ID CRYAA_HUMAN Reviewed; 173 AA. AC P02489; A0A140G945; E9PHE4; Q53X53; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 2. DT 27-MAR-2024, entry version 232. DE RecName: Full=Alpha-crystallin A chain; DE AltName: Full=Heat shock protein beta-4; DE Short=HspB4; DE Contains: DE RecName: Full=Alpha-crystallin A(1-172); DE Contains: DE RecName: Full=Alpha-crystallin A(1-168); DE Contains: DE RecName: Full=Alpha-crystallin A(1-162); GN Name=CRYAA; Synonyms=CRYA1, HSPB4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP PRELIMINARY PROTEIN SEQUENCE, AND ACETYLATION AT MET-1. RX PubMed=817940; DOI=10.1016/0014-5793(75)80286-9; RA de Jong W.W., Terwindt E.C., Bloemendal H.; RT "The amino acid sequence of the A chain of human alpha-crystallin."; RL FEBS Lett. 58:310-313(1975). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lens; RX PubMed=8587135; DOI=10.1007/bf00173170; RA Jaworski C.J.; RT "A reassessment of mammalian alpha A-crystallin sequences using DNA RT sequencing: implications for anthropoid affinities of tarsier."; RL J. Mol. Evol. 41:901-908(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lens; RX PubMed=8943244; DOI=10.1074/jbc.271.50.31973; RA Andley U.P., Mathur S., Griest T.A., Petrash J.M.; RT "Cloning, expression, and chaperone-like activity of human alphaA- RT crystallin."; RL J. Biol. Chem. 271:31973-31980(1996). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lens; RA Rajkumar S.; RT "Functional candidate gene approach to study genetic polymorphisms in lens RT specific genes."; RL Submitted (JUL-2014) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-104. RX PubMed=2918909; DOI=10.1038/337752a0; RA Jaworski C.J., Piatigorsky J.; RT "A pseudo-exon in the functional human alpha A-crystallin gene."; RL Nature 337:752-754(1989). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-63 AND 166-173. RC TISSUE=Spleen; RX PubMed=3758227; DOI=10.1016/s0014-4835(86)80098-7; RA McDevitt D.S., Hawkins J.W., Jaworski C.J., Piatigorsky J.; RT "Isolation and partial characterization of the human alpha A-crystallin RT gene."; RL Exp. Eye Res. 43:285-291(1986). RN [11] RP PROTEIN SEQUENCE OF 13-21 AND 79-88. RX PubMed=8999933; DOI=10.1074/jbc.272.4.2268; RA Lampi K.J., Ma Z., Shih M., Shearer T.R., Smith J.B., Smith D.L., RA David L.L.; RT "Sequence analysis of betaA3, betaB3, and betaA4 crystallins completes the RT identification of the major proteins in young human lens."; RL J. Biol. Chem. 272:2268-2275(1997). RN [12] RP STRUCTURE OF CARBOHYDRATE. RX PubMed=1730617; DOI=10.1016/s0021-9258(18)48530-4; RA Roquemore E.P., Dell A., Morris H.R., Panico M., Reason A.J., Savoy L.-A., RA Wistow G.J., Zigler J.S. Jr., Earles B.J., Hart G.W.; RT "Vertebrate lens alpha-crystallins are modified by O-linked N- RT acetylglucosamine."; RL J. Biol. Chem. 267:555-563(1992). RN [13] RP PHOSPHORYLATION AT SER-122, DISULFIDE BOND, PROTEOLYTIC PROCESSING OF RP C-TERMINAL, DEAMIDATION AT ASN-101, AND MASS SPECTROMETRY. RX PubMed=8175657; DOI=10.1016/s0021-9258(18)99902-3; RA Miesbauer L.R., Zhou X., Yang Z., Yang Z., Sun Y., Smith D.L., Smith J.B.; RT "Post-translational modifications of water-soluble human lens crystallins RT from young adults."; RL J. Biol. Chem. 269:12494-12502(1994). RN [14] RP PHOSPHORYLATION AT SER-122. RX PubMed=8759518; DOI=10.1006/exer.1996.0060; RA Takemoto L.J.; RT "Differential phosphorylation of alpha-A crystallin in human lens of RT different age."; RL Exp. Eye Res. 62:499-504(1996). RN [15] RP PROTEOLYTIC PROCESSING, SUSCEPTIBILITY TO OXIDATION, PHOSPHORYLATION AT RP SER-45 AND SER-122, DISULFIDE BOND, DEAMIDATION AT GLN-6; GLN-50; GLN-90; RP ASN-101 AND GLN-147, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=9068373; DOI=10.1006/exer.1996.0160; RA Lund A.L., Smith J.B., Smith D.L.; RT "Modifications of the water-insoluble human lens alpha-crystallins."; RL Exp. Eye Res. 63:661-672(1996). RN [16] RP DEAMIDATION AT ASN-101. RX PubMed=9543632; DOI=10.1076/ceyr.17.3.247.5218; RA Takemoto L.J.; RT "Quantitation of asparagine-101 deamidation from alpha-A crystallin during RT aging of the human lens."; RL Curr. Eye Res. 17:247-250(1998). RN [17] RP PROTEOLYTIC PROCESSING OF C-TERMINAL, ACETYLATION AT LYS-70, RP PHOSPHORYLATION, DEAMIDATION AT ASN-101, AND MASS SPECTROMETRY. RX PubMed=9655350; DOI=10.1002/pro.5560070622; RA Lin P.P., Barry R.C., Smith D.L., Smith J.B.; RT "In vivo acetylation identified at lysine 70 of human lens alphaA- RT crystallin."; RL Protein Sci. 7:1451-1457(1998). RN [18] RP PHOSPHORYLATION, SUSCEPTIBILITY TO OXIDATION, PROTEOLYTIC PROCESSING OF RP C-TERMINAL, AND MASS SPECTROMETRY. RX PubMed=10930324; DOI=10.1006/exer.2000.0868; RA Hanson S.R.A., Hasan A., Smith D.L., Smith J.B.; RT "The major in vivo modifications of the human water-insoluble lens RT crystallins are disulfide bonds, deamidation, methionine oxidation and RT backbone cleavage."; RL Exp. Eye Res. 71:195-207(2000). RN [19] RP REVIEW. RX PubMed=12369933; DOI=10.2174/1389203013381107; RA Ganea E.; RT "Chaperone-like activity of alpha-crystallin and other small heat shock RT proteins."; RL Curr. Protein Pept. Sci. 2:205-225(2001). RN [20] RP PROTEOLYTIC PROCESSING, AND TISSUE SPECIFICITY. RX PubMed=12356833; RA Thampi P., Hassan A., Smith J.B., Abraham E.C.; RT "Enhanced C-terminal truncation of alphaA- and alphaB-crystallins in RT diabetic lenses."; RL Invest. Ophthalmol. Vis. Sci. 43:3265-3272(2002). RN [21] RP DEAMIDATION AT ASN-123, AND MUTAGENESIS OF ASN-123. RX PubMed=18754677; DOI=10.1021/bi8001902; RA Chaves J.M., Srivastava K., Gupta R., Srivastava O.P.; RT "Structural and functional roles of deamidation and/or truncation of N- or RT C-termini in human alpha A-crystallin."; RL Biochemistry 47:10069-10083(2008). RN [22] RP SUBUNIT. RX PubMed=17909943; DOI=10.1007/s11010-007-9615-2; RA Kallur L.S., Aziz A., Abraham E.C.; RT "C-Terminal truncation affects subunit exchange of human alphaA-crystallin RT with alphaB-crystallin."; RL Mol. Cell. Biochem. 