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Q9UBH0 (I36RA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-36 receptor antagonist protein
Alternative name(s):
FIL1 delta
IL-1-related protein 3
Short name=IL-1RP3
Interleukin-1 HY1
Short name=IL-1HY1
Interleukin-1 delta
Short name=IL-1 delta
Interleukin-1 family member 5
Short name=IL-1F5
Interleukin-1 receptor antagonist homolog 1
Short name=IL-1ra homolog 1
Interleukin-1-like protein 1
Short name=IL-1L1
Gene names
Name:IL36RN
Synonyms:FIL1D, IL1F5, IL1HY1, IL1L1, IL1RP3
ORF Names:UNQ1896/PRO4342
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length155 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Is a highly and a specific antagonist of the IL-1 receptor-related protein 2/IL1RL2-mediated response to interleukin IL36G. Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response.

Subcellular location

Secreted.

Tissue specificity

Predominantly expressed in keratinocytes but not in fibroblasts, endothelial cells or melanocytes. Detected also in the spleen, brain leukocyte and macrophage cell types. Increased in lesional psoriasis skin.

Induction

By phorbol ester (PMA) and bacterial lipopolysaccharides (LPS) treatment in macrophage cell line.

Involvement in disease

Psoriasis generalized pustular (PSORP) [MIM:614204]: A life-threatening disease defined by repeated flares of sudden onset consisting of diffuse erythematous skin eruption characterized by rapid coverage with pustules, high-grade fever, asthenia, marked leukocytosis, and elevated serum levels of C-reactive protein.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14 Ref.15

Sequence similarities

Belongs to the IL-1 family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   Molecular functionCytokine
   PTMDisulfide bond
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of cytokine-mediated signaling pathway

Traceable author statement Ref.2. Source: GOC

negative regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functioninterleukin-1 receptor antagonist activity

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 155155Interleukin-36 receptor antagonist protein
PRO_0000153642

Amino acid modifications

Disulfide bond8 ↔ 154 By similarity

Natural variations

Natural variant271L → P in PSORP; expression of the protein is severely impaired compared to wild-type; the mutant protein is substantially less able to inhibit IL1RL2 signaling than wild-type. Ref.14
VAR_066646
Natural variant471N → S. Ref.9
Corresponds to variant rs28938777 [ dbSNP | Ensembl ].
VAR_023239
Natural variant481R → W in PSORP. Ref.13
VAR_066647
Natural variant1131S → L in PSORP. Ref.13
Corresponds to variant rs144478519 [ dbSNP | Ensembl ].
VAR_066648
Natural variant1231T → R in PSORP; shows impaired expression of the mutant protein which fails to antagonize the IL-36 signaling pathway. Ref.15
VAR_068972

Sequences

Sequence LengthMass (Da)Tools
Q9UBH0 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: B96DB5EFA2612E25

FASTA15516,962
        10         20         30         40         50         60 
MVLSGALCFR MKDSALKVLY LHNNQLLAGG LHAGKVIKGE EISVVPNRWL DASLSPVILG 

        70         80         90        100        110        120 
VQGGSQCLSC GVGQEPTLTL EPVNIMELYL GAKESKSFTF YRRDMGLTSS FESAAYPGWF 

       130        140        150 
LCTVPEADQP VRLTQLPENG GWNAPITDFY FQQCD 

« Hide

References

« Hide 'large scale' references
[1]"Four new members expand the IL-1 superfamily."
Smith D.E., Renshaw B.R., Ketchem R.R., Kubin M., Garka K.E., Sims J.E.
J. Biol. Chem. 275:1169-1175(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[2]"IL1HY1: a novel interleukin-1 receptor antagonist gene."
Mulero J.J., Pace A.M., Nelken S.T., Loeb D.B., Correa T.R., Drmanac R., Ford J.E.
Biochem. Biophys. Res. Commun. 263:702-706(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal skin.
[3]"A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities."
Barton J.L., Herbst R., Bosisio D., Higgins L., Nicklin M.J.H.
Eur. J. Immunol. 30:3299-3308(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[4]"Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2."
Debets R., Timans J.C., Homey B., Zurawski S., Sana T.R., Lo S., Wagner J., Edwards G., Clifford T., Menon S., Bazan J.F., Kastelein R.A.
J. Immunol. 167:1440-1446(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Identification and gene organization of three novel members of the IL-1 family on human chromosome 2."
Busfield S.J., Comrack C.A., Yu G., Chickering T.W., Smutko J.S., Zhou H., Leiby K.R., Holmgren L.M., Gearing D.P., Pan Y.
Genomics 66:213-216(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"A sequence-based map of the nine genes of the human interleukin-1 cluster."
Nicklin M.J.H., Barton J.L., Nguyen M., Fitzgerald M.G., Duff W.G., Kornman K.
Genomics 79:718-725(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cervix.
[9]SeattleSNPs variation discovery resource
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-47.
[10]"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].
[11]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]"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: Placenta.
[13]"Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis."
Onoufriadis A., Simpson M.A., Pink A.E., Di Meglio P., Smith C.H., Pullabhatla V., Knight J., Spain S.L., Nestle F.O., Burden A.D., Capon F., Trembath R.C., Barker J.N.
Am. J. Hum. Genet. 89:432-437(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PSORP TRP-48 AND LEU-113.
[14]"Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis."
Marrakchi S., Guigue P., Renshaw B.R., Puel A., Pei X.Y., Fraitag S., Zribi J., Bal E., Cluzeau C., Chrabieh M., Towne J.E., Douangpanya J., Pons C., Mansour S., Serre V., Makni H., Mahfoudh N., Fakhfakh F. expand/collapse author list , Bodemer C., Feingold J., Hadj-Rabia S., Favre M., Genin E., Sahbatou M., Munnich A., Casanova J.L., Sims J.E., Turki H., Bachelez H., Smahi A.
N. Engl. J. Med. 365:620-628(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PSORP PRO-27, CHARACTERIZATION OF VARIANT PSORP PRO-27.
[15]"Mutation analysis of the IL36RN gene in 14 Japanese patients with generalized pustular psoriasis."
Farooq M., Nakai H., Fujimoto A., Fujikawa H., Matsuyama A., Kariya N., Aizawa A., Fujiwara H., Ito M., Shimomura Y.
Hum. Mutat. 34:176-183(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PSORP ARG-123, CHARACTERIZATION OF VARIANT PSORP ARG-123.
+Additional computationally mapped references.

