Genomes and Genes
Gene Symbol: CRYAA
Description: crystallin alpha A
Alias: CRYA1, CTRCT9, HSPB4, alpha-crystallin A chain, crystallin, alpha-1, heat shock protein beta-4, human alphaA-crystallin (CRYA1)
- Sreelakshmi Y, Sharma K. Recognition sequence 2 (residues 60-71) plays a role in oligomerization and exchange dynamics of alphaB-crystallin. Biochemistry. 2005;44:12245-52 pubmed..Our results establish the importance of residues 60-71 in oligomerization of alphaB-crystallin and subunit interaction between alphaB- and alphaA-crystallins. ..
- Li F, Yang M, Ma X, Zhang Q, Zhang M, Wang S, et al. Autosomal dominant congenital nuclear cataracts caused by a CRYAA gene mutation. Curr Eye Res. 2010;35:492-8 pubmed publisher..Genetic analysis revealed a heterozygous previously described Arg116Cys mutation in the CRYAA gene in all of the affected members of the family but not in unaffected or 100 normal, unrelated individuals...
- Sun W, Xiao X, Li S, Guo X, Zhang Q. Mutational screening of six genes in Chinese patients with congenital cataract and microcornea. Mol Vis. 2011;17:1508-13 pubmed..To identify mutations in 6 genes of 9 Chinese families with congenital cataract and microcornea...
- Hanson S, Hasan A, Smith D, Smith J. The major in vivo modifications of the human water-insoluble lens crystallins are disulfide bonds, deamidation, methionine oxidation and backbone cleavage. Exp Eye Res. 2000;71:195-207 pubmed
- Sun W, Xiao X, Li S, Guo X, Zhang Q. Mutation analysis of 12 genes in Chinese families with congenital cataracts. Mol Vis. 2011;17:2197-206 pubmed..and adjacent intronic regions of 12 genes were analyzed by cycle sequencing, including the alpha A crystallin (CRYAA), alpha B crystallin (CRYAB), beta A1 crystallin (CRYBA1), beta A4 crystallin (CRYBA4), beta B1 crystallin (CRYBB1)..
- Gu F, Luo W, Li X, Wang Z, Lu S, Zhang M, et al. A novel mutation in AlphaA-crystallin (CRYAA) caused autosomal dominant congenital cataract in a large Chinese family. Hum Mutat. 2008;29:769 pubmed publisher..43 and 4.27 at theta=0) were obtained for markers D21S1411 and D21S1890 on chromosome 21q22.3, flanking the CRYAA (alphaA-crystallin-encoding gene) locus. Sequencing of CRYAA revealed a novel heterozygous G>A transition (c...
- Singh D, Raman B, Ramakrishna T, Rao C. Mixed oligomer formation between human alphaA-crystallin and its cataract-causing G98R mutant: structural, stability and functional differences. J Mol Biol. 2007;373:1293-304 pubmed
- Andley U, Mathur S, Griest T, Petrash J. Cloning, expression, and chaperone-like activity of human alphaA-crystallin. J Biol Chem. 1996;271:31973-80 pubmed
- Miesbauer L, Zhou X, Yang Z, Sun Y, Smith D, Smith J. Post-translational modifications of water-soluble human lens crystallins from young adults. J Biol Chem. 1994;269:12494-502 pubmed..This mass spectrometric characterization of the total water-soluble proteins from normal young adult lenses provides a reference data base for future investigations of the modifications present in aged and cataractous lenses. ..
- Beby F, Commeaux C, Bozon M, Denis P, Edery P, Morlé L. New phenotype associated with an Arg116Cys mutation in the CRYAA gene: nuclear cataract, iris coloboma, and microphthalmia. Arch Ophthalmol. 2007;125:213-6 pubmedTo describe a new phenotype with an arginine-to-cysteine mutation at position 116 (Arg116Cys) in the CRYAA gene...