308:85-91(2008). RN [23] RP SUBCELLULAR LOCATION. RX PubMed=19464326; DOI=10.1016/j.bbamcr.2009.05.005; RA Vos M.J., Kanon B., Kampinga H.H.; RT "HSPB7 is a SC35 speckle resident small heat shock protein."; RL Biochim. Biophys. Acta 1793:1343-1353(2009). RN [24] RP SUBUNIT. RX PubMed=20836128; DOI=10.1002/iub.373; RA Srinivas P., Narahari A., Petrash J.M., Swamy M.J., Reddy G.B.; RT "Importance of eye lens alpha-crystallin heteropolymer with 3:1 alphaA to RT alphaB ratio: stability, aggregation, and modifications."; RL IUBMB Life 62:693-702(2010). RN [25] RP FUNCTION, AND ACETYLATION AT LYS-70 AND LYS-99. RX PubMed=22120592; DOI=10.1016/j.bbadis.2011.11.011; RA Nagaraj R.H., Nahomi R.B., Shanthakumar S., Linetsky M., Padmanabha S., RA Pasupuleti N., Wang B., Santhoshkumar P., Panda A.K., Biswas A.; RT "Acetylation of alphaA-crystallin in the human lens: effects on structure RT and chaperone function."; RL Biochim. Biophys. Acta 1822:120-129(2012). RN [26] RP SUBUNIT, AND ZINC-BINDING SITES. RX PubMed=22890888; DOI=10.1007/s10930-012-9439-0; RA Karmakar S., Das K.P.; RT "Identification of histidine residues involved in Zn(2+) binding to RT alphaA- and alphaB-Crystallin by chemical modification and MALDI TOF mass RT spectrometry."; RL Protein J. 31:623-640(2012). RN [27] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH BFSP1 AND BFSP2. RX PubMed=28935373; DOI=10.1016/j.bbrc.2017.09.088; RA Chaves J.M., Gupta R., Srivastava K., Srivastava O.; RT "Human alpha A-crystallin missing N-terminal domain poorly complexes with RT filensin and phakinin."; RL Biochem. Biophys. Res. Commun. 494:402-408(2017). RN [28] {ECO:0007744|PDB:6T1R} RP STRUCTURE BY ELECTRON MICROSCOPY (9.80 ANGSTROMS), HOMOMERIZATION, RP DISULFIDE BOND, AND FUNCTION. RX PubMed=31792453; DOI=10.1038/s41594-019-0332-9; RA Kaiser C.J.O., Peters C., Schmid P.W.N., Stavropoulou M., Zou J., RA Dahiya V., Mymrikov E.V., Rockel B., Asami S., Haslbeck M., Rappsilber J., RA Reif B., Zacharias M., Buchner J., Weinkauf S.; RT "The structure and oxidation of the eye lens chaperone alphaA-crystallin."; RL Nat. Struct. Mol. Biol. 26:1141-1150(2019). RN [29] RP VARIANT CTRCT9 CYS-116. RX PubMed=9467006; DOI=10.1093/hmg/7.3.471; RA Litt M., Kramer P., la Morticella D.M., Murphey W., Lovrien E.W., RA Weleber R.G.; RT "Autosomal dominant congenital cataract associated with a missense mutation RT in the human alpha crystallin gene CRYAA."; RL Hum. Mol. Genet. 7:471-474(1998). RN [30] RP CHARACTERIZATION OF VARIANT CTRCT9 CYS-116. RX PubMed=11123904; DOI=10.1021/bi001453j; RA Cobb B.A., Petrash J.M.; RT "Structural and functional changes in the alpha A-crystallin R116C mutant RT in hereditary cataracts."; RL Biochemistry 39:15791-15798(2000). RN [31] RP VARIANT CTRCT9 9-TRP--SER-173 DEL. RX PubMed=11006246; RA Pras E., Frydman M., Levy-Nissenbaum E., Bakhan T., Raz J., Assia E.I., RA Goldman B., Pras E.; RT "A nonsense mutation (W9X) in CRYAA causes autosomal recessive cataract in RT an inbred Jewish Persian family."; RL Invest. Ophthalmol. Vis. Sci. 41:3511-3515(2000). RN [32] RP VARIANT CTRCT9 CYS-49, AND SUBCELLULAR LOCATION. RX PubMed=14512969; DOI=10.1038/sj.ejhg.5201046; RA Mackay D.S., Andley U.P., Shiels A.; RT "Cell death triggered by a novel mutation in the alphaA-crystallin gene RT underlies autosomal dominant cataract linked to chromosome 21q."; RL Eur. J. Hum. Genet. 11:784-793(2003). RN [33] RP VARIANT CTRCT9 LEU-21. RX PubMed=16453125; DOI=10.1007/s00417-005-0234-x; RA Graw J., Klopp N., Illig T., Preising M.N., Lorenz B.; RT "Congenital cataract and macular hypoplasia in humans associated with a de RT novo mutation in CRYAA and compound heterozygous mutations in P."; RL Graefes Arch. Clin. Exp. Ophthalmol. 244:912-919(2006). RN [34] RP VARIANT CTRCT9 CYS-116. RX PubMed=16735993; RA Vanita V., Singh J.R., Hejtmancik J.F., Nuernberg P., Hennies H.C., RA Singh D., Sperling K.; RT "A novel fan-shaped cataract-microcornea syndrome caused by a mutation of RT CRYAA in an Indian family."; RL Mol. Vis. 12:518-522(2006). RN [35] RP VARIANT CTRCT9 ARG-98. RX PubMed=16862070; RA Santhiya S.T., Soker T., Klopp N., Illig T., Prakash M.V., Selvaraj B., RA Gopinath P.M., Graw J.; RT "Identification of a novel, putative cataract-causing allele in CRYAA RT (G98R) in an Indian family."; RL Mol. Vis. 12:768-773(2006). RN [36] RP VARIANT [LARGE SCALE ANALYSIS] HIS-105. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [37] RP VARIANT CTRCT9 CYS-54. RX PubMed=17937925; DOI=10.1016/j.ajo.2007.08.005; RA Khan A.O., Aldahmesh M.A., Meyer B.; RT "Recessive congenital total cataract with microcornea and heterozygote RT carrier signs caused by a novel missense CRYAA mutation (R54C)."; RL Am. J. Ophthalmol. 144:949-952(2007). RN [38] RP VARIANT CTRCT9 CYS-116. RX PubMed=17296897; DOI=10.1001/archopht.125.2.213; RA Beby F., Commeaux C., Bozon M., Denis P., Edery P., Morle L.; RT "New phenotype associated with an Arg116Cys mutation in the CRYAA gene: RT nuclear cataract, iris coloboma, and microphthalmia."; RL Arch. Ophthalmol. 125:213-216(2007). RN [39] RP VARIANTS CTRCT9 CYS-12 AND TRP-21. RX PubMed=17724170; DOI=10.1167/iovs.07-0013; RA Hansen L., Yao W., Eiberg H., Kjaer K.W., Baggesen K., Hejtmancik J.F., RA Rosenberg T.; RT "Genetic heterogeneity in microcornea-cataract: five novel mutations in RT CRYAA, CRYGD, and GJA8."; RL Invest. Ophthalmol. Vis. Sci. 48:3937-3944(2007). RN [40] RP CHARACTERIZATION OF VARIANT CTRCT9 ARG-98, AND FUNCTION. RX PubMed=18199971; RA Murugesan R., Santhoshkumar P., Sharma K.K.; RT "Cataract-causing alphaAG98R mutant shows substrate-dependent chaperone RT activity."; RL Mol. Vis. 13:2301-2309(2007). RN [41] RP FUNCTION, AND VARIANT CTRCT9 HIS-116. RX PubMed=18302245; DOI=10.1002/ajmg.a.32236; RA Richter L., Flodman P., Barria von-Bischhoffshausen F., Burch D., Brown S., RA Nguyen L., Turner J., Spence M.A., Bateman J.B.; RT "Clinical variability of autosomal dominant cataract, microcornea and RT corneal opacity and novel mutation in the alpha A crystallin gene RT (CRYAA)."; RL Am. J. Med. Genet. A 146:833-842(2008). RN [42] RP VARIANT CTRCT9 HIS-116, AND CHARACTERIZATION OF VARIANT CTRCT9 HIS-116. RX PubMed=18407550; DOI=10.1002/humu.20724; RA Gu F., Luo W., Li X., Wang Z., Lu S., Zhang M., Zhao B., Zhu S., Feng S., RA Yan Y.