Protein: Interleukin-17A (IL-17) (IL-17A) (Cytotoxic T-lymphocyte-associated antigen 8) (CTLA-8) (Q16552)
Organism: Homo sapiens (Human)
Function: Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. 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. 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 (By similarity). In airway epithelium, mediates neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines (By similarity). 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 (By similarity). 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 (By similarity). Effector cytokine of innate immune cells including invariant natural killer cell (iNKT) and group 3 innate lymphoid cells that mediate initial neutrophilic inflammation (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). Involved in antiviral host defense through various mechanisms (By similarity). Enhances immunity against West Nile virus by promoting T cell cytotoxicity (By similarity). May play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung (By similarity). 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 (By similarity).
Subcellular location: Secreted {ECO:0000269|PubMed:17763419, ECO:0000269|PubMed:8676080}.
Sequence: MTPGKTSLVSLLLLLSLEAIVKAGITIPRNPGCPNSEDKNFPRTVMVNLNIHNRNTNTNPKRSSDYYNRSTSPWNLHRNEDPERYPSVIWEAKCRHLGCINADGNVDYHMNSVPIQQEILVLRREPPHCPNSFRLEKILVSVGCTCVTPIVHHVA
InterPro domains: - IPR010345: Interleukin-17 family (family) [70-148]
- IPR020440: Interleukin-17, chordata (family) [72-147]
- IPR029034: Cystine-knot cytokine (homologous_superfamily) [24-155]
Interaction partners: - Interleukin-17 receptor A
- Interleukin-17 receptor C
- Interleukin-17F
- Interleukin-2
- Interleukin-10
- Interleukin-6
- Interferon gamma
- Interleukin-22
- T-cell surface glycoprotein CD4
- Interleukin-1 beta
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0098772 (molecular function regulator activity), GO:0030545 (signaling receptor regulator activity), GO:0140677 (molecular function activator activity), GO:0005515 (protein binding), GO:0042802 (identical protein binding), GO:0030546 (signaling receptor activator activity), GO:0005102 (signaling receptor binding), GO:0019955 (cytokine binding), GO:0046983 (protein dimerization activity), GO:0042803 (protein homodimerization activity), GO:0048018 (receptor ligand activity), GO:0005125 (cytokine activity)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0051240 (positive regulation of multicellular organismal process), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0050793 (regulation of developmental process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0051093 (negative regulation of developmental process), GO:0007165 (signal transduction), GO:0007154 (cell communication), GO:0090287 (regulation of cellular response to growth factor stimulus), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0001817 (regulation of cytokine production), GO:1901343 (negative regulation of vasculature development), GO:0010033 (response to organic substance), GO:2000026 (regulation of multicellular organismal development), GO:0009888 (tissue development), GO:0010646 (regulation of cell communication), GO:0070887 (cellular response to chemical stimulus), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0007166 (cell surface receptor signaling pathway), GO:0001819 (positive regulation of cytokine production), GO:0080090 (regulation of primary metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:1903555 (regulation of tumor necrosis factor superfamily cytokine production), GO:0034097 (response to cytokine), GO:0051216 (cartilage development), GO:0032663 (regulation of interleukin-2 production), GO:0051246 (regulation of protein metabolic process), GO:0071310 (cellular response to organic substance), GO:0032642 (regulation of chemokine production), GO:0032722 (positive regulation of chemokine production), GO:0061448 (connective tissue development), GO:1903557 (positive regulation of tumor necrosis factor superfamily cytokine production), GO:1901342 (regulation of vasculature development), GO:0090092 (regulation of transmembrane receptor protein serine/threonine kinase signaling pathway), GO:0032755 (positive regulation of interleukin-6 production), GO:0032675 (regulation of interleukin-6 production), GO:0010628 (positive regulation of gene expression), GO:0010468 (regulation of gene expression), GO:0032677 (regulation of interleukin-8 production), GO:0001501 (skeletal system development), GO:0051247 (positive regulation of protein metabolic process), GO:0045765 (regulation of angiogenesis), GO:1903844 (regulation of cellular response to transforming growth factor beta stimulus), GO:0019221 (cytokine-mediated signaling pathway), GO:2000181 (negative regulation of blood vessel morphogenesis), GO:0016525 (negative regulation of angiogenesis), GO:0097396 (response to interleukin-17), GO:0017015 (regulation of transforming growth factor beta receptor signaling pathway), GO:0071345 (cellular response to cytokine stimulus)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005576 (extracellular region)