IL17RC

This gene encodes a single-pass type I membrane protein that shares similarity with the interleukin-17 receptor (IL-17RA). Unlike IL-17RA, which is predominantly expressed in hemopoietic cells, and binds with high affinity to only IL-17A, this protein is expressed in nonhemopoietic tissues, and binds both IL-17A and IL-17F with similar affinities. The proinflammatory cytokines, IL-17A and IL-17F, have been implicated in the progression of inflammatory and autoimmune diseases. Multiple alternatively spliced transcript variants encoding different isoforms have been detected for this gene, and it has been proposed that soluble, secreted proteins lacking transmembrane and intracellular domains may function as extracellular antagonists to cytokine signaling. [provided by RefSeq, Feb 2011]

Full Name

Interleukin 17 Receptor C

Function

Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (By similarity).

Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:16785495).

Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (PubMed:18684971).

Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (PubMed:17911633).

Upon binding of IL17F homodimer triggers downstream activation of TRAF6 and NF-kappa-B signaling pathway (PubMed:16785495, PubMed:32187518).

Induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi (By similarity).

Promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression (By similarity).

Binding of IL17A-IL17F to IL17RA-IL17RC heterodimeric receptor complex triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. 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:18684971, PubMed:17911633).

Primarily induces neutrophil activation and recruitment at infection and inflammatory sites (By similarity).

Stimulates 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).

Isoform 5&8:
Receptor for both IL17A and IL17F.

Isoform 6&7:
Does not bind IL17A or IL17F.

Biological Process

Inflammatory response Source: UniProtKB-KW

Cellular Location

Cell membrane. Soluble isoforms may be produced.

Involvement in disease

Candidiasis, familial, 9 (CANDF9):
A disorder characterized by altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.

Topology

Extracellular: 21-538
Helical: 539-559
Cytoplasmic: 560-791