Ank2

Summary

Gene Symbol: Ank2
Description: ankyrin 2, brain
Alias: 100043364, AI835472, AW491075, Ank-2, Gm4392, ankyrin-2, ankyrin-B
Species: mouse
Products:     Ank2

Top Publications

  1. Mohler P, Davis J, Bennett V. Ankyrin-B coordinates the Na/K ATPase, Na/Ca exchanger, and InsP3 receptor in a cardiac T-tubule/SR microdomain. PLoS Biol. 2005;3:e423 pubmed
    ..Ankyrin-B also is not abundantly expressed in smooth muscle. We propose that the ankyrin-B-based complex is a specialized adaptation of cardiomyocytes with a role for cytosolic Ca2+ modulation. ..
  2. Mohler P, Yoon W, Bennett V. Ankyrin-B targets beta2-spectrin to an intracellular compartment in neonatal cardiomyocytes. J Biol Chem. 2004;279:40185-93 pubmed
    ..This work also establishes a functional hierarchy in which ankyrin-B determines the localization of beta(2)-spectrin and operates independently of beta(2)-spectrin in its role in organizing membrane-spanning proteins. ..
  3. Mohler P, Schott J, Gramolini A, Dilly K, Guatimosim S, duBell W, et al. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature. 2003;421:634-9 pubmed
    ..We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters, causes dominantly inherited type 4 long-QT cardiac ..
  4. Bhasin N, Cunha S, Mudannayake M, Gigena M, Rogers T, Mohler P. Molecular basis for PP2A regulatory subunit B56alpha targeting in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2007;293:H109-19 pubmed
    ..These new data implicate ankyrin-B as a critical targeting component for PP2A in heart and identify a new class of signaling proteins targeted by ankyrin polypeptides. ..
  5. Mohler P, Le Scouarnec S, Denjoy I, Lowe J, Guicheney P, Caron L, et al. Defining the cellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes. Circulation. 2007;115:432-41 pubmed
    Mutations in the ankyrin-B gene (ANK2) cause type 4 long-QT syndrome and have been described in kindreds with other arrhythmias...
  6. Scotland P, Zhou D, Benveniste H, Bennett V. Nervous system defects of AnkyrinB (-/-) mice suggest functional overlap between the cell adhesion molecule L1 and 440-kD AnkyrinB in premyelinated axons. J Cell Biol. 1998;143:1305-15 pubmed
    ..These findings provide the first evidence for a role of ankyrinB in the nervous system and support an interaction between 440-kD ankyrinB and L1 that is essential for maintenance of premyelinated axons in vivo. ..
  7. Mohler P, Splawski I, Napolitano C, Bottelli G, Sharpe L, Timothy K, et al. A cardiac arrhythmia syndrome caused by loss of ankyrin-B function. Proc Natl Acad Sci U S A. 2004;101:9137-42 pubmed
  8. Mohler P, Gramolini A, Bennett V. The ankyrin-B C-terminal domain determines activity of ankyrin-B/G chimeras in rescue of abnormal inositol 1,4,5-trisphosphate and ryanodine receptor distribution in ankyrin-B (-/-) neonatal cardiomyocytes. J Biol Chem. 2002;277:10599-607 pubmed
    ..C-terminal domains are the most divergent between ankyrin isoforms and are candidates to encode the signal(s) that enable ankyrins to selectively target proteins to diverse cellular sites. ..
  9. Tse W, Menninger J, Yang Feng T, Francke U, Sahr K, Lux S, et al. Isolation and chromosomal localization of a novel nonerythroid ankyrin gene. Genomics. 1991;10:858-66 pubmed
    ..1991), suggesting that the genomic clone is part of a gene for nonerythroid ankyrin, which we have designated ANK2. By analysis of somatic cell hybrids and fluorescence in situ hybridization, we assigned ANK2 to human chromosome 4 ..

More Information

Publications58

  1. Ayalon G, Davis J, Scotland P, Bennett V. An ankyrin-based mechanism for functional organization of dystrophin and dystroglycan. Cell. 2008;135:1189-200 pubmed publisher
    ..Dynactin-4 and a subset of microtubules disappear from sarcolemmal sites in ankyrin-B-depleted muscle. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4...
  2. Ogawa Y, Schafer D, Horresh I, Bar V, Hales K, Yang Y, et al. Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton. J Neurosci. 2006;26:5230-9 pubmed
    ..Our results demonstrate that the paranodal junction contains specialized cytoskeletal components that may be important to stabilize axon-glia interactions and contribute to the membrane protein diffusion barrier found at paranodes. ..