-B., Huang S., Ma X.; RT "A novel mutation in AlphaA-crystallin (CRYAA) caused autosomal dominant RT congenital cataract in a large Chinese family."; RL Hum. Mutat. 29:769-769(2008). RN [43] RP VARIANTS CTRCT9 CYS-12; TRP-21 AND CYS-54. RX PubMed=18587492; RA Devi R.R., Yao W., Vijayalakshmi P., Sergeev Y.V., Sundaresan P., RA Hejtmancik J.F.; RT "Crystallin gene mutations in Indian families with inherited pediatric RT cataract."; RL Mol. Vis. 14:1157-1170(2008). RN [44] RP VARIANT CTRCT9 LEU-71, CHARACTERIZATION OF VARIANT CTRCT9 LEU-71, AND RP FUNCTION. RX PubMed=19595763; DOI=10.1016/j.bbadis.2009.06.011; RA Bhagyalaxmi S.G., Srinivas P., Barton K.A., Kumar K.R., Vidyavathi M., RA Petrash J.M., Bhanuprakash Reddy G., Padma T.; RT "A novel mutation (F71L) in alphaA-crystallin with defective chaperone-like RT function associated with age-related cataract."; RL Biochim. Biophys. Acta 1792:974-981(2009). RN [45] RP VARIANT CTRCT9 CYS-12. RX PubMed=19390652; RA Santana A., Waiswol M., Arcieri E.S., Cabral de Vasconcellos J.P., RA Barbosa de Melo M.; RT "Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal RT dominant congenital cataract in Brazilian families."; RL Mol. Vis. 15:793-800(2009). RN [46] RP CHARACTERIZATION OF VARIANT CTRCT9 CYS-12, AND SUBCELLULAR LOCATION. RX PubMed=19503744; RA Zhang L.Y., Yam G.H., Tam P.O., Lai R.Y., Lam D.S., Pang C.P., Fan D.S.; RT "An alphaA-crystallin gene mutation, Arg12Cys, causing inherited cataract- RT microcornea exhibits an altered heat-shock response."; RL Mol. Vis. 15:1127-1138(2009). RN [47] RP VARIANTS CTRCT9 TRP-21 AND CYS-49. RX PubMed=19182255; DOI=10.1167/iovs.08-3149; RA Hansen L., Mikkelsen A., Nuernberg P., Nuernberg G., Anjum I., Eiberg H., RA Rosenberg T.; RT "Comprehensive mutational screening in a cohort of Danish families with RT hereditary congenital cataract."; RL Invest. Ophthalmol. Vis. Sci. 50:3291-3303(2009). RN [48] RP VARIANT CTRCT9 CYS-116. RX PubMed=20465443; DOI=10.3109/02713681003624901; RA Li F.F., Yang M., Ma X., Zhang Q., Zhang M., Wang S.Z., Zhu S.Q.; RT "Autosomal dominant congenital nuclear cataracts caused by a CRYAA gene RT mutation."; RL Curr. Eye Res. 35:492-498(2010). RN [49] RP VARIANT CTRCT9 CYS-12. RX PubMed=21686328; RA Sun W., Xiao X., Li S., Guo X., Zhang Q.; RT "Mutational screening of six genes in Chinese patients with congenital RT cataract and microcornea."; RL Mol. Vis. 17:1508-1513(2011). RN [50] RP VARIANTS CTRCT9 ARG-98 AND 117-ARG-TYR-118 DELINS HIS. RX PubMed=21866213; RA Sun W., Xiao X., Li S., Guo X., Zhang Q.; RT "Mutation analysis of 12 genes in Chinese families with congenital RT cataracts."; RL Mol. Vis. 17:2197-2206(2011). RN [51] RP VARIANT CTRCT9 HIS-116. RX PubMed=22065922; RA Zhang L., Zhang Y., Liu P., Cao W., Tang X., Su S.; RT "Congenital anterior polar cataract associated with a missense mutation in RT the human alpha crystallin gene CRYAA."; RL Mol. Vis. 17:2693-2697(2011). RN [52] RP VARIANT CTRCT9 PRO-54. RX PubMed=23288997; RA Su D., Guo Y., Li Q., Guan L., Zhu S., Ma X.; RT "A novel mutation in CRYAA is associated with autosomal dominant suture RT cataracts in a Chinese family."; RL Mol. Vis. 18:3057-3063(2012). RN [53] RP VARIANT CTRCT9 HIS-116. RX PubMed=22216983; DOI=10.3109/13816810.2011.642451; RA Wang B., Wang K.J., Zhu S.Q., Wang J., Ma X.; RT "Identification of the p. R116H mutation in a Chinese family with novel RT variable cataract phenotype: evidence for a mutational hot spot in alphaA- RT crystallin gene."; RL Ophthalmic Genet. 33:134-138(2012). RN [54] RP VARIANT CTRCT9 LEU-54. RX PubMed=24074001; DOI=10.3109/02713683.2013.811260; RA Yang Z., Su D., Li Q., Ma Z., Yang F., Zhu S., Ma X.; RT "A R54L mutation of CRYAA associated with autosomal dominant nuclear RT cataracts in a Chinese family."; RL Curr. Eye Res. 38:1221-1228(2013). RN [55] RP VARIANT CTRCT9 CYS-12. RX PubMed=23508780; DOI=10.1007/s00439-013-1289-0; RA Reis L.M., Tyler R.C., Muheisen S., Raggio V., Salviati L., Han D.P., RA Costakos D., Yonath H., Hall S., Power P., Semina E.V.; RT "Whole exome sequencing in dominant cataract identifies a new causative RT factor, CRYBA2, and a variety of novel alleles in known genes."; RL Hum. Genet. 132:761-770(2013). RN [56] RP CHARACTERIZATION OF VARIANT CTRCT9 GLN-21, SUBUNIT, AND TISSUE SPECIFICITY. RX PubMed=23255486; DOI=10.1002/humu.22260; RA Laurie K.J., Dave A., Straga T., Souzeau E., Chataway T., Sykes M.J., RA Casey T., Teo T., Pater J., Craig J.E., Sharma S., Burdon K.P.; RT "Identification of a novel oligomerization disrupting mutation in CRYAlphaA RT associated with congenital cataract in a South Australian family."; RL Hum. Mutat. 34:435-438(2013). RN [57] RP VARIANT CTRCT9 TRP-21. RX PubMed=23441109; RA Kondo Y., Saitsu H., Miyamoto T., Lee B.J., Nishiyama K., Nakashima M., RA Tsurusaki Y., Doi H., Miyake N., Kim J.H., Yu Y.S., Matsumoto N.; RT "Pathogenic mutations in two families with congenital cataract identified RT with whole-exome sequencing."; RL Mol. Vis. 19:384-389(2013). RN [58] RP VARIANT CTRCT9 ARG-117 DEL. RX PubMed=25729975; DOI=10.4238/2015.january.23.16; RA Kong X.D., Liu N., Shi H.R., Dong J.M., Zhao Z.H., Liu J., Li-Ling J., RA Yang Y.X.; RT "A novel 3-base pair deletion of the CRYAA gene identified in a large RT Chinese pedigree featuring autosomal dominant congenital perinuclear RT cataract."; RL Genet. Mol. Res. 14:426-432(2015). RN [59] RP VARIANT CTRCT9 PRO-139, AND SUBCELLULAR LOCATION. RX PubMed=26004348; DOI=10.3892/mmr.2015.3819; RA Liang C., Liang H., Yang Y., Ping L., Jie Q.; RT "Mutation analysis of two families with inherited congenital cataracts."; RL Mol. Med. Report. 