ID CRYAB_HUMAN Reviewed; 175 AA. AC P02511; O43416; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1990, sequence version 2. DT 23-JAN-2007, entry version 89. DE Alpha crystallin B chain (Alpha(B)-crystallin) (Rosenthal fiber DE component) (Heat-shock protein beta-5) (HspB5) (Renal carcinoma DE antigen NY-REN-27). GN Name=CRYAB; Synonyms=CRYA2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP PRELIMINARY PROTEIN SEQUENCE. RX MEDLINE=77116204; PubMed=838078; DOI=10.1016/0014-5793(77)80757-6; RA Kramps J.A., de Man B.M., de Jong W.W.; RT "The primary structure of the B2 chain of human alpha-crystallin."; RL FEBS Lett. 74:82-84(1977). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=90353958; PubMed=2387586; RA Dubin R.A., Ally A.H., Chung S., Piatigorsky J.; RT "Human alpha B-crystallin gene and preferential promoter function in RT lens."; RL Genomics 7:594-601(1990). RN [3] RP NUCLEOTIDE SEQUENCE. RX MEDLINE=93025869; PubMed=1407707; DOI=10.1016/0304-3940(92)90689-5; RA Iwaki A., Iwaki T., Goldman J.E., Ogomori K., Tateishi J., Sakaki Y.; RT "Accumulation of alpha B-crystallin in brains of patients with RT Alexander's disease is not due to an abnormality of the 5'-flanking RT and coding sequence of the genomic DNA."; RL Neurosci. Lett. 140:89-92(1992). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Yu W., Sarginson J., Gibbs R.A.; RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 107-175. RX MEDLINE=89195224; PubMed=2539261; DOI=10.1016/0092-8674(89)90173-6; RA Iwaki T., Kume-Iwaki A., Liem R.K.H., Goldman J.E.; RT "Alpha B-crystallin is expressed in non-lenticular tissues and RT accumulates in Alexander's disease brain."; RL Cell 57:71-78(1989). RN [8] RP PROTEIN SEQUENCE OF 83-89 AND 164-172. RC TISSUE=Heart; RX MEDLINE=96007936; PubMed=7498159; RA Kovalyov L.I., Shishkin S.S., Efimochkin A.S., Kovalyova M.A., RA Ershova E.S., Egorov T.A., Musalyamov A.K.; RT "The major protein expression profile and two-dimensional protein RT database of human heart."; RL Electrophoresis 16:1160-1169(1995). RN [9] RP PROTEIN SEQUENCE OF 57-66. RX MEDLINE=97152999; 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 RT the identification of the major proteins in young human lens."; RL J. Biol. Chem. 272:2268-2275(1997). RN [10] RP RACEMIZATION/ISOMERIZATION OF SPECIFIC ASP. RX MEDLINE=94190996; PubMed=8142454; DOI=10.1016/0167-4838(94)90003-5; RA Fujii N., Ishibashi Y., Satoh K., Fujino M., Harada K.; RT "Simultaneous racemization and isomerization at specific aspartic acid RT residues in alpha B-crystallin from the aged human lens."; RL Biochim. Biophys. Acta 1204:157-163(1994). RN [11] RP PHOSPHORYLATION AT SER-19; SER-45 AND SER-59, AND MASS SPECTROMETRY. RX PubMed=8175657; RA Miesbauer L.R., Zhou X., Yang Z., Yang Z., Sun Y., Smith D.L., RA Smith J.B.; RT "Post-translational modifications of water-soluble human lens RT crystallins from young adults."; RL J. Biol. Chem. 269:12494-12502(1994). RN [12] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX MEDLINE=99438124; PubMed=10508479; RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal- RT cell carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [13] RP MASS SPECTROMETRY, SUSCEPTIBILITY TO OXIDATION, AND PHOSPHORYLATION. 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 [14] RP PHOSPHORYLATION AT SER-45 AND SER-59. RX MEDLINE=21103870; PubMed=11158243; RA Kato K., Inaguma Y., Ito H., Iida K., Iwamoto I., Kamei K., Ochi N., RA Ohta H., Kishikawa M.; RT "Ser-59 is the major phosphorylation site in alphaB-crystallin RT accumulated in the brains of patients with Alexander's disease."; RL J. Neurochem. 