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Protein

Interleukin-36 alpha

Gene

IL36A

Organism
Homo sapiens (Human)
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. In cultured keratinocytes induces the expression of macrophage, T-cell, and neutrophil chemokines, such as CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CL20, CCL5, CCL2, CCL17, CCL22, CXCL8, CCL20 and CXCL1, and the production of proinflammatory cytokines such as TNF-alpha, IL-8 and IL-6. In cultured monocytes upregulates expression of IL-1A, IL-1B and IL-6. In myeloid dendritic cells involved in cell maturation by upregulating surface expression of CD83, CD86 and HLA-DR. In monocyte-derived dendritic cells facilitates dendritic cell maturation and drives T-cell proliferation. May play a role in proinflammatory effects in the lung.4 Publications

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

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
Gene namesi
Name:IL36A
Synonyms:FIL1E, IL1E, IL1F6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:15562. IL36A.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
  • extracellular space Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38389.

Polymorphism and mutation databases

BioMutaiIL36A.
DMDMi25008601.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – 551 PublicationPRO_0000430545
Chaini6 – 158153Interleukin-36 alphaPRO_0000153644Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei96 – 961Nitrated tyrosineCombined sources

Post-translational modificationi

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

Keywords - PTMi

Nitration

Proteomic databases

PaxDbiQ9UHA7.
PRIDEiQ9UHA7.

PTM databases

PhosphoSiteiQ9UHA7.

Expressioni

Tissue specificityi

Expressed in immune system and fetal brain, but not in other tissues tested or in multiple hematopoietic cell lines. Predominantly expressed in skin keratinocytes but not in fibroblasts, endothelial cells or melanocytes. Increased in lesional psoriasis skin.1 Publication

Inductioni

By Il-1 and TNF-alpha.1 Publication

Gene expression databases

BgeeiQ9UHA7.
CleanExiHS_IL1F6.
GenevisibleiQ9UHA7. HS.

Organism-specific databases

HPAiHPA035615.

Interactioni

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi118055. 11 interactions.
STRINGi9606.ENSP00000259211.

Structurei

3D structure databases

ProteinModelPortaliQ9UHA7.
SMRiQ9UHA7. Positions 10-156.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGiENOG410JBMR. Eukaryota.
ENOG41118FS. LUCA.
GeneTreeiENSGT00530000062899.
HOVERGENiHBG052100.
InParanoidiQ9UHA7.
KOiK05484.
OMAiPGWFIAV.
OrthoDBiEOG7034JW.
PhylomeDBiQ9UHA7.
TreeFamiTF300203.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR003294. IL-1_alpha/beta.
IPR000975. IL-1_fam.
IPR027163. IL-36_alpha.
[Graphical view]
PANTHERiPTHR10078:SF25. PTHR10078:SF25. 1 hit.
PfamiPF00340. IL1. 1 hit.
[Graphical view]
PRINTSiPR00264. INTERLEUKIN1.
PR01357. INTRLEUKN1AB.
SUPFAMiSSF50353. SSF50353. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q9UHA7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKALKIDTP QQGSIQDINH RVWVLQDQTL IAVPRKDRMS PVTIALISCR
60 70 80 90 100
HVETLEKDRG NPIYLGLNGL NLCLMCAKVG DQPTLQLKEK DIMDLYNQPE
110 120 130 140 150
PVKSFLFYHS QSGRNSTFES VAFPGWFIAV SSEGGCPLIL TQELGKANTT

DFGLTMLF
Length:158
Mass (Da):17,684
Last modified:May 1, 2000 - v1
Checksum:i469AC84306B0E280
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121Q → R.2 Publications
Corresponds to variant rs895497 [ dbSNP | Ensembl ].
VAR_024504
Natural varianti63 – 631I → T.1 Publication
Corresponds to variant rs28938798 [ dbSNP | Ensembl ].
VAR_025055
Natural varianti134 – 1341G → R.1 Publication
Corresponds to variant rs28947175 [ dbSNP | Ensembl ].
VAR_025056

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201831 mRNA. Translation: AAF25211.1.
BN000002 Genomic DNA. Translation: CAD29875.1.
AK314149 mRNA. Translation: BAG36836.1.
AY944686 Genomic DNA. Translation: AAX20113.1.
AC016724 Genomic DNA. Translation: AAY14988.1.
BC107042 mRNA. Translation: AAI07043.1.
BC107043 mRNA. Translation: AAI07044.1.
CCDSiCCDS42734.1.
RefSeqiNP_055255.1. NM_014440.2.
XP_005263696.1. XM_005263639.2.
XP_011509267.1. XM_011510965.1.
UniGeneiHs.278910.

