SPTBN2

Summary

Gene Symbol: SPTBN2
Description: spectrin beta, non-erythrocytic 2
Alias: GTRAP41, SCA5, SCAR14, spectrin beta chain, non-erythrocytic 2, beta-III spectrin, glutamate transporter EAAT4-associated protein 41, spectrin beta III sigma 2, spectrin beta chain, brain 2, spectrin, non-erythroid beta chain 2, spinocerebellar ataxia 5 protein
Species: human
Products:     SPTBN2

Top Publications

  1. Sakaguchi G, Orita S, Naito A, Maeda M, Igarashi H, Sasaki T, et al. A novel brain-specific isoform of beta spectrin: isolation and its interaction with Munc13. Biochem Biophys Res Commun. 1998;248:846-51 pubmed
    ..Because spectrin has been shown to interact with the actin cytoskeleton which is involved in the exocytotic process, the present results suggest that the Munc13-beta SpIII sigma 1 interactions play a role in neurotransmitter release. ..
  2. Zuhlke C, Bernard V, Dalski A, Lorenz P, Mitulla B, Gillessen Kaesbach G, et al. Screening of the SPTBN2 (SCA5) gene in German SCA patients. J Neurol. 2007;254:1649-52 pubmed
    ..two deletions as well as one missense mutation in the beta-III spectrin gene (STBN2) were identified causing SCA5. To evaluate the clinical relevance of these mutations, we screened 310 familial and sporadic patients with ataxia...
  3. Stankewich M, Tse W, Peters L, Ch ng Y, John K, Stabach P, et al. A widely expressed betaIII spectrin associated with Golgi and cytoplasmic vesicles. Proc Natl Acad Sci U S A. 1998;95:14158-63 pubmed
    ..All of the tested tissues contain major 9.0-kb and minor 11.3-kb transcripts. The human betaIII spectrin gene (SPTBN2) maps to chromosome 11q13 and the mouse gene (Spnb3) maps to a syntenic region close to the centromere on ..
  4. Perkins E, Clarkson Y, Sabatier N, Longhurst D, Millward C, Jack J, et al. Loss of beta-III spectrin leads to Purkinje cell dysfunction recapitulating the behavior and neuropathology of spinocerebellar ataxia type 5 in humans. J Neurosci. 2010;30:4857-67 pubmed publisher
    Mutations in SPTBN2, the gene encoding beta-III spectrin, cause spinocerebellar ataxia type 5 in humans (SCA5), a neurodegenerative disorder resulting in loss of motor coordination...
  5. Ikeda Y, Dick K, Weatherspoon M, Gincel D, Armbrust K, Dalton J, et al. Spectrin mutations cause spinocerebellar ataxia type 5. Nat Genet. 2006;38:184-90 pubmed
    We have discovered that beta-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred descended from President Lincoln's grandparents and two additional families...
  6. Lise S, Clarkson Y, Perkins E, Kwasniewska A, Sadighi Akha E, Schnekenberg R, et al. Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development. PLoS Genet. 2012;8:e1003074 pubmed publisher
    ..Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly ..
  7. Klockgether T, Mariotti C, Paulson H. Spinocerebellar ataxia. Nat Rev Dis Primers. 2019;5:24 pubmed publisher
    ..SCAs, such as SCA3/Machado-Joseph disease (MJD), and rare SCAs that are caused by non-repeat mutations, such as SCA5. Most SCA mutations cause prominent damage to cerebellar Purkinje neurons with consecutive cerebellar atrophy, ..
  8. Mizuno T, Kashimada A, Nomura T, Moriyama K, Yokoyama H, Hasegawa S, et al. Infantile-onset spinocerebellar ataxia type 5 associated with a novel SPTBN2 mutation: A case report. Brain Dev. 2019;: pubmed publisher
    ..ataxia type 5 (SCA5), a dominant spinocerebellar ataxia is caused by spectrin beta nonerythrocytic 2 gene (SPTBN2) mutation. It typically consists of a slow progressive cerebellar ataxia with an onset principally in adulthood...
