Summary: A family of membrane-associated proteins responsible for the attachment of the cytoskeleton. Erythrocyte-related isoforms of ankyrin attach the SPECTRIN cytoskeleton to a transmembrane protein (ANION EXCHANGE PROTEIN 1, ERYTHROCYTE) in the erythrocyte plasma membrane. Brain-related isoforms of ankyrin also exist.

Top Publications

  1. Brechet A, Fache M, Brachet A, Ferracci G, Baude A, Irondelle M, et al. Protein kinase CK2 contributes to the organization of sodium channels in axonal membranes by regulating their interactions with ankyrin G. J Cell Biol. 2008;183:1101-14 pubmed publisher
    ..that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. Furthermore, we observed that CK2 is highly enriched at the AIS and the nodes of Ranvier in vivo...
  2. Cooper E. Made for "anchorin": Kv7.2/7.3 (KCNQ2/KCNQ3) channels and the modulation of neuronal excitability in vertebrate axons. Semin Cell Dev Biol. 2011;22:185-92 pubmed publisher
    ..The natural selection for KCNQ2 and KCNQ3 appears to hinge on these subunits' unique ability to be coordinately localized with Na(V) channels by ankyrin-G, and the resulting enhancement in the reliability of neuronal excitability. ..
  3. Merrill A, Cuellar J, Judd J, Carstens M, Carstens E. Effects of TRPA1 agonists mustard oil and cinnamaldehyde on lumbar spinal wide-dynamic range neuronal responses to innocuous and noxious cutaneous stimuli in rats. J Neurophysiol. 2008;99:415-25 pubmed
    ..CA did not directly excite WDR neurons, and significantly enhanced responses to noxious heat while not affecting windup or responses to skin cooling or mechanical stimulation, indicating a peripheral sensitization of heat nociceptors. ..
  4. Hortsch M, Nagaraj K, Godenschwege T. The interaction between L1-type proteins and ankyrins--a master switch for L1-type CAM function. Cell Mol Biol Lett. 2009;14:57-69 pubmed publisher
    ..The interaction with ankyrins directs L1-type adhesive proteins into different functional contexts, either ankyrin-independent functions, such ..
  5. Das A, Base C, Dhulipala S, Dubreuil R. Spectrin functions upstream of ankyrin in a spectrin cytoskeleton assembly pathway. J Cell Biol. 2006;175:325-35 pubmed
    ..The results suggest an alternate pathway in which spectrin directs ankyrin assembly and in which some important functions of spectrin are independent of ankyrin. ..
  6. Ferreira M, O Donovan M, Meng Y, Jones I, Ruderfer D, Jones L, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet. 2008;40:1056-8 pubmed publisher
    ..0 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder. ..
  7. Kolondra A, Grzybek M, Chorzalska A, Sikorski A. The 22.5 kDa spectrin-binding domain of ankyrinR binds spectrin with high affinity and changes the spectrin distribution in cells in vivo. Protein Expr Purif. 2008;60:157-64 pubmed publisher
    It was previously shown that ankyrins play a crucial role in the membrane skeleton arrangement. Purifying ankyrinR obtained from erythrocytes is a time-consuming process...
  8. Dunham J, Kelly S, Donaldson L. Inflammation reduces mechanical thresholds in a population of transient receptor potential channel A1-expressing nociceptors in the rat. Eur J Neurosci. 2008;27:3151-60 pubmed publisher
    ..Our data show that a subset of afferents is sensitized to mechanical stimulation by inflammation and that these afferents are defined by expression of TRPA1. ..
  9. Rasmussen H, Frøkjaer Jensen C, Jensen C, Jensen H, Jørgensen N, Misonou H, et al. Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment. J Cell Sci. 2007;120:953-63 pubmed
    ..By contrast, deletion of the ankyrin-G-binding motif in KCNQ3 significantly reduces AIS enrichment of the complex, implicating KCNQ3 as a major determinant of M channel localization to the AIS. ..

