Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Drosophila gene ten-m is the first pair-rule gene not encoding a transcription factor, but an extracellular protein. We have characterized a highly conserved chicken homologue that we call teneurin-1. The C-terminal part harbors 26 repetitive sequence motifs termed YD-repeats. The YD-repeats are most similar to the core of the rhs elements of Escherichia coli. Related repeats in toxin A of Clostridium difficile are known to bind specific carbohydrates. We show that recombinantly expressed proteins containing the YD-repeats of teneurin-1 bind to heparin. Furthermore, heparin lyase treatment of extracts of cells expressing recombinant YD-repeat protein releases this protein from high molecular mass aggregates. In situ hybridization and immunostaining reveals teneurin-1 expression in neurons of the developing visual system of chicken and Drosophila. This phylogenetic conservation of neuronal expression from flies to birds implies fundamental roles for teneurin-1 in neurogenesis. This is supported by the neurite outgrowth occurring on substrates made of recombinant YD-repeat proteins, which can be inhibited by heparin. Database searches resulted in the identification of ESTs encoding at least three further members of the teneurin family of proteins. Furthermore, the human teneurin-1 gene could be identified on chromosome Xq24/25, a region implied in an X-linked mental retardation syndrome.
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PMID:Teneurin-1, a vertebrate homologue of the Drosophila pair-rule gene ten-m, is a neuronal protein with a novel type of heparin-binding domain. 1034 Dec 19

Teneurins are a novel family of transmembrane proteins conserved between invertebrates and vertebrates. There are two members in Drosophila, one in C. elegans and four members in mouse. Here, we describe the analysis of the genomic structure of the human teneurin-1 gene. The entire human teneurin-1 (TEN1) gene is contained in eight PAC clones representing part of the chromosomal locus Xq25. Interestingly, many X-linked mental retardation syndromes (XLMR) and non-specific mental retardation (MRX) are mapped to this region. The location of the human TEN1 together with the neuronal expression makes TEN1 a candidate gene for XLMR and MRX. We also identified large parts of the human teneurin-2 sequence on chromosome 5 and sections of human teneurin-4 at chromosomal position 11q14. Database searches resulted in the identification of ESTs encoding parts of all four human members of the teneurin family. Analysis of the genomic organization of the Drosophila ten-a gene revealed the presence of exons encoding a long form of ten-a, which can be aligned with all other teneurins known. Sequence comparison and phylogenetic trees of teneurins show that insects and vertebrates diverged before the teneurin ancestor was duplicated independently in the two phyla. This is supported by the presence of conserved intron positions between teneurin genes of man, Drosophila and C. elegans. It is therefore not possible to class any of the vertebrate teneurins with either Drosophila Ten-a or Ten-m. The C-terminal part of all teneurins harbours 26 repetitive sequence motifs termed YD-repeats. YD-repeats are most similar to the repeats encoded by the core of the rearrangement hot spot (rhs) elements of Escherichia coli. This makes the teneurin ancestor a candidate gene for the source of the rhs core acquired by horizontal gene transfer.
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PMID:Phylogenetic analysis of teneurin genes and comparison to the rearrangement hot spot elements of E. coli. 1105 71

Teneurins are a novel family of transmembrane proteins expressed during pattern formation and morphogenesis. Originally discovered as ten-m and ten-a in Drosophila, four vertebrate teneurins as well as a Caenorhabditis elegans homologue were identified. The conserved domain architecture of teneurins includes an intracellular domain containing polyproline motifs. The long extracellular domain consists of eight EGF-like repeats, a region of conserved cysteines and unique YD-repeats. Vertebrate teneurins are most prominently expressed in the developing central nervous system, but are also expressed in developing limbs. In C. elegans, RNAi experiments and studies of mutants reveal that teneurins are required during fundamental developmental processes like cell migration and axon pathfinding. Cell culture experiments suggest that the intracellular domain of teneurins translocates to the nucleus following release from the membrane by proteolytic processing. Interestingly, the human teneurin-1 gene is located on the X-chromosome in a region where several families with X-linked mental retardation are mapped.
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PMID:Teneurins: transmembrane proteins with fundamental roles in development. 1709 84