IL36A

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

Miscellaneous

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

GO - Molecular functionⁱ

cytokine activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
interleukin-1 receptor binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cellular response to lipopolysaccharide
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cytokine-mediated signaling pathway
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
immune response
Source: UniProtKB
Non-traceable author statementⁱ
- 10625660
inflammatory response Source: UniProtKB-KW
innate immune response Source: UniProtKB-KW
neutrophil chemotaxis
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
positive regulation of I-kappaB kinase/NF-kappaB signaling
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
positive regulation of interleukin-6 production
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
positive regulation of JNK cascade
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Cytokine
Biological process	Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

Reactomeⁱ	R-HSA-9014826 Interleukin-36 pathway

Reactomeⁱ

R-HSA-9014826 Interleukin-36 pathway

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 2

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000136694.8
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:15562 IL36A
MIMⁱ	605509 gene
neXtProtⁱ	NX_Q9UHA7

Keywords - Cellular componentⁱ

Secreted

Pathology & Biotechⁱ

Organism-specific databases

DisGeNET More...DisGeNETⁱ	27179
Open Targets More...OpenTargetsⁱ	ENSG00000136694
PharmGKBⁱ	PA38389

Polymorphism and mutation databases

BioMutaⁱ	IL36A
DMDMⁱ	25008601

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
PropeptideⁱPRO_0000430545	1 – 5	1 Publication		5
ChainⁱPRO_0000153644	6 – 158	Interleukin-36 alphaAdd BLAST		153

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	96	Nitrated tyrosineCombined sources		1

Post-translational modificationⁱ

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

Keywords - PTMⁱ

Nitration

Proteomic databases

PaxDbⁱ	Q9UHA7
PeptideAtlas More...PeptideAtlasⁱ	Q9UHA7
PRIDEⁱ	Q9UHA7
ProteomicsDBⁱ	84293

PTM databases

iPTMnetⁱ	Q9UHA7
PhosphoSitePlusⁱ	Q9UHA7

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

Bgeeⁱ	ENSG00000136694 Expressed in 54 organ(s), highest expression level in lower esophagus mucosa
CleanExⁱ	HS_IL1F6
Genevisibleⁱ	Q9UHA7 HS

Interactionⁱ

GO - Molecular functionⁱ

cytokine activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
interleukin-1 receptor binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	118055, 12 interactors
IntActⁱ	Q9UHA7, 1 interactor
STRINGⁱ	9606.ENSP00000259211

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q9UHA7
SMRⁱ	Q9UHA7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGⁱ	ENOG410JBMR Eukaryota ENOG41118FS LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00900000141014
HOVERGENⁱ	HBG052100
InParanoidⁱ	Q9UHA7
KEGG Orthology (KO) More...KOⁱ	K05484
OMAⁱ	PFLFYHN
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0V8E
PhylomeDBⁱ	Q9UHA7
TreeFamⁱ	TF300203

Family and domain databases

InterProⁱ	View protein in InterPro IPR000975 IL-1_fam IPR027163 IL-36_alpha IPR008996 IL1/FGF
PANTHERⁱ	PTHR10078:SF25 PTHR10078:SF25, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00340 IL1, 1 hit
PRINTSⁱ	PR00264 INTERLEUKIN1
SUPFAMⁱ	SSF50353 SSF50353, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

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

Q9UHA7-1 [UniParc]FASTA Add 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 key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_024504	12	Q → R2 PublicationsCorresponds to variant dbSNP:rs895497Ensembl.	1
Natural variantⁱVAR_025055	63	I → T1 PublicationCorresponds to variant dbSNP:rs28938798Ensembl.	1
Natural variantⁱVAR_025056	134	G → R1 PublicationCorresponds to variant dbSNP:rs28947175Ensembl.	1

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS42734.1
NCBI Reference Sequences More...RefSeqⁱ	NP_055255.1, NM_014440.2 XP_005263696.1, XM_005263639.2 XP_011509267.1, XM_011510965.1 XP_016859295.1, XM_017003806.1
UniGeneⁱ	Hs.278910

