Q61730 (IL1AP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-1 receptor accessory protein
Short name=IL-1 receptor accessory protein
Short name=IL-1RAcP

Gene names

Name:

Il1rap

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	570 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Coreceptor with IL1R1. Associates with IL1R1 bound to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Recruits TOLLIP to the signaling complex. Does not bind to interleukin-1 alone; binding of IL1RN to IL1R1, prevents its association with IL1R1 to form a signaling complex. The cellular response is modulated through a non-signaling association with the membrane IL1R2 decoy receptor. Secreted forms (isoforms 2 and 3) associate with secreted ligand-bound IL1R2 and increase the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors By similarity.
Subunit structure	The interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP. Associates with IL1R2 to form a non-signaling interleukin-1 receptor complex.
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.1. Isoform 2: Secreted Ref.1.
Tissue specificity	Detected in lung, brain, spleen, thymus and liver. Ref.1
Sequence similarities	Belongs to the interleukin-1 receptor family. Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 TIR domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	innate immune response Inferred from electronic annotation. Source: InterPro interleukin-2 biosynthetic process Inferred from direct assay Ref.6. Source: MGI
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intracellular Inferred from electronic annotation. Source: InterPro plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	interleukin-1 receptor activity Inferred from direct assay Ref.6. Source: MGI protein binding Inferred from physical interaction Ref.5. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Tollip	Q9QZ06	2	EBI-525035,EBI-74272

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q61730-1)

Also known as: MuIL-1R AcP;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q61730-2)

Also known as: SmuIL-1R AcP;

