Ankyrin-1 Explained

Ankyrin 1, also known as ANK-1, and erythrocyte ankyrin, is a protein that in humans is encoded by the ANK1 gene.^{[1] [2]}

Tissue distribution

The protein encoded by this gene, Ankyrin 1, is the prototype of the ankyrin family, was first discovered in erythrocytes, but since has also been found in brain and muscles.^[2]

Genetics

Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described, however, the precise functions of the various isoforms are not known. Alternative polyadenylation accounting for the different sized erythrocytic ankyrin 1 mRNAs, has also been reported. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified.^[2]

Disease linkage

Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis.^[2]

ANK1 shows altered methylation and expression in Alzheimer's disease.^{[3] [4]} A gene expression study of postmortem brains has suggested ANK1 interacts with interferon-γ signalling.^[5]

Function

The ANK1 protein belongs to the ankyrin family that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin-binding domain; and a carboxy-terminal regulatory domain, which is the least conserved and subject to variation.^[2]

The small ANK1 (sAnk1) protein splice variants makes contacts with obscurin, a giant protein surrounding the contractile apparatus in striated muscle.^[6]

Interactions

ANK1 has been shown to interact with T-cell lymphoma invasion and metastasis-inducing protein 1,^[7] Titin,^[8] RHAG^[9] and OBSCN.^[10]

See also

• Ankyrin

References

Further reading

• Bennett V, Baines AJ . Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. . Physiol. Rev. . 81 . 3 . 1353–92 . 2001 . 11427698 . 10.1152/physrev.2001.81.3.1353. 15307181 .
• Bennett V . Immunoreactive forms of human erythrocyte ankyrin are present in diverse cells and tissues. . Nature . 281 . 5732 . 597–9 . 1979 . 492324 . 10.1038/281597a0 . 1979Natur.281..597B . 263106 .
• Lambert S, Yu H, Prchal JT . cDNA sequence for human erythrocyte ankyrin. . Proc. Natl. Acad. Sci. U.S.A. . 87 . 5 . 1730–4 . 1990 . 1689849 . 10.1073/pnas.87.5.1730 . 53556 . etal. 1990PNAS...87.1730L. free .
• Fujimoto T, Lee K, Miwa S, Ogawa K . Immunocytochemical localization of fodrin and ankyrin in bovine chromaffin cells in vitro. . J. Histochem. Cytochem. . 39 . 11 . 1485–93 . 1991 . 1833445 . 10.1177/39.11.1833445. free .
• Lux SE, John KM, Bennett V . Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins. . Nature . 344 . 6261 . 36–42 . 1990 . 2137557 . 10.1038/344036a0 . 1990Natur.344...36L . 4351060 .
• Davis LH, Bennett V . Mapping the binding sites of human erythrocyte ankyrin for the anion exchanger and spectrin. . J. Biol. Chem. . 265 . 18 . 10589–96 . 1990 . 10.1016/S0021-9258(18)86987-3 . 2141335 . free .
• Korsgren C, Cohen CM . Associations of human erythrocyte band 4.2. Binding to ankyrin and to the cytoplasmic domain of band 3. . J. Biol. Chem. . 263 . 21 . 10212–8 . 1988 . 10.1016/S0021-9258(19)81500-4 . 2968981 . free .
• Cianci CD, Giorgi M, Morrow JS . Phosphorylation of ankyrin down-regulates its cooperative interaction with spectrin and protein 3. . J. Cell. Biochem. . 37 . 3 . 301–15 . 1988 . 2970468 . 10.1002/jcb.240370305 . 42349239 .
• Steiner JP, Bennett V . Ankyrin-independent membrane protein-binding sites for brain and erythrocyte spectrin. . J. Biol. Chem. . 263 . 28 . 14417–25 . 1988 . 10.1016/S0021-9258(18)68236-5 . 2971657 . free .
• Hargreaves WR, Giedd KN, Verkleij A, Branton D . Reassociation of ankyrin with band 3 in erythrocyte membranes and in lipid vesicles. . J. Biol. Chem. . 255 . 24 . 11965–72 . 1981 . 10.1016/S0021-9258(19)70228-2 . 6449514 . free .
• Bourguignon LY, Lokeshwar VB, Chen X, Kerrick WG . Hyaluronic acid-induced lymphocyte signal transduction and HA receptor (GP85/CD44)-cytoskeleton interaction. . J. Immunol. . 151 . 12 . 6634–44 . 1994 . 10.4049/jimmunol.151.12.6634 . 7505012 . 25287008 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Morgans CW, Kopito RR . Association of the brain anion exchanger, AE3, with the repeat domain of ankyrin. . 105 . J. Cell Sci. . (Pt 4) . 1137–42 . 1993 . 4 . 10.1242/jcs.105.4.1137 . 8227202 .
• Bourguignon LY, Jin H, Iida N . The involvement of ankyrin in the regulation of inositol 1,4,5-trisphosphate receptor-mediated internal Ca2+ release from Ca2+ storage vesicles in mouse T-lymphoma cells. . J. Biol. Chem. . 268 . 10 . 7290–7 . 1993 . 10.1016/S0021-9258(18)53175-6 . 8385102 . etal. free .
• Eber SW, Gonzalez JM, Lux ML . Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis. . Nat. Genet. . 13 . 2 . 214–8 . 1996 . 8640229 . 10.1038/ng0696-214 . 10946374 . etal.
• Lanfranchi G, Muraro T, Caldara F . Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization. . Genome Res. . 6 . 1 . 35–42 . 1996 . 8681137 . 10.1101/gr.6.1.35 . etal. free .
• del Giudice EM, Hayette S, Bozon M . Ankyrin Napoli: a de novo deletional frameshift mutation in exon 16 ankyrin gene (ANK1) associated with spherocytosis. . Br. J. Haematol. . 93 . 4 . 828–34 . 1996 . 8703812 . 10.1046/j.1365-2141.1996.d01-1746.x . 28906962 . etal.
• Zhou D, Birkenmeier CS, Williams MW . Small, membrane-bound, alternatively spliced forms of ankyrin 1 associated with the sarcoplasmic reticulum of mammalian skeletal muscle. . J. Cell Biol. . 136 . 3 . 621–31 . 1997 . 9024692 . 10.1083/jcb.136.3.621 . 2134284 . etal.
• Gallagher PG, Tse WT, Scarpa AL . Structure and organization of the human ankyrin-1 gene. Basis for complexity of pre-mRNA processing. . J. Biol. Chem. . 272 . 31 . 19220–8 . 1997 . 9235914 . 10.1074/jbc.272.31.19220 . etal. free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.