12:3469-3475(2015). RN [60] RP VARIANT CTRCT9 GLN-21. RX PubMed=26867756; DOI=10.1186/s13104-016-1890-0; RA Javadiyan S., Craig J.E., Souzeau E., Sharma S., Lower K.M., Pater J., RA Casey T., Hodson T., Burdon K.P.; RT "Recurrent mutation in the crystallin alpha A gene associated with RT inherited paediatric cataract."; RL BMC Res. Notes 9:83-83(2016). RN [61] RP VARIANT CTRCT9 CYS-54. RX PubMed=28839118; DOI=10.1534/g3.117.300109; RA Javadiyan S., Craig J.E., Souzeau E., Sharma S., Lower K.M., Mackey D.A., RA Staffieri S.E., Elder J.E., Taranath D., Straga T., Black J., Pater J., RA Casey T., Hewitt A.W., Burdon K.P.; RT "High-Throughput Genetic Screening of 51 Pediatric Cataract Genes RT Identifies Causative Mutations in Inherited Pediatric Cataract in South RT Eastern Australia."; RL G3 (Bethesda) 7:3257-3268(2017). RN [62] RP VARIANTS CTRCT9 GLN-65 AND HIS-119. RX PubMed=28690483; DOI=10.1159/000471992; RA Patel R., Zenith R.K., Chandra A., Ali A.; RT "Novel Mutations in the Crystallin Gene in Age-Related Cataract Patients RT from a North Indian Population."; RL Mol. Syndromol. 8:179-186(2017). RN [63] RP VARIANT CTRCT9 TRP-21. RX PubMed=29386872; RA Sun Z., Zhou Q., Li H., Yang L., Wu S., Sui R.; RT "Mutations in crystallin genes result in congenital cataract associated RT with other ocular abnormalities."; RL Mol. Vis. 23:977-986(2017). RN [64] RP VARIANT CTRCT9 LEU-12, CHARACTERIZATION OF VARIANT CTRCT9 LEU-12, AND RP SUBCELLULAR LOCATION. RX PubMed=30340470; DOI=10.1186/s12881-018-0695-5; RA Song Z., Si N., Xiao W.; RT "A novel mutation in the CRYAA gene associated with congenital cataract and RT microphthalmia in a Chinese family."; RL BMC Med. Genet. 19:190-190(2018). RN [65] RP VARIANT CTRCT9 TRP-21. RX PubMed=29914532; DOI=10.1186/s13023-018-0828-0; RA Li J., Leng Y., Han S., Yan L., Lu C., Luo Y., Zhang X., Cao L.; RT "Clinical and genetic characteristics of Chinese patients with familial or RT sporadic pediatric cataract."; RL Orphanet J. Rare Dis. 13:94-94(2018). RN [66] RP VARIANTS CTRCT9 LEU-12; TRP-21 AND CYS-116. RX PubMed=31523120; RA Zhuang J., Cao Z., Zhu Y., Liu L., Tong Y., Chen X., Wang Y., Lu C., Ma X., RA Yang J.; RT "Mutation screening of crystallin genes in Chinese families with congenital RT cataracts."; RL Mol. Vis. 25:427-437(2019). RN [67] RP VARIANT CTRCT9 CYS-12. RX PubMed=32010934; DOI=10.1042/bsr20191349; RA Liu Q., Zhu S.; RT "Clinical characteristics of congenital lamellar cataract and myopia in a RT Chinese family."; RL Biosci. Rep. 40:0-0(2020). RN [68] RP VARIANT CTRCT9 CYS-49. RX PubMed=33243271; DOI=10.1186/s13023-020-01613-3; RA Berry V., Ionides A., Pontikos N., Georgiou M., Yu J., Ocaka L.A., RA Moore A.T., Quinlan R.A., Michaelides M.; RT "The genetic landscape of crystallins in congenital cataract."; RL Orphanet J. Rare Dis. 15:333-333(2020). CC -!- FUNCTION: Contributes to the transparency and refractive index of the CC lens (PubMed:18302245). In its oxidized form (absence of intramolecular CC disulfide bond), acts as a chaperone, preventing aggregation of various CC proteins under a wide range of stress conditions (PubMed:22120592, CC PubMed:31792453, PubMed:18199971, PubMed:19595763). Required for the CC correct formation of lens intermediate filaments as part of a complex CC composed of BFSP1, BFSP2 and CRYAA (PubMed:28935373). CC {ECO:0000269|PubMed:18199971, ECO:0000269|PubMed:19595763, CC ECO:0000269|PubMed:22120592, ECO:0000269|PubMed:28935373, CC ECO:0000269|PubMed:31792453, ECO:0000303|PubMed:18302245}. CC -!- SUBUNIT: Heteropolymer composed of three CRYAA and one CRYAB subunits CC (PubMed:20836128). Inter-subunit bridging via zinc ions enhances CC stability, which is crucial as there is no protein turn over in the CC lens (PubMed:22890888). Can also form homodimers and homotetramers CC (dimers of dimers) which serve as the building blocks of homooligomers CC (PubMed:17909943, PubMed:31792453, PubMed:23255486). Within CC homooligomers, the zinc-binding motif is created from residues of 3 CC different molecules. His-100 and Glu-102 from one molecule are ligands CC of the zinc ion, and His-107 and His-154 residues from additional CC molecules complete the site with tetrahedral coordination geometry (By CC similarity). Part of a complex required for lens intermediate filament CC formation composed of BFSP1, BFSP2 and CRYAA (PubMed:28935373). CC {ECO:0000250|UniProtKB:P02470, ECO:0000269|PubMed:17909943, CC ECO:0000269|PubMed:20836128, ECO:0000269|PubMed:22890888, CC ECO:0000269|PubMed:23255486, ECO:0000269|PubMed:28935373, CC ECO:0000269|PubMed:31792453}. CC -!- INTERACTION: CC P02489; Q8NC06-3: ACBD4; NbExp=3; IntAct=EBI-6875961, EBI-12811089; CC P02489; P35611: ADD1; NbExp=3; IntAct=EBI-6875961, EBI-2809187; CC P02489; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-6875961, EBI-2875816; CC P02489; O95817: BAG3; NbExp=3; IntAct=EBI-6875961, EBI-747185; CC P02489; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-6875961, EBI-742750; CC P02489; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-6875961, EBI-9092016; CC P02489; Q9H0W9-3: C11orf54; NbExp=3; IntAct=EBI-6875961, EBI-12108466; CC P02489; Q9NNX6-10: CD209; NbExp=3; IntAct=EBI-6875961, EBI-12300031; CC P02489; Q9BXL8: CDCA4; NbExp=3; IntAct=EBI-6875961, EBI-1773949; CC P02489; P49336-2: CDK8; NbExp=3; IntAct=EBI-6875961, EBI-11039720; CC P02489; P20849: COL9A1; NbExp=3; IntAct=EBI-6875961, EBI-2528238; CC P02489; Q86WV2: COX4I1; NbExp=3; IntAct=EBI-6875961, EBI-10260134; CC P02489; P02489: CRYAA; NbExp=12; IntAct=EBI-6875961, EBI-6875961; CC P02489; P02511: CRYAB; NbExp=18; IntAct=EBI-6875961, EBI-739060; CC P02489; P26998: CRYBB3; NbExp=3; IntAct=EBI-6875961, EBI-1965681; CC P02489; P07315: CRYGC; NbExp=3; IntAct=EBI-6875961, EBI-6875941; CC P02489; Q9Y6W6: DUSP10; NbExp=3; IntAct=EBI-6875961, EBI-3443946; CC P02489; Q99944: EGFL8; NbExp=4; IntAct=EBI-6875961, EBI-3924130; CC P02489; P60228: EIF3E; NbExp=3; IntAct=EBI-6875961, EBI-347740; CC P02489; P23588: EIF4B; NbExp=3; IntAct=EBI-6875961, EBI-970310; CC P02489; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-6875961, EBI-10213520; CC P02489; Q6NXG1-3: ESRP1; NbExp=3; IntAct=EBI-6875961, EBI-21567429; CC P02489; Q6NZ36-4: FAAP20; NbExp=3; IntAct=EBI-6875961, EBI-12013806; CC P02489; Q96GL9: FAM163A; NbExp=3; IntAct=EBI-6875961, EBI-11793142; CC P02489; Q06547-2: GABPB1; NbExp=3; IntAct=EBI-6875961, EBI-618189; CC