Disease relevance of TXNL4A

• The gene coding for the human spliceosomal U5 snRNP-specific 15 kDa protein (U5-15kD) was overexpressed in Escherichia coli, its product purified to homogeneity and crystallized [1].
• Of the identified proteins, transketolase, Dim1p, v-Ha-ras oncogene, type I collagen pro alpha, tumor necrosis factor (ligand) superfamily member 4, and pirin etc, have shown associations with distinct aspect of tumor metastasis to some extent [2].

High impact information on TXNL4A

• In support of a role at the spindle, two-hybrid library screening with HEF1 identifies the human homolog of the G2/M spindle-regulatory protein Dim1p as a specific interactor with a region of HEF1 encompassed in p55(HEF1) [3].
• DLP, a novel Dim1 family protein implicated in pre-mRNA splicing and cell cycle progression [4].
• With respect to human thioredoxin the U5-15kD protein contains 37 additional residues causing structural changes which most likely form putative binding sites for other spliceosomal proteins or RNA [5].
• Biochemical characterization and crystal structure of a Dim1 family associated protein: Dim2 [6].
• Saturating alanine scanning mutagenesis of Dim1 allowed delineation of amino acids essential for its ability to interact with its defined partners: mapping these residues on the structural coordinates of hDim1 defined an interactive sector of the protein [7].

Biological context of TXNL4A

• These results parallel the arrest phenotypes associated with global disruption of zygotic gene expression, suggesting that Dim1 proteins maintain an essential function in gene expression in higher eukaryotes [7].
• To date, the mechanism of Dim1 function remains poorly defined, in part because of the absence of informative sequence homologies between Dim1 and other functionally defined proteins or protein domains [8].
• A homology search of GenBank showed that As37 has significant similarity to Caenorhabditis elegans DIM-1 protein and has low similarity to part of the multi-repeat Ig domain from nematode twitchin and mammalian skeleton muscle titin, and to members of the IgSF at the amino acid sequence level [9].

Other interactions of TXNL4A

• The evolutionarily conserved Dim1 protein defines a novel branch of the thioredoxin fold superfamily [8].

Analytical, diagnostic and therapeutic context of TXNL4A

• Overproduction, purification, crystallization and preliminary x-ray diffraction studies of the human spliceosomal protein U5-15kD [1].

References