- Kondo Y, Saitsu H, Miyamoto T, Lee B, Nishiyama K, Nakashima M, et al. Pathogenic mutations in two families with congenital cataract identified with whole-exome sequencing. Mol Vis. 2013;19:384-9 pubmed..The detected variants were confirmed with direct sequencing. WES readily identified a CRYAA mutation in family A and a CRYGC mutation in family B. The c.61C>T (p...
- Pang M, Su J, Feng S, Tang Z, Gu F, Zhang M, et al. Effects of congenital cataract mutation R116H on alphaA-crystallin structure, function and stability. Biochim Biophys Acta. 2010;1804:948-56 pubmed publisher..These results suggested that both the aggregation of the mutant upon stress and co-deposition with the target proteins were likely to be responsible for the onset of cataract. ..
- Su D, Guo Y, Li Q, Guan L, Zhu S, Ma X. A novel mutation in CRYAA is associated with autosomal dominant suture cataracts in a Chinese family. Mol Vis. 2012;18:3057-63 pubmed..Direct sequencing revealed a c.161G>C transversion in exon 1 of crystallin, alpha A (CRYAA)...
- Mao Y, Liu J, Xiang H, Li D. Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. Cell Death Differ. 2004;11:512-26 pubmed..Thus, our results demonstrate a novel antiapoptotic mechanism for alpha-crystallins. ..
- Bera S, Thampi P, Cho W, Abraham E. A positive charge preservation at position 116 of alpha A-crystallin is critical for its structural and functional integrity. Biochemistry. 2002;41:12421-6 pubmed..Thus, a positive charge must be preserved at this position for the structural and functional integrity of alphaA-crystallin. ..
- Thampi P, Hassan A, Smith J, Abraham E. Enhanced C-terminal truncation of alphaA- and alphaB-crystallins in diabetic lenses. Invest Ophthalmol Vis Sci. 2002;43:3265-72 pubmed..Loss of alphaA-crystallin chaperone activity seems to be related to truncation of the C-terminal amino acid residues. ..
- Litt M, Kramer P, LaMorticella D, Murphey W, Lovrien E, Weleber R. Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Hum Mol Genet. 1998;7:471-4 pubmed..We have mapped an ADCC gene in family ADCC-2 to chromosome 21q22.3 near the alpha-crystallin gene CRYAA. By sequencing the coding regions of CRYAA, we found that a missense mutation, R116C, is associated with ADCC in ..
- Murugesan R, Santhoshkumar P, Sharma K. Cataract-causing alphaAG98R mutant shows substrate-dependent chaperone activity. Mol Vis. 2007;13:2301-9 pubmed..The accumulation of mutant protein-substrate complexes may be the reason for cataract development in individuals carrying the G98R mutation in alphaA-crystallin. ..
- Ahmad M, Singh D, Taiyab A, Ramakrishna T, Raman B, Rao C. Selective Cu2+ binding, redox silencing, and cytoprotective effects of the small heat shock proteins alphaA- and alphaB-crystallin. J Mol Biol. 2008;382:812-24 pubmed publisher..Thus, our study ascribes a novel functional role to alpha-crystallins in Cu(2+) homeostasis and helps in understanding their protective role in neurodegenerative diseases and cataract. ..
- Mackay D, Andley U, Shiels A. Cell death triggered by a novel mutation in the alphaA-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q. Eur J Hum Genet. 2003;11:784-93 pubmed..The alphaA-crystallin (CRYAA) gene (CRYAA) encodes a member of the small-heat-shock protein (sHSP) family of molecular chaperones and is ..
- Graw J, Klopp N, Illig T, Preising M, Lorenz B. Congenital cataract and macular hypoplasia in humans associated with a de novo mutation in CRYAA and compound heterozygous mutations in P. Graefes Arch Clin Exp Ophthalmol. 2006;244:912-9 pubmed..Blood was taken from the proband and his parents, genomic DNA was isolated and some candidate genes for cataract (CRYAA, CRYBB2, GJA8) or macular hypoplasia (OA1, P) or both (PAX6) were analyzed...