P02489; P15976-2: GATA1; NbExp=3; IntAct=EBI-6875961, EBI-9090198; CC P02489; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-6875961, EBI-8799578; CC P02489; Q9H8Y8: GORASP2; NbExp=12; IntAct=EBI-6875961, EBI-739467; CC P02489; Q13322-4: GRB10; NbExp=3; IntAct=EBI-6875961, EBI-12353035; CC P02489; V9HW27: HEL-S-101; NbExp=3; IntAct=EBI-6875961, EBI-10178933; CC P02489; Q9P0W2: HMG20B; NbExp=3; IntAct=EBI-6875961, EBI-713401; CC P02489; Q4VB01: HOXB1; NbExp=3; IntAct=EBI-6875961, EBI-17494170; CC P02489; P04792: HSPB1; NbExp=4; IntAct=EBI-6875961, EBI-352682; CC P02489; O43464: HTRA2; NbExp=3; IntAct=EBI-6875961, EBI-517086; CC P02489; P42858: HTT; NbExp=3; IntAct=EBI-6875961, EBI-466029; CC P02489; Q14005-2: IL16; NbExp=3; IntAct=EBI-6875961, EBI-17178971; CC P02489; Q0VD86: INCA1; NbExp=3; IntAct=EBI-6875961, EBI-6509505; CC P02489; O60333-2: KIF1B; NbExp=3; IntAct=EBI-6875961, EBI-10975473; CC P02489; P57682: KLF3; NbExp=3; IntAct=EBI-6875961, EBI-8472267; CC P02489; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-6875961, EBI-714379; CC P02489; Q14533: KRT81; NbExp=3; IntAct=EBI-6875961, EBI-739648; CC P02489; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-6875961, EBI-1048945; CC P02489; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-6875961, EBI-10241353; CC P02489; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-6875961, EBI-10261141; CC P02489; Q92615: LARP4B; NbExp=3; IntAct=EBI-6875961, EBI-1052558; CC P02489; Q14847-2: LASP1; NbExp=3; IntAct=EBI-6875961, EBI-9088686; CC P02489; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-6875961, EBI-9088829; CC P02489; Q96JB6: LOXL4; NbExp=3; IntAct=EBI-6875961, EBI-749562; CC P02489; Q99683: MAP3K5; NbExp=3; IntAct=EBI-6875961, EBI-476263; CC P02489; Q15759: MAPK11; NbExp=3; IntAct=EBI-6875961, EBI-298304; CC P02489; Q8N6R0: METTL13; NbExp=3; IntAct=EBI-6875961, EBI-1053295; CC P02489; Q92886: NEUROG1; NbExp=3; IntAct=EBI-6875961, EBI-10279647; CC P02489; Q9Y239: NOD1; NbExp=3; IntAct=EBI-6875961, EBI-1051262; CC P02489; Q96HA8: NTAQ1; NbExp=7; IntAct=EBI-6875961, EBI-741158; CC P02489; Q9Y266: NUDC; NbExp=3; IntAct=EBI-6875961, EBI-357298; CC P02489; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-6875961, EBI-9091052; CC P02489; Q495U3: PANX2; NbExp=3; IntAct=EBI-6875961, EBI-17242559; CC P02489; O15160: POLR1C; NbExp=3; IntAct=EBI-6875961, EBI-1055079; CC P02489; P19388: POLR2E; NbExp=3; IntAct=EBI-6875961, EBI-395189; CC P02489; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-6875961, EBI-25835994; CC P02489; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-6875961, EBI-2860740; CC P02489; P41219: PRPH; NbExp=3; IntAct=EBI-6875961, EBI-752074; CC P02489; P60891: PRPS1; NbExp=3; IntAct=EBI-6875961, EBI-749195; CC P02489; P61289: PSME3; NbExp=3; IntAct=EBI-6875961, EBI-355546; CC P02489; P53801: PTTG1IP; NbExp=3; IntAct=EBI-6875961, EBI-3906138; CC P02489; Q9NWB1-5: RBFOX1; NbExp=3; IntAct=EBI-6875961, EBI-12123390; CC P02489; Q9BWF3: RBM4; NbExp=3; IntAct=EBI-6875961, EBI-2856454; CC P02489; Q8WZ73-3: RFFL; NbExp=3; IntAct=EBI-6875961, EBI-25839575; CC P02489; P47804-3: RGR; NbExp=3; IntAct=EBI-6875961, EBI-25834767; CC P02489; Q9H4E5: RHOJ; NbExp=3; IntAct=EBI-6875961, EBI-6285694; CC P02489; Q969K3: RNF34; NbExp=3; IntAct=EBI-6875961, EBI-2340642; CC P02489; P08865: RPSA; NbExp=3; IntAct=EBI-6875961, EBI-354112; CC P02489; P48443: RXRG; NbExp=3; IntAct=EBI-6875961, EBI-712405; CC P02489; Q8N488: RYBP; NbExp=3; IntAct=EBI-6875961, EBI-752324; CC P02489; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-6875961, EBI-25837959; CC P02489; O00560: SDCBP; NbExp=7; IntAct=EBI-6875961, EBI-727004; CC P02489; Q86SQ7-2: SDCCAG8; NbExp=3; IntAct=EBI-6875961, EBI-10696955; CC P02489; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-6875961, EBI-9089805; CC P02489; Q2NKQ1-4: SGSM1; NbExp=3; IntAct=EBI-6875961, EBI-10182463; CC P02489; Q5T0L3: SPATA46; NbExp=3; IntAct=EBI-6875961, EBI-750105; CC P02489; Q496A3: SPATS1; NbExp=3; IntAct=EBI-6875961, EBI-3923692; CC P02489; Q9NZD8: SPG21; NbExp=7; IntAct=EBI-6875961, EBI-742688; CC P02489; Q9C004: SPRY4; NbExp=3; IntAct=EBI-6875961, EBI-354861; CC P02489; Q96BD6: SPSB1; NbExp=3; IntAct=EBI-6875961, EBI-2659201; CC P02489; O75558: STX11; NbExp=3; IntAct=EBI-6875961, EBI-714135; CC P02489; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-6875961, EBI-11123832; CC P02489; O15273: TCAP; NbExp=3; IntAct=EBI-6875961, EBI-954089; CC P02489; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-6875961, EBI-3923210; CC P02489; Q96A09: TENT5B; NbExp=3; IntAct=EBI-6875961, EBI-752030; CC P02489; Q9BXU0: TEX12; NbExp=3; IntAct=EBI-6875961, EBI-12090309; CC P02489; O60830: TIMM17B; NbExp=3; IntAct=EBI-6875961, EBI-2372529; CC P02489; Q8IU80-2: TMPRSS6; NbExp=3; IntAct=EBI-6875961, EBI-25839648; CC P02489; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-6875961, EBI-9089156; CC P02489; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-6875961, EBI-2509913; CC P02489; Q96A04: TSACC; NbExp=3; IntAct=EBI-6875961, EBI-740411; CC P02489; O60636: TSPAN2; NbExp=3; IntAct=EBI-6875961, EBI-3914288; CC P02489; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-6875961, EBI-9088812; CC P02489; Q13404: UBE2V1; NbExp=3; IntAct=EBI-6875961, EBI-1050671; CC P02489; Q9H9P5-5: UNKL; NbExp=3; IntAct=EBI-6875961, EBI-12817837; CC P02489; Q9NVA1: UQCC1; NbExp=3; IntAct=EBI-6875961, EBI-11911675; CC P02489; Q9NX94: WBP1L; NbExp=3; IntAct=EBI-6875961, EBI-10316321; CC P02489; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-6875961, EBI-12040603; CC P02489; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-6875961, EBI-25830993; CC P02489; Q8WUU4: ZNF296; NbExp=3; IntAct=EBI-6875961, EBI-8834821; CC P02489; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-6875961, EBI-12010736; CC P02489; Q7Z783; NbExp=3; IntAct=EBI-6875961, EBI-9088990; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14512969, CC ECO:0000269|PubMed:19464326, ECO:0000269|PubMed:19503744, CC ECO:0000269|PubMed:26004348, ECO:0000269|PubMed:30340470}. Nucleus CC {ECO:0000269|PubMed:19464326}. Note=Translocates to the nucleus during CC heat shock and resides in sub-nuclear structures known as SC35 speckles CC or nuclear splicing speckles. CC -!