P27930 (IL1R2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-1 receptor type 2
Short name=IL-1R-2
Short name=IL-1RT-2
Short name=IL-1RT2

Alternative name(s):
CD121 antigen-like family member B
CDw121b
IL-1 type II receptor
Interleukin-1 receptor beta
Short name=IL-1R-beta
Interleukin-1 receptor type II
CD_antigen=CD121b

Cleaved into the following 2 chains:

1. Interleukin-1 receptor type 2, membrane form
   Short name=mIL-1R2
   Short name=mIL-1RII
2. Interleukin-1 receptor type 2, soluble form
   Short name=sIL-1R2
   Short name=sIL-1RII

Gene names

Name:	IL1R2
Synonyms:	IL1RB

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	398 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	Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competetive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular response through non-signaling association with IL1RAP after binding to IL1B. IL1R2 (membrane and secreted forms) preferentially binds IL1B and poorly IL1A and IL1RN. The secreted IL1R2 recruits secreted IL1RAP with high affinity; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors. Ref.8 Ref.11 Ref.12 Ref.13
Subunit structure	Associates with IL1RAP to form a non-signaling interleukin-1 receptor complex. Ref.14
Subcellular location	Isoform Short: Secreted Ref.2. Isoform Long: Cell membrane; Single-pass type I membrane protein Ref.2.
Post-translational modification	A soluble form (sIL1R2) can also be produced by proteolytic cleavage at the cell surface (shedding) involving a metalloproteinase; hovever, several sIL1R2 forms ranging from 45 and 60 kDa are reported.
Sequence similarities	Belongs to the interleukin-1 receptor family. Contains 3 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing 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 8898719. Source: ProtInc
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	interleukin-1 receptor activity Traceable author statement PubMed 10191101. Source: ProtInc interleukin-1, Type II, blocking receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform Long (identifier: P27930-1)

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 Short (identifier: P27930-2)

The sequence of this isoform differs from the canonical sequence as follows:
     297-398: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 13

13

Potential

Chain

14 – 398

385

Interleukin-1 receptor type 2, membrane form

PRO_0000015439

Chain

14 – ?

Interleukin-1 receptor type 2, soluble form

PRO_0000415348

Regions

Topological domain

14 – 343

330

Extracellular Potential

Transmembrane

344 – 369

26

Helical; Potential

Topological domain

370 – 398

29

Cytoplasmic Potential

Domain

18 – 124

107

Ig-like C2-type 1

Domain

134 – 223

90

Ig-like C2-type 2

Domain

237 – 349

113

Ig-like C2-type 3

Region

329 – 343

15

Contains proteolytic cleavage site Probable

Amino acid modifications

Modified residue

22

1

Phosphothreonine By similarity

Modified residue

109

1

Phosphothreonine By similarity

Glycosylation

66

1

N-linked (GlcNAc...) Potential

Glycosylation

72

1

N-linked (GlcNAc...) Potential

Glycosylation

112

1

N-linked (GlcNAc...) Ref.14

Glycosylation

219

1

N-linked (GlcNAc...) Ref.14

Glycosylation

277

1

N-linked (GlcNAc...) Potential

Disulfide bond

28 ↔ 116

Ref.14

Disulfide bond

50 ↔ 108

Ref.14

Disulfide bond

152 ↔ 207

Ref.14

Disulfide bond

258 ↔ 326

Ref.14

Natural variations

Alternative sequence

297 – 398

102

Missing in isoform Short.

VSP_042222

Natural variant

181

1

E → K. Ref.4
Corresponds to variant rs28385682 [ dbSNP | Ensembl ].

VAR_019132

Natural variant

292

1

E → K. Ref.4
Corresponds to variant rs3218976 [ dbSNP | Ensembl ].

VAR_019133

Experimental info

Sequence conflict

123

1

L → F in AAD00242. Ref.2

Sequence conflict

171

1

K → R in AAD00242. Ref.2

Sequence conflict

199

1

L → Q in AAD00242. Ref.2

Secondary structure

1

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398

Helix Strand Turn

Details...

