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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Ankyrin Repeat

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Disease relevance of Ankyrin Repeat

  • The three genes completely deleted were a homologue of dUTPase, a gene that encodes a protein containing ankyrin-like repeats and a homologue of the 5K gene of the vaccinia virus WR strain [1].
  • Vertebrate poxviruses encode numerous proteins with the ankyrin (ANK) repeat, protein-protein interaction motif but little is known about the role(s) of this large family of poxvirus proteins [2].
  • This splice variant of ANKHD1, which we designated as HIV-1 Vpr-binding ankyrin repeat protein (VBARP), does not contain the signature KH domain, and codes for only a single ankyrin repeat motif [3].

High impact information on Ankyrin Repeat

  • It shows a stack of six IkappaBalpha ankyrin repeats facing the C-terminal domains of the NF-kappaB Rel homology regions [4].
  • The structure of the IkappaBalpha ankyrin repeat domain, bound to a partially truncated NF-kappaB heterodimer (p50/ p65), has been determined by X-ray crystallography at 2.7 A resolution [4].
  • NPR1 was cloned using a map-based approach and was found to encode a novel protein containing ankyrin repeats [5].
  • Nrarp is a member of the Delta-Notch synexpression group and encodes a small protein containing two ankyrin repeats [6].
  • Pct1+ is related to, but distinct from, the res1+/sct1+ gene that also encodes a p85cdc10 partner. p73pct1 has centrally located ankyrin repeats and a putative amino-terminal DNA-binding domain that has extensive sequence similarity to the DNA-binding domains of the Saccharomyces cerevisiae SWI4 and MBP1 proteins [7].

Biological context of Ankyrin Repeat

  • The NH(2)-terminal region of myopalladin specifically binds to the cardiac ankyrin repeat protein (CARP), a nuclear protein involved in control of muscle gene expression [8].
  • In a search for interacting co-factors, a nuclear ankyrin-like repeat protein CARP (cardiac ankyrin repeat protein) was isolated from a rat neonatal heart cDNA library by yeast two-hybrid screening, using YB-1 as the bait [9].
  • Remarkably, transgenic overexpression of Lbh in mice throughout the embryonic myocardium from a cardiomyocyte-specific promoter of the cardiac ankyrin repeat protein gene (Carp/Ankrd1) models CHD reported in humans with partial trisomy 2p syndrome [10].
  • Results from the two-hybrid system indicated two binding sites for PP1c on M130: one site in the NH2-terminal 38 residues and a weaker site(s) in the ankyrin repeats region [11].
  • The ankyrin repeat domain (ARD) of ankyrin is responsible for binding IP3 receptor to CD44v10 at lipid rafts and subsequently triggering HA/CD44v10-mediated intracellular calcium (Ca2+) mobilization leading to a variety of endothelial cell functions such as nitric oxide (NO) production, cell adhesion and proliferation [12].

Anatomical context of Ankyrin Repeat


Associations of Ankyrin Repeat with chemical compounds

  • Integrin-linked kinase (ILK) is an ankyrin-repeat containing serine-threonine protein kinase capable of interacting with the cytoplasmic domains of integrin beta1, beta2, and beta3 subunits [16].
  • Shank contains multiple domains for protein-protein interaction including ankyrin repeats, an SH3 domain, a PSD-95/Dlg/ZO-1 domain, a sterile alpha motif domain, and a proline-rich region [17].
  • The alpha-helical D1 domain of the tobacco bZIP transcription factor BZI-1 interacts with the ankyrin-repeat protein ANK1 and is important for BZI-1 function, both in auxin signaling and pathogen response [18].
  • The second is just C-terminal to the Notch ankyrin repeats, overlapping or identical to two previously proposed nuclear localization sequences, in a domain we term PPD (potential phosphorylated domain) [19].
  • Synamon has seven ankyrin repeats at the NH(2) terminus followed by one src homology 3 domain and one PSD-95/Dlg-A/ZO-1 domain, and several proline-rich regions at the carboxyl terminus [20].