- TISSUE SPECIFICITY: Expressed in the eye lens (at protein level). CC {ECO:0000269|PubMed:12356833, ECO:0000269|PubMed:23255486}. CC -!- PTM: O-glycosylated; contains N-acetylglucosamine side chains. CC -!- PTM: Deamidation of Asn-101 in lens occurs mostly during the first 30 CC years of age, followed by a small additional amount of deamidation CC (approximately 5%) during the next approximately 38 years, resulting in CC a maximum of approximately 50% deamidation during the lifetime of the CC individual. {ECO:0000269|PubMed:18754677, ECO:0000269|PubMed:8175657, CC ECO:0000269|PubMed:9068373, ECO:0000269|PubMed:9543632, CC ECO:0000269|PubMed:9655350}. CC -!- PTM: Phosphorylation on Ser-122 seems to be developmentally regulated. CC Absent in the first months of life, it appears during the first 12 CC years of human lifetime. The relative amount of phosphorylated form CC versus unphosphorylated form does not change over the lifetime of the CC individual. {ECO:0000269|PubMed:10930324, ECO:0000269|PubMed:8175657, CC ECO:0000269|PubMed:8759518, ECO:0000269|PubMed:9068373, CC ECO:0000269|PubMed:9655350}. CC -!- PTM: Acetylation at Lys-70 may increase chaperone activity. CC {ECO:0000269|PubMed:22120592, ECO:0000269|PubMed:817940, CC ECO:0000269|PubMed:9655350}. CC -!- PTM: Undergoes age-dependent proteolytical cleavage at the C-terminus. CC Alpha-crystallin A(1-172) is the most predominant form produced most CC rapidly during the first 12 years of age and after this age is present CC in approximately 50% of the lens molecules. CC {ECO:0000269|PubMed:10930324, ECO:0000269|PubMed:12356833, CC ECO:0000269|PubMed:8175657, ECO:0000269|PubMed:9068373, CC ECO:0000269|PubMed:9655350}. CC -!- PTM: In young individuals and during the first approximately 30 years CC of life, less than half molecules contain an intramolecular disulfide CC bond (oxidized form), while in the remaining fraction the cysteines are CC in the free sulfhydryl form (reduced form). With aging, the amount of CC oxidized form increases up to 90% and it becomes a major constituent of CC high molecular weight aggregates, concomitant with an age-dependent CC loss of its chaperone activity. The reduced form is undetectable in CC cataractous lenses. {ECO:0000305|PubMed:31792453}. CC -!- MASS SPECTROMETRY: [Alpha-crystallin A chain]: Mass=19950; CC Method=Electrospray; Evidence={ECO:0000269|PubMed:8175657}; CC -!- MASS SPECTROMETRY: [Alpha-crystallin A(1-172)]: Mass=19863; CC Method=Electrospray; Evidence={ECO:0000269|PubMed:8175657}; CC -!- MASS SPECTROMETRY: [Alpha-crystallin A chain]: Mass=20029; CC Method=Electrospray; Note=With 1 phosphate group.; CC Evidence={ECO:0000269|PubMed:8175657}; CC -!- MASS SPECTROMETRY: [Alpha-crystallin A chain]: Mass=19951; CC Method=Electrospray; Evidence={ECO:0000269|PubMed:9655350}; CC -!- MASS SPECTROMETRY: [Alpha-crystallin A(1-172)]: Mass=19864; CC Method=Electrospray; Evidence={ECO:0000269|PubMed:9655350}; CC -!- MASS SPECTROMETRY: [Alpha-crystallin A chain]: Mass=19947; CC Method=Electrospray; Evidence={ECO:0000269|PubMed:10930324}; CC -!- MASS SPECTROMETRY: [Alpha-crystallin A(1-172)]: Mass=19851; CC Method=Electrospray; Evidence={ECO:0000269|PubMed:10930324}; CC -!- DISEASE: Note=Alpha-crystallin A 1-172 is found at nearly twofold CC higher levels in diabetic lenses than in age-matched control lenses. CC {ECO:0000269|PubMed:12356833}. CC -!- DISEASE: Cataract 9, multiple types (CTRCT9) [MIM:604219]: An CC opacification of the crystalline lens of the eye that frequently CC results in visual impairment or blindness. Opacities vary in CC morphology, are often confined to a portion of the lens, and may be CC static or progressive. In general, the more posteriorly located and CC dense an opacity, the greater the impact on visual function. CTRCT9 CC includes nuclear, zonular central nuclear, anterior polar, cortical, CC embryonal, anterior subcapsular, fan-shaped, and total cataracts, among CC others. In some cases cataract is associated with microcornea without CC any other systemic anomaly or dysmorphism. Microcornea is defined by a CC corneal diameter inferior to 10 mm in both meridians in an otherwise CC normal eye. {ECO:0000269|PubMed:11006246, ECO:0000269|PubMed:11123904, CC ECO:0000269|PubMed:14512969, ECO:0000269|PubMed:16453125, CC ECO:0000269|PubMed:16735993, ECO:0000269|PubMed:16862070, CC ECO:0000269|PubMed:17296897, ECO:0000269|PubMed:17724170, CC ECO:0000269|PubMed:17937925, ECO:0000269|PubMed:18199971, CC ECO:0000269|PubMed:18302245, ECO:0000269|PubMed:18407550, CC ECO:0000269|PubMed:18587492, ECO:0000269|PubMed:19182255, CC ECO:0000269|PubMed:19390652, ECO:0000269|PubMed:19503744, CC ECO:0000269|PubMed:19595763, ECO:0000269|PubMed:20465443, CC ECO:0000269|PubMed:21686328, ECO:0000269|PubMed:21866213, CC ECO:0000269|PubMed:22065922, ECO:0000269|PubMed:22216983, CC ECO:0000269|PubMed:23255486, ECO:0000269|PubMed:23288997, CC ECO:0000269|PubMed:23441109, ECO:0000269|PubMed:23508780, CC ECO:0000269|PubMed:24074001, ECO:0000269|PubMed:25729975, CC ECO:0000269|PubMed:26004348, ECO:0000269|PubMed:26867756, CC ECO:0000269|PubMed:28690483, ECO:0000269|PubMed:28839118, CC ECO:0000269|PubMed:29386872, ECO:0000269|PubMed:29914532, CC ECO:0000269|PubMed:30340470, ECO:0000269|PubMed:31523120, CC ECO:0000269|PubMed:32010934, ECO:0000269|PubMed:33243271, CC ECO:0000269|PubMed:9467006}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the small heat shock protein (HSP20) family. CC {ECO:0000255|PROSITE-ProRule:PRU00285}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U05569; AAA97523.1; -; mRNA. DR EMBL; U66584; AAC50900.1; -; mRNA. DR EMBL; X14789; CAA32891.1; -; mRNA. DR EMBL; KM220588; AMM63583.1; -; mRNA. DR EMBL; KM220592; AMM63587.1; -; mRNA. DR EMBL; KM220591; AMM63586.1; -; mRNA. DR EMBL; KM220590; AMM63585.1; -; mRNA. DR EMBL; KM220589; AMM63584.1; -; mRNA. DR EMBL; CR407691; CAG28619.1; -; mRNA. DR EMBL; AP001631; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP001748; BAA95535.