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 . Physiological Reviews . 81 . 3 . 1353–1392 . July 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 . 597–599 . October 1979 . 492324 . 10.1038/281597a0 . 263106 . 1979Natur.281..597B .
• Lambert S, Yu H, Prchal JT, Lawler J, Ruff P, Speicher D, Cheung MC, Kan YW, Palek J . cDNA sequence for human erythrocyte ankyrin . Proceedings of the National Academy of Sciences of the United States of America . 87 . 5 . 1730–1734 . March 1990 . 1689849 . 53556 . 10.1073/pnas.87.5.1730 . free . 1990PNAS...87.1730L .
• Fujimoto T, Lee K, Miwa S, Ogawa K . Immunocytochemical localization of fodrin and ankyrin in bovine chromaffin cells in vitro . The Journal of Histochemistry and Cytochemistry . 39 . 11 . 1485–1493 . November 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 . March 1990 . 2137557 . 10.1038/344036a0 . 4351060 . 1990Natur.344...36L .
• Davis LH, Bennett V . Mapping the binding sites of human erythrocyte ankyrin for the anion exchanger and spectrin . The Journal of Biological Chemistry . 265 . 18 . 10589–10596 . June 1990 . 2141335 . 10.1016/S0021-9258(18)86987-3 . free .
• Korsgren C, Cohen CM . Associations of human erythrocyte band 4.2. Binding to ankyrin and to the cytoplasmic domain of band 3 . The Journal of Biological Chemistry . 263 . 21 . 10212–10218 . July 1988 . 2968981 . 10.1016/S0021-9258(19)81500-4 . free .
• Cianci CD, Giorgi M, Morrow JS . Phosphorylation of ankyrin down-regulates its cooperative interaction with spectrin and protein 3 . Journal of Cellular Biochemistry . 37 . 3 . 301–315 . July 1988 . 2970468 . 10.1002/jcb.240370305 . 42349239 .
• Steiner JP, Bennett V . Ankyrin-independent membrane protein-binding sites for brain and erythrocyte spectrin . The Journal of Biological Chemistry . 263 . 28 . 14417–14425 . October 1988 . 2971657 . 10.1016/S0021-9258(18)68236-5 . free .
• Daniel Branton . Hargreaves WR, Giedd KN, Verkleij A, Branton D . Reassociation of ankyrin with band 3 in erythrocyte membranes and in lipid vesicles . The Journal of Biological Chemistry . 255 . 24 . 11965–11972 . December 1980 . 6449514 . 10.1016/S0021-9258(19)70228-2 . free .
• Bourguignon LY, Lokeshwar VB, Chen X, Kerrick WG . Hyaluronic acid-induced lymphocyte signal transduction and HA receptor (GP85/CD44)-cytoskeleton interaction . Journal of Immunology . 151 . 12 . 6634–6644 . December 1993 . 7505012 . 10.4049/jimmunol.151.12.6634 . 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 . 171–174 . January 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 . Journal of Cell Science . 105 . 4 . 1137–1142 . August 1993 . 8227202 . 10.1242/jcs.105.4.1137 . 105 .
• Bourguignon LY, Jin H, Iida N, Brandt NR, Zhang SH . 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 . The Journal of Biological Chemistry . 268 . 10 . 7290–7297 . April 1993 . 8385102 . 10.1016/S0021-9258(18)53175-6 . free .
• Eber SW, Gonzalez JM, Lux ML, Scarpa AL, Tse WT, Dornwell M, Herbers J, Kugler W, Ozcan R, Pekrun A, Gallagher PG, Schröter W, Forget BG, Lux SE . Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis . Nature Genetics . 13 . 2 . 214–218 . June 1996 . 8640229 . 10.1038/ng0696-214 . 10946374 .
• Lanfranchi G, Muraro T, Caldara F, Pacchioni B, Pallavicini A, Pandolfo D, Toppo S, Trevisan S, Scarso S, Valle G . Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization . Genome Research . 6 . 1 . 35–42 . January 1996 . 8681137 . 10.1101/gr.6.1.35 . free .
• del Giudice EM, Hayette S, Bozon M, Perrotta S, Alloisio N, Vallier A, Iolascon A, Delaunay J, Morlé L . Ankyrin Napoli: a de novo deletional frameshift mutation in exon 16 of ankyrin gene (ANK1) associated with spherocytosis . British Journal of Haematology . 93 . 4 . 828–834 . June 1996 . 8703812 . 10.1046/j.1365-2141.1996.d01-1746.x . 28906962 .