- Koteiche H, McHaourab H. Mechanism of a hereditary cataract phenotype. Mutations in alphaA-crystallin activate substrate binding. J Biol Chem. 2006;281:14273-9 pubmed
- Devi R, Yao W, Vijayalakshmi P, Sergeev Y, Sundaresan P, Hejtmancik J. Crystallin gene mutations in Indian families with inherited pediatric cataract. Mol Vis. 2008;14:1157-70 pubmed..Genetic analysis was extended to screen the entire coding region of the CRYAA, CRYAB, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, and CRYGS genes using single stranded conformational ..
- Richter L, Flodman P, Barria von Bischhoffshausen F, Burch D, Brown S, Nguyen L, et al. Clinical variability of autosomal dominant cataract, microcornea and corneal opacity and novel mutation in the alpha A crystallin gene (CRYAA). Am J Med Genet A. 2008;146A:833-42 pubmed publisher..were designed for the three coding exons, including intron-exon borders, of the candidate gene alpha A crystallin (CRYAA)...
- Hawkins J, Van Keuren M, Piatigorsky J, Law M, Patterson D, Kao F. Confirmation of assignment of the human alpha 1-crystallin gene (CRYA1) to chromosome 21 with regional localization to q22.3. Hum Genet. 1987;76:375-80 pubmed..The alpha-crystallin gene family consists of alpha 1-crystallin (CRYA1) and alpha 2-crystallin (CRYA2) genes (previously designated alpha A- and alpha B-crystallin, respectively), which ..
- Fujii N, Nakamura T, Sadakane Y, Saito T, Fujii N. Differential susceptibility of alpha A- and alpha B-crystallin to gamma-ray irradiation. Biochim Biophys Acta. 2007;1774:345-50 pubmed..5 kGy. Our results indicate that alpha A-crystallin is more stable to gamma irradiation than alpha B-crystallin. ..
- Biswas A, Miller A, Oya Ito T, Santhoshkumar P, Bhat M, Nagaraj R. Effect of site-directed mutagenesis of methylglyoxal-modifiable arginine residues on the structure and chaperone function of human alphaA-crystallin. Biochemistry. 2006;45:4569-77 pubmed
- Fu L, Liang J. Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay. J Biol Chem. 2002;277:4255-60 pubmed..These results show that the two-hybrid system can detect interactions among various crystallins and may be used in mapping interaction domains. ..
- Singh D, Raman B, Ramakrishna T, Rao C. The cataract-causing mutation G98R in human alphaA-crystallin leads to folding defects and loss of chaperone activity. Mol Vis. 2006;12:1372-9 pubmed..Tendency to aggregate and loss of chaperone activity could be contributing to turbidity and loss of transparency of the lens. ..
- Swaim C, Smith D, Smith J. The reaction of alpha-crystallin with the cross-linker 3,3'-dithiobis(sulfosuccinimidyl propionate) demonstrates close proximity of the C termini of alphaA and alphaB in the native assembly. Protein Sci. 2004;13:2832-5 pubmed..This cross-link provides experimental evidence supporting theoretical structural models that place the C termini of alphaA and alphaB within close proximity in the native aggregate. ..
- Kumarasamy A, Abraham E. Interaction of C-terminal truncated human alphaA-crystallins with target proteins. PLoS ONE. 2008;3:e3175 pubmed publisher..The predominantly hydrophilic flexible arm appears to be needed to keep the chaperone-target protein complex soluble. ..
- Fu L, Liang J. Alteration of protein-protein interactions of congenital cataract crystallin mutants. Invest Ophthalmol Vis Sci. 2003;44:1155-9 pubmed..The current study extends those findings to the following crystallin genes involved in some congenital cataracts: CRYAA (R116C), CRYAB (R120G), and CRYGC (T5P)...
