MID2 shares high structural and functional similarities with MID1, an ubiquitin E3 ligase that regulates the turnover of microtubular protein phosphatase 2Ac. MID2 interacts with Astrin (a microtubule-organizing protein) and regulates Astrin levels to promote cell division []. MID1 and MID2 may play roles in regulating tissue remodelling in early development [].Mutations in the MID2 gene cause mental retardation, X-linked 101 (MRX101) [].
This domain is found near the C terminus of Mid2, which contains a transmembrane region. The remainder of the protein sequence is serine-rich and of low complexity, and is therefore impossible to align accurately. Mid2 is thought to act as a mechanosensor of cell wall stress. The C-terminal cytoplasmic region of Mid2 is known to interact with Rom2, a guanine nucleotide exchange factor (GEF) for Rho1, which is part of the cell wall integrity signalling pathway [].
This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM1 (also known as MID2 or midline 2). MID2 and its close homologue, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Mid1 and Mid2 are ubiquitin ligases that regulate microtubule dynamics and whose mutation is associated with X-linked developmental disorders. Mid2 regulates cell division through the ubiquitination of astrin on K409, which is critical for its degradation and proper cytokinesis [].
This entry represents the COS domain found in the C-I subfamily of the tripartite motif (TRIM) family of E3 ubiquitin ligases.The C-1 subfamily includes MID1 (TRIM18), MID2 (TRIM1), TRIM9, TNL (TRIM67), TRIM36 and TRIFIC (TRIM46) [, , ]. The C-I subfamily contains C-terminal FNIII and B30.2 domains which are associated with microtubules [, ]. C-I subfamily members also contain a relatively conserved region of approximately 60 amino acids, termed the C-terminal subgroup One Signature (COS) domain []. The human Midline-1 (MID1) COS domain has a helix-loop-helix structure in which the N- and C-terminal ends are in close proximity []. Deletion of the human MID1 COS domain does not affect MID1 dimerisation but disrupts localisation to the microtubules [].The COS domain is also observed within the TRIM C-II subgroup, which consists of the MURF1-3 proteins that do not contain the FNIII and B30.2domains. MUF1-3 proteins are also associated with microtubules [].