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09497.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09498.1; -; Genomic_DNA. DR EMBL; BC069528; AAH69528.1; -; mRNA. DR EMBL; BC113598; AAI13599.1; -; mRNA. DR EMBL; M35628; AAA52106.1; -; Genomic_DNA. DR EMBL; M35629; AAA52105.1; -; Genomic_DNA. DR CCDS; CCDS13695.1; -. DR PIR; S03344; CYHUAA. DR RefSeq; NP_000385.1; NM_000394.3. DR RefSeq; NP_001300979.1; NM_001314050.2. DR PDB; 6T1R; EM; 9.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-173. DR PDBsum; 6T1R; -. DR AlphaFoldDB; P02489; -. DR EMDB; EMD-4894; -. DR EMDB; EMD-4895; -. DR EMDB; EMD-4896; -. DR SMR; P02489; -. DR BioGRID; 107799; 193. DR BioGRID; 3195755; 7. DR DIP; DIP-41265N; -. DR IntAct; P02489; 107. DR MINT; P02489; -. DR STRING; 9606.ENSP00000291554; -. DR BindingDB; P02489; -. DR ChEMBL; CHEMBL4296283; -. DR MoonDB; P02489; Curated. DR TCDB; 8.A.172.1.2; the Alpha-crystallin chaperone (crya) family. DR GlyConnect; 33; 1 O-GlcNAc glycan. DR GlyCosmos; P02489; 1 site, 1 glycan. DR GlyGen; P02489; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; P02489; -. DR PhosphoSitePlus; P02489; -. DR BioMuta; CRYAA; -. DR DMDM; 1706112; -. DR MassIVE; P02489; -. DR PaxDb; 9606-ENSP00000291554; -. DR PeptideAtlas; P02489; -. DR PRIDE; P02489; -. DR ProteomicsDB; 20516; -. DR ProteomicsDB; 51526; -. DR Antibodypedia; 23982; 498 antibodies from 30 providers. DR Antibodypedia; 78327; 2 antibodies from 1 providers. DR DNASU; 1409; -. DR Ensembl; ENST00000291554.6; ENSP00000291554.2; ENSG00000160202.7. DR GeneID; 102724652; -. DR GeneID; 1409; -. DR KEGG; hsa:102724652; -. DR KEGG; hsa:1409; -. DR MANE-Select; ENST00000291554.6; ENSP00000291554.2; NM_000394.4; NP_000385.1. DR UCSC; uc002zdd.3; human. DR UCSC; uc061ywn.1; human. DR AGR; HGNC:2388; -. DR CTD; 1409; -. DR DisGeNET; 102724652; -. DR DisGeNET; 1409; -. DR GeneCards; CRYAA; -. DR HGNC; HGNC:2388; CRYAA. DR HPA; ENSG00000160202; Group enriched (kidney, retina). DR MalaCards; CRYAA; -. DR MIM; 123580; gene. DR MIM; 604219; phenotype. DR neXtProt; NX_P02489; -. DR OpenTargets; ENSG00000160202; -. DR Orphanet; 1377; Cataract-microcornea syndrome. DR Orphanet; 98988; Early-onset anterior polar cataract. DR Orphanet; 441452; Early-onset lamellar cataract. DR Orphanet; 98991; Early-onset nuclear cataract. DR Orphanet; 98994; Total early-onset cataract. DR PharmGKB; PA26906; -. DR VEuPathDB; HostDB:ENSG00000160202; -. DR VEuPathDB; HostDB:ENSG00000276076; -. DR eggNOG; KOG3591; Eukaryota. DR GeneTree; ENSGT00940000160159; -. DR HOGENOM; CLU_095001_2_0_1; -. DR InParanoid; P02489; -. DR OMA; QSAMICI; -. DR OrthoDB; 3014506at2759; -. DR PhylomeDB; P02489; -. DR TreeFam; TF105049; -. DR PathwayCommons; P02489; -. DR SignaLink; P02489; -. DR SIGNOR; P02489; -. DR BioGRID-ORCS; 102724652; 0 hits in 4 CRISPR screens. DR BioGRID-ORCS; 1409; 9 hits in 1139 CRISPR screens. DR GeneWiki; CRYAA; -. DR Pharos; P02489; Tchem. DR PRO; PR:P02489; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P02489; Protein. DR Bgee; ENSG00000160202; Expressed in adult mammalian kidney and 31 other cell types or tissues. DR ExpressionAtlas; P02489; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005212; F:structural constituent of eye lens; IEA:UniProtKB-KW. DR GO; GO:0005198; F:structural molecule activity; IDA:UniProtKB. DR GO; GO:0051082; F:unfolded protein binding; IMP:UniProtKB. DR GO; GO:0002088; P:lens development in camera-type eye; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:HGNC-UCL. DR GO; GO:0032387; P:negative regulation of intracellular transport; IDA:HGNC-UCL. DR GO; GO:0042026; P:protein refolding; IBA:GO_Central. DR GO; GO:0050821; P:protein stabilization; IMP:CAFA. DR GO; GO:0009408; P:response to heat; IBA:GO_Central. DR GO; GO:0007601; P:visual perception; IMP:UniProtKB. DR CDD; cd06497; ACD_alphaA-crystallin_HspB4; 1. DR Gene3D; 2.60.40.790; -; 1. DR InterPro; IPR002068; A-crystallin/Hsp20_dom. DR InterPro; IPR001436; Alpha-crystallin/sHSP_animal. DR InterPro; IPR003090; Alpha-crystallin_N. DR InterPro; IPR008978; HSP20-like_chaperone. DR PANTHER; PTHR45640:SF14; ALPHA-CRYSTALLIN A CHAIN; 1. DR PANTHER; PTHR45640; HEAT SHOCK PROTEIN HSP-12.2-RELATED; 1. DR Pfam; PF00525; Crystallin; 1. DR Pfam; PF00011; HSP20; 1. DR PIRSF; PIRSF036514; Sm_HSP_B1; 1. DR PRINTS; PR00299; ACRYSTALLIN. DR SUPFAM; SSF49764; HSP20-like chaperones; 1. DR PROSITE; PS01031; SHSP; 1. DR SWISS-2DPAGE; P02489; -. DR Genevisible; P02489; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cataract; Chaperone; Cytoplasm; KW Direct protein sequencing; Disease variant; Disulfide bond; KW Eye lens protein; Glycoprotein; Metal-binding; Nucleus; Oxidation; KW Phosphoprotein; Reference proteome; Sensory transduction; Vision; Zinc. FT CHAIN 1..173 FT /note="Alpha-crystallin A chain" FT /id="PRO_0000125865" FT CHAIN 1..172 FT /note="Alpha-crystallin A(1-172)" FT /id="PRO_0000226639" FT CHAIN 1..168 FT /note="Alpha-crystallin A(1-168)" FT /id="PRO_0000423503" FT CHAIN 1..162 FT /note="Alpha-crystallin A(1-162)" FT /id="PRO_0000423504" FT DOMAIN 52..164 FT /note="sHSP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00285" FT REGION 1..63 FT /note="Required for complex formation with BFSP1 and BFSP2; FT during homooligomerization, mediates the association of 2 FT dimers to form a tetramer" FT /evidence="ECO:0000269|PubMed:28935373, FT ECO:0000269|PubMed:31792453" FT BINDING 100 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P02470" FT BINDING 102 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P02470" FT BINDING 107 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:22890888" FT BINDING 154 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P02470" FT SITE 1 FT /note="Susceptible to oxidation" FT SITE 18 FT /note="Susceptible to oxidation" FT SITE 34 FT /note="Susceptible to oxidation" FT SITE 138 FT /note="Susceptible to oxidation" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|PubMed:817940" FT