Q62386 · IL17_MOUSE

  • Protein
    Interleukin-17A
  • Gene
    Il17a
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:18025225, PubMed:19144317, PubMed:26431948).
Signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:16200068, PubMed:17911633, PubMed:19144317, PubMed:26431948).
Plays an important role in connecting T cell-mediated adaptive immunity and acute inflammatory response to destroy extracellular bacteria and fungi. As a signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites (PubMed:18025225).
In airway epithelium, mediates neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines (PubMed:18025225, PubMed:27923703).
In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (PubMed:18157131).
Effector cytokine of a subset of gamma-delta T cells that functions as part of an inflammatory circuit downstream IL1B, TLR2 and IL23A-IL12B to promote neutrophil recruitment for efficient bacterial clearance (PubMed:17372004, PubMed:20364087, PubMed:28709803).
Effector cytokine of innate immune cells including invariant natural killer cell (iNKT) and group 3 innate lymphoid cells that mediate initial neutrophilic inflammation (PubMed:17470641, PubMed:23255360).
Involved in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Upon acute injury, has a direct role in epithelial barrier formation by regulating OCLN localization and tight junction biogenesis (PubMed:26431948).
As part of the mucosal immune response induced by commensal bacteria, enhances host's ability to resist pathogenic bacterial and fungal infections by promoting neutrophil recruitment and antimicrobial peptides release (PubMed:28709803).
In synergy with IL17F, mediates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (PubMed:19144317).
Involved in antiviral host defense through various mechanisms (PubMed:21946434, PubMed:26735852, PubMed:27795421).
Enhances immunity against West Nile virus by promoting T cell cytotoxicity (PubMed:27795421).
May play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung (PubMed:21946434).
Contributes to influenza A virus (H1N1) clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (PubMed:26735852).

GO annotations

AspectTerm
Cellular Componentexternal side of plasma membrane
Cellular Componentextracellular space
Molecular Functioncytokine activity
Molecular Functionprotein heterodimerization activity
Molecular Functionprotein homodimerization activity
Biological Processadaptive immune response
Biological Processcellular response to glucocorticoid stimulus
Biological Processcellular response to interleukin-1
Biological Processdefense response to fungus
Biological Processdefense response to Gram-negative bacterium
Biological Processdefense response to Gram-positive bacterium
Biological Processfibroblast activation
Biological Processgene expression
Biological Processgranulocyte migration
Biological Processinflammatory response
Biological Processinnate immune response
Biological Processinterleukin-17-mediated signaling pathway
Biological Processinterleukin-17A-mediated signaling pathway
Biological Processintestinal epithelial structure maintenance
Biological Processkeratinocyte differentiation
Biological Processkeratinocyte proliferation
Biological Processnegative regulation of inflammatory response to wounding
Biological ProcessNotch signaling pathway
Biological Processpositive regulation of antimicrobial peptide production
Biological Processpositive regulation of bicellular tight junction assembly
Biological Processpositive regulation of chemokine (C-X-C motif) ligand 1 production
Biological Processpositive regulation of cytokine production involved in inflammatory response
Biological Processpositive regulation of interleukin-1 beta production
Biological Processpositive regulation of interleukin-12 production
Biological Processpositive regulation of interleukin-16 production
Biological Processpositive regulation of interleukin-23 production
Biological Processpositive regulation of interleukin-6 production
Biological Processpositive regulation of osteoclast differentiation
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processpositive regulation of tumor necrosis factor production
Biological Processresponse to wounding

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Interleukin-17A
  • Short names
    IL-17; IL-17A
  • Alternative names
    • Cytotoxic T-lymphocyte-associated antigen 8 (CTLA-8)

Gene names

    • Name
      Il17a
    • Synonyms
      Ctla8, Il17

Organism names

  • Taxonomic identifier
  • Strains
    • BALB/cJ
    • 129/Sv
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q62386
  • Secondary accessions
    • Q60971

