Disease relevance of MID2

• Primate tripartite motif 5alpha (TRIM5alpha) proteins mediate innate intracellular resistance to retroviruses [1].
• The TRIM5alpha (tripartite motif 5alpha protein) has been linked to the cross-species restriction in human immunodeficiency virus type 1 (HIV-1) infection of non-human cells, but the mechanism by which this occurs remains to be fully elucidated [2].
• Human immunodeficiency virus type 1 (HIV-1) is blocked in the cells of Old World monkeys by TRIM5alpha, a tripartite motif (TRIM) protein composed of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains [3].
• TRIM-Cyp, but not TRIM5alpha, recruits its tripartite motif to HIV-1 capsid via cyclophilin A and, therefore, HIV-1 G89V is insensitive to TRIM-Cyp but sensitive to TRIM5alpha [4].
• By reviewing all the MID1-mutated OS patients so far described, we confirmed that hypertelorism and hypospadias are the most frequent manifestations, being present in almost every XLOS individual [5].

High impact information on MID2

• MID1 encodes a member of the B-box family of proteins, which contain protein-protein interaction domains, including a RING finger, and are implicated in fundamental processes such as body axis patterning and control of cell proliferation [6].
• These results suggest that Mid2p influences septin ring organization at the site of cell division and its turnover might normally be required to permit septin ring disassembly [7].
• An anillin homologue, Mid2p, acts during fission yeast cytokinesis to organize the septin ring and promote cell separation [7].
• In the presence of a nondegradable Mid2p fragment, the septin ring is stabilized and cell cycle progression is delayed [7].
• We hypothesize that the Trim family of proteins plays a widespread role in innate immunity to viral infection [8].

Biological context of MID2

• MID2 maps to Xq22 in human and to the syntenic region on the mouse X chromosome [9].
• CONCLUSIONS: Our findings not only implicate Alpha 4 in the pathogenesis of Opitz GBBB syndrome but also support our earlier hypothesis that MID2 is a modifier of the X-linked phenotype [10].
• The tripartite motif is characteristic of a family of proteins, named the B-box family, involved in cell proliferation and development [11].
• Overproduction of Mid2p depolarizes cell growth and affects the organization of both the septin and actin cytoskeletons [7].
• Mid2p localizes as a single ring in the middle of the cell after anaphase in a septin- and actin-dependent manner and splits into two rings during septation [7].

Anatomical context of MID2

• A protein highly related to MID1, called MID2, has also been described that similarly associates with microtubules [10].
• Mid1 could recruit alpha4 onto microtubules, and high levels of alpha4 could displace Mid1 into the cytosol [12].

Associations of MID2 with chemical compounds

• On the basis of our results, the mutation in the tripartite-motif-containing gene (TRIM32) that replaces aspartate with asparagine at position 487 appears to be the causative mutation of LGMD2H [13].
• A tripartite motif located in the centre of the 7.5 kb exon 26 of apolipoprotein B (apoB) mRNA directs editosome assembly and site-specific cytidine-to-uridine editing at nucleotide 6666. apoB mRNA editing is a post-transcriptional event, occurring primarily at the time exon 26 is spliced or at a time after splicing, but before nuclear export [14].
• Rfp becomes oncogenic when its tripartite motif is recombined with the tyrosine kinase domain from the c-ret proto-oncogene [15].
• A monoclonal antibody, MID 2, which reacts with an epitope common to all human leucocytes, was used to show that the leucocyte common antigen can be resolved into four glycoprotein components with molecular weights of 220 K, 200 K, 180 K and 160 K [16].
• The effective barrier properties were investigated following treatment for 15 min with one of: acid etchant, Trim, cavity varnish, Hibiscrub, Hydrex and Vitremer using a dye permeability test [17].

Regulatory relationships of MID2

• Candidate yeast mRNA substrates were identified based on their homology with the mooring sequence-containing tripartite motif at the editing site of apoB mRNA and their ability to be edited by ectopically expressed APOBEC-1 [18].

Other interactions of MID2

• Together, these data suggest that midin and MID2 have a similar biochemical function but a different physiological role during development [9].
• The critical interaction between CA and Trim-CypA appears to take place soon after viral entry [19].
• The exceptions were TRIM1, TRIM5 and TRIM34 proteins [20].
• Since FG and Opitz G/BBB syndromes share many manifestations we considered MID2 a candidate gene for FG syndrome [21].
• Mutations in TRIM37 encoding a tripartite motif (TRIM, RING-B-box-coiled-coil)-family protein underlie mulibrey nanism [22].

Analytical, diagnostic and therapeutic context of MID2

• The expression pattern studied by RNA in situ hybridization in mouse revealed that Mid2 is expressed early in development and the highest level of expression is detected in the heart, unlike Mid1 for which no expression was detected in the developing heart [9].
• Immunoprecipitation experiments demonstrated the ability of the tripartite motif to mediate midin homodimerization, consistent with the evidence, obtained by gel filtration analysis, that midin exists in the form of large protein complexes [11].
• We confirmed by immunoprecipitation that this interaction occurs in vivo and that it is mediated by the Mid1 coiled-coil domain [23].
• Accordingly, we observed differential MID1 transcript patterns in a tissue-specific manner by Northern blot and RT-PCR [24].
• Gene mapping has identified OS mutations within a protein called Mid1 [12].

References