76:730-736(2001). RN [15] RP ACETYLATION AT LYS-92. RX PubMed=11369851; DOI=10.1110/ps.40901; RA Lapko V.N., Smith D.L., Smith J.B.; RT "In vivo carbamylation and acetylation of water-soluble human lens RT alphaB-crystallin lysine 92."; RL Protein Sci. 10:1130-1136(2001). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-21; SER-43; RP SER-45; SER-53; SER-59 AND SER-76, METHYLATION AT ARG-22 AND ARG-50, RP ACETYLATION AT LYS-92, SUSCEPTIBILITY TO OXIDATION, AND MASS RP SPECTROMETRY. RX MEDLINE=22056091; PubMed=12060738; DOI=10.1073/pnas.122231399; RA MacCoss M.J., McDonald W.H., Saraf A., Sadygov R., Clark J.M., RA Tasto J.J., Gould K.L., Wolters D., Washburn M., Weiss A., Clark J.I., RA Yates J.R. III; RT "Shotgun identification of protein modifications from protein RT complexes and lens tissue."; RL Proc. Natl. Acad. Sci. U.S.A. 99:7900-7905(2002). RN [17] RP INVOLVEMENT IN ALPHA-B CRYSTALLINOPATHY. RX PubMed=14681890; DOI=10.1002/ana.10767; RA Selcen D., Engel A.G.; RT "Myofibrillar myopathy caused by novel dominant negative alpha B- RT crystallin mutations."; RL Ann. Neurol. 54:804-810(2003). RN [18] RP INTERACTION WITH TTN. RX PubMed=14676215; DOI=10.1074/jbc.M307473200; RA Bullard B., Ferguson C., Minajeva A., Leake M.C., Gautel M., RA Labeit D., Ding L., Labeit S., Horwitz J., Leonard K.R., Linke W.A.; RT "Association of the chaperone alphaB-crystallin with titin in heart RT muscle."; RL J. Biol. Chem. 279:7917-7924(2004). RN [19] RP VARIANT ALPHA-B CRYSTALLINOPATHY GLY-120. RX MEDLINE=98400266; PubMed=9731540; DOI=10.1038/1765; RA Vicart P., Caron A., Guicheney P., Li Z., Prevost M.-C., Faure A., RA Chateau D., Chapon F., Tome F., Dupret J.-M., Paulin D., Fardeau M.; RT "A missense mutation in the alphaB-crystallin chaperone gene causes a RT desmin-related myopathy."; RL Nat. Genet. 20:92-95(1998). RN [20] RP CHARACTERIZATION OF VARIANTS ALPHA-B CRYSTALLINOPATHY GLY-120. RX MEDLINE=22489080; PubMed=12601044; DOI=10.1167/iovs.02-0950; RA Fu L., Liang J.J.; RT "Alteration of protein-protein interactions of congenital cataract RT crystallin mutants."; RL Invest. Ophthalmol. Vis. Sci. 44:1155-1159(2003). CC -!- FUNCTION: May contribute to the transparency and refractive index CC of the lens. CC -!- SUBUNIT: Aggregates with homologous proteins, including CRYAA and CC the small heat shock protein HSP28, to form large heteromeric CC complexes. Interacts with TTN/titin. CC -!- INTERACTION: CC Q9UJY1:HSPB8; NbExp=1; IntAct=EBI-739060, EBI-739074; CC -!- TISSUE SPECIFICITY: Lens as well as other tissues. CC -!- MASS SPECTROMETRY: MW=20201; METHOD=Electrospray; RANGE=1-175; CC NOTE=Ref.11. CC -!- MASS SPECTROMETRY: MW=20281; METHOD=Electrospray; RANGE=1-175; CC NOTE=With one phosphorylation (Ref.11). CC -!- MASS SPECTROMETRY: MW=20360; METHOD=Electrospray; RANGE=1-175; CC NOTE=With two phosphorylations (Ref.11). CC -!- MASS SPECTROMETRY: MW=20199; METHOD=Electrospray; RANGE=1-175; CC NOTE=Ref.13. CC -!- MASS SPECTROMETRY: MW=20278; METHOD=Electrospray; RANGE=1-175; CC NOTE=With one phosphorylation (Ref.13). CC -!- DISEASE: Seen as Rosenthal fiber protein in the brain tissue of CC patients with Alexander disease [MIM:203450]. CC -!- DISEASE: Defects in CRYAB are the cause of alpha-B CC crystallinopathy [MIM:608810]. Alpha-B crystallinopathy is a an CC autosomal dominant form of desmin-related myopathy (DRM) that CC results in weakness of the proximal and distal limb muscle CC (including neck, velopharynx, and trunk muscles), signs of CC cardiomyopathy and cataract. Patients with progressive myopathy CC characterized by myofibrillar degeneration that commences at the CC Z-disk, have been described. Mutations truncate the essential C- CC terminal domain of the protein required for the chaperone CC function. CC -!