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Q9UBH0

- I36RA_HUMAN

UniProt

Q9UBH0 - I36RA_HUMAN

Protein

Interleukin-36 receptor antagonist protein

Gene

IL36RN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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.

    GO - Molecular functioni

    1. interleukin-1 receptor antagonist activity Source: ProtInc

    GO - Biological processi

    1. negative regulation of cytokine-mediated signaling pathway Source: GOC
    2. negative regulation of interleukin-6 production Source: Ensembl

    Keywords - Molecular functioni

    Cytokine

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:IL36RN
    Synonyms:FIL1D, IL1F5, IL1HY1, IL1L1, IL1RP3
    ORF Names:UNQ1896/PRO4342
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:15561. IL36RN.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular space Source: UniProtKB-KW

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti27 – 271L → 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. 1 Publication
    VAR_066646
    Natural varianti48 – 481R → W in PSORP. 1 Publication
    VAR_066647
    Natural varianti113 – 1131S → L in PSORP. 1 Publication
    Corresponds to variant rs144478519 [ dbSNP | Ensembl ].
    VAR_066648
    Natural varianti123 – 1231T → R in PSORP; shows impaired expression of the mutant protein which fails to antagonize the IL-36 signaling pathway. 1 Publication
    VAR_068972

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi614204. phenotype.
    Orphaneti163931. Acrodermatitis continua suppurativa of Hallopeau.
    247353. Generalized pustular psoriasis.
    163927. Pustulosis palmaris et plantaris.
    PharmGKBiPA38388.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 155155Interleukin-36 receptor antagonist proteinPRO_0000153642Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi8 ↔ 154By similarity

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiQ9UBH0.
    PRIDEiQ9UBH0.

    Expressioni

    Tissue specificityi

    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.

    Inductioni

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

    Gene expression databases

    ArrayExpressiQ9UBH0.
    BgeeiQ9UBH0.
    CleanExiHS_IL1F5.
    GenevestigatoriQ9UBH0.

    Organism-specific databases

    HPAiHPA034542.

    Interactioni

    Protein-protein interaction databases

    BioGridi117728. 5 interactions.
    IntActiQ9UBH0. 5 interactions.
    MINTiMINT-1194342.
    STRINGi9606.ENSP00000259212.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UBH0.
    SMRiQ9UBH0. Positions 2-155.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the IL-1 family.Curated

    Phylogenomic databases

    eggNOGiNOG46537.
    HOVERGENiHBG052099.
    InParanoidiQ9UBH0.
    KOiK05483.
    OMAiFYRRDMG.
    OrthoDBiEOG7QG45K.
    PhylomeDBiQ9UBH0.
    TreeFamiTF300203.

    Family and domain databases

    InterProiIPR008996. Cytokine_IL1-like.
    IPR020877. IL-1_CS.
    IPR000975. IL-1_fam.
    IPR003297. IL-1RA/IL-36.
    IPR027171. IL-36RA.
    [Graphical view]
    PANTHERiPTHR10078:SF7. PTHR10078:SF7. 1 hit.
    PfamiPF00340. IL1. 1 hit.
    [Graphical view]
    PRINTSiPR00264. INTERLEUKIN1.
    PR01360. INTRLEUKIN1X.
    SUPFAMiSSF50353. SSF50353. 1 hit.
    PROSITEiPS00253. INTERLEUKIN_1. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9UBH0-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVLSGALCFR MKDSALKVLY LHNNQLLAGG LHAGKVIKGE EISVVPNRWL    50
    DASLSPVILG VQGGSQCLSC GVGQEPTLTL EPVNIMELYL GAKESKSFTF 100
    YRRDMGLTSS FESAAYPGWF LCTVPEADQP VRLTQLPENG GWNAPITDFY 150
    FQQCD 155
    Length:155
    Mass (Da):16,962
    Last modified:May 1, 2000 - v1
    Checksum:iB96DB5EFA2612E25
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti27 – 271L → 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. 1 Publication
    VAR_066646
    Natural varianti47 – 471N → S.1 Publication
    Corresponds to variant rs28938777 [ dbSNP | Ensembl ].
    VAR_023239
    Natural varianti48 – 481R → W in PSORP. 1 Publication
    VAR_066647
    Natural varianti113 – 1131S → L in PSORP. 1 Publication
    Corresponds to variant rs144478519 [ dbSNP | Ensembl ].
    VAR_066648
    Natural varianti123 – 1231T → R in PSORP; shows impaired expression of the mutant protein which fails to antagonize the IL-36 signaling pathway. 1 Publication
    VAR_068972