Notes and References

1. Lambert S, Yu H, Prchal JT . cDNA sequence for human erythrocyte ankyrin . Proc. Natl. Acad. Sci. U.S.A. . 87 . 5 . 1730–4 . March 1990 . 1689849 . 53556 . 10.1073/pnas.87.5.1730. etal. 1990PNAS...87.1730L . free .
2. Web site: Entrez Gene: ANK1 ankyrin 1, erythrocytic.
3. 25129075. 2014. De Jager. P. L.. Alzheimer's disease: Early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nature Neuroscience. 17. 9. 1156–63. Srivastava. G. Lunnon. K. Burgess. J. Schalkwyk. L. C.. Yu. L. Eaton. M. L.. Keenan. B. T.. Ernst. J. McCabe. C. Tang. A. Raj. T. Replogle. J. Brodeur. W. Gabriel. S. Chai. H. S.. Younkin. C. Younkin. S. G.. Zou. F. Szyf. M. Epstein. C. B.. Schneider. J. A.. Bernstein. B. E.. Meissner. A. Ertekin-Taner. N. Chibnik. L. B.. Kellis. M. Mill. J. Bennett. D. A.. 10.1038/nn.3786 . 4292795.
4. 25129077. 2014. Lunnon. K. Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nature Neuroscience. 17. 9. 1164–70. Smith. R. Hannon. E. De Jager. P. L.. Srivastava. G. Volta. M. Troakes. C. Al-Sarraj. S. Burrage. J. MacDonald. R. Condliffe. D. Harries. L. W.. Katsel. P. Haroutunian. V. Kaminsky. Z. Joachim. C. Powell. J. Lovestone. S. Bennett. D. A.. Schalkwyk. L. C.. Mill. J. 10.1038/nn.3782 . 4410018.
5. 25493648. 4262449. 2014. Liscovitch. N. Differential Co-Expression between α-Synuclein and IFN-γ Signaling Genes across Development and in Parkinson's Disease. PLOS ONE. 9. 12. e115029. French. L. 10.1371/journal.pone.0115029. 2014PLoSO...9k5029L. free.
6. Borzok MA, Catino DH, Nicholson JD, Kontrogianni-Konstantopoulos A, Bloch RJ . Mapping the binding site on small ankyrin 1 for obscurin . J. Biol. Chem. . 282 . 44 . 32384–96 . November 2007 . 17720975 . 10.1074/jbc.M704089200 . free .
7. 10.1083/jcb.150.1.177 . Bourguignon . L Y . Zhu H . Shao L . Chen Y W . July 2000 . Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration . J. Cell Biol. . 150 . 1 . 177–91 . 0021-9525. 10893266 . 2185563 .
8. Kontrogianni-Konstantopoulos . Aikaterini . Bloch Robert J . February 2003 . The hydrophilic domain of small ankyrin-1 interacts with the two N-terminal immunoglobulin domains of titin . J. Biol. Chem. . 278 . 6 . 3985–91 . 0021-9258. 12444090 . 10.1074/jbc.M209012200 . free .
9. Nicolas . Virginie . Le Van Kim . Caroline . Gane . Pierre . Birkenmeier . Connie . Cartron . Jean-Pierre . Colin . Yves . Mouro-Chanteloup . Isabelle . July 2003 . Rh-RhAG/ankyrin-R, a new interaction site between the membrane bilayer and the red cell skeleton, is impaired by Rh(null)-associated mutation . J. Biol. Chem. . 278 . 28 . 25526–33 . 0021-9258. 12719424 . 10.1074/jbc.M302816200 . free .
10. Kontrogianni-Konstantopoulos . Aikaterini . Jones Ellene M . Van Rossum Damian B . Bloch Robert J . March 2003 . Obscurin is a ligand for small ankyrin 1 in skeletal muscle . Mol. Biol. Cell . 14 . 3 . 1138–48 . 1059-1524. 12631729 . 10.1091/mbc.E02-07-0411 . 151585 .