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

Mutant mice are born at the expected Mendelian ratio, are fertile, and have no apparent phenotypic abnormalities. They are protected against chronic autoimmune and allergic reactions, as observed in models of spontaneous or induced rheumatoid arthritis, experimental autoimmune encephalomyelitis and chemical allergen-induced contact hypersensitivity (PubMed:19144317).
In a model of acute intestinal injury, mutant mice show epithelial disruption, presence of abscesses associated with enhanced bleeding into the mucosal lumen and increased cellular infiltrate into the submucosal layer (PubMed:26431948).
Mutant mice show increased susceptibility to West Nile virus infection characterized by deficient virus clearance from brain and spleen (PubMed:27795421).
Mutant mice are deficient in clearing influenza A virus (H1N1) pulmonary infection due to increased immune inflammation and lung damage (PubMed:26735852).

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 6 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for signal, chain, glycosylation, disulfide bond.

TypeIDPosition(s)Description
Signal1-25
ChainPRO_000001542426-158Interleukin-17A
Glycosylation71N-linked (GlcNAc...) asparagine
Disulfide bond97↔147
Disulfide bond102↔149

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed by Th17 cell lineage (at protein level). The expression pattern reflects the differentiation state, with IL17A-IL17F heterodimers produced at higher levels than IL17A-IL17A and IL17F-IL17F dimers in fully differentiated Th17 cells (PubMed:16990136, PubMed:18025225).
Expressed in innate lymphoid cells (at protein level) (PubMed:23255360, PubMed:28709803).
Expressed in gamma-delta T cell subsets (at protein level) (PubMed:17372004, PubMed:20364087, PubMed:26431948, PubMed:28709803).
Expressed in iNKT cells (at protein level) (PubMed:17470641).

Induction

Induced upon differentiation of CD4-positive T cells toward Th17 effector cells upon antigen receptor binding in the presence of IL6 and TGFB1 (PubMed:16200068, PubMed:16990136, PubMed:18025225).
Up-regulated by IL23A-IL12B, IL1B and TNF and inhibited by IFNG and IL4 (PubMed:16200068, PubMed:18025225).
Up-regulated by pro-inflammatory cytokines in response to microbes in various immune cells: induced in innate lymphoid cells upon fungal infection, in Vdelta4-positive gamma-delta T cells upon C.mastitidis infection, in Vdelta5-positive gamma-delta T cells upon S.aureus infection and in Vdelta1-positive gamma-delta T cells upon E.coli infection (PubMed:17372004, PubMed:20364087, PubMed:23255360, PubMed:28709803).
Induced in gamma-delta T cells in intestinal lamina propria upon acute injury (PubMed:26431948).
Induced in KLRB1/NK1.1-negative iNKT cell subset upon CD1D stimulation (PubMed:17470641).

Gene expression databases

Interaction

Subunit

Homodimer (PubMed:18025225).
Forms complexes with IL17RA and IL17RC receptors with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule (By similarity).
IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex (By similarity).
IL17A homodimer adopts an asymmetrical ternary structure with one IL17RA molecule, allowing for high affinity interactions of one IL17A monomer with one IL17RA molecule (via D1 and D2 domains), while disfavoring binding of a second IL17RA molecule on the other IL17A monomer (By similarity).
Heterodimer with IL17F (PubMed:18025225).
IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer (By similarity).
IL17RA and IL17RC chains cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (By similarity).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Sequence similarities

Belongs to the IL-17 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    158
  • Mass (Da)
    17,490
  • Last updated
    1996-11-01 v1
  • Checksum
    3505C143435F4653
MSPGRASSVSLMLLLLLSLAATVKAAAIIPQSSACPNTEAKDFLQNVKVNLKVFNSLGAKVSSRRPSDYLNRSTSPWTLHRNEDPDRYPSVIWEAQCRHQRCVNAEGKLDHHMNSVLIQQEILVLKREPESCPFTFRVEKMLVGVGCTCVASIVRQAA

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U43088
EMBL· GenBank· DDBJ
AAB05222.1
EMBL· GenBank· DDBJ
mRNA
U35108
EMBL· GenBank· DDBJ
AAA93253.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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