  9. Lalonde R, Strazielle C. Motor Performances of Spontaneous and Genetically Modified Mutants with Cerebellar Atrophy. Cerebellum. 2019;: pubmed publisher
    ..Among experimental models of autosomal dominant SCA, rotorod deficits were reported in SCA1 to 3, SCA5 to 8, SCA14, SCA17, and SCA27 and stationary beam deficits in SCA1 to 3, SCA5, SCA6, SCA13, SCA17, and SCA27...

More Information

Publications52

  1. Xu W, Liyanage V, MacAulay A, Levy R, Curtis K, Olson C, et al. Genome-Wide Transcriptome Landscape of Embryonic Brain-Derived Neural Stem Cells Exposed to Alcohol with Strain-Specific Cross-Examination in BL6 and CD1 Mice. Sci Rep. 2019;9:206 pubmed publisher
    ..We identified Sptbn2, Dcc, and Scn3a as candidate genes which may link alcohol-induced neuronal morphology to brain structural ..
  2. Zhao Y, Wilmarth P, Cheng C, Limi S, Fowler V, Zheng D, et al. Proteome-transcriptome analysis and proteome remodeling in mouse lens epithelium and fibers. Exp Eye Res. 2019;179:32-46 pubmed publisher
    ..g. non-muscle myosin IIA heavy chain (Myh9) and βB2-spectrin (Sptbn2)] and membrane proteins in lens formation and maturation...
  3. Brown A, Meera P, Altindag B, Chopra R, Perkins E, Paul S, et al. MTSS1/Src family kinase dysregulation underlies multiple inherited ataxias. Proc Natl Acad Sci U S A. 2018;115:E12407-E12416 pubmed publisher
    ..Surprisingly, mouse models for SCA1, SCA2, and SCA5 show elevated SFK activity, with SCA1 and SCA2 displaying dramatically reduced MTSS1 protein levels through reduced ..
  4. Kashimada A, Hasegawa S, Nomura T, Shiraku H, Moriyama K, Suzuki T, et al. Genetic analysis of undiagnosed ataxia-telangiectasia-like disorders. Brain Dev. 2019;41:150-157 pubmed publisher
    ..1 (AOA1); one ataxia with oculomotor apraxia type 2 (AOA2); two types of autosomal dominant spinocerebellar ataxia (SCA5, SCA29); two CACNA1A-related ataxias; one microcephaly with or without chorioretinopathy, lymphedema, or mental ..
  5. Cruz R, Huesgen P, Riley S, Wlodawer A, Faro C, Overall C, et al. RC1339/APRc from Rickettsia conorii is a novel aspartic protease with properties of retropepsin-like enzymes. PLoS Pathog. 2014;10:e1004324 pubmed publisher
    ..catalyze the in vitro processing of two conserved high molecular weight autotransporter adhesin/invasion proteins, Sca5/OmpB and Sca0/OmpA, thereby suggesting the participation of this enzyme in a relevant proteolytic pathway in ..
  6. Sun M, Johnson A, Nelakuditi V, Guidugli L, Fischer D, Arndt K, et al. Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes. Genet Med. 2019;21:195-206 pubmed publisher
    ..genes were implicated, with the six most commonly mutated genes being SPG7, SYNE1, ADCK3, CACNA1A, ATP1A3, and SPTBN2, which accounted for >40% of the positive cases...
  7. van de Leemput J, Wavrant De Vrièze F, Rafferty I, Bras J, Giunti P, Fisher E, et al. Sequencing analysis of the ITPR1 gene in a pure autosomal dominant spinocerebellar ataxia series. Mov Disord. 2010;25:771-3 pubmed publisher
    ..Mutation at SCA5, 10, and 27 was also excluded in some families...
  8. Perkins E, Suminaite D, Clarkson Y, Lee S, Lyndon A, Rothstein J, et al. Posterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of β-III spectrin and GLAST. Hum Mol Genet. 2016;25:4448-4461 pubmed publisher
    Clinical phenotypes of spinocerebellar ataxia type-5 (SCA5) and spectrin-associated autosomal recessive cerebellar ataxia type-1 (SPARCA1) are mirrored in mice lacking β-III spectrin (β-III-/-)...
  9. Paddock C, Allerdice M, Karpathy S, Nicholson W, Levin M, Smith T, et al. Unique Strain of Rickettsia parkeri Associated with the Hard Tick Dermacentor parumapertus Neumann in the Western United States. Appl Environ Microbiol. 2017;83: pubmed publisher
    ..Black Gap, was cultivated in Vero E6 cells, and sequence analysis of the rrs, gltA, sca0, sca5, and sca4 genes also revealed the closest genetic identity to Rickettsia sp...
