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P14778 (IL1R1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 177. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-1 receptor type 1

Short name=IL-1R-1
Short name=IL-1RT-1
Short name=IL-1RT1
Alternative name(s):
CD121 antigen-like family member A
Interleukin-1 receptor alpha
Short name=IL-1R-alpha
Interleukin-1 receptor type I
p80
CD_antigen=CD121a

Cleaved into the following 2 chains:

  1. Interleukin-1 receptor type 1, membrane form
    Short name=mIL-1R1
    Short name=mIL-1RI
  2. Interleukin-1 receptor type 1, soluble form
    Short name=sIL-1R1
    Short name=sIL-1RI
Gene names
Name:IL1R1
Synonyms:IL1R, IL1RA, IL1RT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length569 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the corecptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK 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. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling complex. Ref.11

Subunit structure

The interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP. Interacts with PIK3R1. Ref.9 Ref.10

Subcellular location

Membrane; Single-pass type I membrane protein. Cell membrane Probable. Secreted Ref.7.

Post-translational modification

A soluble form (sIL1R1) is probably produced by proteolytic cleavage at the cell surface (shedding).

Rapidly phosphorylated on Tyr-496 in response to IL-1, which creates a SH2 binding site for the PI 3-kinase regulatory subunit PIK3R1. Ref.10

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 componentCell membrane
Membrane
Secreted
   Coding sequence diversityPolymorphism
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell surface receptor signaling pathway

Traceable author statement PubMed 1833184. Source: ProtInc

immune response

Traceable author statement PubMed 9120302. Source: ProtInc

interleukin-1-mediated signaling pathway

Inferred from direct assay PubMed 10383454. Source: BHF-UCL

regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from direct assay PubMed 10383454. Source: BHF-UCL

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement Ref.2. Source: ProtInc

membrane

Inferred from direct assay PubMed 16477012. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioninterleukin-1 receptor activity

Inferred from direct assay PubMed 10383454. Source: BHF-UCL

interleukin-1, Type I, activating receptor activity

Traceable author statement PubMed 9120302. Source: ProtInc

platelet-derived growth factor receptor binding

Inferred from physical interaction PubMed 16477012. Source: BHF-UCL

signal transducer activity

Traceable author statement Ref.2PubMed 9120302. Source: ProtInc

transmembrane signaling receptor activity

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TRAF6Q9Y4K32EBI-525905,EBI-359276

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717
Chain18 – 569552Interleukin-1 receptor type 1, membrane form
PRO_0000015435
Chain18 – ?Interleukin-1 receptor type 1, soluble formPRO_0000415344

Regions

Topological domain18 – 336319Extracellular Potential
Transmembrane337 – 35620Helical; Potential
Topological domain357 – 569213Cytoplasmic Potential
Domain23 – 11088Ig-like C2-type 1
Domain118 – 21093Ig-like C2-type 2
Domain226 – 328103Ig-like C2-type 3
Domain383 – 541159TIR

Amino acid modifications

Modified residue4961Phosphotyrosine Ref.10
Glycosylation1001N-linked (GlcNAc...) Potential
Glycosylation1931N-linked (GlcNAc...) Potential
Glycosylation2331N-linked (GlcNAc...) Potential
Glycosylation2491N-linked (GlcNAc...) Potential
Glycosylation2631N-linked (GlcNAc...) Potential
Glycosylation2971N-linked (GlcNAc...) Potential
Disulfide bond23 ↔ 104
Disulfide bond44 ↔ 96
Disulfide bond121 ↔ 164
Disulfide bond142 ↔ 196
Disulfide bond248 ↔ 312

Natural variations

Natural variant1241A → G. Ref.3
Corresponds to variant rs2228139 [ dbSNP | Ensembl ].
VAR_019131
Natural variant3441T → M.
Corresponds to variant rs28362304 [ dbSNP | Ensembl ].
VAR_029189

Experimental info

Mutagenesis3691D → A: Reduces NF-kappa-B activation. Ref.11
Mutagenesis4281R → A: Reduces NF-kappa-B activation and receptor-associated kinase activation. Ref.11

Secondary structure

.................................................................... 569
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P14778 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 5BAA83F8F0225C25

