FCRL3
Developmental stage
Expressed in mature metaphase II (MII) stage oocytes (at protein level) (PubMed:36070373). In B-cells, expression increases as a function of differentiation and peaks on memory B-cells.
Function
Promotes TLR9-induced B-cell proliferation, activation and survival but inhibits antibody production and suppresses plasma cell differentiation. Enhances activation of NF-kappa-B and MAPK signaling pathways in TLR9 stimulated B-cells (PubMed:23857366). Has inhibitory potentional on B-cell receptor (BCR)-mediated signaling, possibly through association with SH2 domain-containing phosphatases. Inhibits cell tyrosine phosphorylation, calcium mobilization and activation-induced cell death induced through BCR signaling (PubMed:19843936). Regulatory T-cells expressing FCRL3 exhibit a memory phenotype, are relatively nonresponsive to antigenic stimulation in presence of IL2 and have reduced capacity to suppress the proliferation of effector T-cells (PubMed:19494275, PubMed:20190142). Acts as a human-specific epitope on the cell surface of oocytes (oolemma) and plays a role during sperm-egg adhesion and fusion (PubMed:36070373). Interacts with the IZUMO1-IZUMO1R/JUNO sperm-egg complex and replaces IZUMO1R/JUNO as IZUMO1 receptor during fertilization, thereby permitting species-specific gamete fusion (PubMed:36070373).
Involvement in disease
Rheumatoid arthritis
RA
An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Genetic variation in FCRL3 may influence susceptibility to autoimmune disorders, including Graves disease or multiple sclerosis. Graves disease is an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism. Multiple sclerosis is an autoimmune/inflammatory neurodegenerative disease which mainly affects young adults and is characterized by destruction of myelin in the central nervous system.
Post-translational modifications
Phosphorylated on cytoplasmic tyrosines; required for interaction with protein tyrosine phosphatases and protein tyrosine kinases.
Tissue Specificity
Primarily expressed in secondary lymphoid tissues by mature subsets of B-cells. Low expression on transitional B cells which increases to higher surface expression on mature and memory B-cells with innate-like features (at protein level) (PubMed:23857366). Expressed a low levels in naive and germinal center B-cells but also expressed in NK cells (at protein level) (PubMed:20190142). Expressed in unfertilized oocytes (at protein level) (PubMed:36070373). Expressed in a population of thymically derived naturally occurring regulatory T-cells that exhibits a memory phenotype, specialized in suppressing immune response to self-antigens (PubMed:20190142). Detected in spleen, lymph node, peripheral blood lymphocytes, thymus, bone marrow, kidney, salivary gland, adrenal gland and uterus.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Cell projection
- Microvillus membrane
- Localized along the oolemma microvilli of unfertilized oocytes.
Alternative names
CD307c, FCRH3, IFGP3, IRTA3, SPAP2, FCRL3, Fc receptor-like protein 3, FcR-like protein 3, FcRL3, Fc receptor homolog 3, IFGP family protein 3, Immune receptor translocation-associated protein 3, MAIA, SH2 domain-containing phosphatase anchor protein 2, FcRH3, hIFGP3