Web resources

Wikipedia

Interleukin-1 entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF201830 mRNA. Translation: AAF25210.1.
AF186094 mRNA. Translation: AAF02757.1.
AJ242737 mRNA. Translation: CAB59822.1.
AJ242738 mRNA. Translation: CAB59823.1.
AJ271338 Genomic DNA. Translation: CAB67704.1.
AF216693 Genomic DNA. Translation: AAF76981.1.
AF230377 mRNA. Translation: AAF91274.1.
BN000002 Genomic DNA. Translation: CAD29877.1.
AY359117 mRNA. Translation: AAQ89475.1.
AK290249 mRNA. Translation: BAF82938.1.
AY972853 Genomic DNA. Translation: AAX59031.1.
AC016724 Genomic DNA. Translation: AAY14990.1.
CH471217 Genomic DNA. Translation: EAW73617.1.
BC024747 mRNA. Translation: AAH24747.1.
PIRJC7104.
RefSeqNP_036407.1. NM_012275.2.
NP_775262.1. NM_173170.1.
XP_005263695.1. XM_005263638.1.
UniGeneHs.516301.

3D structure databases

ProteinModelPortalQ9UBH0.
SMRQ9UBH0. Positions 2-155.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117728. 5 interactions.
IntActQ9UBH0. 5 interactions.
MINTMINT-1194342.
STRING9606.ENSP00000259212.

Polymorphism databases

DMDM25008600.

Proteomic databases

PaxDbQ9UBH0.
PRIDEQ9UBH0.

Protocols and materials databases

DNASU26525.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000346807; ENSP00000259212; ENSG00000136695.
ENST00000393200; ENSP00000376896; ENSG00000136695.
GeneID26525.
KEGGhsa:26525.
UCSCuc002tis.3. human.

Organism-specific databases

CTD26525.
GeneCardsGC02P113817.
HGNCHGNC:15561. IL36RN.
HPAHPA034542.
MIM605507. gene.
614204. phenotype.
neXtProtNX_Q9UBH0.
Orphanet163931. Acrodermatitis continua suppurativa of Hallopeau.
247353. Generalized pustular psoriasis.
163927. Pustulosis palmaris et plantaris.
PharmGKBPA38388.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46537.
HOVERGENHBG052099.
InParanoidQ9UBH0.
KOK05483.
OMAMKDSALK.
OrthoDBEOG7QG45K.
PhylomeDBQ9UBH0.
TreeFamTF300203.

Gene expression databases

ArrayExpressQ9UBH0.
BgeeQ9UBH0.
CleanExHS_IL1F5.
GenevestigatorQ9UBH0.

Family and domain databases

InterProIPR008996. Cytokine_IL1-like.
IPR000975. IL-1.
IPR020877. IL-1_CS.
IPR003297. IL-1RA/IL-36.
IPR027171. IL-36RA.
[Graphical view]
PANTHERPTHR10078:SF7. PTHR10078:SF7. 1 hit.
PfamPF00340. IL1. 1 hit.
[Graphical view]
PRINTSPR00264. INTERLEUKIN1.
PR01360. INTRLEUKIN1X.
SMARTSM00125. IL1. 1 hit.
[Graphical view]
SUPFAMSSF50353. SSF50353. 1 hit.
PROSITEPS00253. INTERLEUKIN_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiIL1F5.
GenomeRNAi26525.
NextBio48854.
PROQ9UBH0.
SOURCESearch...

Entry information

Entry nameI36RA_HUMAN
AccessionPrimary (citable) accession number: Q9UBH0
Secondary accession number(s): A8K2I4, Q56AT9, Q7RTZ6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 118 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

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