CRYAA explained

Alpha-crystallin A chain is a protein that in humans is encoded by the CRYAA gene.^[1]

Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. Alpha crystallins can be induced by heat shock and are members of the small heat shock protein (sHSP also known as the HSP20) family. They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead they hold them in large soluble aggregates. Post-translational modifications decrease the ability to chaperone. These heterogeneous aggregates consist of 30-40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively. Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Defects in this gene cause autosomal dominant congenital cataract (ADCC).^[1]

Interactions

CRYAA has been shown to interact with CRYBB2,^[2] Hsp27,^[2] CRYGC^[2] and CRYAB.^[2]

Further reading

• Derham BK, Harding JJ . Alpha-crystallin as a molecular chaperone. . Progress in Retinal and Eye Research . 18 . 4 . 463–509 . 1999 . 10217480 . 10.1016/S1350-9462(98)00030-5 . 25124893 .
• de Jong WW, Terwindt EC, Bloemendal H . The amino acid sequence of the A chain of human alpha-crystallin. . FEBS Lett. . 58 . 1 . 310–3 . 1976 . 817940 . 10.1016/0014-5793(75)80286-9 . 83739751 . free .
• Ortwerth BJ, Slight SH, Prabhakaram M . Site-specific glycation of lens crystallins by ascorbic acid. . Biochim. Biophys. Acta . 1117 . 2 . 207–15 . 1992 . 1525182 . 10.1016/0304-4165(92)90081-5. etal.
• Roquemore EP, Dell A, Morris HR . Vertebrate lens alpha-crystallins are modified by O-linked N-acetylglucosamine. . J. Biol. Chem. . 267 . 1 . 555–63 . 1992 . 10.1016/S0021-9258(18)48530-4 . 1730617 . etal. free .
• Jaworski CJ, Piatigorsky J . A pseudo-exon in the functional human alpha A-crystallin gene. . Nature . 337 . 6209 . 752–4 . 1989 . 2918909 . 10.1038/337752a0 . 1989Natur.337..752J . 4272504 .
• Hawkins JW, Van Keuren ML, Piatigorsky J . Confirmation of assignment of the human alpha 1-crystallin gene (CRYA1) to chromosome 21 with regional localization to q22.3. . Hum. Genet. . 76 . 4 . 375–80 . 1987 . 3610158 . 10.1007/BF00272448 . 19506423 . etal.
• McDevitt DS, Hawkins JW, Jaworski CJ, Piatigorsky J . Isolation and partial characterization of the human alpha A-crystallin gene. . Exp. Eye Res. . 43 . 2 . 285–91 . 1986 . 3758227 . 10.1016/S0014-4835(86)80098-7 .
• Caspers GJ, Pennings J, De Jong WW . A partial cDNA sequence corrects the human alpha A-crystallin primary structure. . Exp. Eye Res. . 59 . 1 . 125–6 . 1995 . 7835394 . 10.1006/exer.1994.1089 .
• Miesbauer LR, Zhou X, Yang Z . Post-translational modifications of water-soluble human lens crystallins from young adults. . J. Biol. Chem. . 269 . 17 . 12494–502 . 1994 . 10.1016/S0021-9258(18)99902-3 . 8175657 . etal. free .
• Jaworski CJ . A reassessment of mammalian alpha A-crystallin sequences using DNA sequencing: implications for anthropoid affinities of tarsier. . J. Mol. Evol. . 41 . 6 . 901–8 . 1996 . 8587135 . 10.1007/bf00173170. 1995JMolE..41..901J . 22878315 .
• Takemoto LJ . Differential phosphorylation of alpha-A crystallin in human lens of different age. . Exp. Eye Res. . 62 . 5 . 499–504 . 1996 . 8759518 . 10.1006/exer.1996.0060 .
• Prabhakaram M, Katz ML, Ortwerth BJ . Glycation mediated crosslinking between alpha-crystallin and MP26 in intact lens membranes. . Mech. Ageing Dev. . 91 . 1 . 65–78 . 1997 . 8910261 . 10.1016/0047-6374(96)01781-2 . 53227438 .
• Andley UP, Mathur S, Griest TA, Petrash JM . Cloning, expression, and chaperone-like activity of human alphaA-crystallin. . J. Biol. Chem. . 271 . 50 . 31973–80 . 1997 . 8943244 . 10.1074/jbc.271.50.31973 . free .
• Lampi KJ, Ma Z, Shih M . Sequence analysis of betaA3, betaB3, and betaA4 crystallins completes the identification of the major proteins in young human lens. . J. Biol. Chem. . 272 . 4 . 2268–75 . 1997 . 8999933 . 10.1074/jbc.272.4.2268 . etal. free .
• Lindner RA, Kapur A, Carver JA . The interaction of the molecular chaperone, alpha-crystallin, with molten globule states of bovine alpha-lactalbumin. . J. Biol. Chem. . 272 . 44 . 27722–9 . 1997 . 9346914 . 10.1074/jbc.272.44.27722 . free .
• Litt M, Kramer P, LaMorticella DM . Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. . Hum. Mol. Genet. . 7 . 3 . 471–4 . 1998 . 9467006 . 10.1093/hmg/7.3.471 . etal. free .
• Takemoto LJ . Quantitation of asparagine-101 deamidation from alpha-A crystallin during aging of the human lens. . Curr. Eye Res. . 17 . 3 . 247–50 . 1998 . 9543632 . 10.1076/ceyr.17.3.247.5218 .
• Doss EW, Ward KA, Koretz JF . Investigation of the 'fines' hypothesis of primary open-angle glaucoma: the possible role of alpha-crystallin. . Ophthalmic Res. . 30 . 3 . 142–56 . 1998 . 9618718 . 10.1159/000055468 . 46813838 .
• Lin PP, Barry RC, Smith DL, Smith JB . In vivo acetylation identified at lysine 70 of human lens alphaA-crystallin. . Protein Sci. . 7 . 6 . 1451–7 . 1998 . 9655350 . 10.1002/pro.5560070622 . 2144031 .

Notes and References

1. Web site: Entrez Gene: CRYAA crystallin, alpha A.
2. Fu . Ling . Liang Jack J-N . Feb 2002 . Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay . J. Biol. Chem. . 277 . 6 . 4255–60 . United States. 0021-9258. 11700327 . 10.1074/jbc.M110027200 . free .