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS2111.1.
    PIRiJC7104.
    RefSeqiNP_036407.1. NM_012275.2.
    NP_775262.1. NM_173170.1.
    XP_005263695.1. XM_005263638.1.
    UniGeneiHs.516301.

    Genome annotation databases

    EnsembliENST00000346807; ENSP00000259212; ENSG00000136695.
    ENST00000393200; ENSP00000376896; ENSG00000136695.
    GeneIDi26525.
    KEGGihsa:26525.
    UCSCiuc002tis.3. human.

    Polymorphism databases

    DMDMi25008600.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Interleukin-1 entry

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS2111.1.
    PIRi JC7104.
    RefSeqi NP_036407.1. NM_012275.2.
    NP_775262.1. NM_173170.1.
    XP_005263695.1. XM_005263638.1.
    UniGenei Hs.516301.

    3D structure databases

    ProteinModelPortali Q9UBH0.
    SMRi Q9UBH0. Positions 2-155.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117728. 5 interactions.
    IntActi Q9UBH0. 5 interactions.
    MINTi MINT-1194342.
    STRINGi 9606.ENSP00000259212.

    Polymorphism databases

    DMDMi 25008600.

    Proteomic databases

    PaxDbi Q9UBH0.
    PRIDEi Q9UBH0.

    Protocols and materials databases

    DNASUi 26525.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000346807 ; ENSP00000259212 ; ENSG00000136695 .
    ENST00000393200 ; ENSP00000376896 ; ENSG00000136695 .
    GeneIDi 26525.
    KEGGi hsa:26525.
    UCSCi uc002tis.3. human.

    Organism-specific databases

    CTDi 26525.
    GeneCardsi GC02P113817.
    HGNCi HGNC:15561. IL36RN.
    HPAi HPA034542.
    MIMi 605507. gene.
    614204. phenotype.
    neXtProti NX_Q9UBH0.
    Orphaneti 163931. Acrodermatitis continua suppurativa of Hallopeau.
    247353. Generalized pustular psoriasis.
    163927. Pustulosis palmaris et plantaris.
    PharmGKBi PA38388.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG46537.
    HOVERGENi HBG052099.
    InParanoidi Q9UBH0.
    KOi K05483.
    OMAi FYRRDMG.
    OrthoDBi EOG7QG45K.
    PhylomeDBi Q9UBH0.
    TreeFami TF300203.

    Miscellaneous databases

    GeneWikii IL1F5.
    GenomeRNAii 26525.
    NextBioi 48854.
    PROi Q9UBH0.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UBH0.
    Bgeei Q9UBH0.
    CleanExi HS_IL1F5.
    Genevestigatori Q9UBH0.

    Family and domain databases

    InterProi IPR008996. Cytokine_IL1-like.
    IPR020877. IL-1_CS.
    IPR000975. IL-1_fam.
    IPR003297. IL-1RA/IL-36.
    IPR027171. IL-36RA.
    [Graphical view ]
    PANTHERi PTHR10078:SF7. PTHR10078:SF7. 1 hit.
    Pfami PF00340. IL1. 1 hit.
    [Graphical view ]
    PRINTSi PR00264. INTERLEUKIN1.
    PR01360. INTRLEUKIN1X.
    SUPFAMi SSF50353. SSF50353. 1 hit.
    PROSITEi PS00253. INTERLEUKIN_1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Placenta.
    2. 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. 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.
      , 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.
      , 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. 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. 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.

    Entry informationi

    Entry nameiI36RA_HUMAN
    AccessioniPrimary (citable) accession number: Q9UBH0
    Secondary accession number(s): A8K2I4, Q56AT9, Q7RTZ6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 8, 2002
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3