Evolutionary conservation and genomic organization of XAP-4, an Xq28 located gene coding for a human rab GDP-dissociation inhibitor (GDI)

Abstract

After the development of efficient methods for the construction of transcription maps of defined genomic regions, the rate-limiting step in the analysis of the coding potentials of these regions is the elucidation of function of the novel genes and the examination of their possible involvement in hereditary diseases localized to the region. This can be greatly facilitated by the detection of sequence homology to a gene of known function. XAP-4 is one of the genes identified in the G6PD region of the human Xq28 by direct cDNA selection. The rapid assembly of this gene and the determination of its function was possible because of its sequence homology with the bovine smg p25A/rab3A GDP dissociation inhibitor (GDI). Sequence comparison with other GDIs in the databases has revealed that XAP-4 belongs to one of at least two distinct classes of mammalian rab GDIs. The rab GDIs, which play an important role in the regulation of cellular transport, are highly evolutionarily conserved, as are several other genes identified in the neighborhood of XAP-4. This genomic region is very gene dense, and all the cDNA clones from the approximately 2.5-kb-long transcript of XAP-4 map to a single 7.5-kb genomic EcoRI fragment. The genomic organization of XAP-4 has been examined to determine the distribution of the exonic sequences within this short segment of genomic DNA. It was found that, similar to several other genes from the region, XAP-4 is split into exons of average size, which are interrupted by very short introns.

Withdrawal: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model

“…43,44) Rab guanosine 5′-triphosphatases (GTPases), one of the Ras superfamily members of monomeric GTPases, are small G proteins and involved in membrane trafficking. 45,46) The Rab GTPase controls a fast endocytic recycling pathway and must be activated for septin cytoskeleton localization at the intercellular bridge, and thus for completion of cytokinesis. 47) Above these reasons, it is possible that it may be caused cytoskeleton disfunction mediated by global cerebral ischemia.…”

Rab3A small GTP‐binding protein in Ca2+‐dependent exocytosis

“…The tissue distribution of Rab GDI has not been examined. The human Rab GDI gene has been shown to be located in chromosome X, with a regional localization on Xq28 (Sedlacek et al 1994). Rab GDI is found in yeast and Drosophila, as well as in mammal, and is named GDI1 and dGDI, respectively, (Zahner & Cheney 1993;Garrett et al 1994).…”

Role of Rab GDP dissociation inhibitor α in regulating plasticity of hippocampal neurotransmission

“…Genetic analysis of X-linked nonspecific mental retardation (XLMR) has revealed that mutations of the Rab GDI␣ gene can cause this disease (11). It is of note that Rab GDI␣ is localized to the distal part of chromosome Xq28 (12), because genetic defects mapped in this region have recently been described to cause a syndromic form of XLMR that comprises epileptic seizures (13). These observations suggest that Rab GDI␣ has a specialized function of the neuronal cells that may be related to suppress hyperexcitability.…”