Gene Symbol: Ank3
Description: ankyrin 3
Alias: ANK-3, ankyrin-3, ankyrin 3 (G), ankyrin 3, epithelial, ankyrin 3, node of Ranvier (ankyrin G), ankyrin-G
Species: rat
Products:     Ank3

Top Publications

  1. Zhang X, Bennett V. Restriction of 480/270-kD ankyrin G to axon proximal segments requires multiple ankyrin G-specific domains. J Cell Biol. 1998;142:1571-81 pubmed
    ..This complex behavior explains ability of ankyrinB and ankyrinG to sort to distinct sites in neurons and the fact that these ankyrins do not compensate for each other in ankyrin gene knockouts in mice. ..
  2. 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. ..
  3. Lowe J, Palygin O, Bhasin N, Hund T, Boyden P, Shibata E, et al. Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. J Cell Biol. 2008;180:173-86 pubmed publisher
    ..These data are the first report of a cellular pathway required for Na(v) channel trafficking in the heart and suggest that ankyrin-G is critical for cardiac depolarization and Na(v) channel organization in multiple excitable tissues. ..
  4. 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 sodium channels complexed with adhesion molecules (neurofascin [NF] 186 and NrCAM) and cytoskeletal proteins (ankyrin G and betaIV spectrin)...
  5. Kizhatil K, Bennett V. Lateral membrane biogenesis in human bronchial epithelial cells requires 190-kDa ankyrin-G. J Biol Chem. 2004;279:16706-14 pubmed
    ..Moreover, analysis of rat 190-kDa ankyrin G/ankyrin B chimeras shows that all three domains of 190-kDa ankyrin-G are required for preservation of the ..
  6. Lencesova L, O Neill A, Resneck W, Bloch R, Blaustein M. Plasma membrane-cytoskeleton-endoplasmic reticulum complexes in neurons and astrocytes. J Biol Chem. 2004;279:2885-93 pubmed
    ..with NCX1, including the Na(+) pump alpha1 isoform, PM Ca(2+) pump type 1 (PMCA1), beta-fodrin, and Ank 3. In reciprocal experiments, immunoprecipitation with antibodies to the Na(+) pump alpha2 and alpha3 isoforms, but ..
  7. Kordeli E, Ludosky M, Deprette C, Frappier T, Cartaud J. AnkyrinG is associated with the postsynaptic membrane and the sarcoplasmic reticulum in the skeletal muscle fiber. J Cell Sci. 1998;111 ( Pt 15):2197-207 pubmed
    ..Ank1 and Ank3 transcripts were previously detected in skeletal muscle by northern blot analysis...
  8. Boiko T, Vakulenko M, Ewers H, Yap C, Norden C, Winckler B. Ankyrin-dependent and -independent mechanisms orchestrate axonal compartmentalization of L1 family members neurofascin and L1/neuron-glia cell adhesion molecule. J Neurosci. 2007;27:590-603 pubmed
    ..Our results suggest that NF and L1/NgCAM accumulate in the axon by an ankyrin-independent pathway, but retention at the IS requires ankyrin binding. ..
  9. Pan Z, Kao T, Horvath Z, Lemos J, Sul J, Cranstoun S, et al. A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J Neurosci. 2006;26:2599-613 pubmed
    ..This includes the historical period when myelin also evolved. ..

More Information


  1. Mohler P, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori S, et al. Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A. 2004;101:17533-8 pubmed
    ..Together with previous work in neurons, these results in cardiomyocytes suggest that ankyrin-G participates in a common pathway for localization of voltage-gated Na(v) channels at sites of function in multiple excitable cell types. ..
  2. Ango F, Di Cristo G, Higashiyama H, Bennett V, Wu P, Huang Z. Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment. Cell. 2004;119:257-72 pubmed
    ..Disruption of NF186-ankyrinG interactions at AIS reduced pinceau synapse formation. These results implicate ankyrin-based localization of L1CAMs in subcellular organization of GABAergic synapses. ..
  3. Zhou D, Lambert S, Malen P, Carpenter S, Boland L, Bennett V. AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J Cell Biol. 1998;143:1295-304 pubmed
    ..These results demonstrate that ankyrinG is essential for clustering NaCh and neurofascin at axon initial segments and is required for physiological levels of sodium channel activity. ..
  4. Peters L, John K, Lu F, Eicher E, Higgins A, Yialamas M, et al. Ank3 (epithelial ankyrin), a widely distributed new member of the ankyrin gene family and the major ankyrin in kidney, is expressed in alternatively spliced forms, including forms that lack the repeat domain. J Cell Biol. 1995;130:313-30 pubmed
    We cloned a novel ankyrin, Ank3, from mouse kidney cDNA...
