Dysbindin-1 and Its Protein Family
Variation in the gene encoding dysbindin-1 (i.e., dystrobrevin-binding protein 1: DTNBP1) has frequently been associated with schizophrenia. Several studies have also found that dysbindin-1 gene and protein expression are altered in two affected brain are
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Dysbindin-1 and Its Protein Family With Special Attention to the Potential Role of Dysbindin-1 in Neuronal Functions and the Pathophysiology of Schizophrenia
K. Talbot . W.-Y. Ong . D. J. Blake . J. Tang . N. Louneva . G. C. Carlson . S. E. Arnold
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
2 2.1 2.2 2.2.1 2.2.2 2.2.3
Members of the Dysbindin Protein Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 Family Membership Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 Paralogs and Their Isoforms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Dysbindin-1 (=DTNBP1 Protein) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Dysbindin-2 (=Dysbindin Domain-Containing Protein 2, DBNDD2) . . . . . . . . . . . . . . . . . . . . . . . . 124 Dysbindin-3 (=Dysbindin Domain-Containing Protein 1, DBNDD1) . . . . . . . . . . . . . . . . . . . . . . . . 125
3 3.1 3.2 3.3 3.3.1 3.3.2 3.3.3
Components of Dysbindin Family Members and Their Predicted Phosphorylation Sites . . . 125 Amino Terminal Region (NTR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 Coiled Coil Domain (CCD) and Its Leucine Zipper (LZ) Motif . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 Carboxy Terminal Region (CTR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Dysbindin Domain (DD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 PEST Domain (PD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Uncharacterized CTR Segments (X1–3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
4 4.1 4.2 4.3
Intracellular Localization of Dysbindin Family Members and Their Functional Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Unlikely Sites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 Likely Sites: Cytoplasmic, Cytoskeletal, and Synaptic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Nuclear Localization . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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