FCMR
Domain
The Ig-like V-set domain comprises three loops analogous to the complementarity-determining regions (CDR) of Ig variable domains, which are responsible for engaging IgM. Mediates multivalent interactions with the CH4 domains of pentameric IgM, facilitating receptor clustering and signaling.
Function
High-affinity Fc receptor for immunoglobulin M (IgM), both secreted and membrane-bound IgM (PubMed:19858324, PubMed:22675200, PubMed:36949194, PubMed:37095205). Primarily regulates IgM transport and homeostasis. In lymphoid cells, enables exocytosis of membrane-bound IgM on the plasma membrane as well as endocytosis of IgM-antigen complexes toward lysosomes for degradation. In mucosal epithelium, mediates retrotranscytosis of antigen-IgM complexes across mucosal M cells toward antigen-presenting cells in mucosal lymphoid tissues (PubMed:21908732, PubMed:28230186). Triggers costimulatory signaling and mediates most of IgM effector functions involved in B cell development and primary immune response to infection. Likely limits tonic IgM BCR signaling to self-antigens for proper negative selection of autoreactive B cells in the bone marrow and for the maintenance of regulatory B cell pool in peripheral lymphoid organs. Mediates antibody responses to T cell-dependent and T cell-independent antigens and promotes induction of an efficient neutralizing IgG response. Engages in cross-talk with antigen-receptor signaling via the non-canonical NF-kappa-B, MAP kinases and calcium signaling pathways (PubMed:19858324, PubMed:22675200, PubMed:25601920, PubMed:30840890).
Post-translational modifications
Phosphorylated on both Tyr and Ser residues.
O-glycosylated. Sialylated. O-linked glycans regulate trafficking to the plasma membrane.
Tissue Specificity
Expressed by CD19-positive B cells and CD4-positive and CD8-positive T cell populations in primary and secondary lymphoid tissues (at protein level). Among B cell subsets, detected in a subset of bone marrow pro- and pre-B cells, in most follicular and memory B cells and in a small subset of germinal center B cells (at protein level). Expressed at lower levels in CD56-positive NK cells (at protein level) (PubMed:19858324, PubMed:21908732, PubMed:22675200, PubMed:30840890). Expressed in lymph nodes, lung, thymus and kidneys. Very weak expression detected in spleen, liver, heart, and salivary gland.
Cellular localization
- Cell membrane
- Single-pass membrane protein
- Early endosome membrane
- Single-pass membrane protein
- Golgi apparatus
- trans-Golgi network membrane
- Single-pass membrane protein
- Lysosome membrane
- Single-pass membrane protein
- Continuously recycles between cytoplasmic pool and the plasma membrane to bind as much IgM as possible.
- Isoform 3
- Secreted
- Detected in the serum.
Alternative names
FAIM3, TOSO, FCMR, Immunoglobulin mu Fc receptor, IgM FcR, Fas apoptotic inhibitory molecule 3, Regulator of Fas-induced apoptosis Toso