  5. Jenkins S, Bennett V. Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje neuron initial segments. J Cell Biol. 2001;155:739-46 pubmed
  6. Bailey S, Stocksley M, Buckel A, Young C, Slater C. Voltage-gated sodium channels and ankyrinG occupy a different postsynaptic domain from acetylcholine receptors from an early stage of neuromuscular junction maturation in rats. J Neurosci. 2003;23:2102-11 pubmed
  7. Thevananther S, Kolli A, Devarajan P. Identification of a novel ankyrin isoform (AnkG190) in kidney and lung that associates with the plasma membrane and binds alpha-Na, K-ATPase. J Biol Chem. 1998;273:23952-8 pubmed
    ..Thus, ankyrins may interact with integral membrane proteins in a pleiotropic manner that may involve complex tertiary structural determinants. ..
  8. Sato P, Coombs W, Lin X, Nekrasova O, Green K, Isom L, et al. Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc. Circ Res. 2011;109:193-201 pubmed publisher
    ..Possible implications to the pathophysiology of inherited arrhythmias (such as arrhythmogenic right ventricular cardiomyopathy) are discussed. ..
  9. Devaux J, Alcaraz G, Grinspan J, Bennett V, Joho R, Crest M, et al. Kv3.1b is a novel component of CNS nodes. J Neurosci. 2003;23:4509-18 pubmed
    ..1b and Na+ channels are observed even in regions devoid of oligodendrocytes. Ankyrin G coimmunoprecipitates Kv3.1b in vivo, indicating that these two proteins may interact in the CNS at nodes...
  10. San Cristobal P, Lainez S, Dimke H, de Graaf M, Hoenderop J, Bindels R. Ankyrin-3 is a novel binding partner of the voltage-gated potassium channel Kv1.1 implicated in renal magnesium handling. Kidney Int. 2014;85:94-102 pubmed publisher
    ..1 as bait were used in mouse kidney lysates. Ankyrin-3 (ANK3) was identified as a binding partner of Kv1...
  11. Smith K, Kopeikina K, Fawcett Patel J, Leaderbrand K, Gao R, Schürmann B, et al. Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses. Neuron. 2014;84:399-415 pubmed publisher
    ..Common and rare variants in the ANK3 gene, encoding ankyrin-G, have been associated with bipolar disorder, schizophrenia, and autism...
  12. Sohn P, Tracy T, Son H, Zhou Y, Leite R, Miller B, et al. Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment. Mol Neurodegener. 2016;11:47 pubmed publisher
    ..AIS cytoskeletal proteins, including ankyrin G and ?IV-spectrin, were downregulated in AD brains and negatively correlated with an increase in tau acetylated ..
  13. Leterrier C, Vacher H, Fache M, d Ortoli S, Castets F, Autillo Touati A, et al. End-binding proteins EB3 and EB1 link microtubules to ankyrin G in the axon initial segment. Proc Natl Acad Sci U S A. 2011;108:8826-31 pubmed publisher
    ..We identified a direct interaction between EB3/EB1 and the AIS scaffold protein ankyrin G (ankG)...
  14. Maiweilidan Y, Klauza I, Kordeli E. Novel interactions of ankyrins-G at the costameres: the muscle-specific Obscurin/Titin-Binding-related Domain (OTBD) binds plectin and filamin C. Exp Cell Res. 2011;317:724-36 pubmed publisher
    ..In striated muscle, tissue-dependent alternative splicing generates unique Ank3 gene products (ankyrins-G); they share the Obscurin/Titin-Binding-related Domain (OTBD), a muscle-specific insert ..
  15. Kosaka T, Komada M, Kosaka K. Sodium channel cluster, betaIV-spectrin and ankyrinG positive "hot spots" on dendritic segments of parvalbumin-containing neurons and some other neurons in the mouse and rat main olfactory bulbs. Neurosci Res. 2008;62:176-86 pubmed publisher
    ..Our study suggested that these morphologically identified dendritic "hot spots" might correspond to dendritic spike generation sites of those neurons. ..
  16. Geisler S, Green K, Isom L, Meshinchi S, Martens J, Delmar M, et al. Ordered assembly of the adhesive and electrochemical connections within newly formed intercalated disks in primary cultures of adult rat cardiomyocytes. J Biomed Biotechnol. 2010;2010:624719 pubmed publisher
    ..Defining the relationships that are the foundation of disk assembly has important implications for understanding the mechanical dysfunction and cardiac arrhythmias that accompany alterations of ID architecture. ..