Gene context of Ankyrin Repeat

  • This report identifies two mutants that block uptake by blocking ubiquitination, these being mutant either for the ankyrin repeat protein Akr1p or for the redundant type I casein kinases Yck1p and Yck2p [21].
  • We discovered that ANKRA2, the closest paralogue of RFXANK, can substitute for RFXANK in the activation of MHC-II genes and that this ability is mediated by its ankyrin repeat domain (ARD) [22].
  • We demonstrate that the ankyrin repeats of Swi4 mediate the interaction with Clb2/Cdc28 kinase [23].
  • Akr1p, which contains six ankyrin repeats, was identified during a screen for mutations that displayed synthetic lethality with a mutant allele of the bud emergence gene BEM1 [24].
  • Transactivation by the activating regions of Swi6 is antagonised when either are combined with the central ankyrin repeat motifs [25].

Analytical, diagnostic and therapeutic context of Ankyrin Repeat


  1. Genomic analysis of a transposition-deletion variant of orf virus reveals a 3.3 kbp region of non-essential DNA. Fleming, S.B., Lyttle, D.J., Sullivan, J.T., Mercer, A.A., Robinson, A.J. J. Gen. Virol. (1995) [Pubmed]
  2. F-Box-Like Domains are Present in Most Poxvirus Ankyrin Repeat Proteins. Mercer, A.A., Fleming, S.B., Ueda, N. Virus Genes (2005) [Pubmed]
  3. Molecular and functional characterization of a novel splice variant of ANKHD1 that lacks the KH domain and its role in cell survival and apoptosis. Miles, M.C., Janket, M.L., Wheeler, E.D., Chattopadhyay, A., Majumder, B., Dericco, J., Schafer, E.A., Ayyavoo, V. FEBS J. (2005) [Pubmed]
  4. Structure of an IkappaBalpha/NF-kappaB complex. Jacobs, M.D., Harrison, S.C. Cell (1998) [Pubmed]
  5. The Arabidopsis NPR1 gene that controls systemic acquired resistance encodes a novel protein containing ankyrin repeats. Cao, H., Glazebrook, J., Clarke, J.D., Volko, S., Dong, X. Cell (1997) [Pubmed]
  6. Nrarp is a novel intracellular component of the Notch signaling pathway. Lamar, E., Deblandre, G., Wettstein, D., Gawantka, V., Pollet, N., Niehrs, C., Kintner, C. Genes Dev. (2001) [Pubmed]
  7. pct1+, which encodes a new DNA-binding partner of p85cdc10, is required for meiosis in the fission yeast Schizosaccharomyces pombe. Zhu, Y., Takeda, T., Nasmyth, K., Jones, N. Genes Dev. (1994) [Pubmed]
  8. Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. Bang, M.L., Mudry, R.E., McElhinny, A.S., Trombitás, K., Geach, A.J., Yamasaki, R., Sorimachi, H., Granzier, H., Gregorio, C.C., Labeit, S. J. Cell Biol. (2001) [Pubmed]
  9. CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway. Zou, Y., Evans, S., Chen, J., Kuo, H.C., Harvey, R.P., Chien, K.R. Development (1997) [Pubmed]
  10. Congenital heart disease reminiscent of partial trisomy 2p syndrome in mice transgenic for the transcription factor Lbh. Briegel, K.J., Baldwin, H.S., Epstein, J.A., Joyner, A.L. Development (2005) [Pubmed]
  11. Interactions of the subunits of smooth muscle myosin phosphatase. Hirano, K., Phan, B.C., Hartshorne, D.J. J. Biol. Chem. (1997) [Pubmed]
  12. CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signaling leading to nitric oxide production and endothelial cell adhesion and proliferation. Singleton, P.A., Bourguignon, L.Y. Exp. Cell Res. (2004) [Pubmed]
