CRYAB

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CRYAB
Protein CRYAB PDB 2KLR.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCRYAB, CMD1II, CRYA2, CTPP2, CTRCT16, HEL-S-101, HSPB5, MFM2, crystallin alpha B
External IDsMGI: 88516 HomoloGene: 68209 GeneCards: CRYAB
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for CRYAB
Genomic location for CRYAB
Band11q23.1Start111,908,565 bp[1]
End111,923,722 bp[1]
RNA expression pattern
PBB GE CRYAB 209283 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001289807
NM_001289808
NM_001885
NM_001330379

NM_001289782
NM_001289784
NM_001289785
NM_009964

RefSeq (protein)

NP_001276736
NP_001276737
NP_001317308
NP_001876

NP_001276711
NP_001276713
NP_001276714
NP_034094

Location (UCSC)Chr 11: 111.91 – 111.92 MbChr 9: 50.75 – 50.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Alpha-crystallin B chain is a protein that in humans is encoded by the CRYAB gene.[5] It is part of the small heat shock protein family and functions as molecular chaperone that primarily binds misfolded proteins to prevent protein aggregation, as well as inhibit apoptosis and contribute to intracellular architecture.[6][7][8] Post-translational modifications decrease the ability to chaperone.[6][8] Defects in this gene/protein have been associated with cancer and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.[6][7][8]

Structure[edit]

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. These heterogeneous aggregates consist of 30–40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively.[6]

Function[edit]

Alpha B chain crystallins (αBC) can be induced by heat shock, ischemia, and oxidation, and are members of the small heat shock protein (sHSP also known as the HSP20) family.[6][9] They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead, they bind improperly folded proteins to prevent protein aggregation.[6][7][8]

Furthermore, αBC may confer stress resistance to cells by inhibiting the processing of the pro-apoptotic protein caspase-3.[8] 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. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy.[6]

Clinical significance[edit]

Although not yet clearly understood, defective chaperone activity is expected to trigger the accumulation of protein aggregates and underlie the development of α-crystallinopathy, or the failure of protein quality control, resulting in protein deposition diseases such as Alzheimer’s disease and Parkinson’s disease. Mutations in CRYAB could also cause restrictive cardiomyopathy.[10] ER-anchored αBC can suppress aggregate formation mediated by the disease mutant.Thus, modulation of the micromilieu surrounding the ER membrane can serve as a potential target in developing pharmacological interventions for protein deposition disease.[7]

Though expressed highly in eye lens and muscle tissues, αBC can also be found in several types of cancer, among which head and neck squamous cell carcinoma (HNSCC) and breast carcinomas, as well as in patients with tuberous sclerosis.[11] αBC expression is associated with metastasis formation in HNSCC and in breast carcinomas and in other types of cancer, expression is often correlated with poor prognosis as well.[12] The expression of αBC can be increased during various stresses, like heat shock, osmotic stress or exposure to heavy metals, which then may lead to prolonged survival of cells under these conditions.[8]

Interactions[edit]

CRYAB has been shown to interact with:

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000109846 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032060 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Jeanpierre C, Austruy E, Delattre O, Jones C, Junien C (March 1993). "Subregional physical mapping of an alpha B-crystallin sequence and of a new expressed sequence D11S877E to human 11q". Mammalian Genome. 4 (2): 104–8. doi:10.1007/BF00290434. PMID 8431633. 
  6. ^ a b c d e f g "Entrez Gene: CRYAB crystallin, alpha B". 
  7. ^ a b c d Yamamoto S, Yamashita A, Arakaki N, Nemoto H, Yamazaki T (December 2014). "Prevention of aberrant protein aggregation by anchoring the molecular chaperone αB-crystallin to the endoplasmic reticulum". Biochemical and Biophysical Research Communications. 455 (3-4): 241–5. doi:10.1016/j.bbrc.2014.10.151. PMID 25449278. 
  8. ^ a b c d e f van de Schootbrugge C, Schults EM, Bussink J, Span PN, Grénman R, Pruijn GJ, Kaanders JH, Boelens WC (April 2014). "Effect of hypoxia on the expression of αB-crystallin in head and neck squamous cell carcinoma". BMC Cancer. 14: 252. doi:10.1186/1471-2407-14-252. PMC 3990244Freely accessible. PMID 24725344. 
  9. ^ Easterbrook M, Trope G (1989). "Value of Humphrey perimetry in the detection of early chloroquine retinopathy". Lens and Eye Toxicity Research. 6 (1-2): 255–68. PMID 2488020. 
  10. ^ Brodehl A, Gaertner-Rommel A, Klauke B, Grewe SA, Schirmer I, Peterschröder A, Faber L, Vorgerd M, Gummert J, Anselmetti D, Schulz U, Paluszkiewicz L, Milting H (August 2017). "The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy". Human Mutation. 38 (8): 947–952. doi:10.1002/humu.23248. PMID 28493373. 
  11. ^ Wang F, Chen X, Li C, Sun Q, Chen Y, Wang Y, Peng H, Liu Z, Chen R, Liu K, Yan H, Ye BH, Kwiatkowski DJ, Zhang H (August 2014). "Pivotal role of augmented αB-crystallin in tumor development induced by deficient TSC1/2 complex". Oncogene. 33 (34): 4352–8. doi:10.1038/onc.2013.401. PMID 24077282. 
  12. ^ Moyano JV, Evans JR, Chen F, Lu M, Werner ME, Yehiely F, Diaz LK, Turbin D, Karaca G, Wiley E, Nielsen TO, Perou CM, Cryns VL (January 2006). "AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer". The Journal of Clinical Investigation. 116 (1): 261–70. doi:10.1172/JCI25888. PMC 1323258Freely accessible. PMID 16395408. 
  13. ^ a b c d Fu L, Liang JJ (February 2002). "Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay". The Journal of Biological Chemistry. 277 (6): 4255–60. doi:10.1074/jbc.M110027200. PMID 11700327. 
  14. ^ Sugiyama Y, Suzuki A, Kishikawa M, Akutsu R, Hirose T, Waye MM, Tsui SK, Yoshida S, Ohno S (January 2000). "Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation". The Journal of Biological Chemistry. 275 (2): 1095–104. doi:10.1074/jbc.275.2.1095. PMID 10625651. 
  15. ^ Kato K, Shinohara H, Goto S, Inaguma Y, Morishita R, Asano T (April 1992). "Copurification of small heat shock protein with alpha B crystallin from human skeletal muscle". The Journal of Biological Chemistry. 267 (11): 7718–25. PMID 1560006. 
  16. ^ Boelens WC, Croes Y, de Jong WW (January 2001). "Interaction between alphaB-crystallin and the human 20S proteasomal subunit C8/alpha7". Biochimica et Biophysica Acta. 1544 (1-2): 311–9. doi:10.1016/S0167-4838(00)00243-0. PMID 11341940. 

Further reading[edit]

  • Derham BK, Harding JJ (July 1999). "Alpha-crystallin as a molecular chaperone". Progress in Retinal and Eye Research. 18 (4): 463–509. doi:10.1016/S1350-9462(98)00030-5. PMID 10217480. 
  • Calinisan V, Gravem D, Chen RP, Brittin S, Mohandas N, Lecomte MC, Gascard P (May 2006). "New insights into potential functions for the protein 4.1 superfamily of proteins in kidney epithelium". Frontiers in Bioscience. 11: 1646–66. doi:10.2741/1911. PMID 16368544. 

External links[edit]