Scientific Experts

More Information


  1. Grubb M, Burrone J. Building and maintaining the axon initial segment. Curr Opin Neurobiol. 2010;20:481-8 pubmed publisher
  2. Nangola S, Minard P, Tayapiwatana C. Appraisal of translocation pathways for displaying ankyrin repeat protein on phage particles. Protein Expr Purif. 2010;74:156-61 pubmed publisher
    ..Interestingly, the Tat pathway efficiently directed ARP through its translocon without fusing with pIII. Furthermore, the soluble form of ARP was detected in Escherichia coli periplasm. ..
  3. Athanasiu L, Mattingsdal M, Kähler A, Brown A, Gustafsson O, Agartz I, et al. Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. J Psychiatr Res. 2010;44:748-53 pubmed publisher
    ..The association of ANK3 with schizophrenia is intriguing in light of recent associations of ANK3 with bipolar disorder, thereby supporting the hypothesis of an overlap in genetic susceptibility between these psychopathological entities. ..
  4. 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. ..
  5. Hedstrom K, Rasband M. Intrinsic and extrinsic determinants of ion channel localization in neurons. J Neurochem. 2006;98:1345-52 pubmed
  6. Song A, Wang D, Chen G, Li Y, Luo J, Duan S, et al. A selective filter for cytoplasmic transport at the axon initial segment. Cell. 2009;136:1148-60 pubmed publisher
    ..This selective AIS filtering may contribute to preferential trafficking and segregation of cellular components in polarized neurons. ..
  7. Stabach P, Simonovic I, Ranieri M, Aboodi M, Steitz T, Simonovic M, et al. The structure of the ankyrin-binding site of beta-spectrin reveals how tandem spectrin-repeats generate unique ligand-binding properties. Blood. 2009;113:5377-84 pubmed publisher
    ..The putative coupling of flexibility and ligand binding suggests a mechanism by which spectrin might participate in mechanosensory regulation. ..
  8. Lee M, Chen C, Lee C, Chen C, Chong M, Ouyang W, et al. Genome-wide association study of bipolar I disorder in the Han Chinese population. Mol Psychiatry. 2011;16:548-56 pubmed publisher
    ..55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder. ..
  9. Piao L, Fujita T, Jiang C, Liu T, Yue H, Nakatsuka T, et al. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase. Biochem Biophys Res Commun. 2009;379:980-4 pubmed publisher
    ..In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate. ..
  10. Kolondra A, Lenoir M, Wolny M, Czogalla A, Overduin M, Sikorski A, et al. The role of hydrophobic interactions in ankyrin-spectrin complex formation. Biochim Biophys Acta. 2010;1798:2084-9 pubmed publisher
    ..Finally, we present data showing that minimal ankyrin binding site in spectrin is formed by helix 14C together with the loop between helices 15 B/C. ..
  11. Leussis M, Berry Scott E, Saito M, Jhuang H, De Haan G, Alkan O, et al. The ANK3 bipolar disorder gene regulates psychiatric-related behaviors that are modulated by lithium and stress. Biol Psychiatry. 2013;73:683-90 pubmed publisher
  12. Czogalla A, Jaszewski A, Diakowski W, Bok E, Jezierski A, Sikorski A. Structural insight into an ankyrin-sensitive lipid-binding site of erythroid beta-spectrin. Mol Membr Biol. 2007;24:215-24 pubmed
    ..A model based on the obtained data provides direct evidence that the examined lipid-binding site is a highly amphipathic helix, which is correlated with the specific conformation of its N-terminal fragment. ..
  13. Duron O, Boureux A, Echaubard P, Berthomieu A, Berticat C, Fort P, et al. Variability and expression of ankyrin domain genes in Wolbachia variants infecting the mosquito Culex pipiens. J Bacteriol. 2007;189:4442-8 pubmed
    ..Further analysis of ANK gene expression evidenced host- and sex-dependent variations, which did not improve the correlation. Taken together, these data do not support the direct implication of ANK genes in CI determinism. ..
