Abstract
PDZ domains play a pivotal role in the synaptic localization of ion channels, receptors, signaling enzymes, and cell adhesion molecules. These domains mediate protein-protein interactions via the recognition of a conserved sequence motif at the extreme C terminus of their target proteins. By means of a yeast two-hybrid screen using the C terminus of the G protein-coupled alpha-latrotoxin receptor CL1 as bait, three PDZ domain proteins of the Shank family were identified. These proteins belong to a single protein family characterized by a common domain organization. The PDZ domain is highly conserved among the family members, significantly different from other known PDZ domains, and specifically binds to the C terminus of CL1. Shank1 and CL1 are expressed primarily in brain, and both proteins co-enrich in the postsynaptic density. Furthermore, Shank1 induces a clustering of CL1 in transfected cells, strongly supporting an interaction of both proteins in vivo.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Cloning, Molecular
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Heterotrimeric GTP-Binding Proteins / metabolism*
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Humans
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Microscopy, Fluorescence
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Protein Binding
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Protein Structure, Tertiary
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Receptors, Peptide / chemistry
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Receptors, Peptide / genetics
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Receptors, Peptide / metabolism*
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Recombinant Fusion Proteins
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Sequence Alignment
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Transfection
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Two-Hybrid System Techniques
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Receptors, Peptide
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Recombinant Fusion Proteins
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SHANK2 protein, human
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SHANK3 protein, human
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Shank1 protein, rat
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Shank2 protein, rat
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Shank3 protein, rat
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alpha-latrotoxin receptor
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Heterotrimeric GTP-Binding Proteins
Associated data
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GENBANK/AF159046
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GENBANK/AF159047
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GENBANK/AF159048