- Heys K, Friedrich M, Truscott R. Presbyopia and heat: changes associated with aging of the human lens suggest a functional role for the small heat shock protein, alpha-crystallin, in maintaining lens flexibility. Aging Cell. 2007;6:807-15 pubmed..Presbyopia may be the result of a loss of alpha-crystallin coupled with progressive heat-induced denaturation of structural proteins in the lens during the first five decades of life...
- Lindner R, Kapur A, Carver J. The interaction of the molecular chaperone, alpha-crystallin, with molten globule states of bovine alpha-lactalbumin. J Biol Chem. 1997;272:27722-9 pubmed..e. the protein must be in a disordered molten globule state for a significant length of time and on the pathway to aggregation and precipitation for interaction to occur. ..
- Raju I, Abraham E. Congenital cataract causing mutants of ?A-crystallin/sHSP form aggregates and aggresomes degraded through ubiquitin-proteasome pathway. PLoS ONE. 2011;6:e28085 pubmed publisher..The mutant, R116C protein degraded faster than wild-type control and increased ubiquitination was evident in R116C expressing cells. ..
- Deng M, Chen P, Xie S, Zhao J, Gong L, Liu J, et al. The small heat shock protein alphaA-crystallin is expressed in pancreas and acts as a negative regulator of carcinogenesis. Biochim Biophys Acta. 2010;1802:621-31 pubmed publisher..Finally, expression of alphaA-crystallin in a pancreatic cancer cell line, MiaPaCa, results in retarded cell migration. Together, these results suggest that alphaA-crystallin seems to negatively regulate pancreatic carcinogenesis...
- Bhagyalaxmi S, Srinivas P, Barton K, Kumar K, Vidyavathi M, Petrash J, et al. A novel mutation (F71L) in alphaA-crystallin with defective chaperone-like function associated with age-related cataract. Biochim Biophys Acta. 2009;1792:974-81 pubmed publisher..In the present work, we identified a genetic variation (F71L) in the exon-2 of CRYAA (alphaA-crystallin) gene in three unrelated female sporadic cases among 711 ARC patients but not in 265 normal non-..
- de Jong W, Terwindt E, Bloemendal H. The amino acid sequence of the A chain of human alpha-crystallin. FEBS Lett. 1975;58:310-3 pubmed
- Khan A, Aldahmesh M, Meyer B. Recessive congenital total cataract with microcornea and heterozygote carrier signs caused by a novel missense CRYAA mutation (R54C). Am J Ophthalmol. 2007;144:949-952 pubmed..3, the region of the gene for the alpha-A component of alpha-crystallin (CRYAA), with a logarithm of odds (LOD) score of 2.5...
- Raju I, Oonthonpan L, Abraham E. Mutations in human ?A-crystallin/sHSP affect subunit exchange interaction with ?B-crystallin. PLoS ONE. 2012;7:e31421 pubmed publisher..Structural changes occurring in these mutants, as reported earlier, could be the underlying cause for the decreased interaction with ?B may contribute to development of congenital cataract. ..
- Gupta R, Srivastava O. Deamidation affects structural and functional properties of human alphaA-crystallin and its oligomerization with alphaB-crystallin. J Biol Chem. 2004;279:44258-69 pubmed
- Saha S, Das K. Relationship between chaperone activity and oligomeric size of recombinant human alphaA- and alphaB-crystallin: a tryptic digestion study. Proteins. 2004;57:610-7 pubmed..The results also suggest that the presence of the alpha-crystallin domain and hydrophobic clefts on the protein surface, which correlate poorly with oligomeric size, are important for chaperone function...
- Santana A, Waiswol M, Arcieri E, Cabral de Vasconcellos J, Barbosa de Melo M. Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal dominant congenital cataract in Brazilian families. Mol Vis. 2009;15:793-800 pubmed..The purpose of this study was to investigate mutations in alphaA-crystallin (CRYAA), gammaC-crystallin (CRYGC), and gammaD-crystallin (CRYGD) in Brazilian families with nuclear and lamellar ..