  14. Dzhashiashvili Y, Zhang Y, Galinska J, Lam I, Grumet M, Salzer J. Nodes of Ranvier and axon initial segments are ankyrin G-dependent domains that assemble by distinct mechanisms. J Cell Biol. 2007;177:857-70 pubmed
  15. Shirahata E, Iwasaki H, Takagi M, Lin C, Bennett V, Okamura Y, et al. Ankyrin-G regulates inactivation gating of the neuronal sodium channel, Nav1.6. J Neurophysiol. 2006;96:1347-57 pubmed
    ..6. These results suggest that ankyrin-G regulates neuronal excitability not only through clustering Nav channels but also by directly modifying their channel gating. ..
  16. Dedman A, McQuillin A, Kandaswamy R, Sharp S, Anjorin A, Gurling H. Sequencing of the ANKYRIN 3 gene (ANK3) encoding ankyrin G in bipolar disorder reveals a non-conservative amino acid change in a short isoform of ankyrin G. Am J Med Genet B Neuropsychiatr Genet. 2012;159B:328-35 pubmed publisher
  17. Lange S, Ouyang K, Meyer G, Cui L, Cheng H, Lieber R, et al. Obscurin determines the architecture of the longitudinal sarcoplasmic reticulum. J Cell Sci. 2009;122:2640-50 pubmed publisher
    ..Finally, obscurin knockout mice display centralized nuclei in skeletal muscles as a sign of mild myopathy, but have normal sarcomeric structure and preserved muscle function. ..
  18. Ipsaro J, MONDRAGON A. Structural basis for spectrin recognition by ankyrin. Blood. 2010;115:4093-101 pubmed publisher
    ..The structure represents not only the first of a spectrin fragment in complex with its binding partner, but also that of an intermolecular complex involving a ZU5 domain. ..
  19. Guan H, Maness P. Perisomatic GABAergic innervation in prefrontal cortex is regulated by ankyrin interaction with the L1 cell adhesion molecule. Cereb Cortex. 2010;20:2684-93 pubmed publisher
    ..These results suggest a novel role for L1 engagement with the actin cytoskeleton in development of inhibitory connectivity within the cingulate cortex. ..
  20. Frederick J, Buck M, Matson D, Cortright D. Increased TRPA1, TRPM8, and TRPV2 expression in dorsal root ganglia by nerve injury. Biochem Biophys Res Commun. 2007;358:1058-64 pubmed
    ..Our findings support the hypothesis that increased TRP channel expression in sensory neurons may contribute to mechanical and cold hypersensitivity...
  21. Wang S, Dai Y, Fukuoka T, Yamanaka H, Kobayashi K, Obata K, et al. Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain. Brain. 2008;131:1241-51 pubmed publisher
    ..Collectively, these results represent a novel mechanism through which bradykinin released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation. ..
  22. Gallagher P, Steiner L, Liem R, Owen A, Cline A, Seidel N, et al. Mutation of a barrier insulator in the human ankyrin-1 gene is associated with hereditary spherocytosis. J Clin Invest. 2010;120:4453-65 pubmed publisher
    ..These data indicate that an upstream region of the ankyrin-1 erythroid promoter acts as a barrier insulator and identify disruption of the barrier element as a potential pathogenetic mechanism of human disease. ..
  23. Ishmael N, Dunning Hotopp J, Ioannidis P, Biber S, Sakamoto J, Siozios S, et al. Extensive genomic diversity of closely related Wolbachia strains. Microbiology. 2009;155:2211-22 pubmed publisher
    ..Overall, these insect-associated Wolbachia have highly mosaic genomes, with lateral gene transfer playing an important role in their diversity and evolution. ..
  24. 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. ..
  25. Enneking E, Kudumala S, Moreno E, Stephan R, Boerner J, Godenschwege T, et al. Transsynaptic coordination of synaptic growth, function, and stability by the L1-type CAM Neuroglian. PLoS Biol. 2013;11:e1001537 pubmed publisher
  26. Giacomello E, Sorrentino V. Localization of ank1.5 in the sarcoplasmic reticulum precedes that of SERCA and RyR: relationship with the organization of obscurin in developing sarcomeres. Histochem Cell Biol. 2009;131:371-82 pubmed publisher
    ..Why this occurs is not clear, yet these data indicate that the organization of obscurin at different locations in the sarcomere changes during muscle development and that this might affect the interaction with ank1.5. ..
