Igsf8
Developmental stage
Expressed at 9.5 dpc in the ventral domain of the neural tube, with dorsal expression apparent at 10.5 dpc, as well as in the dorsal bud of the pancreas. Detected at 11.5 dpc within the ventricular zone of the neural tube in the hindbrain, diencephalon and telencephalon; also detected in the epithelial lining of the bronchi and esophagus. At 12.5 dpc, expressed in the bronchi, in the atrial and ventricular myocardium, the dorsal root ganglia and the epithelial lining of the rectum and bladder. At 15.5 dpc, detected in the developing choroid plexus epithelium, neural retina, olfactory epithelium and developing vomeronasal organ.
Domain
The Ig-like C2-type domains 3 and 4 are required for interaction with CD81.
The short cytoplasmic domain is very basic, interacts with membrane PIPs, and mediates plasma membrane localization.
Function
Member of the immunoglobulin superfamily (IgSF) that links tetraspanin-enriched microdomains to the actin cytoskeleton and plays several important roles in innate and adaptive immunity (PubMed:11673522). Acts as an inducible receptor of HSPA8 on dendritic cells to enhance the CCL21/SLC-dependent migration of activated mature dendritic cells while attenuating their antigen-specific stimulatory capacities. In complex with alpha-actinins ACTN1 and ACTN4, regulates actin dynamics in the immune synapse and subsequent T-cell activation. Inhibits the entry of several viruses such as hepatitis C Virus (HCV) or HIV-1. Mechanistically, promotes a change in CD81 organization at the plasma membrane by significantly restricting its diffusion which in turn influences CD81 interaction with Claudin-1/CLDN1, preventing CLDN1 from acting as a co-receptor required for HCV entry. Accumulates at the presynaptic terminal, the producer cell side of the virological synapse, to prevent HIV-1 Env-mediated cell-cell fusion. Highly expressed on malignant cells with antigen presentation defects, interacts with NK receptor KLRA9 to suppress NK-cell cytotoxicity (PubMed:38657602). May participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain (PubMed:16203089).
Tissue Specificity
Expressed in lymphocytes as well as in many tissues with higher expression in brain. Detected in all regions of the brain with weak expression in the pituitary. Expressed selectively by neurons but not by glial cells. Expressed in myoblasts (at protein level).
Cellular localization
- Cell membrane
- Single-pass membrane protein
Alternative names
CD316, Ewi2, Kct4, Pgrl, Igsf8, Immunoglobulin superfamily member 8, IgSF8, CD81 partner 3, Glu-Trp-Ile EWI motif-containing protein 2, Keratinocyte-associated transmembrane protein 4, Prostaglandin regulatory-like protein, EWI-2, KCT-4, PGRL