• Zhou D, Birkenmeier CS, Williams MW, Sharp JJ, Barker JE, Bloch RJ . Small, membrane-bound, alternatively spliced forms of ankyrin 1 associated with the sarcoplasmic reticulum of mammalian skeletal muscle . The Journal of Cell Biology . 136 . 3 . 621–631 . February 1997 . 9024692 . 2134284 . 10.1083/jcb.136.3.621 .
• Gallagher PG, Tse WT, Scarpa AL, Lux SE, Forget BG . Structure and organization of the human ankyrin-1 gene. Basis for complexity of pre-mRNA processing . The Journal of Biological Chemistry . 272 . 31 . 19220–19228 . August 1997 . 9235914 . 10.1074/jbc.272.31.19220 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .

Notes and References

1. Lambert S, Yu H, Prchal JT, Lawler J, Ruff P, Speicher D, Cheung MC, Kan YW, Palek J . cDNA sequence for human erythrocyte ankyrin . Proceedings of the National Academy of Sciences of the United States of America . 87 . 5 . 1730–1734 . March 1990 . 1689849 . 53556 . 10.1073/pnas.87.5.1730 . free . 1990PNAS...87.1730L .
2. Web site: Entrez Gene: ANK1 ankyrin 1, erythrocytic.
3. De Jager PL, Srivastava G, Lunnon K, Burgess J, Schalkwyk LC, Yu L, Eaton ML, Keenan BT, Ernst J, McCabe C, Tang A, Raj T, Replogle J, Brodeur W, Gabriel S, Chai HS, Younkin C, Younkin SG, Zou F, Szyf M, Epstein CB, Schneider JA, Bernstein BE, Meissner A, Ertekin-Taner N, Chibnik LB, Kellis M, Mill J, Bennett DA . Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci . Nature Neuroscience . 17 . 9 . 1156–1163 . September 2014 . 25129075 . 4292795 . 10.1038/nn.3786 .
4. Lunnon K, Smith R, Hannon E, De Jager PL, Srivastava G, Volta M, Troakes C, Al-Sarraj S, Burrage J, Macdonald R, Condliffe D, Harries LW, Katsel P, Haroutunian V, Kaminsky Z, Joachim C, Powell J, Lovestone S, Bennett DA, Schalkwyk LC, Mill J . Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease . Nature Neuroscience . 17 . 9 . 1164–1170 . September 2014 . 25129077 . 4410018 . 10.1038/nn.3782 .
5. Liscovitch N, French L . Differential Co-Expression between α-Synuclein and IFN-γ Signaling Genes across Development and in Parkinson's Disease . PLOS ONE . 9 . 12 . e115029 . 2014 . 25493648 . 4262449 . 10.1371/journal.pone.0115029 . free . 2014PLoSO...9k5029L .
6. Borzok MA, Catino DH, Nicholson JD, Kontrogianni-Konstantopoulos A, Bloch RJ . Mapping the binding site on small ankyrin 1 for obscurin . The Journal of Biological Chemistry . 282 . 44 . 32384–32396 . November 2007 . 17720975 . 10.1074/jbc.M704089200 . free .
7. Bourguignon LY, Zhu H, Shao L, Chen YW . Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration . The Journal of Cell Biology . 150 . 1 . 177–191 . July 2000 . 10893266 . 2185563 . 10.1083/jcb.150.1.177 .
8. Kontrogianni-Konstantopoulos A, Bloch RJ . The hydrophilic domain of small ankyrin-1 interacts with the two N-terminal immunoglobulin domains of titin . The Journal of Biological Chemistry . 278 . 6 . 3985–3991 . February 2003 . 12444090 . 10.1074/jbc.M209012200 . free .
9. Nicolas V, Le Van Kim C, Gane P, Birkenmeier C, Cartron JP, Colin Y, Mouro-Chanteloup I . Rh-RhAG/ankyrin-R, a new interaction site between the membrane bilayer and the red cell skeleton, is impaired by Rh(null)-associated mutation . The Journal of Biological Chemistry . 278 . 28 . 25526–25533 . July 2003 . 12719424 . 10.1074/jbc.M302816200 . free .
10. Kontrogianni-Konstantopoulos A, Jones EM, Van Rossum DB, Bloch RJ . Obscurin is a ligand for small ankyrin 1 in skeletal muscle . Molecular Biology of the Cell . 14 . 3 . 1138–1148 . March 2003 . 12631729 . 151585 . 10.1091/mbc.E02-07-0411 .