Genome annotation databases

EnsembliENST00000259211; ENSP00000259211; ENSG00000136694.
GeneIDi27179.
KEGGihsa:27179.
UCSCiuc010yxr.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Interleukin-1 entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201831 mRNA. Translation: AAF25211.1.
BN000002 Genomic DNA. Translation: CAD29875.1.
AK314149 mRNA. Translation: BAG36836.1.
AY944686 Genomic DNA. Translation: AAX20113.1.
AC016724 Genomic DNA. Translation: AAY14988.1.
BC107042 mRNA. Translation: AAI07043.1.
BC107043 mRNA. Translation: AAI07044.1.
CCDSiCCDS42734.1.
RefSeqiNP_055255.1. NM_014440.2.
XP_005263696.1. XM_005263639.2.
XP_011509267.1. XM_011510965.1.
UniGeneiHs.278910.

3D structure databases

ProteinModelPortaliQ9UHA7.
SMRiQ9UHA7. Positions 10-156.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118055. 11 interactions.
STRINGi9606.ENSP00000259211.

PTM databases

PhosphoSiteiQ9UHA7.

Polymorphism and mutation databases

BioMutaiIL36A.
DMDMi25008601.

Proteomic databases

PaxDbiQ9UHA7.
PRIDEiQ9UHA7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259211; ENSP00000259211; ENSG00000136694.
GeneIDi27179.
KEGGihsa:27179.
UCSCiuc010yxr.3. human.

Organism-specific databases

CTDi27179.
GeneCardsiIL36A.
HGNCiHGNC:15562. IL36A.
HPAiHPA035615.
MIMi605509. gene.
neXtProtiNX_Q9UHA7.
PharmGKBiPA38389.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JBMR. Eukaryota.
ENOG41118FS. LUCA.
GeneTreeiENSGT00530000062899.
HOVERGENiHBG052100.
InParanoidiQ9UHA7.
KOiK05484.
OMAiPGWFIAV.
OrthoDBiEOG7034JW.
PhylomeDBiQ9UHA7.
TreeFamiTF300203.

Miscellaneous databases

GeneWikiiIL1F6.
GenomeRNAii27179.
NextBioi50004.
PROiQ9UHA7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UHA7.
CleanExiHS_IL1F6.
GenevisibleiQ9UHA7. HS.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR003294. IL-1_alpha/beta.
IPR000975. IL-1_fam.
IPR027163. IL-36_alpha.
[Graphical view]
PANTHERiPTHR10078:SF25. PTHR10078:SF25. 1 hit.
PfamiPF00340. IL1. 1 hit.
[Graphical view]
PRINTSiPR00264. INTERLEUKIN1.
PR01357. INTRLEUKN1AB.
SUPFAMiSSF50353. SSF50353. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "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].
  3. "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], VARIANT ARG-12.
    Tissue: Esophagus.
  4. SeattleSNPs variation discovery resource
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-12; THR-63 AND ARG-134.
  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. "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].
  7. "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: TISSUE SPECIFICITY, INDUCTION.
  8. "Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs."
    Towne J.E., Garka K.E., Renshaw B.R., Virca G.D., Sims J.E.
    J. Biol. Chem. 279:13677-13688(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Nitroproteins from a human pituitary adenoma tissue discovered with a nitrotyrosine affinity column and tandem mass spectrometry."
    Zhan X., Desiderio D.M.
    Anal. Biochem. 354:279-289(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-96, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Pituitary adenoma.
  10. "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.
  11. "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: FUNCTION.
  12. "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_HUMAN
AccessioniPrimary (citable) accession number: Q9UHA7
Secondary accession number(s): B2RAD9
, Q53SR7, Q5BLR4, Q7RTZ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: May 1, 2000
Last modified: May 11, 2016
This is version 124 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

Miscellaneous

Initial experiments using non-processed full length protein found in vitro activity only in the µg range.1 Publication

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

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.