Ankyrin 1, also known as ANK-1, and erythrocyte ankyrin, is a
protein that in humans is encoded by the ANK1gene.[5][6]
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.[6]
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.[6]
Disease linkage
Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary
spherocytosis.[6]
ANK1 shows altered methylation and expression in Alzheimer's disease.[7][8] A gene expression study of postmortem brains has suggested ANK1 interacts with
interferon-γ signalling.[9]
Function
The ANK1 protein belongs to the
ankyrin family that are believed to link the integral
membrane proteins to the underlying
spectrin-
actincytoskeleton 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.[6]
The small ANK1 (sAnk1) protein splice variants makes contacts with
obscurin, a giant protein surrounding the contractile apparatus in
striated muscle.[10]
^De Jager, P. L.; 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. (2014).
"Alzheimer's disease: Early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci". Nature Neuroscience. 17 (9): 1156–63.
doi:
10.1038/nn.3786.
PMC4292795.
PMID25129075.
Lux SE, John KM, Bennett V (1990). "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.
Bibcode:
1990Natur.344...36L.
doi:
10.1038/344036a0.
PMID2137557.
S2CID4351060.
Cianci CD, Giorgi M, Morrow JS (1988). "Phosphorylation of ankyrin down-regulates its cooperative interaction with spectrin and protein 3". J. Cell. Biochem. 37 (3): 301–15.
doi:
10.1002/jcb.240370305.
PMID2970468.
S2CID42349239.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Morgans CW, Kopito RR (1993). "Association of the brain anion exchanger, AE3, with the repeat domain of ankyrin". J. Cell Sci. 105. ( Pt 4) (4): 1137–42.
doi:
10.1242/jcs.105.4.1137.
PMID8227202.
Eber SW, Gonzalez JM, Lux ML, et al. (1996). "Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis". Nat. Genet. 13 (2): 214–8.
doi:
10.1038/ng0696-214.
PMID8640229.
S2CID10946374.
del Giudice EM, Hayette S, Bozon M, et al. (1996). "Ankyrin Napoli: a de novo deletional frameshift mutation in exon 16 ankyrin gene (ANK1) associated with spherocytosis". Br. J. Haematol. 93 (4): 828–34.
doi:
10.1046/j.1365-2141.1996.d01-1746.x.
PMID8703812.
S2CID28906962.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56.
doi:
10.1016/S0378-1119(97)00411-3.
PMID9373149.