P14778 (IL1R1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	569 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	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). Rapidely 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 component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	immune response Traceable author statement PubMed 9120302. Source: ProtInc
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.2. Source: ProtInc
Molecular_function	interleukin-1, Type I, activating receptor activity Traceable author statement PubMed 9120302. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TRAF6	Q9Y4K3	2	EBI-525905,EBI-359276

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Chain

18 – 569

552

Interleukin-1 receptor type 1, membrane form

PRO_0000015435

Chain

18 – ?

Interleukin-1 receptor type 1, soluble form

PRO_0000415344

Regions

Topological domain

18 – 336

319

Extracellular Potential

Transmembrane

337 – 356

20

Helical; Potential

Topological domain

357 – 569

213

Cytoplasmic Potential

Domain

23 – 110

88

Ig-like C2-type 1

Domain

118 – 210

93

Ig-like C2-type 2

Domain

226 – 328

103

Ig-like C2-type 3

Domain

383 – 541

159

TIR

Amino acid modifications

Modified residue

496

1

Phosphotyrosine Ref.10

Glycosylation

100

1

N-linked (GlcNAc...) Potential

Glycosylation

193

1

N-linked (GlcNAc...) Potential

Glycosylation

233

1

N-linked (GlcNAc...) Potential

Glycosylation

249

1

N-linked (GlcNAc...) Potential

Glycosylation

263

1

N-linked (GlcNAc...) Potential

Glycosylation

297

1

N-linked (GlcNAc...) Potential

Disulfide bond

23 ↔ 104

Disulfide bond

44 ↔ 96

Disulfide bond

121 ↔ 164

Disulfide bond

142 ↔ 196

Disulfide bond

248 ↔ 312

Natural variations

Natural variant

124

1

A → G. Ref.3
Corresponds to variant rs2228139 [ dbSNP | Ensembl ].

VAR_019131

Natural variant

344

1

T → M.
Corresponds to variant rs28362304 [ dbSNP | Ensembl ].

VAR_029189

Experimental info

Mutagenesis

369

1

D → A: Reduces NF-kappa-B activation. Ref.11

Mutagenesis

428

1

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

Secondary structure

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569

Helix Strand Turn

Details...

Beta strand

25 – 28

4

Beta strand

33 – 35

3

Beta strand

40 – 42

3

Helix

48 – 50

3

Beta strand

52 – 58

7

Beta strand

72 – 76

5

Beta strand

78 – 82

5

Helix

88 – 90

3

Beta strand

95 – 99

5

Beta strand

100 – 102

3

Beta strand

104 – 108

5

Beta strand

112 – 114

3

Beta strand

120 – 122

3

Helix

124 – 126

3

Beta strand

127 – 133

7

Beta strand

135 – 137

3

Beta strand

138 – 141

4

Turn

146 – 148

3

Turn

150 – 153

4

Beta strand

159 – 162

4

Beta strand

171 – 177

7

Beta strand

180 – 185

6

Helix

188 – 190

3

Beta strand

192 – 202

11

Beta strand

205 – 218

14

Beta strand

227 – 230

4

Beta strand

233 – 237

5

Beta strand

240 – 242

3

Beta strand

244 – 252

9

Beta strand

256 – 262

7

Beta strand

272 – 281

10

Helix

287 – 289

3

Beta strand

290 – 300

11

Helix

303 – 306

4

Beta strand

310 – 315

6

Beta strand

321 – 328

8

Sequences

	Sequence		Length	Mass (Da)
	P14778 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 5BAA83F8F0225C25	FASTA	569	65,402
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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

SeattleSNPs

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.

IPI

IPI00027508.

PIR

A36187.

RefSeq

NP_000868.1. NM_000877.2.

UniGene

Hs.701982.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G0Y	X-ray	3.00	R	21-332	[»]
1IRA	X-ray	2.70	Y	18-336	[»]
1ITB	X-ray	2.50	B	18-332	[»]
4DEP	X-ray	3.10	B/E	18-336	[»]
4GAF	X-ray	2.15	B	18-336	[»]

ProteinModelPortal

P14778.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-93N.

IntAct

P14778. 6 interactions.

STRING

9606.ENSP00000233946.

PTM databases

PhosphoSite

P14778.

Polymorphism databases

DMDM

124308.

Proteomic databases

PaxDb

P14778.

PRIDE

P14778.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000233946; ENSP00000233946; ENSG00000115594.
ENST00000410023; ENSP00000386380; ENSG00000115594.

GeneID

3554.

KEGG

hsa:3554.

UCSC

uc002tbq.3. human.

Organism-specific databases

CTD

3554.

GeneCards

GC02P102681.

HGNC

HGNC:5993. IL1R1.

HPA

CAB007779.

MIM

147810. gene.

neXtProt

NX_P14778.

PharmGKB

PA29809.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40914.

HOGENOM

HOG000253916.

HOVERGEN

HBG052103.

InParanoid

P14778.

KO

K04386.

OMA

IQDYEKM.

OrthoDB

EOG46HG9Q.

PhylomeDB

P14778.

Enzyme and pathway databases

Pathway_Interaction_DB

il1pathway. IL1-mediated signaling events.
il12_2pathway. IL12-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P14778.

Bgee

P14778.

CleanEx

HS_IL1R1.

Genevestigator

P14778.

GermOnline

ENSG00000115594. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 3 hits.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR015621. IL1-receptor_fam.
IPR004074. IL1_rcpt_I/II.
IPR004076. IL1R_rcpt.
IPR000157. TIR_dom.
[Graphical view]

PANTHER

PTHR11890. PTHR11890. 1 hit.

Pfam

PF07679. I-set. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]

PRINTS

PR01538. INTRLEUKN1R1.
PR01536. INTRLKN1R12F.

SMART

SM00409. IG. 2 hits.
SM00255. TIR. 1 hit.
[Graphical view]

SUPFAM

SSF52200. TIR. 1 hit.

PROSITE

PS50835. IG_LIKE. 3 hits.
PS50104. TIR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1959.

ChiTaRS

IL1R1. human.

DrugBank

DB00026. Anakinra.

EvolutionaryTrace

P14778.

GenomeRNAi

3554.

NextBio

13876.

SOURCE

Search...

Entry information

Entry name

IL1R1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 167 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.