Taxonomic distribution of proteins containing MIT domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing MIT domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia.

Ciccarelli FD, Proukakis C, Patel H, Cross H, Azam S, Patton MA, Bork P, Crosby AH
Genomics. 2003; 81: 437-41

Multiple sequence alignment has revealed the presence of a sequence domain of approximately 80 amino acids in two molecules, spartin and spastin, mutated in hereditary spastic paraplegia. The domain, which corresponds to a slightly extended version of the recently described ESP domain of unknown function, was also identified in VPS4, SKD1, RPK118, and SNX15, all of which have a well established and consistent role in endosomal trafficking. Recent functional information indicates that spastin is likely to be involved in microtubule interaction. With this new information relating to its likely function, we propose the more descriptive name 'MIT' (contained within microtubule-interacting and trafficking molecules) for the domain and predict endosomal trafficking as the principal functionality of all molecules in which it is present.

SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia.

Patel H, Cross H, Proukakis C, Hershberger R, Bork P, Ciccarelli FD, Patton MA, McKusick VA, Crosby AH
Nat Genet. 2002; 31: 347-8

Troyer syndrome (TRS) is an autosomal recessive complicated hereditary spastic paraplegia (HSP) that occurs with high frequency in the Old Order Amish. We report mapping of the TRS locus to chromosome 13q12.3 and identify a frameshift mutation in SPG20, encoding spartin. Comparative sequence analysis indicates that spartin shares similarity with molecules involved in endosomal trafficking and with spastin, a molecule implicated in microtubule interaction that is commonly mutated in HSP.