  13. Molecular cloning of cDNA encoding the 110 kDa and 21 kDa regulatory subunits of smooth muscle protein phosphatase 1M. Chen, Y.H., Chen, M.X., Alessi, D.R., Campbell, D.G., Shanahan, C., Cohen, P., Cohen, P.T. FEBS Lett. (1994) [Pubmed]
  14. Cardiac ankyrin repeat protein (CARP) expression in human and murine atherosclerotic lesions: activin induces CARP in smooth muscle cells. de Waard, V., van Achterberg, T.A., Beauchamp, N.J., Pannekoek, H., de Vries, C.J. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  15. Developmentally regulated expression of two members of the Nrarp family in zebrafish. Topczewska, J.M., Topczewski, J., Szostak, A., Solnica-Krezel, L., Hogan, B.L. Gene Expr. Patterns (2003) [Pubmed]
  16. Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Delcommenne, M., Tan, C., Gray, V., Rue, L., Woodgett, J., Dedhar, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  17. Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development. Lim, S., Naisbitt, S., Yoon, J., Hwang, J.I., Suh, P.G., Sheng, M., Kim, E. J. Biol. Chem. (1999) [Pubmed]
  18. The alpha-helical D1 domain of the tobacco bZIP transcription factor BZI-1 interacts with the ankyrin-repeat protein ANK1 and is important for BZI-1 function, both in auxin signaling and pathogen response. Kuhlmann, M., Horvay, K., Strathmann, A., Heinekamp, T., Fischer, U., Böttner, S., Dröge-Laser, W. J. Biol. Chem. (2003) [Pubmed]
  19. Identification of two binding regions for the suppressor of hairless protein within the intracellular domain of Drosophila notch. Le Gall, M., Giniger, E. J. Biol. Chem. (2004) [Pubmed]
  20. Synamon, a novel neuronal protein interacting with synapse-associated protein 90/postsynaptic density-95-associated protein. Yao, I., Hata, Y., Hirao, K., Deguchi, M., Ide, N., Takeuchi, M., Takai, Y. J. Biol. Chem. (1999) [Pubmed]
  21. Akr1p and the type I casein kinases act prior to the ubiquitination step of yeast endocytosis: Akr1p is required for kinase localization to the plasma membrane. Feng, Y., Davis, N.G. Mol. Cell. Biol. (2000) [Pubmed]
  22. New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis study. Krawczyk, M., Masternak, K., Zufferey, M., Barras, E., Reith, W. Mol. Cell. Biol. (2005) [Pubmed]
  23. The Saccharomyces cerevisiae Start-specific transcription factor Swi4 interacts through the ankyrin repeats with the mitotic Clb2/Cdc28 kinase and through its conserved carboxy terminus with Swi6. Siegmund, R.F., Nasmyth, K.A. Mol. Cell. Biol. (1996) [Pubmed]
  24. Interactions between the ankyrin repeat-containing protein Akr1p and the pheromone response pathway in Saccharomyces cerevisiae. Kao, L.R., Peterson, J., Ji, R., Bender, L., Bender, A. Mol. Cell. Biol. (1996) [Pubmed]
  25. Structural and functional architecture of the yeast cell-cycle transcription factor swi6. Sedgwick, S.G., Taylor, I.A., Adam, A.C., Spanos, A., Howell, S., Morgan, B.A., Treiber, M.K., Kanuga, N., Banks, G.R., Foord, R., Smerdon, S.J. J. Mol. Biol. (1998) [Pubmed]
  26. The novel ankyrin-repeat containing kinase ARCK-1 acts as a suppressor of the Spalten signaling pathway during Dictyostelium development. Aubry, L., Lee, S., Ravanel, K., Firtel, R.A. Dev. Biol. (2003) [Pubmed]
  27. Salicylic acid and NIM1/NPR1-independent gene induction by incompatible Peronospora parasitica in arabidopsis. Rairdan, G.J., Donofrio, N.M., Delaney, T.P. Mol. Plant Microbe Interact. (2001) [Pubmed]
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