- Rao G, Santhoshkumar P, Sharma K. Anti-chaperone betaA3/A1(102-117) peptide interacting sites in human alphaB-crystallin. Mol Vis. 2008;14:666-74 pubmed..The binding of betaA3/A1(102-117) peptide to the chaperone site and the COOH-terminal extension of alphaB-crystallin may explain its anti-chaperone property. ..
- Biswas A, Goshe J, Miller A, Santhoshkumar P, Luckey C, Bhat M, et al. Paradoxical effects of substitution and deletion mutation of Arg56 on the structure and chaperone function of human alphaB-crystallin. Biochemistry. 2007;46:1117-27 pubmed
- Biswas A, Das K. Zn2+ enhances the molecular chaperone function and stability of alpha-crystallin. Biochemistry. 2008;47:804-16 pubmed..The implications of enhanced stability and molecular chaperone activity of alpha-crystallin in the presence of Zn2+ are discussed in terms of its role in the long-term maintenance of lens transparency and cataract formation. ..
- Andley U, Patel H, Xi J. The R116C mutation in alpha A-crystallin diminishes its protective ability against stress-induced lens epithelial cell apoptosis. J Biol Chem. 2002;277:10178-86 pubmed..We propose that the diminished protective ability of the R116C mutant in lens epithelial cells may contribute to the pathogenesis of cataract. ..
- Pasupuleti N, Matsuyama S, Voss O, Doseff A, Song K, Danielpour D, et al. The anti-apoptotic function of human ?A-crystallin is directly related to its chaperone activity. Cell Death Dis. 2010;1:e31 pubmed publisher..Together, our study results show that ?A-crystallin inhibits apoptosis by enhancing PI3K activity and inactivating phosphatase tensin homologue and that the antiapoptotic function is directly related to its chaperone activity. ..
- Rajaraman K, Raman B, Ramakrishna T, Rao C. Interaction of human recombinant alphaA- and alphaB-crystallins with early and late unfolding intermediates of citrate synthase on its thermal denaturation. FEBS Lett. 2001;497:118-23 pubmed
- Kore R, Hedges R, Oonthonpan L, Santhoshkumar P, Sharma K, Abraham E. Quaternary structural parameters of the congenital cataract causing mutants of ?A-crystallin. Mol Cell Biochem. 2012;362:93-102 pubmed publisher..Although a specific change in the ?A-crystallin behavior that is common to all the mutants was not evident, each mutant showed one or more perturbation as the end effect that leads to cataract. ..
- Hansen L, Yao W, Eiberg H, Kjaer K, Baggesen K, Hejtmancik J, et al. Genetic heterogeneity in microcornea-cataract: five novel mutations in CRYAA, CRYGD, and GJA8. Invest Ophthalmol Vis Sci. 2007;48:3937-44 pubmed..Three of these affected the crystallin, alpha-A gene (CRYAA), including two mutations (R12C and R21W) in the crystallin domain and one mutation (R116H) in the small heat ..
- Lampi K, Ma Z, Shih M, Shearer T, Smith J, Smith D, et al. Sequence analysis of betaA3, betaB3, and betaA4 crystallins completes the identification of the major proteins in young human lens. J Biol Chem. 1997;272:2268-75 pubmed..These studies were a prerequisite for future studies to determine how human lens proteins are altered during aging and cataract formation. ..
- Xi J, Bai F, Gross J, Townsend R, Menko A, Andley U. Mechanism of small heat shock protein function in vivo: a knock-in mouse model demonstrates that the R49C mutation in alpha A-crystallin enhances protein insolubility and cell death. J Biol Chem. 2008;283:5801-14 pubmedalphaA-crystallin (Cryaa/HSPB4) is a small heat shock protein and molecular chaperone that prevents nonspecific aggregation of denaturing proteins...