CRYBB1 explained

Beta-crystallin B1 is a protein that in humans is encoded by the CRYBB1 gene.^{[1] [2]} Variants in CRYBB1 are associated with autosomal dominant congenital cataract. ^{[3] [4]}

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.

Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group, none in the acidic group). Beta-crystallins form aggregates of different sizes and are able to self-associate to form dimers or to form heterodimers with other beta-crystallins. This gene, a beta basic group member, undergoes extensive cleavage at its N-terminal extension during lens maturation. It is also a member of a gene cluster with beta-A4, beta-B2, and beta-B3.

Further reading

• David LL, Lampi KJ, Lund AL, Smith JB . The sequence of human betaB1-crystallin cDNA allows mass spectrometric detection of betaB1 protein missing portions of its N-terminal extension . J. Biol. Chem. . 271 . 8 . 4273–9 . 1996 . 8626774 . 10.1074/jbc.271.8.4273 . free .
• Lampi KJ . Age-related changes in human lens crystallins identified by two-dimensional electrophoresis and mass spectrometry . Exp. Eye Res. . 67 . 1 . 31–43 . 1998 . 9702176 . 10.1006/exer.1998.0481 . Ma Z . Hanson SR . 3 . Azuma . M . Shih . M . Shearer . TR . Smith . DL . Smith . JB . David . LL .
• Dunham I . The DNA sequence of human chromosome 22 . Nature . 402 . 6761 . 489–95 . 1999 . 10591208 . 10.1038/990031 . Shimizu N . Roe BA . 3 . Bruskiewich . R. . Beare . D. M. . Clamp . M. . Smink . L. J. . Ainscough . R. . Almeida . J. P. . 1999Natur.402..489D . free .
• MacCoss MJ . Shotgun identification of protein modifications from protein complexes and lens tissue . Proc. Natl. Acad. Sci. U.S.A. . 99 . 12 . 7900–5 . 2002 . 12060738 . 10.1073/pnas.122231399 . 122992 . McDonald WH . Saraf A . 3 . Sadygov . R . Clark . JM . Tasto . JJ . Gould . KL . Wolters . D . Washburn . M . 2002PNAS...99.7900M . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Stempel D . BetaB1-crystallin: identification of a candidate ciliary body uveitis antigen . Invest. Ophthalmol. Vis. Sci. . 44 . 1 . 203–9 . 2003 . 12506076 . 10.1167/iovs.01-1261 . Sandusky H . Lampi K . 3 . Cilluffo . M . Horwitz . J . Braun . J . Goodglick . L . Gordon . LK . free .
• Babenko AP, Bryan J . Sur domains that associate with and gate KATP pores define a novel gatekeeper . J. Biol. Chem. . 278 . 43 . 41577–80 . 2004 . 12941953 . 10.1074/jbc.C300363200 . free .
• Van Montfort RL, Bateman OA, Lubsen NH, Slingsby C . Crystal structure of truncated human betaB1-crystallin . Protein Sci. . 12 . 11 . 2606–12 . 2004 . 14573871 . 10.1110/ps.03265903 . 2366963 .
• Harms MJ . Laser light-scattering evidence for an altered association of beta B1-crystallin deamidated in the connecting peptide . Protein Sci. . 13 . 3 . 678–86 . 2004 . 14978307 . 10.1110/ps.03427504 . 2286738 . Wilmarth PA . Kapfer DM . 3 . Steel . EA . David . LL . Bächinger . HP . Lampi . KJ .
• Collins JE . A genome annotation-driven approach to cloning the human ORFeome . Genome Biol. . 5 . 10 . R84 . 2005 . 15461802 . 10.1186/gb-2004-5-10-r84 . 545604 . Wright CL . Edwards CA . 3 . Davis . Matthew P . Grinham . James A . Cole . Charlotte G . Goward . Melanie E . Aguado . Begoña . Mallya . Meera . free .
• Gerhard DS . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Annunziata O . Oligomerization and phase transitions in aqueous solutions of native and truncated human beta B1-crystallin . Biochemistry . 44 . 4 . 1316–28 . 2005 . 15667225 . 10.1021/bi048419f . Pande A . Pande J . 3 . Ogun . Olutayo . Lubsen . Nicolette H. . Benedek . George B. . 10.1.1.330.9588 .
• Willoughby CE . CRYBB1 mutation associated with congenital cataract and microcornea . Mol. Vis. . 11 . 587–93 . 2006 . 16110300 . Shafiq A . Ferrini W . 3 . Chan . LL . Billingsley . G . Priston . M . Mok . C . Chandna . A . Kaye . S .
• Hou HH, Kuo MY, Luo YW, Chang BE . Recapitulation of human betaB1-crystallin promoter activity in transgenic zebrafish . Dev. Dyn. . 235 . 2 . 435–43 . 2006 . 16331646 . 10.1002/dvdy.20652 . free .
• Smith MA, Bateman OA, Jaenicke R, Slingsby C . Mutation of interfaces in domain-swapped human betaB2-crystallin . Protein Sci. . 16 . 4 . 615–25 . 2007 . 17327390 . 10.1110/ps.062659107 . 2203347 .
• Koteiche HA, Kumar MS, McHaourab HS . Analysis of betaB1-crystallin unfolding equilibrium by spin and fluorescence labeling: evidence of a dimeric intermediate . FEBS Lett. . 581 . 10 . 1933–8 . 2007 . 17448466 . 10.1016/j.febslet.2007.04.004 . 2394508 .
• Cohen D . Homozygous CRYBB1 deletion mutation underlies autosomal recessive congenital cataract . Invest. Ophthalmol. Vis. Sci. . 48 . 5 . 2208–13 . 2007 . 17460281 . 10.1167/iovs.06-1019 . Bar-Yosef U . Levy J . 3 . Gradstein . L. . Belfair . N. . Ofir . R. . Joshua . S. . Lifshitz . T. . Carmi . R. . free .
• Wang J . A missense mutation S228P in the CRYBB1 gene causes autosomal dominant congenital cataract . Chin. Med. J. . 120 . 9 . 820–4 . 2007 . 17531125 . 10.1097/00029330-200705010-00015. Ma X . Gu F . 3 . Liu . NP . Hao . XL . Wang . KJ . Wang . NL . Zhu . SQ . free .

Notes and References

1. Hulsebos TJ, Gilbert DJ, Delattre O, Smink LJ, Dunham I, Westerveld A, Thomas G, Jenkins NA, Copeland NG . Assignment of the beta B1 crystallin gene (CRYBB1) to human chromosome 22 and mouse chromosome 5 . Genomics . 29 . 3 . 712–8 . Mar 1996 . 8575764 . 10.1006/geno.1995.9947 .
2. Web site: Entrez Gene: CRYBB1 crystallin, beta B1.
3. Mackay DS, Boskovska OB, Knopf HL, Lampi KJ, Shiels A . A nonsense mutation in CRYBB1 associated with autosomal dominant cataract linked to human chromosome 22q . Am J Hum Genet . 71 . 5 . 1216–21 . Oct 2002 . 12360425 . 385100 . 10.1086/344212 .
4. Siggs OM, Javadiyan S, Sharma S, Souzeau E, Lower KM, Taranath DA, Black J, Pater J, Willoughby JG, Burdon KP, Craig JE . 6. Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract . Eur. J. Hum. Genet. . 25 . 6 . 711–718 . June 2017 . 28272538 . 5477362 . 10.1038/ejhg.2017.33 .