Disease relevance of TRAPPC2

• Mutations in the SEDL gene, located at human chromosome Xp22, has recently been implicated with an X-linked genetic disease, although the function of SEDL gene product was not determined (A. K. Gedeon et al., Nat. Genet. 22:400-404, 1999) [1].
• Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda [2].
• SEDL was overexpressed in Escherichia coli and crystallized using the hanging-drop vapour-diffusion method at 298 K [3].
• Identification of a SEDL gene mutation in an individual with Leber hereditary optic neuropathy and spondyloepiphyseal dysplasia [4].

Psychiatry related information on TRAPPC2

• Although there is no specific treatment for SEDT, preexpression molecular testing of SEDL could be helpful if avoiding physical activities potentially injurious to the spine and the joints proves beneficial [5].

High impact information on TRAPPC2

• SEDL encodes a 140 amino acid protein with a putative role in endoplasmic reticulum (ER)-to-Golgi vesicular transport [2].
• Deletions or point mutations in the SEDL gene are responsible for the genetic disease spondyloepiphyseal dysplasia tarda (SEDT), an X-linked skeletal disorder [6].
• SEDL has been identified as a component of the transport protein particle (TRAPP), critically involved in endoplasmic reticulum-to-Golgi vesicle transport [6].
• Herein, we report the 2.4 A resolution structure of SEDL, which reveals an unexpected similarity to the structures of the N-terminal regulatory domain of two SNAREs, Ykt6p and Sec22b, despite no sequence homology to these proteins [6].
• A novel 2-base pair (bp) deletion in exon 5 of SEDL was found in the propositus by polymerase chain reaction (PCR) amplification and sequencing of all four coding exons [5].

Biological context of TRAPPC2

• Comparison of the cDNA sequence and genomic sequence identified six sedlin exons of 67, 142, 112, 147, 84, and 2259 bp [7].
• Sedlin is expressed from both the active and the inactive human X chromosomes helping to explain the recessive nature and consistent presentation of the disease [7].
• Four mRNA sizes were detected with the major band being 3 kb and minor bands of 5, 1.6, and 0.9 kb (the smallest product may reflect a sedlin pseudogene) [7].
• The sedlin gene for spondyloepiphyseal dysplasia tarda escapes X-inactivation and contains a non-canonical splice site [7].
• Spondyloepiphyseal dysplasia tarda (SEDL) is a radiologically distinct, X-chromosome linked primary skeletal dysplasia characterised by disproportionate short-trunked short stature, dysplasia of the large joints (hip) and flattened thoracic and lumber vertebral bodies [8].

Anatomical context of TRAPPC2

• While the SEDL gene mutations cause a tissue-specific (epiphyses) and relatively mild phenotype, the Trs20p function is essential for the yeast cell [9].
• Northern blot analysis showed expression of the sedlin gene in all human adult and fetal tissues tested, with the highest levels in kidney, heart, skeletal muscle, liver, and placenta [7].

Associations of TRAPPC2 with chemical compounds

• The link between Sedlin and the intracellular chloride channels is the first step to understand their functional interplays [10].
• This Japanese family was found to have an intragenic deletion flanking intron 2 and exon 3 of the SEDL gene that not only included the 5' untranslated region but also the coding sequence for the first methionine through the 25th alanine [11].

Physical interactions of TRAPPC2

• Green fluorescence protein-CLIC1 readily co-immunoprecipitated with FLAG-Sedlin [10].

Other interactions of TRAPPC2

• Interaction of Sedlin with chloride intracellular channel proteins [10].
• Sedlin also associated with CLIC2 in yeast two-hybrid assays [10].
• Here, the intracellular chloride channel protein CLIC1 was shown to associate with Sedlin by yeast two-hybrid screening [10].
• X-linked spondyloepiphyseal dysplasia tarda (SEDT, or SEDL) is a primary skeletal dysplasia affecting mostly spinal vertebral bodies and epiphyses [9].

Analytical, diagnostic and therapeutic context of TRAPPC2

• Sedlin was finely mapped in Xp22.2 by Southern blot analysis on a yeast artificial chromosome/bacterial artificial chromosome map [7].
• After polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis and DNA sequencing, a previously unreported deletion of T in exon 5 of SEDL gene (i.e. 293delT) was observed and seven individuals in the family carried the mutation [12].
• Crystallization and preliminary X-ray crystallographic analysis of SEDL [3].

References