Abstract
TIP-15 was previously identified as a cellular protein that can bind to the C-terminal end of the HTLV-1 Tax protein via its two PDZ domains. The sequence of the N-terminal part of TIP-15 is identical to that of the synaptic protein PSD-95. Both proteins are likely to be produced from the same gene by alternative splicing. Whereas expression of the PSD-95 mRNA was detected only with brain RNAs, that of TIP-15 was detected with RNAs from thymus, brain, skeletal muscle and Jurkat cells. The TIP-15 protein exhibits an apparent molecular weight of 40 kD and is weakly expressed in T cell lines. A two-hybrid screen performed with TIP-15 as bait revealed the presence of a PDZ binding site (PDZ-BS) in the following proteins: Lysyl tRNA synthetase, 6-phosphogluconolactonase (6-GPL), Stress-activated protein kinase 3 (SAPK3), NET-1, Diacylglycerol kinase zeta, MTMR1, MCM7, and hSec8. The sequence at the C-terminal ends of these proteins matches the X-S/T-X-V-COOH consensus previously defined for PDZ-BSs, with the exception of 6-GPL and SAPK3 which include a leucine as the C-terminal residue. For Lysyl tRNA synthetase, NET1, MTMR1 and hSec8, binding to TIP-15 was confirmed by co-immunoprecipitation experiments performed with the extracts of transfected COS7 cells. These results show the existence of functional PDZ-BSs in these proteins, but future studies will be necessary to establish whether or not TIP-15 represents a physiological partner. The significance of the presence of a PDZ-BS in these various proteins is discussed with respect to their function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Brain / metabolism
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COS Cells
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Carboxylic Ester Hydrolases / chemistry
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Carrier Proteins / chemistry
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Cell Cycle Proteins / chemistry
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DNA-Binding Proteins / chemistry
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Diacylglycerol Kinase / chemistry
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Disks Large Homolog 4 Protein
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Gene Products, tax / chemistry*
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Guanylate Kinases
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Humans
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Intracellular Signaling Peptides and Proteins
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Jurkat Cells
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Membrane Proteins
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Mice
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Minichromosome Maintenance Complex Component 7
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Mitogen-Activated Protein Kinase 12
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Mitogen-Activated Protein Kinases / chemistry
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Molecular Sequence Data
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Muscle, Skeletal / metabolism
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Nerve Tissue Proteins / metabolism
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Nuclear Proteins / chemistry
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Oncogene Proteins / chemistry
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Plasmids / metabolism
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Precipitin Tests
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Protein Binding
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Protein Structure, Tertiary*
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases, Non-Receptor
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Synapses / metabolism
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Two-Hybrid System Techniques
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Vesicular Transport Proteins
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beta-Galactosidase / metabolism
Substances
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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EXOC4 protein, human
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Gene Products, tax
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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NET1 protein, human
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Nerve Tissue Proteins
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Net1 protein, mouse
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Nuclear Proteins
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Oncogene Proteins
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RNA, Messenger
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Sec8l1 protein, mouse
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Vesicular Transport Proteins
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postsynaptic density proteins
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Mitogen-Activated Protein Kinase 12
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Diacylglycerol Kinase
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Mitogen-Activated Protein Kinases
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Guanylate Kinases
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Carboxylic Ester Hydrolases
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6-phosphogluconolactonase
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MTMR1 protein, human
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Protein Tyrosine Phosphatases
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Protein Tyrosine Phosphatases, Non-Receptor
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beta-Galactosidase
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MCM7 protein, human
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Mcm7 protein, mouse
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Minichromosome Maintenance Complex Component 7