Genome annotation databases

Ensemblⁱ	ENST00000259211; ENSP00000259211; ENSG00000136694
GeneIDⁱ	27179
KEGGⁱ	hsa:27179
UCSC genome browser More...UCSCⁱ	uc010yxr.3 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9UHA7	Interleukin-1		MACFA		188	UniRef90_Q9UHA7
Interleukin-1		MACNE		179
Interleukin-1		CHLSB		160
Interleukin-1		PAPAN		158
Interleukin-1		MANLE		158
+20

Protein	Similar proteins		Species	Score	Length	Source
Q9UHA7	Interleukin-36 alpha		MOUSE		160	UniRef50_Q9JLA2
Interleukin-1		ICTTR		160
Interleukin-1		LOXAF		160
Interleukin-1		AOTNA		179
Interleukin-1		Cebus capucinus imitator		155
+90

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
CCDSⁱ	CCDS42734.1
RefSeqⁱ	NP_055255.1, NM_014440.2 XP_005263696.1, XM_005263639.2 XP_011509267.1, XM_011510965.1 XP_016859295.1, XM_017003806.1
UniGeneⁱ	Hs.278910

3D structure databases

ProteinModelPortalⁱ	Q9UHA7
SMRⁱ	Q9UHA7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	118055, 12 interactors
IntActⁱ	Q9UHA7, 1 interactor
STRINGⁱ	9606.ENSP00000259211

PTM databases

iPTMnetⁱ	Q9UHA7
PhosphoSitePlusⁱ	Q9UHA7

Polymorphism and mutation databases

BioMutaⁱ	IL36A
DMDMⁱ	25008601

Proteomic databases

PaxDbⁱ	Q9UHA7
PeptideAtlasⁱ	Q9UHA7
PRIDEⁱ	Q9UHA7
ProteomicsDBⁱ	84293

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000259211; ENSP00000259211; ENSG00000136694
GeneIDⁱ	27179
KEGGⁱ	hsa:27179
UCSCⁱ	uc010yxr.3 human

Organism-specific databases

CTDⁱ	27179
DisGeNETⁱ	27179
EuPathDBⁱ	HostDB:ENSG00000136694.8
GeneCardsⁱ	IL36A
HGNCⁱ	HGNC:15562 IL36A
MIMⁱ	605509 gene
neXtProtⁱ	NX_Q9UHA7
OpenTargetsⁱ	ENSG00000136694
PharmGKBⁱ	PA38389
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410JBMR Eukaryota ENOG41118FS LUCA
GeneTreeⁱ	ENSGT00900000141014
HOVERGENⁱ	HBG052100
InParanoidⁱ	Q9UHA7
KOⁱ	K05484
OMAⁱ	PFLFYHN
OrthoDBⁱ	EOG091G0V8E
PhylomeDBⁱ	Q9UHA7
TreeFamⁱ	TF300203

Enzyme and pathway databases

Reactomeⁱ	R-HSA-9014826 Interleukin-36 pathway

Reactomeⁱ

R-HSA-9014826 Interleukin-36 pathway

Miscellaneous databases

GeneWikiⁱ	IL1F6
GenomeRNAiⁱ	27179
Protein Ontology More...PROⁱ	PR:Q9UHA7
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000136694 Expressed in 54 organ(s), highest expression level in lower esophagus mucosa
CleanExⁱ	HS_IL1F6
Genevisibleⁱ	Q9UHA7 HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR000975 IL-1_fam IPR027163 IL-36_alpha IPR008996 IL1/FGF
PANTHERⁱ	PTHR10078:SF25 PTHR10078:SF25, 1 hit
Pfamⁱ	View protein in Pfam PF00340 IL1, 1 hit
PRINTSⁱ	PR00264 INTERLEUKIN1
SUPFAMⁱ	SSF50353 SSF50353, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	IL36A_HUMAN
Accessionⁱ	Q9UHA7Primary (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:	November 7, 2018
	This is version 140 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

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

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q9UHA7 (IL36A_HUMAN)

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Interleukin-36 alpha

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted

Extracellular region or secreted

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