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Protein

Interleukin-36 alpha

Gene

Il36a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor IL1RAP. Seems to be involved in skin inflammatory response by acting on keratinocytes, dendritic cells and indirectly on T-cells to drive tissue infiltration, cell maturation and cell proliferation. Induces the production of proinflammatory cytokines, including IL-12, Il-1 beta, IL-6, TNF-alpha and IL-23 in bone marrow-derived dendritic cells (BMDCs). Involved in dendritic cell maturation by stimulating the surface expression of CD80, CD86 and MHC class II. Induces the production of IFN-gamma, IL-4 and IL-17 by cultured CD4+ T-cells and splenocytes. May play a role in proinflammatory effects in the lung: induces the expression of CXCL1 and CXCL2 in the lung, and the expression of TNF-alpha, IL-36c, IL-1A, IL-1B, CXCL1 and CXCL2 in isolated splenic CD11c+ alveolar macrophages. May be involved in T-cell maturation by stimulating the surface expression of CD40 and modestly CD80 and CD86 in splenic CD11c+ cells. May be involved in CD4+ T-cell proliferation. Induces NF-kappa B activation in macrophages.4 Publications

GO - Molecular functioni

  • cytokine activity Source: MGI
  • interleukin-1 receptor binding Source: GO_Central

GO - Biological processi

  • cytokine-mediated signaling pathway Source: GO_Central
  • inflammatory response Source: MGI
  • innate immune response Source: UniProtKB-KW
  • positive regulation of cytokine production Source: MGI
  • positive regulation of interleukin-6 production Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-449147. Signaling by Interleukins.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-36 alpha
Alternative name(s):
FIL1 epsilon
Interleukin-1 epsilon
Short name:
IL-1 epsilon
Interleukin-1 family member 6
Short name:
IL-1F6
Interleukin-1 homolog 1
Short name:
IL-1H1
Gene namesi
Name:Il36a
Synonyms:Fil1e, Il1e, Il1f6, Il1h1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1859324. Il1f6.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – 771 PublicationPRO_0000430546
Chaini8 – 160153Interleukin-36 alphaPRO_0000153645Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei98 – 981Nitrated tyrosineBy similarity

Post-translational modificationi

N-terminal truncation leads to a dramatic enhancement of its activity (>1000-fold).1 Publication

Keywords - PTMi

Nitration

Proteomic databases

PaxDbiQ9JLA2.
PRIDEiQ9JLA2.

PTM databases

PhosphoSiteiQ9JLA2.

Expressioni

Tissue specificityi

Highly expressed in embryonic tissue and in tissues containing epithelial cells. Elevated expression levels are detected in chronic kidney disease; expressed inepithelia from the distal convoluted tubules (DCTs) to the cortical collecting ducts (CCDs) in single nephrons (at protein level).2 Publications

Inductioni

By IL-22 in normal and psoriasis-like skin.1 Publication

Gene expression databases

BgeeiQ9JLA2.
CleanExiMM_IL1F6.
ExpressionAtlasiQ9JLA2. baseline and differential.
GenevisibleiQ9JLA2. MM.

Interactioni

GO - Molecular functioni

  • cytokine activity Source: MGI
  • interleukin-1 receptor binding Source: GO_Central

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000028361.

Structurei

3D structure databases

ProteinModelPortaliQ9JLA2.
SMRiQ9JLA2. Positions 17-156.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGiENOG410JBMR. Eukaryota.
ENOG41118FS. LUCA.
GeneTreeiENSGT00530000062899.
HOVERGENiHBG052100.
InParanoidiQ9JLA2.
KOiK05484.
OMAiPGWFIAV.
OrthoDBiEOG7034JW.
PhylomeDBiQ9JLA2.
TreeFamiTF300203.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR000975. IL-1_fam.
IPR003297. IL-1RA/IL-36.
IPR027163. IL-36_alpha.
[Graphical view]
PANTHERiPTHR10078:SF25. PTHR10078:SF25. 1 hit.
PfamiPF00340. IL1. 1 hit.
[Graphical view]
PRINTSiPR01360. INTRLEUKIN1X.
SUPFAMiSSF50353. SSF50353. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9JLA2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNKEKELRAA SPSLRHVQDL SSRVWILQNN ILTAVPRKEQ TVPVTITLLP
60 70 80 90 100
CQYLDTLETN RGDPTYMGVQ RPMSCLFCTK DGEQPVLQLG EGNIMEMYNK
110 120 130 140 150
KEPVKASLFY HKKSGTTSTF ESAAFPGWFI AVCSKGSCPL ILTQELGEIF
160
ITDFEMIVVH
Length:160
Mass (Da):18,015
Last modified:October 1, 2000 - v1
Checksum:iAA0434D68FF62F4A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF200493 mRNA. Translation: AAF69249.1.
AF206697 mRNA. Translation: AAG35671.1.
AK004061 mRNA. Translation: BAB23147.1.
CCDSiCCDS15734.1.
RefSeqiNP_062323.1. NM_019450.3.
UniGeneiMm.133095.

