SPTAN1

SPTAN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2FOT, 3F31, 3FB2
Identifiers
Aliases	SPTAN1, EIEE5, NEAS, SPTA2, spectrin alpha, non-erythrocytic 1, DEE5
External IDs	OMIM: 182810; MGI: 98386; HomoloGene: 2353; GeneCards: SPTAN1; OMA:SPTAN1 - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.11 Start 128,552,558 bp[1] End 128,633,662 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 B|2 20.93 cM Start 29,855,572 bp[2] End 29,921,463 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum right frontal lobe Brodmann area 9 amygdala right uterine tube nucleus accumbens prefrontal cortex Brodmann area 10 cingulate gyrus tibial nerve Top expressed in facial motor nucleus epithelium of lens dentate gyrus of hippocampal formation granule cell ciliary body Rostral migratory stream cerebellar cortex iris anterior horn of spinal cord barrel cortex external carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding metal ion binding calmodulin binding structural constituent of cytoskeleton protein binding actin binding cadherin binding Cellular component cytoplasm extracellular vesicle cytosol spectrin membrane intracellular membrane-bounded organelle microtubule cytoskeleton cell cortex extracellular exosome cytoskeleton extracellular region specific granule lumen tertiary granule lumen Biological process MAPK cascade axon guidance endoplasmic reticulum to Golgi vesicle-mediated transport actin filament capping cytoskeleton organization neutrophil degranulation regulation of molecular function Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6709 20740 Ensembl ENSG00000197694 ENSMUSG00000057738 UniProt Q13813 P16546 RefSeq (mRNA) NM_001130438 NM_001195532 NM_003127 NM_001363759 NM_001363765 NM_001375310 NM_001375311 NM_001375312 NM_001375313 NM_001375314 NM_001375318 NM_001076554 NM_001177667 NM_001177668 NM_001309460 NM_001369325 RefSeq (protein) NP_001123910 NP_001182461 NP_003118 NP_001350688 NP_001350694 NP_001362239 NP_001362240 NP_001362241 NP_001362242 NP_001362243 NP_001362247 NP_001171138 NP_001171139 NP_001296389 NP_001356254 Location (UCSC) Chr 9: 128.55 – 128.63 Mb Chr 2: 29.86 – 29.92 Mb PubMed search [3] [4]
Wikidata
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Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene.^[5][6][7] 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.^[8][9] As opposed to alpha I-spectrin that is principally found in erythrocytes,^[10] 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,^[11][12][13] and in cardiac fibroblasts along the surface of the cytoskeletal network.^[14] Alpha II-spectrin most commonly exists in a heterodimer with alpha II and beta II spectrin subunits; and dimers typically self-associate and heterotetramerize.^[5][15][16]

The spectrins are a family of widely distributed cytoskeletal proteins which are involved in actin crosslinking, cell adhesion, intercellular communication and cell cycle regulation.^[17][18][19] 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.^[16] 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.^[8] 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.^[20] 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.^[8][21] Fourthly, a six amino acid insert in the twenty-first spectrin motif with unknown function has been reported.^[11][22]

Alpha II-spectrin gene expression has been shown to be upregulated in cardiac fibroblasts in response to Angiotensin II-induced cardiac remodeling.^[23]

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.^[24]

Mutations in SPTAN1 are the cause of early infantile epileptic encephalopathy-5.^[25]

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.^[26] Elevated protein expression of alpha II-spectrin has been detected in cerebrospinal fluid in patients with Guillain–Barré syndrome.^[27]

SPTAN1 has been shown to interact with:

• Abl gene,^[28]
• FANCA,^[29][30][31]
• Fanconi anemia, complementation group C,^[29][30]
• GRIA2,^[32]
• Plectin,^[33][34]
• SHANK1,^[35] and
• Vimentin.^[33]

• Sjögren's syndrome