  3. Tuvia S, Buhusi M, Davis L, Reedy M, Bennett V. Ankyrin-B is required for intracellular sorting of structurally diverse Ca2+ homeostasis proteins. J Cell Biol. 1999;147:995-1008 pubmed
    ..Similar mechanisms involving ankyrins may be essential for segregation of functionally defined proteins within specialized regions of the plasma membrane and within the Ca(2+) homeostasis compartment of the ER. ..
  4. Mohler P, Davis J, Davis L, Hoffman J, Michaely P, Bennett V. Inositol 1,4,5-trisphosphate receptor localization and stability in neonatal cardiomyocytes requires interaction with ankyrin-B. J Biol Chem. 2004;279:12980-7 pubmed
    ..These new results provide the first physiological evidence of a molecular partner required for early post-translational stability of InsP(3)R. ..
  5. Galiano M, Jha S, Ho T, Zhang C, Ogawa Y, Chang K, et al. A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon initial segment assembly. Cell. 2012;149:1125-39 pubmed publisher
    ..Thus, the distal axonal cytoskeleton functions as an intra-axonal boundary restricting ankG to the AIS. ..
  6. Cunha S, Hund T, Hashemi S, Voigt N, Li N, Wright P, et al. Defects in ankyrin-based membrane protein targeting pathways underlie atrial fibrillation. Circulation. 2011;124:1212-22 pubmed publisher
    ..b>ANK2 encodes ankyrin-B, a multifunctional adapter molecule implicated in membrane targeting of ion channels, ..
  7. Qu F, LORENZO D, King S, Brooks R, Bear J, Bennett V. Ankyrin-B is a PI3P effector that promotes polarized ?5?1-integrin recycling via recruiting RabGAP1L to early endosomes. elife. 2016;5: pubmed publisher
    ..Our results reveal AnkB as an unexpected key element in coordinating polarized transport of ?5?1-integrin and likely of other specialized endocytic cargos. ..
  8. Peters L, Birkenmeier C, Bronson R, White R, Lux S, Otto E, et al. Purkinje cell degeneration associated with erythroid ankyrin deficiency in nb/nb mice. J Cell Biol. 1991;114:1233-41 pubmed
    ..Ank-2 maps to Chromosome 3 and its expression is unaffected by the nb mutation. We conclude that Ank-1 is specifically required for Purkinje cell stability and, in its absence, Purkinje cell loss and neurological symptoms appear. ..
  9. Stokke M, Tovsrud N, Louch W, Øyehaug L, Hougen K, Sejersted O, et al. I(CaL) inhibition prevents arrhythmogenic Ca(2+) waves caused by abnormal Ca(2+) sensitivity of RyR or SR Ca(2+) accumulation. Cardiovasc Res. 2013;98:315-25 pubmed publisher
    ..Ca(2+) wave prevention through reduced SR Ca(2+) content was also effective in heterozygous ankyrin B knockout mice with excessive SR Ca(2+) accumulation during ?-adrenergic stimulation...
  10. Le Scouarnec S, Bhasin N, Vieyres C, Hund T, Cunha S, Koval O, et al. Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease. Proc Natl Acad Sci U S A. 2008;105:15617-22 pubmed publisher
    ..We mapped two families with highly penetrant and severe SND to the human ANK2 (ankyrin-B/AnkB) locus...
  11. Lopez Santiago L, Meadows L, Ernst S, Chen C, Malhotra J, McEwen D, et al. Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. J Mol Cell Cardiol. 2007;43:636-47 pubmed
    ..Together, these results suggest that beta1 is critical for normal cardiac excitability and loss of beta1 may be associated with a long QT phenotype. ..
  12. Le Bras B, Fréal A, Czarnecki A, Legendre P, Bullier E, Komada M, et al. In vivo assembly of the axon initial segment in motor neurons. Brain Struct Funct. 2014;219:1433-50 pubmed publisher
    ..5 these nascent AISs are already able to generate spikes. Using knock-out mice, we demonstrated that neither ?4-spectrin nor Neurofascin control the distal-to-proximal restriction of AnkG. ..
  13. Chang K, Zollinger D, Susuki K, Sherman D, Makara M, Brophy P, et al. Glial ankyrins facilitate paranodal axoglial junction assembly. Nat Neurosci. 2014;17:1673-81 pubmed publisher
    ..Thus, glial ankyrins function as major scaffolds that facilitate early and efficient paranodal junction assembly in the developing CNS. ..