  27. Su Y, Ding Y, Jiang M, Jiang W, Hu X, Zhang Z. Associations of protein 4.2 with band 3 and ankyrin. Mol Cell Biochem. 2006;289:159-66 pubmed
    ..2. The proper tertiary structures of these protein 4.2 fragments are essential for protein 4.2-ankyrin interaction. Meanwhile, ankyrin can enhance the interaction between protein 4.2 and CDB3. ..
  28. 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. ..
  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. MATTA J, Cornett P, Miyares R, Abe K, Sahibzada N, Ahern G. General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc Natl Acad Sci U S A. 2008;105:8784-9 pubmed publisher
    ..Thus, our results show that TRPA1 is essential for sensing noxious GAs. The pronociceptive effects of GAs combined with surgical tissue damage could lead to a paradoxical increase in postoperative pain and inflammation. ..
  31. Buhusi M, Schlatter M, Demyanenko G, Thresher R, Maness P. L1 interaction with ankyrin regulates mediolateral topography in the retinocollicular projection. J Neurosci. 2008;28:177-88 pubmed publisher
  32. Ruparel N, Patwardhan A, Akopian A, Hargreaves K. Homologous and heterologous desensitization of capsaicin and mustard oil responses utilize different cellular pathways in nociceptors. Pain. 2008;135:271-9 pubmed
    ..The heterologous desensitization of these receptors and corresponding inhibition of nociceptor activity might have potential application as a therapeutic target for developing novel analgesics...
  33. Delaunay J. The molecular basis of hereditary red cell membrane disorders. Blood Rev. 2007;21:1-20 pubmed
    ..The diagnosis, follow-up and treatment of the involved diseases have gradually improved. ..
  34. 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. ..
  35. Ackermann M, Ziman A, Strong J, Zhang Y, Hartford A, Ward C, et al. Integrity of the network sarcoplasmic reticulum in skeletal muscle requires small ankyrin 1. J Cell Sci. 2011;124:3619-30 pubmed publisher
    ..Consistent with the loss of SERCA, uptake and release of Ca(2+) were significantly inhibited. Our results show that sAnk1 stabilizes the nSR and that its absence causes the nSR to fragment into distinct membrane compartments. ..
  36. Roussos P, Katsel P, Davis K, Bitsios P, Giakoumaki S, Jogia J, et al. Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia. Arch Gen Psychiatry. 2012;69:7-15 pubmed publisher
    ..The association of ANK3 with lower brain mRNA expression levels implicates a molecular mechanism for its genetic, clinical, and cognitive associations with SZ. ..
  37. Yang Y, Ogawa Y, Hedstrom K, Rasband M. betaIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG. J Cell Biol. 2007;176:509-19 pubmed
    ..Finally, using adenovirus for transgene delivery into myelinated neurons, we demonstrate that betaIV spectrin recruitment to nodes of Ranvier also depends on binding to ankG. ..
  38. Borzok M, Catino D, Nicholson J, Kontrogianni Konstantopoulos A, Bloch R. Mapping the binding site on small ankyrin 1 for obscurin. J Biol Chem. 2007;282:32384-96 pubmed
    ..Thus, structural and mutational studies of the binding region on sAnk1 for obscurin suggest that it consists of two ankyrin repeats with very similar structures. ..
  39. Pocock R, Benard C, Shapiro L, Hobert O. Functional dissection of the C. elegans cell adhesion molecule SAX-7, a homologue of human L1. Mol Cell Neurosci. 2008;37:56-68 pubmed
    ..Lastly, we show that of the several protein binding motifs present in the intracellular region of SAX-7, only its ankyrin binding motif is required and also solely sufficient to confer the adhesive functions of SAX-7. ..
  40. Rank G, Sutton R, Marshall V, Lundie R, Caddy J, Romeo T, et al. Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant. Blood. 2009;113:3352-62 pubmed publisher
    ..These findings provide novel insights into the role of Ank-1, and define an ideal model for the study of HS and malarial resistance. ..
