SPTAN1

Alpha II-spectrin, also known as Spectrin alpha chain, brain is a is_associated_with::protein that in humans is encoded by the SPTAN1 is_associated_with::gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in is_associated_with::cardiac muscle at Z-disc structures, is_associated_with::costameres and at the is_associated_with::sarcolemma membrane. Mutations in alpha II-spectrin have been associated with early infantile epileptic encephalopathy-5, and alpha II-spectrin may be a valuable biomarker for is_associated_with::Guillain-Barré syndrome and infantile is_associated_with::congenital heart disease.

Structure
Alternate splicing of alpha II-spectrin has been documented and results in multiple transcript variants; specifically, is_associated_with::cardiomyocytes have four identified alpha II-spectrin is_associated_with::splice variants. As opposed to alpha I-spectrin that is principally found in erythrocytes, alpha II-spectrin is expressed in most tissues. In cardiac tissue, alpha II-spectrin is found in is_associated_with::myocytes at Z-discs, is_associated_with::costameres, and the is_associated_with::sarcolemma membrane, and in cardiac is_associated_with::fibroblasts along the surface of the cytoskeletal network. Alpha II-spectrin most commonly exists in a heterodimer with alpha II and beta II spectrin subunits; and dimers typically self-associate and heterotetramerize.

Function
The is_associated_with::spectrins are a family of widely distributed cytoskeletal proteins which are involved in is_associated_with::actin crosslinking, cell adhesion, intercellular communication and cell cycle regulation. Though a role in cardiac muscle is not well understood, it is likely that alpha II-spectrin is involved in organizing sub-is_associated_with::sarcolemmal domains and stabilizing is_associated_with::sarcolemmal membranes against the stresses associated with continuous cardiac contraction. Functional diversity of alpha II-spectrin is manifest through its four splice variants. First, a cardiac-specific, 21 amino acid sequence insert in the 21st spectrin repeat, termed alpha II-cardi+, was identified as an insert that modulates affinity of alpha II-spectrin for binding beta-spectrins and regulates is_associated_with::myocyte growth and differentiation. Secondly, another insert of 20 is_associated_with::amino acids in the 10th spectrin repeat, termed SH3i+, contains is_associated_with::protein kinase A and is_associated_with::protein kinase C phosphorylation sites and modulates Ca2+-dependent cleavage of spectrin and is_associated_with::protein-protein interaction properties. Thirdly, an insert of five is_associated_with::amino acids in the fifteenth spectrin motif bears a highly antigenic epitope resembling an ankyrin-like p53 binding protein binding site. Fourthly, a six is_associated_with::amino acid insert in the twenty-first spectrin motif with unknown function has been reported.

Alpha II-spectrin gene expression has been shown to be upregulated in cardiac is_associated_with::fibroblasts in response to is_associated_with::Angiotensin II-induced cardiac remodeling.

In animal models of disease and injury, alpha II-spectrin has been implicated in diverse functions. In a canine model of hypothermic circulatory arrest, alpha II-spectrin breakdown products have shown to be relevant markers of neurologic injury post-cardiac surgery.

Clinical Significance
Mutations in SPTAN1 are the cause of early infantile epileptic encephalopathy-5.

Alpha II-spectrin has shown promising utility as a biomarker for brain necrosis and apoptosis in infants with is_associated_with::congenital heart disease; breakdown products of alpha II-spectrin have been detected in the serum of is_associated_with::neonates in the perioperative period and following is_associated_with::open-heart surgery. Elevated protein expression of alpha II-spectrin has been detected in is_associated_with::cerebrospinal fluid in patients with is_associated_with::Guillain-Barré syndrome.

Interactions
SPTAN1 has been shown to interact with:
 * is_associated_with::Abl gene,
 * is_associated_with::FANCA,
 * is_associated_with::Fanconi anemia, complementation group C,
 * is_associated_with::GRIA2,
 * is_associated_with::Plectin,
 * is_associated_with::SHANK1, and
 * is_associated_with::Vimentin.