  10. Riley S, Cardwell M, Chan Y, Pruneau L, Del Piero F, Martinez J. Failure of a heterologous recombinant Sca5/OmpB protein-based vaccine to elicit effective protective immunity against Rickettsia rickettsii infections in C3H/HeN mice. Pathog Dis. 2015;73:ftv101 pubmed publisher
    ..Previous reports have demonstrated the feasibility of using recombinant surface cell antigen Sca5/OmpB to elicit protective immunity against homologous challenges using murine models of Mediterranean spotted fever ..
  11. Armbrust K, Wang X, Hathorn T, Cramer S, Chen G, Zu T, et al. Mutant ?-III spectrin causes mGluR1? mislocalization and functional deficits in a mouse model of spinocerebellar ataxia type 5. J Neurosci. 2014;34:9891-904 pubmed publisher
    ..a dominant neurodegenerative disease characterized by profound Purkinje cell loss, is caused by mutations in SPTBN2, a gene that encodes ?-III spectrin...
  12. Oh Y, Fung L. Brain proteins interacting with the tetramerization region of non-erythroid alpha spectrin. Cell Mol Biol Lett. 2007;12:604-20 pubmed
    ..Future structural and functional studies of these proteins to provide interaction mechanisms will no doubt lead to a better understanding of brain physiology and pathophysiology. ..
  13. Dick K, Ikeda Y, Day J, Ranum L. Spinocerebellar ataxia type 5. Handb Clin Neurol. 2012;103:451-9 pubmed publisher
    ..1994). Using a multifaceted mapping approach, Ikeda et al. (2006) discovered that ?-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in the American kindred and two additional independently ..
  14. Salcedo Sicilia L, Granell S, Jovic M, Sicart A, Mato E, Johannes L, et al. ?III spectrin regulates the structural integrity and the secretory protein transport of the Golgi complex. J Biol Chem. 2013;288:2157-66 pubmed publisher
  15. Qu K, Lu Y, Lin N, Singh R, Xu X, Payan D, et al. Computational and experimental studies on human misshapen/NIK-related kinase MINK-1. Curr Med Chem. 2004;11:569-82 pubmed
    ..Further medicinal chemistry compound structure optimization and kinase assays are underway. ..
  16. Al Muhaizea M, AlMutairi F, Almass R, AlHarthi S, Aldosary M, Alsagob M, et al. A Novel Homozygous Mutation in SPTBN2 Leads to Spinocerebellar Ataxia in a Consanguineous Family: Report of a New Infantile-Onset Case and Brief Review of the Literature. Cerebellum. 2018;17:276-285 pubmed publisher
    ..nextgen sequencing, family segregation analysis, and comprehensive neuropanel, we discovered a novel mutation in SPTBN2. Next, we utilized multiple sequence alignment of amino acids from various species as well as crystal structures ..
  17. Yıldız Bölükbaşı E, Afzal M, Mumtaz S, Ahmad N, Malik S, Tolun A. Progressive SCAR14 with unclear speech, developmental delay, tremor, and behavioral problems caused by a homozygous deletion of the SPTBN2 pleckstrin homology domain. Am J Med Genet A. 2017;173:2494-2499 pubmed publisher
    ..By linkage mapping and exome sequencing we identified novel homozygous splicing variant c.6375-1G>C in SPTBN2. To date, only two other SPTBN2 mutations with recessive pattern of inheritance causing SCAR14 (spinocerebellar ..
  18. Perkins E, Suminaite D, Jackson M. Cerebellar ataxias: β-III spectrin's interactions suggest common pathogenic pathways. J Physiol. 2016;594:4661-76 pubmed publisher
    ..Heterozygous mutations in the gene encoding β-III spectrin (SPTBN2) underlie SCA type-5 whereas homozygous mutations cause spectrin associated autosomal recessive ataxia type-1 (..