The sequence of this isoform differs from the canonical sequence as follows:
     351-359: VIPPRYTVE → GNGCTEPMTL
     360-570: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 570	550	Interleukin-1 receptor accessory protein		PRO_0000015452
Regions
	Topological domain	21 – 367	347	Extracellular Potential
	Transmembrane	368 – 388	21	Helical; Potential
	Topological domain	389 – 570	182	Cytoplasmic Potential
	Domain	21 – 128	108	Ig-like C2-type 1
	Domain	139 – 230	92	Ig-like C2-type 2
	Domain	243 – 348	106	Ig-like C2-type 3
	Domain	403 – 549	147	TIR
Amino acid modifications
	Modified residue	395	1	Phosphothreonine Ref.9
	Modified residue	398	1	Phosphothreonine Ref.9
	Modified residue	555	1	Phosphoserine By similarity
	Modified residue	556	1	Phosphoserine By similarity
	Glycosylation	57	1	N-linked (GlcNAc...) Potential
	Glycosylation	107	1	N-linked (GlcNAc...) Potential
	Glycosylation	111	1	N-linked (GlcNAc...) Potential
	Glycosylation	118	1	N-linked (GlcNAc...) Potential
	Glycosylation	196	1	N-linked (GlcNAc...) Potential
	Glycosylation	209	1	N-linked (GlcNAc...) Potential
	Glycosylation	299	1	N-linked (GlcNAc...) Potential
	Disulfide bond	24 ↔ 122		By similarity
	Disulfide bond	47 ↔ 114		By similarity
	Disulfide bond	137 ↔ 181		By similarity
	Disulfide bond	160 ↔ 212		By similarity
	Disulfide bond	266 ↔ 332		By similarity
Natural variations
	Alternative sequence	351 – 359	9	VIPPRYTVE → GNGCTEPMTL in isoform 2.		VSP_008054
	Alternative sequence	360 – 570	211	Missing in isoform 2.		VSP_008055
Experimental info
	Mutagenesis	527 – 534	8	KGEKSKYP → AAAAAAAA: Abolishes interaction with MYD88 and IL-1-dependent activation of NF-kappa-B. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MuIL-1R AcP) [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 4D4B07E0310AFDC5	FASTA	570	65,741
	10 20 30 40 50 60 MGLLWYLMSL SFYGILQSHA SERCDDWGLD TMRQIQVFED EPARIKCPLF EHFLKYNYST 70 80 90 100 110 120 AHSSGLTLIW YWTRQDRDLE EPINFRLPEN RISKEKDVLW FRPTLLNDTG NYTCMLRNTT 130 140 150 160 170 180 YCSKVAFPLE VVQKDSCFNS AMRFPVHKMY IEHGIHKITC PNVDGYFPSS VKPSVTWYKG 190 200 210 220 230 240 CTEIVDFHNV LPEGMNLSFF IPLVSNNGNY TCVVTYPENG RLFHLTRTVT VKVVGSPKDA 250 260 270 280 290 300 LPPQIYSPND RVVYEKEPGE ELVIPCKVYF SFIMDSHNEV WWTIDGKKPD DVTVDITINE 310 320 330 340 350 360 SVSYSSTEDE TRTQILSIKK VTPEDLRRNY VCHARNTKGE AEQAAKVKQK VIPPRYTVEL 370 380 390 400 410 420 ACGFGATVFL VVVLIVVYHV YWLEMVLFYR AHFGTDETIL DGKEYDIYVS YARNVEEEEF 430 440 450 460 470 480 VLLTLRGVLE NEFGYKLCIF DRDSLPGGIV TDETLSFIQK SRRLLVVLSP NYVLQGTQAL 490 500 510 520 530 540 LELKAGLENM ASRGNINVIL VQYKAVKDMK VKELKRAKTV LTVIKWKGEK SKYPQGRFWK 550 560 570 QLQVAMPVKK SPRWSSNDKQ GLSYSSLKNV
	Isoform 2 (SmuIL-1R AcP) [UniParc]. Checksum: E525471759FF7719	FASTA	360	41,567
	10 20 30 40 50 60 MGLLWYLMSL SFYGILQSHA SERCDDWGLD TMRQIQVFED EPARIKCPLF EHFLKYNYST 70 80 90 100 110 120 AHSSGLTLIW YWTRQDRDLE EPINFRLPEN RISKEKDVLW FRPTLLNDTG NYTCMLRNTT 130 140 150 160 170 180 YCSKVAFPLE VVQKDSCFNS AMRFPVHKMY IEHGIHKITC PNVDGYFPSS VKPSVTWYKG 190 200 210 220 230 240 CTEIVDFHNV LPEGMNLSFF IPLVSNNGNY TCVVTYPENG RLFHLTRTVT VKVVGSPKDA 250 260 270 280 290 300 LPPQIYSPND RVVYEKEPGE ELVIPCKVYF SFIMDSHNEV WWTIDGKKPD DVTVDITINE 310 320 330 340 350 360 SVSYSSTEDE TRTQILSIKK VTPEDLRRNY VCHARNTKGE AEQAAKVKQK GNGCTEPMTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex." Greenfeder S.A., Nunes P., Kwee L., Labow M., Chizzonite R.A., Ju G. J. Biol. Chem. 270:13757-13765(1995) [PubMed: 7775431] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH IL1R1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION. Tissue: Fibroblast.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Brain and Spinal cord.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Liver.
