Summary: A heterogeneous family of water-soluble structural proteins found in cells of the vertebrate lens. The presence of these proteins accounts for the transparency of the lens. The family is composed of four major groups, alpha, beta, gamma, and delta, and several minor groups, which are classed on the basis of size, charge, immunological properties, and vertebrate source. Alpha, beta, and delta crystallins occur in avian and reptilian lenses, while alpha, beta, and gamma crystallins occur in all other lenses.

Top Publications

  1. Papanikolopoulou K, Mills Henry I, Thol S, Wang Y, Gross A, Kirschner D, et al. Formation of amyloid fibrils in vitro by human gammaD-crystallin and its isolated domains. Mol Vis. 2008;14:81-9 pubmed
    ..Previous studies have shown that bovine crystallins form amyloid fibers under denaturing conditions and amyloid fibers accumulate in the lens of mice carrying ..
  2. Li H, Yao K, Jin H, Sun L, Lu D, Yu Y. Proteomic analysis of human lens epithelial cells exposed to microwaves. Jpn J Ophthalmol. 2007;51:412-6 pubmed
    ..HSP70 and hnRNP K are involved in the stress reaction of HLECs exposed to microwaves. These cell responses are nonthermal effects of the electromagnetic field. ..
  3. Aravind P, Wistow G, Sharma Y, Sankaranarayanan R. Exploring the limits of sequence and structure in a variant betagamma-crystallin domain of the protein absent in melanoma-1 (AIM1). J Mol Biol. 2008;381:509-18 pubmed publisher
    Betagamma-crystallins belong to a superfamily of proteins in prokaryotes and eukaryotes that are based on duplications of a characteristic, highly conserved Greek key motif...
  4. Huang B, He W. Molecular characteristics of inherited congenital cataracts. Eur J Med Genet. 2010;53:347-57 pubmed publisher
    ..Inherited congenital cataracts have been associated with mutations in specific genes, including those of crystallins, gap junction proteins, membrane transport and channel proteins, the cytoskeleton, and growth and transcription ..
  5. Lassen N, Black W, Estey T, Vasiliou V. The role of corneal crystallins in the cellular defense mechanisms against oxidative stress. Semin Cell Dev Biol. 2008;19:100-12 pubmed
    ..Similarities between the lens and corneal crystallins also suggest that both elements of the refracton may also contribute to the antioxidant defenses of the entire ..
  6. Graw J. Genetics of crystallins: cataract and beyond. Exp Eye Res. 2009;88:173-89 pubmed publisher
    The crystallins were discovered more than 100 years ago by Mörner (1893. Untersuchungen der Proteinsubstanzen in den lichtbrechenden Medien des Auges. Z. Physiol. Chem...
  7. Krishnan K, Kathiresan T, Raman R, Rajini B, Dhople V, Aggrawal R, et al. Ubiquitous lens alpha-, beta-, and gamma-crystallins accumulate in anuran cornea as corneal crystallins. J Biol Chem. 2007;282:18953-9 pubmed
    ..Analogous to lens crystallins, these enzymes and proteins are referred to as corneal crystallins, although their precise function is not ..
  8. Ponce A, Sorensen C, Takemoto L. Role of short-range protein interactions in lens opacifications. Mol Vis. 2006;12:879-84 pubmed
    ..A summary of past and possible future experimental approaches will be reviewed that can be used to ascertain the existence of these interactions and their possible changes during lens opacification. ..
  9. Robinson N, Lampi K, Speir J, Kruppa G, Easterling M, Robinson A. Quantitative measurement of young human eye lens crystallins by direct injection Fourier transform ion cyclotron resonance mass spectrometry. Mol Vis. 2006;12:704-11 pubmed
    Human eye lenses at birth are primarily constructed of 12 distinct crystallins and two truncated crystallins. The molecular weights of these 14 proteins vary between about 20,000 and 30,000 Da...

More Information


  1. 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
    ..Nevertheless, this combination is rare and future studies will focus on identifying similar phenotypes. ..
  2. Slingsby C, Wistow G, Clark A. Evolution of crystallins for a role in the vertebrate eye lens. Protein Sci. 2013;22:367-80 pubmed publisher
    ..The bulk of the lens is formed from proteins belonging to two superfamilies, the ?-crystallins and the ??-crystallins. Tracing their ancestry may throw light on the origin of the optics of the lens...