  19. Smith S, Hughes L, Kline C, Kempton A, Dorn L, Curran J, et al. Dysfunction of the β2-spectrin-based pathway in human heart failure. Am J Physiol Heart Circ Physiol. 2016;310:H1583-91 pubmed publisher
    ..In summary, our findings illustrate that β2-spectrin and downstream molecules are regulated in multiple forms of cardiovascular disease via Ca(2+)- and calpain-dependent proteolysis. ..
  20. Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411:321-5 pubmed
    ..Thus, DKKs inhibit Wnt co-receptor function, exemplifying the modulation of LRP signalling by antagonists. ..
  21. Holleran E, Ligon L, Tokito M, Stankewich M, Morrow J, Holzbaur E. beta III spectrin binds to the Arp1 subunit of dynactin. J Biol Chem. 2001;276:36598-605 pubmed
    ..We hypothesize that the interaction between betaIII spectrin and Arp1 recruits dynein and dynactin to intracellular membranes and provides a direct link between the microtubule motor complex and its membrane-bounded cargo. ..
  22. Brusco A, Gellera C, Cagnoli C, Saluto A, Castucci A, Michielotto C, et al. Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol. 2004;61:727-33 pubmed
    ..In patients negative for defects in known SCA genes, repeat expansion detection data strongly suggest that, at least in our population, CAG/CTG expansions in novel genes should be considered an unlikely cause of the SCA phenotype. ..
  23. Efimova N, Korobova F, Stankewich M, Moberly A, Stolz D, Wang J, et al. ?III Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons. J Neurosci. 2017;37:6442-6459 pubmed publisher
    ..In the absence of ?III spectrin, dendritic spines collapse onto dendrites. As a result, synaptic strength exceeds acceptable levels and damages neurons, explaining pathology of human syndromes caused by ?III spectrin mutations. ..
  24. Song Y, Antoniou C, Memic A, Kay B, Fung L. Apparent structural differences at the tetramerization region of erythroid and nonerythroid beta spectrin as discriminated by phage displayed scFvs. Protein Sci. 2011;20:867-79 pubmed publisher
  25. Baek H, Lee Y, Kim T, Kim J, Park E, Iwabuchi K, et al. Caspase-3/7-mediated Cleavage of β2-spectrin is Required for Acetaminophen-induced Liver Damage. Int J Biol Sci. 2016;12:172-83 pubmed publisher
    ..These findings have extended our knowledge on the spectrum of β2-spectrin functions from a scaffolding protein to a target and transmitter of TGF-β in liver damage. ..
  26. Chen J, Yao Z, Chen J, Gi Y, Muñoz N, Kundra S, et al. TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome. J Clin Invest. 2016;126:527-42 pubmed publisher
  27. Parolin Schnekenberg R, Perkins E, Miller J, Davies W, D Adamo M, Pessia M, et al. De novo point mutations in patients diagnosed with ataxic cerebral palsy. Brain. 2015;138:1817-32 pubmed publisher
    ..or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age...
  28. Shin S, Park J, Kim Y, Oh T, An S, Park C. Differential gene expression profile in PBMCs from subjects with AERD and ATA: a gene marker for AERD. Mol Genet Genomics. 2012;287:361-71 pubmed publisher
    ..multiple logistic regression analysis, among possible 1,023 models (2(10)-1), a model consisting of CNKSR3, SPTBN2, and IMPACT was selected as candidate set, because this set showed the best AUC (0...
  29. Davis L, Abdi K, Machius M, Brautigam C, Tomchick D, Bennett V, et al. Localization and structure of the ankyrin-binding site on beta2-spectrin. J Biol Chem. 2009;284:6982-7 pubmed publisher
    ..Here, we present the crystal structure of the ankyrin-binding domain of human beta2-spectrin at 1.95 A resolution together with mutagenesis data identifying the binding surface for ankyrins on beta2-spectrin. ..
  30. Wang Y, Koh K, Miwa M, Yamashiro N, Shindo K, Takiyama Y. A Japanese SCA5 family with a novel three-nucleotide in-frame deletion mutation in the SPTBN2 gene: a clinical and genetic study. J Hum Genet. 2014;59:569-73 pubmed publisher
    ..spinocerebellar ataxia type 5 (SCA5) with four distinct mutations in the spectrin, beta, nonerythrocytic 2 gene (SPTBN2) have been reported worldwide...