[4]	"The type II IL-1 receptor interacts with the IL-1 receptor accessory protein: a novel mechanism of regulation of IL-1 responsiveness." Lang D., Knop J., Wesche H., Raffetseder U., Kurrle R., Boraschi D., Martin M.U. J. Immunol. 161:6871-6877(1998) [PubMed: 9862719] [Abstract] Cited for: INTERACTION WITH IL1R2.
[5]	"Tollip, a new component of the IL-1R1 pathway, links IRAK to the IL-1 receptor." Burns K., Clatworthy J., Martin L., Martinon F., Plumpton C., Maschera B., Lewis A., Ray K., Tschopp J., Volpe F. Nat. Cell Biol. 2:346-351(2000) [PubMed: 10854325] [Abstract] Cited for: INTERACTION WITH TOLLIP.
[6]	"Identification of essential regions in the cytoplasmic tail of interleukin-1 receptor accessory protein critical for interleukin-1 signaling." Radons J., Gabler S., Wesche H., Korherr C., Hofmeister R., Falk W. J. Biol. Chem. 277:16456-16463(2002) [PubMed: 11880380] [Abstract] Cited for: MUTAGENESIS OF 527-LYS--PRO-534, INTERACTION WITH MYD88, FUNCTION.
[7]	"Characterization of a cascade of protein interactions initiated at the IL-1 receptor." Boch J.A., Yoshida Y., Koyama Y., Wara-Aswapati N., Peng H., Unlu S., Auron P.E. Biochem. Biophys. Res. Commun. 303:525-531(2003) [PubMed: 12659850] [Abstract] Cited for: INTERACTION WITH IRAK2.
[8]	"Soluble interleukin-1 receptor accessory protein ameliorates collagen-induced arthritis by a different mode of action from that of interleukin-1 receptor antagonist." Smeets R.L., Joosten L.A., Arntz O.J., Bennink M.B., Takahashi N., Carlsen H., Martin M.U., van den Berg W.B., van de Loo F.A. Arthritis Rheum. 52:2202-2211(2005) [PubMed: 15986350] [Abstract] Cited for: FUNCTION.
[9]	"A differential phosphoproteomic analysis of retinoic acid-treated P19 cells." Smith J.C., Duchesne M.A., Tozzi P., Ethier M., Figeys D. J. Proteome Res. 6:3174-3186(2007) [PubMed: 17622165] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-395 AND THR-398, MASS SPECTROMETRY. Tissue: Teratocarcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X85999 mRNA. Translation: CAA59991.1. AK039582 mRNA. Translation: BAC30392.1. AK045686 mRNA. Translation: BAC32457.1. BC021159 mRNA. Translation: AAH21159.1.
IPI	IPI00113879. IPI00124823.
PIR	A57535.
RefSeq	NP_032390.1. NM_008364.2. NP_598864.1. NM_134103.2.
UniGene	Mm.253424.
3D structure databases
ProteinModelPortal	Q61730.
SMR	Q61730. Positions 24-346, 403-548.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-296N.
IntAct	Q61730. 3 interactions.
STRING	Q61730.
PTM databases
PhosphoSite	Q61730.
Proteomic databases
PRIDE	Q61730.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000023156; ENSMUSP00000023156; ENSMUSG00000022514. ENSMUST00000174202; ENSMUSP00000134202; ENSMUSG00000022514.
GeneID	16180.
KEGG	mmu:16180.
UCSC	uc007yve.2. mouse.
Organism-specific databases
CTD	3556.
MGI	MGI:104975. Il1rap.
Phylogenomic databases
GeneTree	ENSGT00570000079082.
HOVERGEN	HBG104298.
OMA	VQKITCP.
OrthoDB	EOG46MBJ6.
PhylomeDB	Q61730.
Gene expression databases
ArrayExpress	Q61730.
Bgee	Q61730.
CleanEx	MM_IL1RAP.
Genevestigator	Q61730.
GermOnline	ENSMUSG00000022514. Mus musculus.
Family and domain databases
InterPro	IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR015621. IL1-receptor. IPR004075. IL1_rcpt_1. IPR004074. IL1_rcpt_I/II. IPR000157. TIR_dom. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 3 hits.
KO	K04723.
PANTHER	PTHR11890. IL1-receptor. 1 hit.
Pfam	PF01582. TIR. 1 hit. [Graphical view]
PRINTS	PR01536. INTRLKN1R12F. PR01537. INTRLKN1R1F.
SMART	SM00409. IG. 3 hits. SM00255. TIR. 1 hit. [Graphical view]
SUPFAM	SSF52200. TIR. 1 hit.
PROSITE	PS50835. IG_LIKE. 2 hits. PS50104. TIR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	289053.
SOURCE	Search...

Entry information

Entry name

IL1AP_MOUSE

Accession

Primary (citable) accession number: Q61730
Secondary accession number(s): Q8VCB9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 22, 2003
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program