  3. Ghosh J, Estrada M, Clark J. Interactive domains for chaperone activity in the small heat shock protein, human alphaB crystallin. Biochemistry. 2005;44:14854-69 pubmed
    ..The results suggested that interactive sequences in human alphaB crystallin have dual roles in subunit-subunit assembly and chaperone activity. ..
  4. Liang J, Liu B. Fluorescence resonance energy transfer study of subunit exchange in human lens crystallins and congenital cataract crystallin mutants. Protein Sci. 2006;15:1619-27 pubmed
    ..and analyses using a fluorescent dye-labeled W9F alphaA-crystallin as the acceptor probe and Trp in other crystallins (wild-type and R116C alphaA, wild-type and R120G alphaB, wild-type and Q155* betaB2) as the donor probe and ..
  5. Zhou P, Luo Y, Liu X, Fan L, Lu Y. Down-regulation and CpG island hypermethylation of CRYAA in age-related nuclear cataract. FASEB J. 2012;26:4897-902 pubmed publisher
    ..The evidence presented suggests that CRYAA undergoes epigenetic repression in the lens epithelia in age-related nuclear cataract. ..
  6. Dorsaz N, Thurston G, Stradner A, Schurtenberger P, Foffi G. Colloidal characterization and thermodynamic stability of binary eye lens protein mixtures. J Phys Chem B. 2009;113:1693-709 pubmed publisher
    ..The relevance of these mechanisms as possible sources of the alteration of the spatial distribution of the lens proteins encountered in cataract disease is discussed. ..
  7. Sinha D, Valapala M, Bhutto I, Patek B, Zhang C, Hose S, et al. ?A3/A1-crystallin is required for proper astrocyte template formation and vascular remodeling in the retina. Transgenic Res. 2012;21:1033-42 pubmed publisher
  8. Hains P, Truscott R. Age-dependent deamidation of lifelong proteins in the human lens. Invest Ophthalmol Vis Sci. 2010;51:3107-14 pubmed publisher
    Deamidation is a common posttranslational modification in human lens crystallins and may be a key factor in the age-related denaturation of such lifelong proteins...
  9. Kozmik Z, Swamynathan S, Ruzickova J, Jonasova K, Paces V, Vlcek C, et al. Cubozoan crystallins: evidence for convergent evolution of pax regulatory sequences. Evol Dev. 2008;10:52-61 pubmed publisher
    ..has a large and a small complex, camera-type eye with a cellular lens containing distinct families of crystallins. Here, we have characterized J2-crystallin and its gene in T. cystophora...
  10. Suryanarayana P, Saraswat M, Petrash J, Reddy G. Emblica officinalis and its enriched tannoids delay streptozotocin-induced diabetic cataract in rats. Mol Vis. 2007;13:1291-7 pubmed
    ..The purpose of the current study was to investigate the effect of Emblica and its enriched tannoids on streptozotocin (STZ)-induced diabetic cataract in rats...
  11. 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
  12. Hains P, Truscott R. Proteomic analysis of the oxidation of cysteine residues in human age-related nuclear cataract lenses. Biochim Biophys Acta. 2008;1784:1959-64 pubmed publisher
    ..of age-related nuclear cataract (ARNC), however, little is known about the specific sites of oxidation of the crystallins. We investigated cysteine residues in ARNC lenses and compared them with age-matched normal lenses...
  13. Vanita V, Singh J, Hejtmancik J, Nuernberg P, Hennies H, Singh D, et al. A novel fan-shaped cataract-microcornea syndrome caused by a mutation of CRYAA in an Indian family. Mol Vis. 2006;12:518-22 pubmed
    ..The "fan-shaped cataract" observed in the present family has not been reported before. ..
  14. Hallen A, Cooper A, Jamie J, Haynes P, Willows R. Mammalian forebrain ketimine reductase identified as ?-crystallin; potential regulation by thyroid hormones. J Neurochem. 2011;118:379-87 pubmed publisher
    ..This newly demonstrated enzymatic activity identifies a new role for thyroid hormones in regulating mammalian amino acid metabolism, and a possible reciprocal role of enzyme activity regulating bioavailability of intracellular T3. ..
  15. 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 pubmed
    ..To our knowledge this is the first knock-in mouse model for a crystallin mutation causing hereditary human cataract and establishes that alphaA-R49C promotes protein insolubility and cell death in vivo. ..
  16. Churchill A, Graw J. Clinical and experimental advances in congenital and paediatric cataracts. Philos Trans R Soc Lond B Biol Sci. 2011;366:1234-49 pubmed publisher
    ..from genes coding for transcription factors (such as FoxE3, Maf, Pitx3) and structural proteins such as crystallins or connexins...