FASTA56965,402
        10         20         30         40         50         60 
MKVLLRLICF IALLISSLEA DKCKEREEKI ILVSSANEID VRPCPLNPNE HKGTITWYKD 

        70         80         90        100        110        120 
DSKTPVSTEQ ASRIHQHKEK LWFVPAKVED SGHYYCVVRN SSYCLRIKIS AKFVENEPNL 

       130        140        150        160        170        180 
CYNAQAIFKQ KLPVAGDGGL VCPYMEFFKN ENNELPKLQW YKDCKPLLLD NIHFSGVKDR 

       190        200        210        220        230        240 
LIVMNVAEKH RGNYTCHASY TYLGKQYPIT RVIEFITLEE NKPTRPVIVS PANETMEVDL 

       250        260        270        280        290        300 
GSQIQLICNV TGQLSDIAYW KWNGSVIDED DPVLGEDYYS VENPANKRRS TLITVLNISE 

       310        320        330        340        350        360 
IESRFYKHPF TCFAKNTHGI DAAYIQLIYP VTNFQKHMIG ICVTLTVIIV CSVFIYKIFK 

       370        380        390        400        410        420 
IDIVLWYRDS CYDFLPIKAS DGKTYDAYIL YPKTVGEGST SDCDIFVFKV LPEVLEKQCG 

       430        440        450        460        470        480 
YKLFIYGRDD YVGEDIVEVI NENVKKSRRL IIILVRETSG FSWLGGSSEE QIAMYNALVQ 

       490        500        510        520        530        540 
DGIKVVLLEL EKIQDYEKMP ESIKFIKQKH GAIRWSGDFT QGPQSAKTRF WKNVRYHMPV 

       550        560 
QRRSPSSKHQ LLSPATKEKL QREAHVPLG 

« Hide

References

« Hide 'large scale' references
[1]"Sequence of the cDNA for the human fibroblast type interleukin-1 receptor."
Chua A.O., Gubler U.
Nucleic Acids Res. 17:10114-10114(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Cloning the interleukin 1 receptor from human T cells."
Sims J.E., Acres R.B., Grubin C.E., McMahan C.J., Wignall J.M., March C.J., Dower S.K.
Proc. Natl. Acad. Sci. U.S.A. 86:8946-8950(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: T-cell.
[3]SeattleSNPs variation discovery resource
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-124.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Specific binding of interleukin 1 (IL-1) beta and IL-1 receptor antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to soluble IL-1 receptor type I."
Svenson M., Hansen M.B., Heegaard P., Abell K., Bendtzen K.
Cytokine 5:427-435(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[8]"Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses."
Giri J.G., Wells J., Dower S.K., McCall C.E., Guzman R.N., Slack J., Bird T.A., Shanebeck K., Grabstein K.H., Sims J.E., Alderson M.R.
J. Immunol. 153:5802-5809(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: LIGAND-BINDING.
[9]"Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein."
Huang J., Gao X., Li S., Cao Z.
Proc. Natl. Acad. Sci. U.S.A. 94:12829-12832(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL1RAP AND IRAK1.
Tissue: Placenta.
[10]"Phosphatidylinositol 3-kinase is recruited to a specific site in the activated IL-1 receptor I."
Marmiroli S., Bavelloni A., Faenza I., Sirri A., Ognibene A., Cenni V., Tsukada J., Koyama Y., Ruzzene M., Ferri A., Auron P.E., Toker A., Maraldi N.M.
FEBS Lett. 438:49-54(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-496, INTERACTION WITH PIK3R1.
[11]"Identification of two major sites in the type I interleukin-1 receptor cytoplasmic region responsible for coupling to pro-inflammatory signaling pathways."
Slack J.L., Schooley K., Bonnert T.P., Mitcham J.L., Qwarnstrom E.E., Sims J.E., Dower S.K.
J. Biol. Chem. 275:4670-4678(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-369 AND ARG-428.
[12]"Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1beta."
Vigers G.P.A., Anderson L.J., Caffes P., Brandhuber B.J.
Nature 386:190-194(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-332 IN COMPLEX WITH IL1B.
[13]"A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist."
Schreuder H., Tardif C., Trump-Kallmeyer S., Soffientini A., Sarubbi E., Akeson A., Bowlin T., Yanofsky S., Barrett R.W.
Nature 386:194-200(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 21-331 IN COMPLEX WITH IL1RA.
[14]"X-ray crystal structure of a small antagonist peptide bound to interleukin-1 receptor type 1."
Vigers G.P.A., Dripps D.J., Edwards C.K. III, Brandhuber B.J.
J. Biol. Chem. 275:36927-36933(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 4-315 IN COMPLEX WITH THE ANTAGONIST PEPTIDE AF10847.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X16896 mRNA. Translation: CAA34773.1.
M27492 mRNA. Translation: AAA59137.1.
AF531102 Genomic DNA. Translation: AAM88423.1.
AC007271 Genomic DNA. Translation: AAX81988.1.
CH471127 Genomic DNA. Translation: EAX01799.1.
BC067506 mRNA. Translation: AAH67506.1.
BC075062 mRNA. Translation: AAH75062.1.
BC075063 mRNA. Translation: AAH75063.1.
PIRA36187.
RefSeqNP_000868.1. NM_000877.3.
NP_001275635.1. NM_001288706.1.
XP_005263986.1. XM_005263929.1.
XP_005263987.1. XM_005263930.2.
XP_005263988.1. XM_005263931.1.
XP_005263989.1. XM_005263932.1.
XP_005263990.1. XM_005263933.2.
XP_005263991.1. XM_005263934.2.
UniGeneHs.701982.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1G0YX-ray3.00R21-332[»]
1IRAX-ray2.70Y18-336[»]
1ITBX-ray2.50B18-332[»]
4DEPX-ray3.10B/E18-336[»]
4GAFX-ray2.15B18-336[»]
ProteinModelPortalP14778.
SMRP14778. Positions 23-332, 383-539.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109770. 18 interactions.
DIPDIP-93N.
IntActP14778. 6 interactions.
MINTMINT-262640.
STRING9606.ENSP00000233946.

