRAKTVLTVIKWKGEK
FT SKYPQGRFWKQLQVAMPVKKSPRRSSSDEQGLSYSSLKNV -> ASSKIHSGTGLWFWS
FT HSPASGDSHCCLPCLLARDGPILPGSFWNR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12781872"
FT /id="VSP_008052"
FT VAR_SEQ 351..356
FT /note="VPAPRY -> GNRCGQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10799889,
FT ECO:0000303|PubMed:12781872, ECO:0000303|PubMed:15489334"
FT /id="VSP_008050"
FT VAR_SEQ 357..570
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10799889,
FT ECO:0000303|PubMed:12781872, ECO:0000303|PubMed:15489334"
FT /id="VSP_008051"
FT VAR_SEQ 449..570
FT /note="IVTDETLSFIQKSRRLLVVLSPNYVLQGTQALLELKAGLENMASRGNINVIL
FT VQYKAVKETKVKELKRAKTVLTVIKWKGEKSKYPQGRFWKQLQVAMPVKKSPRRSSSDE
FT QGLSYSSLKNV -> NTVEAVFDFIQRSRRMIVVLSPDYVTEKSISMLEFKLGVMCQNS
FT IATKLIVVEYRPLEHPHPGILQLKESVSFVSWKGEKSKHSGSKFWKALRLALPLRSLSA
FT SSGWNESCSSQSDISLDHVQRRRSRLKEPPELQSSERAAGSPPAPGTMSKHRGKSSATC
FT RCCVTYCEGENHLRNKSRAEIHNQPQWETHLCKPVPQESETQWIQNGTRLEPPAPQISA
FT LALHHFTDLSNNNDFYIL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:17949817,
FT ECO:0000303|PubMed:19481478"
FT /id="VSP_041256"
FT VARIANT 473
FT /note="V -> M (in dbSNP:rs34661910)"
FT /id="VAR_053383"
FT STRAND 25..29
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:3O4O"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:4DEP"
FT HELIX 49..53
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:4DEP"
FT HELIX 58..63
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 67..76
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:4DEP"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:4DEP"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 110..117
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 122..132
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 146..150
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 196..201
FT /evidence="ECO:0007829|PDB:4DEP"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 208..218
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 221..234
FT /evidence="ECO:0007829|PDB:4DEP"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 244..248
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:3O4O"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 279..285
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 300..303
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 310..314
FT /evidence="ECO:0007829|PDB:4DEP"
FT TURN 323..327
FT /evidence="ECO:0007829|PDB:3O4O"
FT STRAND 331..335
FT /evidence="ECO:0007829|PDB:4DEP"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:4DEP"
SQ SEQUENCE 570 AA; 65418 MW; 5F47F8D0ECA98B8A CRC64;
MTLLWCVVSL YFYGILQSDA SERCDDWGLD TMRQIQVFED EPARIKCPLF EHFLKFNYST
AHSAGLTLIW YWTRQDRDLE EPINFRLPEN RISKEKDVLW FRPTLLNDTG NYTCMLRNTT
YCSKVAFPLE VVQKDSCFNS PMKLPVHKLY IEYGIQRITC PNVDGYFPSS VKPTITWYMG
CYKIQNFNNV IPEGMNLSFL IALISNNGNY TCVVTYPENG RTFHLTRTLT VKVVGSPKNA
VPPVIHSPND HVVYEKEPGE ELLIPCTVYF SFLMDSRNEV WWTIDGKKPD DITIDVTINE
SISHSRTEDE TRTQILSIKK VTSEDLKRSY VCHARSAKGE VAKAAKVKQK VPAPRYTVEL
ACGFGATVLL VVILIVVYHV YWLEMVLFYR AHFGTDETIL DGKEYDIYVS YARNAEEEEF
VLLTLRGVLE NEFGYKLCIF DRDSLPGGIV TDETLSFIQK SRRLLVVLSP NYVLQGTQAL
LELKAGLENM ASRGNINVIL VQYKAVKETK VKELKRAKTV LTVIKWKGEK SKYPQGRFWK
QLQVAMPVKK SPRRSSSDEQ GLSYSSLKNV
