This entry represents a family of transmembrane proteins, which function as a negative regulator of MYRF in oligodendrocyte differentiation and myelination. Interacts with the C-terminal of MYRF inhibiting MYRF self-cleavage and N-fragment nuclear translocation []. The secreted TMEM98 form promotes differentiation of T helper 1 cells (Th1) [].
Myelin regulatory factor (Myrf) is a transcription regulator required in vertebrates for expression of central nervous system (CNS) myelin genes such as Mbp and Mog, thereby playing a central role in oligodendrocyte maturation and CNS myelination []. It is also required for the maintenance of expression of myelin genes and the mature oligodendrocytes identity in the adult CNS [, ]. A Caenorhabditis elegans orthologue, pqn-47, may function as a regulator of molting [], while a Dictyostelium orthologue has been described to regulate prestalk differentiation [].This domain is found towards the C terminus of myelin regulatory factor (Myrf) and corresponds to the Intramolecular Chaperone Auto-processing (ICA) domain. It forms a homo-trimer and carries out the auto-cleavage of Myrf releasing the N-terminal homo-trimer from the ER membrane. This allows its entry to the nucleus to function as a homo-trimer transcription factor [].
The Intramolecular Chaperone Auto-processing (ICA) []domain, also called Intramolecuar Chaperone Domain (ICD) []or C-terminal Intramolecular Chaperone Domain (CIMCD) [], is capable of catalysing trimerisation-dependent auto-proteolysis. The ICA domain contains two absolutely conserved serine and lysine residues. They form a catalytic dyad that mediates cleavage at the serine residue. The correct positioning of these catalytic residues, along with an arginine residue that stabilises the oxyanion during the peptide bond breakage, is thought to be achieved only upon folding and trimerisation, enabling the ICA domain to function as a folding sensor. The ICA domain belongs to peptidase family S74.The ICA domain displays an α1-β1-α2-β2-α3-β3-β4-α4 fold. The ICA domain homotrimer has a jellyfish-like outline with a central threefold symmetry axis and mainly consists of α-helices. It comprises a quite globular core and an extended loop region, reminiscent oftentacles, protruding from the centre. The central part of the core is a slightly twisted three helix bundle, forming the trimerisation interface [].Some proteins known to contain an ICA domain are listed below:Animal myelin regulatory factor (MYRF), a key transcriptional regulator for of oligodendrocyte differentiation and central nervous system (CNS) myelination. The MYRF protein undergoes an activating cleavage event to release the functional transcription factor from the transmembrane domain that otherwise anchors it to the endoplasmic reticulum [, ].Tailed bacteriophage (Caudovirus) endosialidases, the tailspike proteins essential for bacteriophages to infect bacteria encapsulated with polysaccharides [].