  41. Ipsaro J, Huang L, MONDRAGON A. Structures of the spectrin-ankyrin interaction binding domains. Blood. 2009;113:5385-93 pubmed publisher
    ..Previously reported mutants of ankyrin that map to this region lie mostly on the surface of the protein, although at least one is likely to be part of the core. ..
  42. 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. ..
  43. Czogalla A, Sikorski A. Do we already know how spectrin attracts ankyrin?. Cell Mol Life Sci. 2010;67:2679-83 pubmed publisher
    ..In this short paper, we briefly summarize the data obtained and compare the resulting conclusions. ..
  44. 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. ..
  45. Busby B, Oashi T, Willis C, Ackermann M, Kontrogianni Konstantopoulos A, MacKerell A, et al. Electrostatic interactions mediate binding of obscurin to small ankyrin 1: biochemical and molecular modeling studies. J Mol Biol. 2011;408:321-34 pubmed publisher
    ..Our results are consistent with a model in which electrostatic interactions between specific pairs of side chains on obscurin and sAnk1 promote binding and complex formation. ..
  46. Peker S, Akar N, Demiralp D. Proteomic identification of erythrocyte membrane protein deficiency in hereditary spherocytosis. Mol Biol Rep. 2012;39:3161-7 pubmed publisher
    ..Spectrin alpha and beta chain, ankyrin and band 3 proteins expression differences were found with PDQuest software 8.0.1. and peptide mass fingerprinting (PMF) analysis performed for identification of proteins in this study. ..
  47. Leffler A, Fischer M, Rehner D, Kienel S, Kistner K, Sauer S, et al. The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons. J Clin Invest. 2008;118:763-76 pubmed publisher
    ..This effect is sufficient to release CGRP, a key component of neurogenic inflammation, and warrants investigation into the role of TRPV1 and TRPA1 in LA-induced neurotoxicity. ..
  48. Mohler P. Ankyrins and human disease: what the electrophysiologist should know. J Cardiovasc Electrophysiol. 2006;17:1153-9 pubmed
    ..b>Ankyrins are a family of "adaptor" proteins, which play critical roles in the proper expression and membrane ..
  49. Buffington S, Sobotzik J, Schultz C, Rasband M. I?B? is not required for axon initial segment assembly. Mol Cell Neurosci. 2012;50:1-9 pubmed publisher
    ..Our results indicate that pI?B? is neither enriched at the AIS nor required for AIS assembly. ..
  50. Shah M, Migliore M, Valencia I, Cooper E, Brown D. Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons. Proc Natl Acad Sci U S A. 2008;105:7869-74 pubmed publisher
    ..These results indicate that axonal Kv7 channels, by controlling axonal RMP and action potential threshold, are fundamental for regulating the inherent firing properties of CA1 hippocampal neurons. ..
  51. Greth A, Lampkin S, Mayura Guru P, Rodda F, Drysdale K, Roberts Thomson M, et al. A novel ENU-mutation in ankyrin-1 disrupts malaria parasite maturation in red blood cells of mice. PLoS ONE. 2012;7:e38999 pubmed publisher
    ..05). We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites. ..
  52. Martin P, Carnaud M, Garcia del Caño G, Irondelle M, Irinopoulou T, Girault J, et al. Schwannomin-interacting protein-1 isoform IQCJ-SCHIP-1 is a late component of nodes of Ranvier and axon initial segments. J Neurosci. 2008;28:6111-7 pubmed publisher
    ..We suggest that IQCJ-SCHIP-1 might participate, along with AnkG and betaIV-spectrin, in the stabilization or function of the multimolecular complexes of AISs and NRs, possibly by participating in Ca(2+)-mediated responses. ..
  53. Koch I, Schwarz H, Beuchle D, Goellner B, Langegger M, Aberle H. Drosophila ankyrin 2 is required for synaptic stability. Neuron. 2008;58:210-22 pubmed publisher
    ..Interestingly, Ank2 functions downstream of spectrin in the anchorage of synaptic microtubules, providing the cytoskeletal scaffold that is essential for synaptic stability. ..