  17. Simpanya M, Ansari R, Suh K, Leverenz V, Giblin F. Aggregation of lens crystallins in an in vivo hyperbaric oxygen guinea pig model of nuclear cataract: dynamic light-scattering and HPLC analysis. Invest Ophthalmol Vis Sci. 2005;46:4641-51 pubmed
    ..HPLC-isolated aggregates contained alphaA-, beta-, gamma-, and zeta-crystallins, but not alphaB-crystallin, which is devoid of -SH groups and thus does not participate in disulfide cross-..
  18. 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
    ..The microcornea may have been caused by an inductive effect on the developing cornea from the abnormal lens and/or reduced CRYAA molecular chaperoning of the cornea. ..
  19. Posner M, Hawke M, Lacava C, Prince C, Bellanco N, Corbin R. A proteome map of the zebrafish (Danio rerio) lens reveals similarities between zebrafish and mammalian crystallin expression. Mol Vis. 2008;14:806-14 pubmed
    ..To characterize the crystallin content of the zebrafish lens using two-dimensional gel electrophoresis (2-DE). These data will facilitate future investigations of vertebrate lens development, function, and disease...
  20. Vasiliou V, Thompson D, Smith C, Fujita M, Chen Y. Aldehyde dehydrogenases: from eye crystallins to metabolic disease and cancer stem cells. Chem Biol Interact. 2013;202:2-10 pubmed publisher
    ..The latter include functioning as structural elements in the eye (crystallins) and as binding molecules to endobiotics and xenobiotics...
  21. Shaham O, Smith A, Robinson M, Taketo M, Lang R, Ashery Padan R. Pax6 is essential for lens fiber cell differentiation. Development. 2009;136:2567-78 pubmed publisher
    ..This study reveals that Pax6 is pivotal for initiation of the lens fiber differentiation program in the mammalian eye...
  22. Chan M, Dolinska M, Sergeev Y, Wingfield P, Hejtmancik J. Association properties of betaB1- and betaA3-crystallins: ability to form heterotetramers. Biochemistry. 2008;47:11062-9 pubmed publisher
    As major constituents of the mammalian lens, beta-crystallins associate into dimers, tetramers, and higher-order complexes to maintain lens transparency and refractivity...
  23. 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. ..
  24. Hansen L, Mikkelsen A, Nurnberg P, Nurnberg G, Anjum I, Eiberg H, et al. Comprehensive mutational screening in a cohort of Danish families with hereditary congenital cataract. Invest Ophthalmol Vis Sci. 2009;50:3291-303 pubmed publisher
    ..Seven families have been published previously, and the data of the remaining 21 families are presented together with an overview of the results in all families...
  25. Gupta R, Srivastava O. Identification of interaction sites between human betaA3- and alphaA/alphaB-crystallins by mammalian two-hybrid and fluorescence resonance energy transfer acceptor photobleaching methods. J Biol Chem. 2009;284:18481-92 pubmed publisher
    Our recent study has shown that betaA3-crystallin along with betaB1- and betaB2-crystallins were part of high molecular weight complex obtained from young, old, and cataractous lenses suggesting potential interactions between alpha- and ..
  26. Sharma K, Santhoshkumar P. Lens aging: effects of crystallins. Biochim Biophys Acta. 2009;1790:1095-108 pubmed publisher
    ..The major proteins in the lens--alpha, beta, and gamma-crystallins--are constantly subjected to age-related changes such as oxidation, deamidation, truncation, glycation, and ..
  27. Barnwal R, Atreya H, Chary K. Chemical shift based editing of CH3 groups in fractionally 13C-labelled proteins using GFT (3, 2)D CT-HCCH-COSY: stereospecific assignments of CH3 groups of Val and Leu residues. J Biomol NMR. 2008;42:149-54 pubmed publisher
    ..The proposed experiment opens up a wide range of applications in resonance assignment strategies and structure determination of proteins. ..
  28. Fan X, Monnier V. Inhibition of crystallin ascorbylation by nucleophilic compounds in the hSVCT2 mouse model of lenticular aging. Invest Ophthalmol Vis Sci. 2008;49:4945-52 pubmed publisher
    ..are associated with oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. This process is partially explained by advanced glycation end products (AGEs) from ascorbic acid (ASA), as the ..
  29. Liu B, Liang J. Confocal fluorescence microscopy study of interaction between lens MIP26/AQP0 and crystallins in living cells. J Cell Biochem. 2008;104:51-8 pubmed
    ..major lens fiber membrane protein and has been reported to interact with many other lens components including crystallins, lipid, and cytoskeletal proteins...