MOD_RES 6 FT /note="Deamidated glutamine; partial" FT /evidence="ECO:0000269|PubMed:9068373" FT MOD_RES 45 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:9068373" FT MOD_RES 50 FT /note="Deamidated glutamine; partial" FT /evidence="ECO:0000269|PubMed:9068373" FT MOD_RES 70 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:22120592, FT ECO:0000269|PubMed:9655350" FT MOD_RES 90 FT /note="Deamidated glutamine; partial" FT /evidence="ECO:0000269|PubMed:9068373" FT MOD_RES 99 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:22120592" FT MOD_RES 101 FT /note="Deamidated asparagine; partial" FT /evidence="ECO:0000269|PubMed:8175657, FT ECO:0000269|PubMed:9068373, ECO:0000269|PubMed:9543632, FT ECO:0000269|PubMed:9655350" FT MOD_RES 122 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:8175657, FT ECO:0000269|PubMed:8759518, ECO:0000269|PubMed:9068373" FT MOD_RES 123 FT /note="Deamidated asparagine; partial" FT /evidence="ECO:0000269|PubMed:18754677" FT MOD_RES 147 FT /note="Deamidated glutamine; partial" FT /evidence="ECO:0000269|PubMed:9068373" FT CARBOHYD 162 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000250" FT DISULFID 131..142 FT /evidence="ECO:0000269|PubMed:31792453, FT ECO:0000269|PubMed:8175657, ECO:0000269|PubMed:9068373" FT VARIANT 9..173 FT /note="Missing (in CTRCT9; uncertain significance; FT dbSNP:rs74315440)" FT /evidence="ECO:0000269|PubMed:11006246" FT /id="VAR_084768" FT VARIANT 12 FT /note="R -> C (in CTRCT9; delays HSP70 expression increase FT in response to heat shock; dbSNP:rs397515624)" FT /evidence="ECO:0000269|PubMed:17724170, FT ECO:0000269|PubMed:18587492, ECO:0000269|PubMed:19390652, FT ECO:0000269|PubMed:19503744, ECO:0000269|PubMed:21686328, FT ECO:0000269|PubMed:23508780, ECO:0000269|PubMed:32010934" FT /id="VAR_070032" FT VARIANT 12 FT /note="R -> L (in CTRCT9; reduces protein solubility)" FT /evidence="ECO:0000269|PubMed:30340470, FT ECO:0000269|PubMed:31523120" FT /id="VAR_084769" FT VARIANT 21 FT /note="R -> L (in CTRCT9)" FT /evidence="ECO:0000269|PubMed:16453125" FT /id="VAR_046892" FT VARIANT 21 FT /note="R -> Q (in CTRCT9; decreases oligomer formation; FT dbSNP:rs397515626)" FT /evidence="ECO:0000269|PubMed:23255486, FT ECO:0000269|PubMed:26867756" FT /id="VAR_084770" FT VARIANT 21 FT /note="R -> W (in CTRCT9; dbSNP:rs397515625)" FT /evidence="ECO:0000269|PubMed:17724170, FT ECO:0000269|PubMed:18587492, ECO:0000269|PubMed:19182255, FT ECO:0000269|PubMed:23441109, ECO:0000269|PubMed:29386872, FT ECO:0000269|PubMed:29914532, ECO:0000269|PubMed:31523120" FT /id="VAR_084771" FT VARIANT 49 FT /note="R -> C (in CTRCT9; dbSNP:rs74315441)" FT /evidence="ECO:0000269|PubMed:14512969, FT ECO:0000269|PubMed:19182255, ECO:0000269|PubMed:33243271" FT /id="VAR_038375" FT VARIANT 54 FT /note="R -> C (in CTRCT9; uncertain significance; FT dbSNP:rs397515623)" FT /evidence="ECO:0000269|PubMed:17937925, FT ECO:0000269|PubMed:18587492, ECO:0000269|PubMed:28839118" FT /id="VAR_084772" FT VARIANT 54 FT /note="R -> L (in CTRCT9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:24074001" FT /id="VAR_084773" FT VARIANT 54 FT /note="R -> P (in CTRCT9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:23288997" FT /id="VAR_084774" FT VARIANT 65 FT /note="R -> Q (in CTRCT9; uncertain significance; FT dbSNP:rs199640007)" FT /evidence="ECO:0000269|PubMed:28690483" FT /id="VAR_084775" FT VARIANT 71 FT /note="F -> L (in CTRCT9; uncertain significance; reduced FT chaperone-like activity in vitro)" FT /evidence="ECO:0000269|PubMed:19595763" FT /id="VAR_084776" FT VARIANT 98 FT /note="G -> R (in CTRCT9; forms inclusion bodies, decreases FT chaperone activity, decreases protein stability at 45 FT degrees Celsius and increases protein aggregate formation FT in response to DTT in vitro; dbSNP:rs398122947)" FT /evidence="ECO:0000269|PubMed:16862070, FT ECO:0000269|PubMed:18199971, ECO:0000269|PubMed:21866213" FT /id="VAR_084777" FT VARIANT 105 FT /note="D -> H (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036564" FT VARIANT 116 FT /note="R -> C (in CTRCT9; zonular central nuclear cataract; FT reduced chaperone-like activity and increased FT membrane-binding capacity; dbSNP:rs74315439)" FT /evidence="ECO:0000269|PubMed:11123904, FT ECO:0000269|PubMed:16735993, ECO:0000269|PubMed:17296897, FT ECO:0000269|PubMed:20465443, ECO:0000269|PubMed:31523120, FT ECO:0000269|PubMed:9467006" FT /id="VAR_003819" FT VARIANT 116 FT /note="R -> H (in CTRCT9; reverse phase-high-performance FT liquid chromatography suggests an increased hydrophobicity FT of the mutant protein; loss of chaperone activity of the FT mutant is seen in DL-dithiothreitol-induced insulin FT aggregation assay; fast protein liquid chromatography FT purification shows that the mutant protein has increased FT binding affinity to lysozyme; dbSNP:rs121912973)" FT /evidence="ECO:0000269|PubMed:18302245, FT ECO:0000269|PubMed:18407550, ECO:0000269|PubMed:22065922, FT ECO:0000269|PubMed:22216983" FT /id="VAR_046893" FT VARIANT 117..118 FT /note="RY -> H (in CTRCT9; uncertain significance; FT dbSNP:rs367826363)" FT /evidence="ECO:0000269|PubMed:21866213" FT /id="VAR_084779" FT VARIANT 117 FT /note="Missing (in CTRCT9)" FT /evidence="ECO:0000269|PubMed:25729975" FT /id="VAR_084778" FT VARIANT 119 FT /note="R -> H (in CTRCT9; uncertain significance; FT dbSNP:rs760170206)" FT /evidence="ECO:0000269|PubMed:28690483" FT /id="VAR_084780" FT VARIANT 139 FT /note="L -> P (in CTRCT9; results in protein aggregation in FT the cytoplasm)" FT /evidence="ECO:0000269|PubMed:26004348" FT /id="VAR_084781" FT MUTAGEN 123 FT /note="N->D: Impairs chaperone activity." FT /evidence="ECO:0000269|PubMed:18754677" FT CONFLICT 45 FT /note="S -> T (in Ref. 10; AAA52105)" FT /evidence="ECO:0000305" FT CONFLICT 153..155 FT /note="THA -> HT (in Ref. 2)" FT /evidence="ECO:0000305" SQ SEQUENCE 173 AA; 19909 MW; 81804A8439837D50 CRC64; MDVTIQHPWF KRTLGPFYPS RLFDQFFGEG LFEYDLLPFL SSTISPYYRQ SLFRTVLDSG ISEVRSDRDK FVIFLDVKHF SPEDLTVKVQ DDFVEIHGKH NERQDDHGYI SREFHRRYRL PSNVDQSALS CSLSADGMLT FCGPKIQTGL DATHAERAIP VSREEKPTSA PSS //