SPTAN1

2FOT, 3F31, 3FB2670920740ENSG00000197694ENSMUSG00000057738Q13813P16546NM_001130438NM_001195532NM_003127NM_001363759NM_001363765NM_001076554NM_001177667NM_001177668NM_001309460NM_001369325NP_001123910NP_001182461NP_003118NP_001350688NP_001350694NP_001171138NP_001171139NP_001296389NP_001356254Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in cardiac muscle at Z-disc structures, costameres and at the 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 Guillain–Barré syndrome and infantile congenital heart disease.1aey: ALPHA-SPECTRIN SRC HOMOLOGY 3 DOMAIN, SOLUTION NMR, 15 STRUCTURES1aj3: SOLUTION STRUCTURE OF THE SPECTRIN REPEAT, NMR, 20 STRUCTURES1bk2: A-SPECTRIN SH3 DOMAIN D48G MUTANT1cun: CRYSTAL STRUCTURE OF REPEATS 16 AND 17 OF CHICKEN BRAIN ALPHA SPECTRIN1e6g: A-SPECTRIN SH3 DOMAIN A11V, V23L, M25I, V53I, V58L MUTANT1e6h: A-SPECTRIN SH3 DOMAIN A11V, M25I, V44I, V58L MUTANTS1e7o: A-SPECTRIN SH3 DOMAIN A11V, V23L, M25V, V44I, V58L MUTATIONS1h8k: A-SPECTRIN SH3 DOMAIN A11V, V23L, M25V, V53I, V58L MUTANT1hd3: A-SPECTRIN SH3 DOMAIN F52Y MUTANT1m8m: SOLID-STATE MAS NMR STRUCTURE OF THE A-SPECTRIN SH3 DOMAIN1pwt: THERMODYNAMIC ANALYSIS OF ALPHA-SPECTRIN SH3 AND TWO OF ITS CIRCULAR PERMUTANTS WITH DIFFERENT LOOP LENGTHS: DISCERNING THE REASONS FOR RAPID FOLDING IN PROTEINS1qkw: ALPHA-SPECTRIN SRC HOMOLOGY 3 DOMAIN, N47G MUTANT IN THE DISTAL LOOP.1qkx: ALPHA-SPECTRIN SRC HOMOLOGY 3 DOMAIN, N47A MUTANT IN THE DISTAL LOOP.1shg: CRYSTAL STRUCTURE OF A SRC-HOMOLOGY 3 (SH3) DOMAIN1u06: crystal structure of chicken alpha-spectrin SH3 domain1u4q: Crystal Structure of Repeats 15, 16 and 17 of Chicken Brain Alpha Spectrin1u5p: Crystal Structure of Repeats 15 and 16 of Chicken Brain Alpha Spectrin1uue: A-SPECTRIN SH3 DOMAIN (V44T, D48G MUTANT)2cdt: ALPHA-SPECTRIN SH3 DOMAIN A56S MUTANT2f2v: alpha-spectrin SH3 domain A56G mutant2f2w: alpha-spectrin SH3 domain R21A mutant2f2x: alpha-spectrin SH3 domain R21G mutant2fot: Crystal structure of the complex between calmodulin and alphaII-spectrin2jm8: R21A Spc-SH3 free2jm9: R21A Spc-SH3 bound2jma: R21A Spc-SH3:P41 complex2nuz: crystal structure of alpha spectrin SH3 domain measured at room temperature Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in cardiac muscle at Z-disc structures, costameres and at the 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 Guillain–Barré syndrome and infantile congenital heart disease. Alternate splicing of alpha II-spectrin has been documented and results in multiple transcript variants; specifically, cardiomyocytes have four identified alpha II-spectrin 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 myocytes at Z-discs, costameres, and the sarcolemma membrane, and in cardiac 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. The spectrins are a family of widely distributed cytoskeletal proteins which are involved in 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-sarcolemmal domains and stabilizing 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 myocyte growth and differentiation. Secondly, another insert of 20 amino acids in the 10th spectrin repeat, termed SH3i+, contains protein kinase A and protein kinase C phosphorylation sites and modulates Ca2+-dependent cleavage of spectrin and protein-protein interaction properties. Thirdly, an insert of five amino acids in the fifteenth spectrin motif bears a highly antigenic epitope resembling an ankyrin-like p53 binding protein binding site. Fourthly, a six 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 fibroblasts in response to 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. 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 congenital heart disease; breakdown products of alpha II-spectrin have been detected in the serum of neonates in the perioperative period and following open-heart surgery. Elevated protein expression of alpha II-spectrin has been detected in cerebrospinal fluid in patients with Guillain–Barré syndrome. SPTAN1 has been shown to interact with: