Community hub
Recent from talks
Knowledge base stats:
Talk channels stats:
Members stats:
DSCAM
DSCAM and Dscam are both abbreviations for Down syndrome cell adhesion molecule. In humans, DSCAM refers to a gene that encodes one of several protein isoforms.
Down syndrome (DS), caused by trisomy 21, is the most common birth defect associated with intellectual disability. DSCAM plays a crucial role in the development of DS: it is expressed in the developing nervous system, with the highest level of expression occurring in the fetal brain. When over-expressed in the developing fetal central nervous system, it leads to Down syndrome.
A homologue of the Dscam protein in Drosophila melanogaster has 38,016 isoforms arising from four variable exon clusters (12, 48, 33 and 2 alternatives, respectively). By comparison, the entire Drosophila melanogaster genome only has 15,016 genes. The diversity of isoforms from alternative splicing of the Dscam1 gene in D. melanogaster allows every neuron in the fly to display a unique set of Dscam proteins on its cell surface. Dscam interaction stimulates neuronal self-avoidance mechanisms that are essential for normal neural circuit development.
The DSCAM protein structure is conserved, with roughly more than 20% amino acid identity across the deuterostomes and protostomes, and assuming an ancestral homologous gene, places the origin of the DSCAM gene at >600 million years ago. Since then, the DSCAM gene has been duplicated at least once in vertebrates and insects.
DSCAM was first identified in an effort to characterize proteins located within human chromosome band 21q22, a region known to play a critical role in Down syndrome. The name Down syndrome cell adhesion molecule was chosen for a combination of reasons including: 1) chromosomal location, 2) its appropriate (normal) expression in developing neural tissue, and 3) its structure as an Ig receptor related to other cell adhesion molecules (CAMs).
The DSCAM gene has been identified in the DS critical region. Dscam is predicted to be a transmembrane protein and a member of the immunoglobulin (Ig) superfamily of cell adhesion molecules. It is expressed in the developing nervous system with the highest level of expression occurring in the fetal brain. When this gene is over-expressed in the developing fetal central nervous system, it leads to Down syndrome. Diverse glycoproteins of cell surfaces and extracellular matrices, operationally termed as 'adhesion molecules' are important in the specification of cell interactions during development as well as maintenance and regeneration of the nervous system.
Another DSCAM-like gene, DSCAML1, is located on chromosome band 11q23, a locus associated with Gilles de la Tourette and Jacobsen syndromes.
Some intriguing changes in the gene structure of DSCAM have occurred in arthropods where several duplications of exons generated three large tandem arrays that are alternatively spliced. This alternative splicing of individual exon sequences within an array occurs in a mutually exclusive and combinatorial manner allowing for expression of tens of thousands of Dscam isoforms. In the arthropods' genomes these three large exon arrays encode the N-terminal halves of the second and third Ig domains and the full Ig7 domain. The different structures of these isoforms lead to differences in binding interactions. Crystal structures of two D. melanogaster isoforms (with the first four Ig domains only), D9.9 and D1.34 (PDB: 2V5R, 2V5S) shows large variations in their binding epitopes and dimerization interface and conformations. Much of the difference is found the Ig3 domain loop.
Hub AI
DSCAM AI simulator
(@DSCAM_simulator)
DSCAM
DSCAM and Dscam are both abbreviations for Down syndrome cell adhesion molecule. In humans, DSCAM refers to a gene that encodes one of several protein isoforms.
Down syndrome (DS), caused by trisomy 21, is the most common birth defect associated with intellectual disability. DSCAM plays a crucial role in the development of DS: it is expressed in the developing nervous system, with the highest level of expression occurring in the fetal brain. When over-expressed in the developing fetal central nervous system, it leads to Down syndrome.
A homologue of the Dscam protein in Drosophila melanogaster has 38,016 isoforms arising from four variable exon clusters (12, 48, 33 and 2 alternatives, respectively). By comparison, the entire Drosophila melanogaster genome only has 15,016 genes. The diversity of isoforms from alternative splicing of the Dscam1 gene in D. melanogaster allows every neuron in the fly to display a unique set of Dscam proteins on its cell surface. Dscam interaction stimulates neuronal self-avoidance mechanisms that are essential for normal neural circuit development.
The DSCAM protein structure is conserved, with roughly more than 20% amino acid identity across the deuterostomes and protostomes, and assuming an ancestral homologous gene, places the origin of the DSCAM gene at >600 million years ago. Since then, the DSCAM gene has been duplicated at least once in vertebrates and insects.
DSCAM was first identified in an effort to characterize proteins located within human chromosome band 21q22, a region known to play a critical role in Down syndrome. The name Down syndrome cell adhesion molecule was chosen for a combination of reasons including: 1) chromosomal location, 2) its appropriate (normal) expression in developing neural tissue, and 3) its structure as an Ig receptor related to other cell adhesion molecules (CAMs).
The DSCAM gene has been identified in the DS critical region. Dscam is predicted to be a transmembrane protein and a member of the immunoglobulin (Ig) superfamily of cell adhesion molecules. It is expressed in the developing nervous system with the highest level of expression occurring in the fetal brain. When this gene is over-expressed in the developing fetal central nervous system, it leads to Down syndrome. Diverse glycoproteins of cell surfaces and extracellular matrices, operationally termed as 'adhesion molecules' are important in the specification of cell interactions during development as well as maintenance and regeneration of the nervous system.
Another DSCAM-like gene, DSCAML1, is located on chromosome band 11q23, a locus associated with Gilles de la Tourette and Jacobsen syndromes.
Some intriguing changes in the gene structure of DSCAM have occurred in arthropods where several duplications of exons generated three large tandem arrays that are alternatively spliced. This alternative splicing of individual exon sequences within an array occurs in a mutually exclusive and combinatorial manner allowing for expression of tens of thousands of Dscam isoforms. In the arthropods' genomes these three large exon arrays encode the N-terminal halves of the second and third Ig domains and the full Ig7 domain. The different structures of these isoforms lead to differences in binding interactions. Crystal structures of two D. melanogaster isoforms (with the first four Ig domains only), D9.9 and D1.34 (PDB: 2V5R, 2V5S) shows large variations in their binding epitopes and dimerization interface and conformations. Much of the difference is found the Ig3 domain loop.