Beta strand

29 – 33

5

Beta strand

38 – 41

4

Beta strand

47 – 49

3

Beta strand

70 – 73

4

Beta strand

82 – 84

3

Beta strand

86 – 89

4

Beta strand

92 – 98

7

Beta strand

104 – 107

4

Beta strand

110 – 112

3

Beta strand

115 – 126

12

Helix

130 – 132

3

Helix

133 – 136

4

Beta strand

138 – 143

6

Beta strand

148 – 151

4

Turn

156 – 158

3

Beta strand

161 – 163

3

Beta strand

170 – 173

4

Beta strand

181 – 185

5

Beta strand

189 – 196

8

Helix

199 – 201

3

Beta strand

203 – 210

8

Beta strand

219 – 229

11

Beta strand

260 – 265

6

Beta strand

271 – 279

9

Beta strand

281 – 285

5

Beta strand

287 – 289

3

Beta strand

301 – 303

3

Beta strand

305 – 308

4

Beta strand

325 – 330

6

Beta strand

333 – 335

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 2C2A03ADA6F3AC5B	FASTA	398	45,421
	10 20 30 40 50 60 MLRLYVLVMG VSAFTLQPAA HTGAARSCRF RGRHYKREFR LEGEPVALRC PQVPYWLWAS 70 80 90 100 110 120 VSPRINLTWH KNDSARTVPG EEETRMWAQD GALWLLPALQ EDSGTYVCTT RNASYCDKMS 130 140 150 160 170 180 IELRVFENTD AFLPFISYPQ ILTLSTSGVL VCPDLSEFTR DKTDVKIQWY KDSLLLDKDN 190 200 210 220 230 240 EKFLSVRGTT HLLVHDVALE DAGYYRCVLT FAHEGQQYNI TRSIELRIKK KKEETIPVII 250 260 270 280 290 300 SPLKTISASL GSRLTIPCKV FLGTGTPLTT MLWWTANDTH IESAYPGGRV TEGPRQEYSE 310 320 330 340 350 360 NNENYIEVPL IFDPVTREDL HMDFKCVVHN TLSFQTLRTT VKEASSTFSW GIVLAPLSLA 370 380 390 FLVLGGIWMH RRCKHRTGKA DGLTVLWPHH QDFQSYPK
	Isoform Short [UniParc]. Checksum: 581AA026BB7DACD5	FASTA	296	33,622
	10 20 30 40 50 60 MLRLYVLVMG VSAFTLQPAA HTGAARSCRF RGRHYKREFR LEGEPVALRC PQVPYWLWAS 70 80 90 100 110 120 VSPRINLTWH KNDSARTVPG EEETRMWAQD GALWLLPALQ EDSGTYVCTT RNASYCDKMS 130 140 150 160 170 180 IELRVFENTD AFLPFISYPQ ILTLSTSGVL VCPDLSEFTR DKTDVKIQWY KDSLLLDKDN 190 200 210 220 230 240 EKFLSVRGTT HLLVHDVALE DAGYYRCVLT FAHEGQQYNI TRSIELRIKK KKEETIPVII 250 260 270 280 290 SPLKTISASL GSRLTIPCKV FLGTGTPLTT MLWWTANDTH IESAYPGGRV TEGPRQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types." McMahan C.J., Slack J.L., Mosley B., Cosman D., Lupton S.D., Brunton L.L., Grubin C.E., Wignall J.M., Jenkins N.A., Brannan C.I., Copeland N.G., Huebner K., Croce C.M., Cannizzarro L.A., Benjamin D., Dower S.K., Spriggs M.K., Sims J.E. EMBO J. 10:2821-2832(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: B-cell.
[2]	"Cloning and characterization of an alternatively processed human type II interleukin-1 receptor mRNA." Liu C., Hart R.P., Liu X.J., Clevenger W., Maki R.A., Souza E.B. J. Biol. Chem. 271:20965-20972(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), IL1B-BINDING, SUBCELLULAR LOCATION (ISOFORM SHORT).
[3]	"Complete nucleotide sequence and expression of the human interleukin-1 receptor type II in human gingival fibroblasts." Chou H.-H., Takashiba T., Takigawa M., Maeda H., Asahara Y., Nishimura F., Arai H., Murayama Y. Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[4]	SeattleSNPs variation discovery resource Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-181 AND LYS-292.
[5]	"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].
[6]	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].
[7]	"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] (ISOFORM LONG). Tissue: Ovary.
[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: FUNCTION, PROTEOLYTIC PROCESSING, LIGAND-BINDING.
[9]	"Soluble type II interleukin 1 (IL-1) receptor binds and blocks processing of IL-1 beta precursor and loses affinity for IL-1 receptor antagonist." Symons J.A., Young P.R., Duff G.W. Proc. Natl. Acad. Sci. U.S.A. 92:1714-1718(1995) [PubMed] [Europe PMC] [Abstract] Cited for: LIGAND-BINDING.
[10]	"Role of metalloproteases in the release of the IL-1 type II decoy receptor." Orlando S., Sironi M., Bianchi G., Drummond A.H., Boraschi D., Yabes D., Mantovani A. J. Biol. Chem. 272:31764-31769(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[11]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH IL1RAP.
[12]	"The membrane form of the type II IL-1 receptor accounts for inhibitory function." Neumann D., Kollewe C., Martin M.U., Boraschi D. J. Immunol. 165:3350-3357(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS DECOY RECEPTOR.
[13]	"The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action." Smith D.E., Hanna R., Friend D., Moore H., Chen H., Farese A.M., MacVittie T.J., Virca G.D., Sims J.E. Immunity 18:87-96(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS DECOY RECEPTOR.
[14]	"Structural insights into the assembly and activation of IL-1beta with its receptors." Wang D., Zhang S., Li L., Liu X., Mei K., Wang X. Nat. Immunol. 11:905-911(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 14-343 IN COMPLEX WITH IL1RAP AND IL1B, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-112 AND ASN-219.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X59770 mRNA. Translation: CAA42441.1.
U64094 mRNA. Translation: AAB05878.1.
U74649 mRNA. Translation: AAD00242.1.
AY124010 Genomic DNA. Translation: AAM64221.1.
AC007165 Genomic DNA. Translation: AAK52072.1.
CH471127 Genomic DNA. Translation: EAX01800.1.
CH471127 Genomic DNA. Translation: EAX01801.1.
CH471127 Genomic DNA. Translation: EAX01802.1.
CH471127 Genomic DNA. Translation: EAX01803.1.
BC039031 mRNA. Translation: AAH39031.1.

