UniProtKB - Q9UHA7 (IL36A_HUMAN)
Interleukin-36 alpha
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 up-regulates expression of IL-1A, IL-1B and IL-6. In myeloid dendritic cells involved in cell maturation by up-regulating 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 PublicationsMiscellaneous
GO - Molecular functioni
- cytokine activity Source: GO_Central
- interleukin-1 receptor binding Source: UniProtKB
GO - Biological processi
- cellular response to lipopolysaccharide Source: GO_Central
- cytokine-mediated signaling pathway Source: GO_Central
- immune response Source: UniProtKB
- inflammatory response Source: GO_Central
- inflammatory response to antigenic stimulus Source: GO_Central
- innate immune response Source: UniProtKB-KW
- positive regulation of gene expression Source: GO_Central
- positive regulation of interleukin-6 production Source: Ensembl
Keywordsi
Molecular function | Cytokine |
Biological process | Immunity, Inflammatory response, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | Q9UHA7 |
Reactomei | R-HSA-9014826, Interleukin-36 pathway |
SignaLinki | Q9UHA7 |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-36 alphaAlternative name(s): FIL1 epsilon Interleukin-1 epsilon Short name: IL-1 epsilon Interleukin-1 family member 6 Short name: IL-1F6 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:15562, IL36A |
MIMi | 605509, gene |
neXtProti | NX_Q9UHA7 |
VEuPathDBi | HostDB:ENSG00000136694 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Note: The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion.1 Publication
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: GO_Central
Other locations
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 27179 |
OpenTargetsi | ENSG00000136694 |
PharmGKBi | PA38389 |
Miscellaneous databases
Pharosi | Q9UHA7, Tbio |
Genetic variation 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 | 3'-nitrotyrosineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
NitrationProteomic databases
MassIVEi | Q9UHA7 |
PaxDbi | Q9UHA7 |
PeptideAtlasi | Q9UHA7 |
PRIDEi | Q9UHA7 |
ProteomicsDBi | 84293 |
PTM databases
iPTMneti | Q9UHA7 |
PhosphoSitePlusi | Q9UHA7 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000136694, Expressed in esophagus and 73 other tissues |
Genevisiblei | Q9UHA7, HS |
Organism-specific databases
HPAi | ENSG00000136694, Group enriched (esophagus, lymphoid tissue) |
Interactioni
Subunit structurei
Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion.
1 PublicationGO - Molecular functioni
- cytokine activity Source: GO_Central
- interleukin-1 receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 118055, 19 interactors |
IntActi | Q9UHA7, 12 interactors |
STRINGi | 9606.ENSP00000259211 |
Miscellaneous databases
RNActi | Q9UHA7, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9UHA7 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502TDU1, Eukaryota |
GeneTreei | ENSGT00950000182943 |
HOGENOMi | CLU_095373_1_0_1 |
InParanoidi | Q9UHA7 |
OMAi | PFLFYHN |
OrthoDBi | 1502484at2759 |
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, PTHR10078, 1 hit PTHR10078:SF25, PTHR10078:SF25, 1 hit |
Pfami | View protein in Pfam PF00340, IL1, 1 hit |
PRINTSi | PR00264, INTERLEUKIN1 |
SUPFAMi | SSF50353, SSF50353, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
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
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | 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 |
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 |
Genome annotation databases
Ensembli | ENST00000259211; ENSP00000259211; ENSG00000136694 |
GeneIDi | 27179 |
KEGGi | hsa:27179 |
MANE-Selecti | ENST00000259211.7; ENSP00000259211.6; NM_014440.3; NP_055255.1 |
UCSCi | uc010yxr.3, human |
Similar proteinsi
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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6HPI | NMR | - | A | 1-158 | [»] | |
SMRi | Q9UHA7 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 118055, 19 interactors |
IntActi | Q9UHA7, 12 interactors |
STRINGi | 9606.ENSP00000259211 |
PTM databases
iPTMneti | Q9UHA7 |
PhosphoSitePlusi | Q9UHA7 |
Genetic variation databases
BioMutai | IL36A |
DMDMi | 25008601 |
Proteomic databases
MassIVEi | Q9UHA7 |
PaxDbi | Q9UHA7 |
PeptideAtlasi | Q9UHA7 |
PRIDEi | Q9UHA7 |
ProteomicsDBi | 84293 |
Protocols and materials databases
Antibodypediai | 33315, 341 antibodies from 31 providers |
DNASUi | 27179 |
Genome annotation databases
Ensembli | ENST00000259211; ENSP00000259211; ENSG00000136694 |
GeneIDi | 27179 |
KEGGi | hsa:27179 |
MANE-Selecti | ENST00000259211.7; ENSP00000259211.6; NM_014440.3; NP_055255.1 |
UCSCi | uc010yxr.3, human |
Organism-specific databases
CTDi | 27179 |
DisGeNETi | 27179 |
GeneCardsi | IL36A |
HGNCi | HGNC:15562, IL36A |
HPAi | ENSG00000136694, Group enriched (esophagus, lymphoid tissue) |
MIMi | 605509, gene |
neXtProti | NX_Q9UHA7 |
OpenTargetsi | ENSG00000136694 |
PharmGKBi | PA38389 |
VEuPathDBi | HostDB:ENSG00000136694 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502TDU1, Eukaryota |
GeneTreei | ENSGT00950000182943 |
HOGENOMi | CLU_095373_1_0_1 |
InParanoidi | Q9UHA7 |
OMAi | PFLFYHN |
OrthoDBi | 1502484at2759 |
PhylomeDBi | Q9UHA7 |
TreeFami | TF300203 |
Enzyme and pathway databases
PathwayCommonsi | Q9UHA7 |
Reactomei | R-HSA-9014826, Interleukin-36 pathway |
SignaLinki | Q9UHA7 |
Miscellaneous databases
BioGRID-ORCSi | 27179, 8 hits in 1026 CRISPR screens |
GeneWikii | IL1F6 |
GenomeRNAii | 27179 |
Pharosi | Q9UHA7, Tbio |
PROi | PR:Q9UHA7 |
RNActi | Q9UHA7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136694, Expressed in esophagus and 73 other tissues |
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, PTHR10078, 1 hit PTHR10078:SF25, PTHR10078:SF25, 1 hit |
Pfami | View protein in Pfam PF00340, IL1, 1 hit |
PRINTSi | PR00264, INTERLEUKIN1 |
SUPFAMi | SSF50353, SSF50353, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IL36A_HUMAN | |
Accessioni | Q9UHA7Primary (citable) accession number: Q9UHA7 Secondary accession number(s): B2RAD9 Q7RTZ8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 8, 2002 |
Last sequence update: | May 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 159 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
3D-structure, Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families