  17. van Beuningen S, Will L, Harterink M, Chazeau A, van Battum E, Frias C, et al. TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays. Neuron. 2015;88:1208-1226 pubmed publisher
    ..Thus, TRIM46 defines a unique axonal cytoskeletal compartment for regulating microtubule organization during neuronal development. ..
  18. Papandréou M, Vacher H, Fache M, Klingler E, Rueda Boroni F, Ferracci G, et al. CK2-regulated schwannomin-interacting protein IQCJ-SCHIP-1 association with AnkG contributes to the maintenance of the axon initial segment. J Neurochem. 2015;134:527-37 pubmed publisher
    ..Overexpressed IQCJ-SCHIP-1 decreased AnkG concentration at the AIS whereas a mutant deleted of the CK2-regulated AnkG interaction site did not. Thus, CK2-regulated IQJC-SCHIP-1 association with AnkG contributes to AIS maintenance. ..
  19. Gumy L, Katrukha E, Grigoriev I, Jaarsma D, Kapitein L, Akhmanova A, et al. MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent Cargo Transport in Sensory Neurons. Neuron. 2017;94:347-362.e7 pubmed publisher
    ..We propose that selective axonal cargo trafficking requires the MAP2-defined pre-axonal filtering zone and the ability of cargos to switch between distinct kinesin motor activities. ..
  20. Hund T, Koval O, Li J, Wright P, Qian L, Snyder J, et al. A ?(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest. 2010;120:3508-19 pubmed publisher
    ..Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain. ..
  21. Chen Z, Chen S, Chen L, Zhou J, Dai Q, Yang L, et al. Long-term increasing co-localization of SCN8A and ankyrin-G in rat hippocampal cornu ammonis 1 after pilocarpine induced status epilepticus. Brain Res. 2009;1270:112-20 pubmed publisher
    ..310, P<0.001). The data revealed that both SCN8A and ankyrin-G increased significantly in the CA1 subfield of the rat hippocampus 60 days following pilocarpine induced status epilepticus and co-localized with each other. ..
  22. Gagelin C, Constantin B, Deprette C, Ludosky M, Recouvreur M, Cartaud J, et al. Identification of Ank(G107), a muscle-specific ankyrin-G isoform. J Biol Chem. 2002;277:12978-87 pubmed
    We previously showed that alternatively spliced ankyrins-G, the Ank3 gene products, are expressed in skeletal muscle and localize to the postsynaptic folds and to the sarcoplasmic reticulum...
  23. Reeves T, Greer J, Vanderveer A, Phillips L. Proteolysis of submembrane cytoskeletal proteins ankyrin-G and ?II-spectrin following diffuse brain injury: a role in white matter vulnerability at Nodes of Ranvier. Brain Pathol. 2010;20:1055-68 pubmed publisher
    ..The time course of such changes were comparable to previously observed functional deficits in callosal fibers. ..
  24. Feinberg K, Eshed Eisenbach Y, Frechter S, Amor V, Salomon D, Sabanay H, et al. A glial signal consisting of gliomedin and NrCAM clusters axonal Na+ channels during the formation of nodes of Ranvier. Neuron. 2010;65:490-502 pubmed publisher
    ..Together, these two cooperating mechanisms ensure fast and efficient conduction in myelinated nerves. ..
  25. Kizhatil K, Davis J, Davis L, Hoffman J, Hogan B, Bennett V. Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos. J Biol Chem. 2007;282:26552-61 pubmed
    ..Biol. Chem. 282, 2029-2037 ). Together with the current findings, these data suggest a ankyrin/spectrin-based mechanism for coordinating membrane assembly with extracellular interactions of E-cadherin at sites of cell-cell contact. ..
  26. Glynn P, Musa H, Wu X, Unudurthi S, Little S, Qian L, et al. Voltage-Gated Sodium Channel Phosphorylation at Ser571 Regulates Late Current, Arrhythmia, and Cardiac Function In Vivo. Circulation. 2015;132:567-77 pubmed publisher
    ..Relevant for improved rational design of potential therapies, our findings demonstrate that Ser571-dependent regulation of Nav1.5 specifically tunes INa,L without altering critical physiological components of the current. ..
  27. Bouzidi M, Tricaud N, Giraud P, Kordeli E, Caillol G, Deleuze C, et al. Interaction of the Nav1.2a subunit of the voltage-dependent sodium channel with nodal ankyrinG. In vitro mapping of the interacting domains and association in synaptosomes. J Biol Chem. 2002;277:28996-9004 pubmed
    ..However, we could not find conditions that allowed for co-immunoprecipitation of ankyrin with the sodium channel beta(1) subunit. ..