IPI

IPI00021382.

PIR

S17428.

RefSeq

NP_001248348.1. NM_001261419.1.
NP_004624.1. NM_004633.3.

UniGene

Hs.25333.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3O4O	X-ray	3.30	C	14-343	[»]

ProteinModelPortal

P27930.

ModBase

Search...

Protein-protein interaction databases

IntAct

P27930. 2 interactions.

STRING

9606.ENSP00000330959.

PTM databases

PhosphoSite

P27930.

Polymorphism databases

DMDM

124310.

Proteomic databases

PaxDb

P27930.

PRIDE

P27930.

Protocols and materials databases

DNASU

7850.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000332549; ENSP00000330959; ENSG00000115590.
ENST00000393414; ENSP00000377066; ENSG00000115590.
ENST00000441002; ENSP00000414611; ENSG00000115590.

GeneID

7850.

KEGG

hsa:7850.

UCSC

uc002tbm.3. human.

Organism-specific databases

CTD

7850.

GeneCards

GC02P102608.

HGNC

HGNC:5994. IL1R2.

HPA

HPA027597.
HPA027598.

MIM

147811. gene.

neXtProt

NX_P27930.

PharmGKB

PA29810.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44340.

HOGENOM

HOG000113036.

HOVERGEN

HBG052104.

InParanoid

P27930.

KO

K04387.

OMA

RQEYSEN.

OrthoDB

EOG45HRZ2.

Enzyme and pathway databases

Pathway_Interaction_DB

il1pathway. IL1-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P27930.

Bgee

P27930.

CleanEx

HS_IL1R2.

Genevestigator

P27930.

GermOnline

ENSG00000115590. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 3 hits.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR015621. IL1-receptor_fam.
IPR004074. IL1_rcpt_I/II.
IPR013151. Immunoglobulin.
IPR004077. Interleukin-1_rcpt_II.
[Graphical view]

PANTHER

PTHR11890. PTHR11890. 1 hit.

Pfam

PF00047. ig. 1 hit.
[Graphical view]

PRINTS

PR01539. INTRLEUKN1R2.
PR01536. INTRLKN1R12F.

SMART

SM00409. IG. 3 hits.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00026. Anakinra.

EvolutionaryTrace

P27930.

GenomeRNAi

7850.

NextBio

30276.

SOURCE

Search...

Entry information

Entry name

IL1R2_HUMAN

Accession

Primary (citable) accession number: P27930
Secondary accession number(s): D3DVJ5, Q6LCE6, Q9UE68

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	May 1, 2013
This is version 130 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.