FAIM3

FAIM3 Full Name

Fas apoptotic inhibitory molecule 3

FAIM3 Introduction

FAIM3 is a type I transmembrane protein. In humans, the gene for this protein is located on chromosome 1q32.2. It is a single-copy gene. The protein contains 390 amino acids. The protein consists of a signal peptide, extracellular region, transmembrane domain and cytoplasmic tail. The protein was initially called TOSO, following its identification as a negative regulator of Fas/CD95 receptor-induced T-cell apoptosis. This initial functional definition led to its classification as a member of the apoptotic inhibitory molecule family. FAIM3 is primarily expressed in adaptive immune cells. For instance, it is highly expressed on the surface of human B cells, T cells, and NK cells, but is not detected in myeloid-derived cells such as monocytes or granulocytes.

The function initially attributed to FAIM3 was that of a negative regulator of apoptosis. Previous work had suggested that TOSO/FAIM3 inhibited Fas-mediated apoptotic signalling by sequestering Fas-associated death domain (FADD) thereby inhibiting caspase-8 activation. FAIM3 was subsequently identified as the long-sought Fc receptor for IgM (FcμR). These findings altered the previously held notion of FAIM3, showing it to bind to the Fc portion of IgM molecules with high affinity and specificity. As FcμR, FAIM3 is involved in the internalization and transport of IgM, as well as the regulation of B cell signaling. Subsequently, debate arose regarding whether its anti-apoptotic function is an intrinsic property. Some studies suggest that its anti-apoptotic effect might be indirect or not its primary physiological function. Therefore, it is now generally accepted that FAIM3 is a molecule with a dual identity: it is both the FcμR and may also regulate apoptosis under specific conditions.

Figure 1. Schematic representation of FcμR. (Source: Kubagawa H, et al. 2014)

As for disease associations, the one that is most clearly defined and deeply investigated is that between FAIM3 and Chronic Lymphocytic Leukemia (CLL). A large body of evidence clearly points out that FAIM3 is significantly overexpressed in CLL malignant B cells and this high expression level is tightly associated with disease progression, poor prognosis and anti-apoptotic capabilities of tumor cells. FAIM3 acts to enhance B-cell receptor (BCR) signaling pathway and inhibit apoptosis in order to promote the survival and proliferation of CLL cells, being thus a very promising therapeutic target and prognostic biomarker for CLL.

Alternate Names for FAIM3

FAIM3; Fas apoptotic inhibitory molecule 3; FCMR; TOSO; fas apoptotic inhibitory molecule 3; Fc mu receptor; IgM Fc receptor; immunoglobulin mu Fc receptor; regulator of Fas-induced apoptosis Toso

• 1. Planells-Ferrer L, et al. Fas apoptosis inhibitory molecules: more than death-receptor antagonists in the nervous system. J Neurochem. 2016 Oct;139(1):11-21.
  2. Kubagawa H, et al. The old but new IgM Fc receptor (FcμR). Curr Top Microbiol Immunol. 2014;382:3-28.