  14. Lorenzo D, Badea A, Davis J, Hostettler J, He J, Zhong G, et al. A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport. J Cell Biol. 2014;207:735-52 pubmed publisher
    ..Our results establish new functional relationships between PIK3C3, dynactin, and AnkB that together promote axonal transport of organelles and are required for normal axon length. ..
  15. Barisoni L, Trudel M, Chretien N, Ward L, van Adelsberg J, D AGATI V. Analysis of the role of membrane polarity in polycystic kidney disease of transgenic SBM mice. Am J Pathol. 1995;147:1728-35 pubmed
  16. Chauhan V, Tuvia S, Buhusi M, Bennett V, Grant A. Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice. Circ Res. 2000;86:441-7 pubmed
    ..In conclusion, Na(+) channels in ankyrin(B)(-/-) display reduced I(Na) density and abnormal kinetics at the whole-cell and single-channel level that contribute to prolonged APD(90) and abnormal QT-rate adaptation. ..
  17. Kline C, Scott J, Curran J, Hund T, Mohler P. Ankyrin-B regulates Cav2.1 and Cav2.2 channel expression and targeting. J Biol Chem. 2014;289:5285-95 pubmed publisher
    ..Collectively, our findings identify an interaction between ankyrin-B and both Cav2.1 and Cav2.2 at the amino acid level that is necessary for proper Cav2.1 and Cav2.2 targeting in vivo. ..
  18. Notwell J, Heavner W, Darbandi S, Katzman S, McKenna W, Ortiz Londono C, et al. TBR1 regulates autism risk genes in the developing neocortex. Genome Res. 2016;26:1013-22 pubmed publisher
    ..Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development. ..
  19. Cunha S, Bhasin N, Mohler P. Targeting and stability of Na/Ca exchanger 1 in cardiomyocytes requires direct interaction with the membrane adaptor ankyrin-B. J Biol Chem. 2007;282:4875-83 pubmed
    ..These results raise exciting new questions regarding potentially dynamic roles for ankyrin proteins in the biogenesis and maintenance of specialized membrane domains in excitable cells. ..
  20. Wang J, Walker H, Lin Q, Jenkins N, Copeland N, Watanabe T, et al. The mouse BP-1 gene: structure, chromosomal localization, and regulation of expression by type I interferons and interleukin-7. Genomics. 1996;33:167-76 pubmed
    ..This finding indicates that the upregulated BP-1 expression can be disassociated from the cell growth signal. ..
  21. Hofmann K. The modular nature of apoptotic signaling proteins. Cell Mol Life Sci. 1999;55:1113-28 pubmed
  22. Moré M, Kirsch F, Rathjen F. Targeted ablation of NrCAM or ankyrin-B results in disorganized lens fibers leading to cataract formation. J Cell Biol. 2001;154:187-96 pubmed
    ..Also, these studies provide genetic evidence of an interaction between NrCAM and ankyrin-B. ..
  23. Gudmundsson H, Hund T, Wright P, Kline C, Snyder J, Qian L, et al. EH domain proteins regulate cardiac membrane protein targeting. Circ Res. 2010;107:84-95 pubmed publisher
    ..Notably, these data provide the first link between EHD proteins and a human disease model. ..
  24. Kashef F, Li J, Wright P, Snyder J, Suliman F, Kilic A, et al. Ankyrin-B protein in heart failure: identification of a new component of metazoan cardioprotection. J Biol Chem. 2012;287:30268-81 pubmed publisher
    ..Ankyrin-B (encoded by ANK2) loss-of-function mutations are directly associated with human cardiovascular phenotypes including sinus node ..
  25. Gompers A, Su Feher L, Ellegood J, Copping N, Riyadh M, Stradleigh T, et al. Germline Chd8 haploinsufficiency alters brain development in mouse. Nat Neurosci. 2017;20:1062-1073 pubmed publisher
    ..This integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development. ..
  26. Li J, Kline C, Hund T, Anderson M, Mohler P. Ankyrin-B regulates Kir6.2 membrane expression and function in heart. J Biol Chem. 2010;285:28723-30 pubmed publisher
    ..Collectively, our new findings define a new role for cardiac ankyrin polypeptides in regulation of ion channel membrane expression in heart...
  27. Ayalon G, Hostettler J, Hoffman J, Kizhatil K, Davis J, Bennett V. Ankyrin-B interactions with spectrin and dynactin-4 are required for dystrophin-based protection of skeletal muscle from exercise injury. J Biol Chem. 2011;286:7370-8 pubmed publisher
    ..Ankyrin-B then interacts with dynactin-4 and dystrophin, whereas dynactin-4 collaborates with dystrophin in coordinating costamere-aligned microtubules. ..
  28. Stankewich M, Cianci C, Stabach P, Ji L, Nath A, Morrow J. Cell organization, growth, and neural and cardiac development require ?II-spectrin. J Cell Sci. 2011;124:3956-66 pubmed publisher
    ..These data indicate that the spectrin-ankyrin scaffold is crucial in vertebrates for cell spreading, tissue patterning and organ development, particularly in the developing brain and heart, but is not required for cell viability. ..
  29. Cunha S, Mohler P. Obscurin targets ankyrin-B and protein phosphatase 2A to the cardiac M-line. J Biol Chem. 2008;283:31968-80 pubmed publisher
    ..In summary, our new findings demonstrate that ANK2 is subject to alternative splicing that gives rise to unique polypeptides with diverse roles in cardiac function.
  30. Malhotra J, Thyagarajan V, Chen C, Isom L. Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J Biol Chem. 2004;279:40748-54 pubmed
    ..5 and pYbeta1 and that these complexes are in close association with both N-cadherin and connexin-43. beta1 phosphorylation appears to regulate its localization to differential subcellular domains. ..
  31. Kline C, Kurata H, Hund T, Cunha S, Koval O, Wright P, et al. Dual role of K ATP channel C-terminal motif in membrane targeting and metabolic regulation. Proc Natl Acad Sci U S A. 2009;106:16669-74 pubmed publisher
    ..Thus, the K(ATP) channel ABM serves as a previously unrecognized bifunctional touch-point for grading K(ATP) channel gating and membrane targeting and may play a fundamental role in controlling excitable cell metabolic regulation. ..
  32. Maddala R, Skiba N, Lalane R, Sherman D, Brophy P, Rao P. Periaxin is required for hexagonal geometry and membrane organization of mature lens fibers. Dev Biol. 2011;357:179-90 pubmed publisher
    ..Hence, there may be functional parallels between the roles of Prx in membrane stabilization of the myelin sheath and the lens fiber cell. ..
  33. Camors E, Mohler P, Bers D, Despa S. Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac myocyte arrhythmic activity. J Mol Cell Cardiol. 2012;52:1240-8 pubmed publisher
    ..This could enhance the propensity for triggered arrhythmias in AnkB(+/-) mice. ..
  34. Maddala R, Walters M, Brophy P, Bennett V, Rao P. Ankyrin-B directs membrane tethering of periaxin and is required for maintenance of lens fiber cell hexagonal shape and mechanics. Am J Physiol Cell Physiol. 2016;310:C115-26 pubmed publisher
    ..Taken together, these observations reveal that AnkB is required for Prx membrane anchoring and for maintenance of lens fiber cell hexagonal geometry, membrane skeleton organization, and biomechanics. ..
  35. Wu H, Yamankurt G, Luo J, Subramaniam J, Hashmi S, Hu H, et al. Identification and characterization of two ankyrin-B isoforms in mammalian heart. Cardiovasc Res. 2015;107:466-77 pubmed publisher
    ..The identification and characterization of two functionally distinct ankyrin-B isoforms in heart provide compelling evidence that alternative splicing of the ANK2 gene regulates the fidelity of ankyrin-B interactions with proteins.
  36. Cunha S, Le Scouarnec S, Schott J, Mohler P. Exon organization and novel alternative splicing of the human ANK2 gene: implications for cardiac function and human cardiac disease. J Mol Cell Cardiol. 2008;45:724-34 pubmed publisher
    ..Specifically, decreased expression of ankyrin-B in mice or human mutations in the ankyrin-B gene (ANK2) results in potentially fatal cardiac arrhythmias...
  37. Wolf R, Glynn P, Hashemi S, Zarei K, Mitchell C, Anderson M, et al. Atrial fibrillation and sinus node dysfunction in human ankyrin-B syndrome: a computational analysis. Am J Physiol Heart Circ Physiol. 2013;304:H1253-66 pubmed publisher
    ..Importantly, ankyrin-B dysfunction involves changes at both the cell and tissue levels that favor the common manifestation of atrial arrhythmias and SAN dysfunction. ..
  38. Popescu I, Galice S, Mohler P, Despa S. Elevated local [Ca2+] and CaMKII promote spontaneous Ca2+ release in ankyrin-B-deficient hearts. Cardiovasc Res. 2016;111:287-94 pubmed publisher
    ..The increased incidence of pro-arrhythmogenic Ca(2+) sparks and waves in AnkB(+/-) hearts is due to enhanced CaMKII-mediated RyR phosphorylation, which is caused by higher junctional [Ca(2+)] and consequent local CaMKII activation. ..
  39. LORENZO D, Healy J, Hostettler J, Davis J, Yang J, Wang C, et al. Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency. J Clin Invest. 2015;125:3087-102 pubmed publisher
  40. Kizhatil K, Sandhu N, Peachey N, Bennett V. Ankyrin-B is required for coordinated expression of beta-2-spectrin, the Na/K-ATPase and the Na/Ca exchanger in the inner segment of rod photoreceptors. Exp Eye Res. 2009;88:57-64 pubmed publisher
    ..These results are consistent with a mechanism where ankyrin-B is required to restrict the Na/K-ATPase and Na/Ca exchanger to the inner segment of rod photoreceptors by tethering these membrane proteins to beta-2-spectrin. ..
  41. Healy J, Nilsson K, Hohmeier H, Berglund J, Davis J, Hoffman J, et al. Cholinergic augmentation of insulin release requires ankyrin-B. Sci Signal. 2010;3:ra19 pubmed publisher
    ..Thus, defective glycemic regulation through loss of ankyrin-B-dependent stabilization of IP3R is a potential risk factor for type 2 diabetes. ..
  42. Hund T, Mohler P. Ankyrin-based targeting pathway regulates human sinoatrial node automaticity. Channels (Austin). 2008;2:404-6 pubmed
    ..Ankyrin-B deficient mice displayed bradycardia and heart rate variability similar to individuals harboring an ANK2 variant...
  43. Glukhov A, Fedorov V, Anderson M, Mohler P, Efimov I. Functional anatomy of the murine sinus node: high-resolution optical mapping of ankyrin-B heterozygous mice. Am J Physiol Heart Circ Physiol. 2010;299:H482-91 pubmed publisher
    ..from the ankyrin-B (AnkB)-deficient mice display severe pacemaking dysfunction similar to individuals harboring ankyrin 2 allele variants...
  44. Mohler P, Healy J, Xue H, Puca A, Kline C, Allingham R, et al. Ankyrin-B syndrome: enhanced cardiac function balanced by risk of cardiac death and premature senescence. PLoS ONE. 2007;2:e1051 pubmed
    Here we report the unexpected finding that specific human ANK2 variants represent a new example of balanced human variants...
  45. Smith S, Sturm A, Curran J, Kline C, Little S, Bonilla I, et al. Dysfunction in the βII spectrin-dependent cytoskeleton underlies human arrhythmia. Circulation. 2015;131:695-708 pubmed publisher
    ..Our findings identify βII spectrin as critical for normal myocyte electric activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology. ..
  46. Ooashi N, Kamiguchi H. The cell adhesion molecule L1 controls growth cone navigation via ankyrin(B)-dependent modulation of cyclic AMP. Neurosci Res. 2009;63:224-6 pubmed publisher
    ..These results indicate that ankyrin(B) regulates axon guidance via cyclic AMP. ..
  47. Tuvim M, Mospan A, Burns K, Chua M, Mohler P, Melicoff E, et al. Synaptotagmin 2 couples mucin granule exocytosis to Ca2+ signaling from endoplasmic reticulum. J Biol Chem. 2009;284:9781-7 pubmed publisher
    ..Hence, Syt2 can serve as an exocytic sensor for diverse Ca(2+) signaling systems, and its levels are limiting for stimulated secretory function in airway goblet cells. ..
  48. Tang Y, Katuri V, Iqbal S, Narayan T, Wang Z, Lu R, et al. ELF a beta-spectrin is a neuronal precursor cell marker in developing mammalian brain; structure and organization of the elf/beta-G spectrin gene. Oncogene. 2002;21:5255-67 pubmed
    ..Based on its expression pattern, ELF may have a role in neural stem cell development and is a marker of axonal sprouting in mid stages of embryonic development. ..
  49. Peters L, Turtzo L, Birkenmeier C, Barker J. Distinct fetal Ank-1 and Ank-2 related proteins and mRNAs in normal and nb/nb mice. Blood. 1993;81:2144-9 pubmed