Genome annotation databases

EnsembliENSMUST00000028361; ENSMUSP00000028361; ENSMUSG00000026984.
GeneIDi54448.
KEGGimmu:54448.
UCSCiuc008ioq.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF200493 mRNA. Translation: AAF69249.1.
AF206697 mRNA. Translation: AAG35671.1.
AK004061 mRNA. Translation: BAB23147.1.
CCDSiCCDS15734.1.
RefSeqiNP_062323.1. NM_019450.3.
UniGeneiMm.133095.

3D structure databases

ProteinModelPortaliQ9JLA2.
SMRiQ9JLA2. Positions 17-156.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000028361.

PTM databases

PhosphoSiteiQ9JLA2.

Proteomic databases

PaxDbiQ9JLA2.
PRIDEiQ9JLA2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028361; ENSMUSP00000028361; ENSMUSG00000026984.
GeneIDi54448.
KEGGimmu:54448.
UCSCiuc008ioq.1. mouse.

Organism-specific databases

CTDi54448.
MGIiMGI:1859324. Il1f6.

Phylogenomic databases

eggNOGiENOG410JBMR. Eukaryota.
ENOG41118FS. LUCA.
GeneTreeiENSGT00530000062899.
HOVERGENiHBG052100.
InParanoidiQ9JLA2.
KOiK05484.
OMAiPGWFIAV.
OrthoDBiEOG7034JW.
PhylomeDBiQ9JLA2.
TreeFamiTF300203.

Enzyme and pathway databases

ReactomeiR-MMU-449147. Signaling by Interleukins.

Miscellaneous databases

PROiQ9JLA2.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JLA2.
CleanExiMM_IL1F6.
ExpressionAtlasiQ9JLA2. baseline and differential.
GenevisibleiQ9JLA2. MM.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR000975. IL-1_fam.
IPR003297. IL-1RA/IL-36.
IPR027163. IL-36_alpha.
[Graphical view]
PANTHERiPTHR10078:SF25. PTHR10078:SF25. 1 hit.
PfamiPF00340. IL1. 1 hit.
[Graphical view]
PRINTSiPR01360. INTRLEUKIN1X.
SUPFAMiSSF50353. SSF50353. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and initial characterization of four novel members of the interleukin-1 family."
    Kumar S., McDonnell P.C., Lehr R., Tierney L., Tzimas M.N., Griswold D.E., Capper E.A., Tal-Singer R., Wells G.I., Doyle M.L., Young P.R.
    J. Biol. Chem. 275:10308-10314(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "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], TISSUE SPECIFICITY.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Embryo.
  4. "Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions."
    Ichii O., Otsuka S., Sasaki N., Yabuki A., Ohta H., Takiguchi M., Hashimoto Y., Endoh D., Kon Y.
    Lab. Invest. 90:459-475(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. Cited for: FUNCTION.
  6. "Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity."
    Towne J.E., Renshaw B.R., Douangpanya J., Lipsky B.P., Shen M., Gabel C.A., Sims J.E.
    J. Biol. Chem. 286:42594-42602(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROCESSING.
  7. "Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis."
    Carrier Y., Ma H.L., Ramon H.E., Napierata L., Small C., O'Toole M., Young D.A., Fouser L.A., Nickerson-Nutter C., Collins M., Dunussi-Joannopoulos K., Medley Q.G.
    J. Invest. Dermatol. 131:2428-2437(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  8. "IL-36alpha exerts pro-inflammatory effects in the lungs of mice."
    Ramadas R.A., Ewart S.L., Iwakura Y., Medoff B.D., LeVine A.M.
    PLoS ONE 7:E45784-E45784(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin."
    Foster A.M., Baliwag J., Chen C.S., Guzman A.M., Stoll S.W., Gudjonsson J.E., Ward N.L., Johnston A.
    J. Immunol. 192:6053-6061(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiIL36A_MOUSE
AccessioniPrimary (citable) accession number: Q9JLA2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: October 1, 2000
Last modified: July 6, 2016
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.