  28. Akin E, Solé L, Dib Hajj S, Waxman S, Tamkun M. Preferential targeting of Nav1.6 voltage-gated Na+ Channels to the axon initial segment during development. PLoS ONE. 2015;10:e0124397 pubmed publisher
    ..6 insertion into the AIS plasma membrane. In contrast, ankyrinG-binding alone does not confer the preferential delivery of proteins to the AIS. ..
  29. Van Wart A, Boiko T, Trimmer J, Matthews G. Novel clustering of sodium channel Na(v)1.1 with ankyrin-G and neurofascin at discrete sites in the inner plexiform layer of the retina. Mol Cell Neurosci. 2005;28:661-73 pubmed
    ..2 to Na(v)1.6 at nodes of Ranvier and initial segments. This represents the first instance of high-density clustering of Na(v)1.1 channels, which may contribute to synaptic interactions among retinal neurons in the inner plexiform layer. ..
  30. Bongenhielm U, Nosrat C, Nosrat I, Eriksson J, Fjell J, Fried K. Expression of sodium channel SNS/PN3 and ankyrin(G) mRNAs in the trigeminal ganglion after inferior alveolar nerve injury in the rat. Exp Neurol. 2000;164:384-95 pubmed
  31. Jenkins P, Kim N, Jones S, Tseng W, Svitkina T, Yin H, et al. Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling. Proc Natl Acad Sci U S A. 2015;112:957-64 pubmed publisher I-connectin/Titin and was acquired after the first round of whole-genome duplication by the ancestral ANK2/ANK3 gene in early vertebrates before development of myelin...
  32. Wang C, Wei Z, Chen K, Ye F, Yu C, Bennett V, et al. Structural basis of diverse membrane target recognitions by ankyrins. elife. 2014;3: pubmed publisher
    ..These structures establish a framework for understanding the evolution of ankyrins' membrane targets, with implications for other proteins containing extended ANK repeat domains. ..
  33. Lopez C, Metral S, Eladari D, Drevensek S, Gane P, Chambrey R, et al. The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells. J Biol Chem. 2005;280:8221-8 pubmed
  34. Hopitzan A, Baines A, Ludosky M, Recouvreur M, Kordeli E. Ankyrin-G in skeletal muscle: tissue-specific alternative splicing contributes to the complexity of the sarcolemmal cytoskeleton. Exp Cell Res. 2005;309:86-98 pubmed
    ..There has been no systematic analysis of the diversity of expression of ankyrins-G, the widely expressed Ank3 gene products, in a complex tissue. We previously described Ank(G107), the first muscle-specific ankyrin-G...
  35. Xu M, Cao R, Xiao R, Zhu M, Gu C. The axon-dendrite targeting of Kv3 (Shaw) channels is determined by a targeting motif that associates with the T1 domain and ankyrin G. J Neurosci. 2007;27:14158-70 pubmed
    ..interaction of a C-terminal axonal targeting motif (ATM) with the N-terminal T1 domain and adaptor protein ankyrin G. In cultured hippocampal neurons, although the two splice variants of Kv3.1, Kv3.1a and Kv3...
  36. 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
    ..precise accumulation of sodium channels at the axonal initial segment (AIS) and in the nodes of Ranvier through ankyrin G scaffolding. We found that the ankyrin-binding motif of Na(v)1...
  37. Gasser A, Ho T, Cheng X, Chang K, Waxman S, Rasband M, et al. An ankyrinG-binding motif is necessary and sufficient for targeting Nav1.6 sodium channels to axon initial segments and nodes of Ranvier. J Neurosci. 2012;32:7232-43 pubmed publisher
    ..Thus, the ankyrinG-binding motif is both necessary and sufficient for the clustering of sodium channels at nodes of Ranvier and the AIS. ..
  38. 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 effect of the ANK3 genotype on the mRNA expression level was tested in postmortem human brain...
  39. Fujiwara Y, Kondo H, Shirota M, Kobayashi M, Takeshita K, Nakagawa A, et al. Structural basis for the membrane association of ankyrinG via palmitoylation. Sci Rep. 2016;6:23981 pubmed publisher
    ..This suggests that AnkG in the juxtamembrane region is primed to accept lipid modification at Cys, and once that happens AnkG constitutes a rigid structural base upon which a membrane-excitation platform can be assembled. ..
  40. Needham L, Thelen K, Maness P. Cytoplasmic domain mutations of the L1 cell adhesion molecule reduce L1-ankyrin interactions. J Neurosci. 2001;21:1490-500 pubmed