Table 3.
VGSC protein partners.
| Gene | Chromosome | Protein | Expression site and function | Reference |
|---|---|---|---|---|
| Cav3 | 3p25.3 | Caveolin-3 | Scaffolding protein within caveolar membranes. Also involved in VGSC regulation by a mechanism involving the α subunit of the stimulatory G protein (Gαs) through the activation of the βARs on the cell surface | Lu et al. (1999), Schwencke et al. (1999), Rybin et al. (2000), Yarbrough et al. (2002) |
| CALM 2 | 2p21 | Calmodulin | “Calcium-Modulated Protein.” Ca2+-binding protein expressed in all eukaryotic cells | Tan et al. (2002) |
| CAMK 2A | 5q32 | CaMKII | Part of a family of serine/threonine kinases that mediate many of the second messenger effects of Ca2+ | Wagner et al. (2006) |
| GJA1 | 6q22.31 | Connexin-43 | Connexins are assembled in groups of six to form hemichannels, or connexons, and two hemichannels then combine to form a gap junction. The connexin gene family is diverse, with 21 identified members in the sequenced human genome | Sato et al. (2011) |
| TCAP | 17q12 | Telethonin | Small protein mainly expressed in skeletal muscle that binds to and is phosphorylated by titin kinase and protein kinase D. Both proteins serve as a scaffold to which myofibrils and other muscle related proteins are attached | Valle et al. (1997), Mayans et al. (1998), Mues et al. (1998), Furukawa et al. (2001), Knoll et al. (2002), Haworth et al. (2004), Kojic et al. (2004), Mazzone et al. (2008) |
| PKP2 | 12p11 | Plakophilin-2 | Fundamental component of the cardiac desmosome, structure present in the intercalated disc | Sato et al. (2009) |
| ANK2 | 4q25–27 | Ankyrin-B (or ankyrin-2) | Cell membrane proteins that link the integral proteins of the membrane to the underlying spectrin-actin cytoskeleton. Mutations in these genes have been related to long QT syndrome type 4 (ANK2) and Brugada like-syndrome (ANK3) | Jenkins and Bennett (2001), Garrido et al. (2003), Lemaillet et al. (2003), Mohler et al. (2004) |
| ANK3 | 10q21 | Ankyrin-G (or ankyrin-3) | ||
| FGF3 | 11q13/13.3 | FHFs (FGFs) | Family of cytoplasmic proteins termed fibroblast growth factor homologous factors that can delay fast inactivation of VGSC | Dover et al. (2010) |
| FGF5 | 4q21/21–21 | |||
| FGF6 | 12q13/13.32 | |||
| FGF11 | 17p13.1 | |||
| FGF12 | 3q28/29 | |||
| FGF13 | Xq26.3/27.1 | |||
| FGF14 | 13q33.1/34 | |||
| Nedd4 Human | 15q–15q21.3 | Nedd4 | Ubiquitin-protein ligases | Rougier et al. (2005) |
| SNTG 1 | 8q11.21 | Syntrophin | The protein encoded by this gene is a member of the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that typically contain 2 pleckstrin homology (PH) domains, a PDZ domain that bisects the first PH domain, and a C-terminal domain that mediates dystrophin binding. This gene is specifically expressed in the brain | Gavillet et al. (2006), Haenggi and Fritschy (2006), Shao et al. (2009) |
| DMD | Xp21.2 | Dystrophin | Rod-shaped cytoplasmic protein, and a vital part of a protein complex (costamere or dystrophin-assoc. prot.s) that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane | |
| SCN1B-SCN4B | 19q13.1 (SCN1B) and 11q23 (SCN2B–4B) | β subunits of VGSC | Regulatory subunits of VGSC expressed in CNS, PNS, and heart (see also Tables 1 and 2) | Isom et al. (1994), Kazarinova-Noyes et al. (2001), Chen et al. (2004), McEwen and Isom (2004), Meadows and Isom (2005) |