  30. Piri N, Song M, Kwong J, Caprioli J. Modulation of alpha and beta crystallin expression in rat retinas with ocular hypertension-induced ganglion cell degeneration. Brain Res. 2007;1141:1-9 pubmed
    ..and Fluorogold retrogradely labeled cells indicated that the cells expressing alpha and beta crystallins in the GCL are RGCs...
  31. Estey T, Cantore M, Weston P, Carpenter J, Petrash J, Vasiliou V. Mechanisms involved in the protection of UV-induced protein inactivation by the corneal crystallin ALDH3A1. J Biol Chem. 2007;282:4382-92 pubmed
    ..This study provides for the first time mechanistic evidence supporting the structural role of the corneal crystallin ALDH3A1 as a UV-absorbing constituent of the cornea. ..
  32. Iqbal J, Kucuk C, Deleeuw R, Srivastava G, Tam W, Geng H, et al. Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies. Leukemia. 2009;23:1139-51 pubmed publisher
    ..ATG5, an essential gene for autophagy and AIM1, a gene implicated in melanoma, may also participate in the functional abnormalities. ..
  33. 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
    ..A new polymorphism (S119S) in CRYGC was also observed in one family. The analysis of nine families excluded possible mutations in the crystallin genes, suggesting that other genes could be involved with congenital cataract. ..
  34. Iwahashi C, Yasui D, An H, Greco C, Tassone F, Nannen K, et al. Protein composition of the intranuclear inclusions of FXTAS. Brain. 2006;129:256-71 pubmed
    ..The list of proteins includes at least two RNA binding proteins, heterogeneous nuclear ribonucleoprotein A2 and muscle blind-like protein 1, which are possible mediators of the RNA gain-of-function in FXTAS. ..
  35. Udupa E, Sharma K. Effect of oxidized betaB3-crystallin peptide on lens betaL-crystallin: interaction with betaB2-crystallin. Invest Ophthalmol Vis Sci. 2005;46:2514-21 pubmed
    ..Peptide-induced aggregation and increased hydrophobicity of the lens crystallin at 37 degrees C are relevant to crystallin aggregation in the aging lenses. ..
  36. Beebe D, Holekamp N, Siegfried C, Shui Y. Vitreoretinal influences on lens function and cataract. Philos Trans R Soc Lond B Biol Sci. 2011;366:1293-300 pubmed publisher
    ..Oxygen reaches the lens nucleus, increasing protein oxidation and aggregation and leading to nuclear cataract. We suggest that maintaining low pO(2) around the lens should prevent the formation of nuclear cataracts...
  37. Raju I, Kumarasamy A, Abraham E. Multiple aggregates and aggresomes of C-terminal truncated human ?A-crystallins in mammalian cells and protection by ?B-crystallin. PLoS ONE. 2011;6:e19876 pubmed publisher
    ..The formation of these post-translationally modified ?A-crystallins is enhanced in diabetes...
  38. Flaugh S, Kosinski Collins M, King J. Interdomain side-chain interactions in human gammaD crystallin influencing folding and stability. Protein Sci. 2005;14:2030-43 pubmed
    ..Features of the interface between the two domains conserved among gamma-crystallins are a central six-residue hydrophobic cluster, and two pairs of interacting residues flanking the cluster...
  39. Strickler A, Byerly M, Jeffery W. Lens gene expression analysis reveals downregulation of the anti-apoptotic chaperone alphaA-crystallin during cavefish eye degeneration. Dev Genes Evol. 2007;217:771-82 pubmed
    ..The genes encoding the lens intrinsic membrane proteins MIP and MP19 and the divergent betaB1- and gammaM2-crystallins are expressed during cavefish lens development, although their levels are reduced because of a smaller lens, ..
  40. Jia S, Omelchenko M, Garland D, Vasiliou V, Kanungo J, Spencer M, et al. Duplicated gelsolin family genes in zebrafish: a novel scinderin-like gene (scinla) encodes the major corneal crystallin. FASEB J. 2007;21:3318-28 pubmed
    ..Our data suggest that scinla and scinlb are diverged paralogs of the vertebrate scinderin gene and show that scinla encodes the zebrafish corneal crystallin previously called C/L-gelsolin. ..
  41. 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 pubmed
    ..Iris coloboma is particularly important in terms of perinatal diagnosis because its detection in the newborn requires a careful and regular examination of the lens. ..