Chemistry

ChEMBLCHEMBL1959.
DrugBankDB00026. Anakinra.

PTM databases

PhosphoSiteP14778.

Polymorphism databases

DMDM124308.

Proteomic databases

PaxDbP14778.
PRIDEP14778.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233946; ENSP00000233946; ENSG00000115594.
ENST00000410023; ENSP00000386380; ENSG00000115594.
GeneID3554.
KEGGhsa:3554.
UCSCuc002tbq.3. human.

Organism-specific databases

CTD3554.
GeneCardsGC02P102681.
HGNCHGNC:5993. IL1R1.
HPACAB007779.
MIM147810. gene.
neXtProtNX_P14778.
PharmGKBPA29809.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40914.
HOGENOMHOG000253916.
HOVERGENHBG052103.
InParanoidP14778.
KOK04386.
OMAIQDYEKM.
OrthoDBEOG7H1JK3.
PhylomeDBP14778.
TreeFamTF325519.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkP14778.

Gene expression databases

ArrayExpressP14778.
BgeeP14778.
CleanExHS_IL1R1.
GenevestigatorP14778.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
3.40.50.10140. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR015621. IL-1_rcpt_fam.
IPR004076. IL-1_rcpt_I-typ.
IPR004074. IL-1_rcpt_I/II-typ.
IPR000157. TIR_dom.
[Graphical view]
PANTHERPTHR11890. PTHR11890. 1 hit.
PfamPF07679. I-set. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PRINTSPR01538. INTRLEUKN1R1.
PR01536. INTRLKN1R12F.
SMARTSM00409. IG. 2 hits.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMSSF52200. SSF52200. 1 hit.
PROSITEPS50835. IG_LIKE. 3 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIL1R1. human.
EvolutionaryTraceP14778.
GeneWikiInterleukin_1_receptor,_type_I.
GenomeRNAi3554.
NextBio13876.
PROP14778.
SOURCESearch...

Entry information

Entry nameIL1R1_HUMAN
AccessionPrimary (citable) accession number: P14778
Secondary accession number(s): Q587I7
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: April 16, 2014
This is version 177 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries