Genomes and Genes
Gene Symbol: Ank2
Description: ankyrin 2, brain
Alias: 100043364, AI835472, AW491075, Ank-2, Gm4392, ankyrin-2, ankyrin-B
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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, ..
- 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. ..
- 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. ..
- 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...
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Hofmann K. The modular nature of apoptotic signaling proteins. Cell Mol Life Sci. 1999;55:1113-28 pubmed
- 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. ..
- 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. ..
- 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 ..
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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.
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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.
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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...
- 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 pubmedHere we report the unexpected finding that specific human ANK2 variants represent a new example of balanced human variants...
- Smith S, Sturm A, Curran J, Kline C, Little S, Bonilla I, et al. Dysfunction in the Î²II spectrin-dependent cytoskeleton underlies human arrhythmia. Circulation. 2015;131:695-708 pubmed publisher..Our findings identify Î²II 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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