  31. Avery A, Crain J, Thomas D, Hays T. A human β-III-spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding. Sci Rep. 2016;6:21375 pubmed publisher
    Spinocerebellar ataxia type 5 (SCA5) is a human neurodegenerative disease that stems from mutations in the SPTBN2 gene encoding the protein β-III-spectrin...
  32. Cho E, Fogel B. A family with spinocerebellar ataxia type 5 found to have a novel missense mutation within a SPTBN2 spectrin repeat. Cerebellum. 2013;12:162-4 pubmed publisher
    ..pure cerebellar ataxia, consistent with spinocerebellar ataxia type 5 (SCA5) but lacking previously reported SPTBN2 mutations, was identified...
  33. Thenappan A, Li Y, Kitisin K, Rashid A, Shetty K, Johnson L, et al. Role of transforming growth factor beta signaling and expansion of progenitor cells in regenerating liver. Hepatology. 2010;51:1373-82 pubmed publisher
  34. Elsayed S, Heller R, Thoenes M, Zaki M, Swan D, Elsobky E, et al. Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations. Eur J Hum Genet. 2014;22:286-8 pubmed publisher
    ..A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate ..
  35. Avery A, Fealey M, Wang F, Orlova A, Thompson A, Thomas D, et al. Structural basis for high-affinity actin binding revealed by a β-III-spectrin SCA5 missense mutation. Nat Commun. 2017;8:1350 pubmed publisher
    Spinocerebellar ataxia type 5 (SCA5) is a neurodegenerative disease caused by mutations in the cytoskeletal protein β-III-spectrin...
  36. Liu L, Ren M, Li M, Ren Y, Sun B, Sun X, et al. A Novel Missense Mutation in the Spectrin Beta Nonerythrocytic 2 Gene Likely Associated with Spinocerebellar Ataxia Type 5. Chin Med J (Engl). 2016;129:2516-2517 pubmed publisher
  37. Abdi K, Bennett V. Adducin promotes micrometer-scale organization of beta2-spectrin in lateral membranes of bronchial epithelial cells. Mol Biol Cell. 2008;19:536-45 pubmed
    ..We conclude that adducin acting through spectrin provides a novel mechanism to regulate global properties of the lateral membrane of bronchial epithelial cells. ..
  38. Zhang R, Zhang C, Zhao Q, Li D. Spectrin: structure, function and disease. Sci China Life Sci. 2013;56:1076-85 pubmed publisher
    ..This review focuses on recent advances in determining the structure and function of spectrin as well as its role in disease. ..
  39. Avery A, Thomas D, Hays T. ?-III-spectrin spinocerebellar ataxia type 5 mutation reveals a dominant cytoskeletal mechanism that underlies dendritic arborization. Proc Natl Acad Sci U S A. 2017;114:E9376-E9385 pubmed publisher
    A spinocerebellar ataxia type 5 (SCA5) L253P mutation in the actin-binding domain (ABD) of ?-III-spectrin causes high-affinity actin binding and decreased thermal stability in vitro...
  40. Ranum L, Schut L, Lundgren J, Orr H, Livingston D. Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. Nat Genet. 1994;8:280-4 pubmed
    ..Disease onset varies from 10-68 years and anticipation is evident. We have mapped this gene, spinocerebellar ataxia type 5 (SCA5), to the centromeric region of chromosome 11.
  41. Shoeman R, Hartig R, Hauses C, Traub P. Organization of focal adhesion plaques is disrupted by action of the HIV-1 protease. Cell Biol Int. 2002;26:529-39 pubmed
    ..Control experiments demonstrated that the effect and protein cleavages described are due to action of the HIV-1 PR and not to the action of endogenous host cell proteases. ..
  42. De Matteis M, Morrow J. Spectrin tethers and mesh in the biosynthetic pathway. J Cell Sci. 2000;113 ( Pt 13):2331-43 pubmed
    ..Two working models accommodate much of the available data: the Golgi mesh hypothesis and the spectrin ankyrin adapter protein tethering system (SAATS) hypothesis. ..
  43. Ohara O, Ohara R, Yamakawa H, Nakajima D, Nakayama M. Characterization of a new beta-spectrin gene which is predominantly expressed in brain. Brain Res Mol Brain Res. 1998;57:181-92 pubmed