- DISEASE: Crystallins do not turn over as the lens ages, providing CC ample opportunity for post-translational modifications or CC oxidations. These modifications may change crystallin solubility CC properties and favor senile cataract. CC -!- SIMILARITY: Belongs to the small heat shock protein (HSP20) CC family. CC -!- WEB RESOURCE: NAME=GeneReviews; CC URL="http://www.genetests.org/query?gene=CRYAB". 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; M28638; AAA52104.1; -; Genomic_DNA. DR EMBL; S45630; AAB23453.1; -; mRNA. DR EMBL; AF007162; AAC19161.1; -; mRNA. DR EMBL; BT006770; AAP35416.1; -; mRNA. DR EMBL; BC007008; AAH07008.1; -; mRNA. DR EMBL; M24906; AAA60267.1; -; mRNA. DR PIR; A35332; CYHUAB. DR UniGene; Hs.408767; -. DR IntAct; P02511; -. DR GlycoSuiteDB; P02511; -. DR SWISS-2DPAGE; P02511; HUMAN. DR HSC-2DPAGE; P02511; HUMAN. DR Ensembl; ENSG00000109846; Homo sapiens. DR KEGG; hsa:1410; -. DR H-InvDB; HIX0010115; -. DR HGNC; HGNC:2389; CRYAB. DR HPA; CAB002053; -. DR MIM; 123590; gene+phenotype. DR MIM; 203450; phenotype. DR MIM; 608810; phenotype. DR ArrayExpress; P02511; -. DR GermOnline; ENSG00000109846; Homo sapiens. DR RZPD-ProtExp; D0298; -. DR RZPD-ProtExp; IOH7286; -. DR RZPD-ProtExp; RZPDo839D0862; -. DR RZPD-ProtExp; RZPDo839D0872; -. DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc. DR GO; GO:0006457; P:protein folding; NAS:ProtInc. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kin...; NAS:UniProtKB. DR InterPro; IPR012273; A-crystallin_B. DR InterPro; IPR011369; Alpha-crystallin. DR InterPro; IPR001436; Crystallin_alpha. DR InterPro; IPR003090; Crystallin_N. DR InterPro; IPR002068; Hsp20. DR InterPro; IPR008978; HSP20_chap. DR Pfam; PF00525; Crystallin; 1. DR Pfam; PF00011; HSP20; 1. DR PIRSF; PIRSF500017; A-crystallin_B; 1. DR PIRSF; PIRSF002280; Alpha-crystallin; 1. DR PRINTS; PR00299; ACRYSTALLIN. DR ProDom; PD001193; Crystallin_N; 1. DR PROSITE; PS01031; HSP20; 1. KW Acetylation; Cataract; Desmin-related myopathy; KW Direct protein sequencing; Disease mutation; Eye lens protein; KW Glycoprotein; Methylation; Oxidation; Phosphorylation; Polymorphism. FT CHAIN 1 175 Alpha crystallin B chain. FT /FTId=PRO_0000125907. FT SITE 48 48 Susceptible to oxidation. FT SITE 60 60 Susceptible to oxidation. FT SITE 68 68 Susceptible to oxidation. FT MOD_RES 1 1 N-acetylmethionine (Probable). FT MOD_RES 19 19 Phosphoserine. FT MOD_RES 21 21 Phosphoserine. FT MOD_RES 22 22 Omega-N-methylated arginine. FT MOD_RES 43 43 Phosphoserine. FT MOD_RES 45 45 Phosphoserine. FT MOD_RES 50 50 Omega-N-methylated arginine. FT MOD_RES 53 53 Phosphoserine. FT MOD_RES 59 59 Phosphoserine. FT MOD_RES 76 76 Phosphoserine. FT MOD_RES 92 92 N6-acetyllysine (partial). FT CARBOHYD 170 170 O-linked (GlcNAc) (By similarity). FT VARIANT 41 41 S -> Y (in dbSNP:rs2234703). FT /FTId=VAR_014607. FT VARIANT 51 51 P -> L (in dbSNP:rs2234704). FT /FTId=VAR_014608. FT VARIANT 120 120 R -> G (in alpha-B crystallinopathy; FT decreased interactions with wild-type FT CRYAA and CRYAB but increased FT interactions with wild-type CRYBB2 and FT CRYGC). FT /FTId=VAR_007899. FT CONFLICT 165 165 E -> K (in Ref. 4). FT CONFLICT 175 175 K -> KKMPFLELHFLKQESFPTSE (in Ref. 4). SQ SEQUENCE 175 AA; 20159 MW; AE08BED46B7849CB CRC64; MDIAIHHPWI RRPFFPFHSP SRLFDQFFGE HLLESDLFPT STSLSPFYLR PPSFLRAPSW FDTGLSEMRL EKDRFSVNLD VKHFSPEELK VKVLGDVIEV HGKHEERQDE HGFISREFHR KYRIPADVDP LTITSSLSSD GVLTVNGPRK QVSGPERTIP ITREEKPAVT AAPKK //