  42. Andley U. Crystallins in the eye: Function and pathology. Prog Retin Eye Res. 2007;26:78-98 pubmed
    b>Crystallins are the predominant structural proteins in the lens that are evolutionarily related to stress proteins...
  43. Medvedovic M, Tomlinson C, Call M, Grogg M, Tsonis P. Gene expression and discovery during lens regeneration in mouse: regulation of epithelial to mesenchymal transition and lens differentiation. Mol Vis. 2006;12:422-40 pubmed
    ..Extension of these studies in mice with known mutations affecting EMT or lens differentiation should allow the identification of the crucial molecular players that could lead to better treatments of secondary cataracts. ..
  44. Fan X, Zhang J, Theves M, Strauch C, Nemet I, Liu X, et al. Mechanism of lysine oxidation in human lens crystallins during aging and in diabetes. J Biol Chem. 2009;284:34618-27 pubmed publisher
    ..An important translational conclusion is that chelating agents might help delay nuclear sclerosis. ..
  45. Barnwal R, Jobby M, Devi K, Sharma Y, Chary K. Solution structure and calcium-binding properties of M-crystallin, a primordial betagamma-crystallin from archaea. J Mol Biol. 2009;386:675-89 pubmed publisher
    ..Based on structural topology, these proteins are considered to be evolutionarily related to lens crystallins, suggesting their origin from a common ancestor...
  46. Rumyantseva Y, Fursova A, Fedoseeva L, Kolosova N. Changes in physicochemical parameters and alpha-crystallin expression in the lens during cataract development in OXYS rats. 5. Biochemistry (Mosc). 2008;73:1176-82 pubmed
    ..The changes observed in OXYS rats are evidently associated with the dystrophic changes in lens epithelium, which we have described earlier, and are consistent with the model of senile cataract...
  47. Hoehenwarter W, Tang Y, Ackermann R, Pleissner K, Schmid M, Stein R, et al. Identification of proteins that modify cataract of mouse eye lens. Proteomics. 2008;8:5011-24 pubmed publisher
    ..The results show HSP27/25 and/or ERp29 are the likely major modifying factors for cataractogenesis. Extension of the results suggests that small heat-shock proteins have a major role for influencing cataract formation in humans. ..
  48. Ninkovic J, Pinto L, Petricca S, Lepier A, Sun J, Rieger M, et al. The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin ?A. Neuron. 2010;68:682-94 pubmed publisher
    ..Strikingly, Pax6 utilizes different DNA-binding domains for its well-known role in fate specification and this role of regulating the survival of specific neuronal subtypes in the mature, healthy brain. ..
  49. Barnwal R, Devi K, Agarwal G, Sharma Y, Chary K. Temperature-dependent oligomerization in M-crystallin: lead or lag toward cataract, an NMR perspective. Proteins. 2011;79:569-80 pubmed publisher
    ..These higher states may co-exist in fast exchange with the monomeric and dimeric M-crystallin at milli-molar to sub-millimolar concentrations and at lower temperature...
  50. 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
    ..The genotype-phenotype correlation of this previously unreported mutation provides evidence that other factors, genetic and/or environmental, may influence the development of cataract as a result of this alteration...
  51. Fris M, Tessem M, Saether O, Midelfart A. Biochemical changes in selenite cataract model measured by high-resolution MAS H NMR spectroscopy. Acta Ophthalmol Scand. 2006;84:684-92 pubmed
    ..For the first time, this study demonstrates the potential to correlate the level of lens opacification with the biochemical changes obtained with HR-MAS (1)H NMR spectroscopy analysis in a selenite cataract model. ..
  52. Gu F, Li R, Ma X, Shi L, Huang S, Ma X. A missense mutation in the gammaD-crystallin gene CRYGD associated with autosomal dominant congenital cataract in a Chinese family. Mol Vis. 2006;12:26-31 pubmed
    ..Bioinformatic analyses also showed that a highly conserved region was located at Arg14. This study is the first reported case with phenotype of coralliform/nuclear cataract that associated with the mutation of Arg14Cys (R14C) CRYGD. ..
  53. Giblin F, David L, Wilmarth P, Leverenz V, Simpanya M. Shotgun proteomic analysis of S-thiolation sites of guinea pig lens nuclear crystallins following oxidative stress in vivo. Mol Vis. 2013;19:267-80 pubmed
    ..occurring at more than 60 cysteine residues of 12 different guinea pig lens water-soluble nuclear crystallins following treatment of the animals with hyperbaric oxygen (HBO)...