CRYAB

Last updated
CRYAB
Protein CRYAB PDB 2KLR.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CRYAB , CMD1II, CRYA2, CTPP2, CTRCT16, HEL-S-101, HSPB5, MFM2, crystallin alpha B
External IDs OMIM: 123590 MGI: 88516 HomoloGene: 68209 GeneCards: CRYAB
Orthologs
SpeciesHumanMouse
Entrez

1410

12955

Ensembl

ENSG00000109846

ENSMUSG00000032060

UniProt

P02511

P23927

RefSeq (mRNA)

NM_001289782
NM_001289784
NM_001289785
NM_009964

RefSeq (protein)

NP_001276711
NP_001276713
NP_001276714
NP_034094

Location (UCSC) Chr 11: 111.91 – 111.92 Mb Chr 9: 50.66 – 50.67 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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] Mutations in CRYAB cause different cardiomyopathies, [9] skeletal myopathies [10] mainly myofibrillar myopathy, [11] and also cataracts. [12] In addition, 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

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

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] [13] 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

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. [14] 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. [15] 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. [16] 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

CRYAB has been shown to interact with:

Related Research Articles

Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including exposure to cold, UV light and during wound healing or tissue remodeling. Many members of this group perform chaperone functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress. This increase in expression is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). HSPs are found in virtually all living organisms, from bacteria to humans.

In anatomy, a crystallin is a water-soluble structural protein found in the lens and the cornea of the eye accounting for the transparency of the structure. It has also been identified in other places such as the heart, and in aggressive breast cancer tumors. Since it has been shown that lens injury may promote nerve regeneration, crystallin has been an area of neural research. So far, it has been demonstrated that crystallin β b2 (crybb2) may be a neurite-promoting factor.

<span class="mw-page-title-main">Desmin</span> Mammalian protein found in Homo sapiens

Desmin is a protein that in humans is encoded by the DES gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture.

<span class="mw-page-title-main">Hsp27</span> Protein-coding gene in the species Homo sapiens

Heat shock protein 27 (Hsp27) also known as heat shock protein beta-1 (HSPB1) is a protein that in humans is encoded by the HSPB1 gene.

<span class="mw-page-title-main">HSP90B1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein 90kDa beta member 1 (HSP90B1), known also as endoplasmin, gp96, grp94, or ERp99, is a chaperone protein that in humans is encoded by the HSP90B1 gene.

<span class="mw-page-title-main">HSP90AB1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein HSP 90-beta also called HSP90beta is a protein that in humans is encoded by the HSP90AB1 gene.

<span class="mw-page-title-main">HSPB8</span>

Heat shock protein beta-8 is a protein that in humans is encoded by the HSPB8 gene.

<span class="mw-page-title-main">HSPA4</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the HSPA4 gene.

<span class="mw-page-title-main">DNAJB1</span> Protein-coding gene in the species Homo sapiens

DnaJ homolog subfamily B member 1 is a protein that in humans is encoded by the DNAJB1 gene.

<span class="mw-page-title-main">ST13</span>

Hsc70-interacting protein also known as suppression of tumorigenicity 13 (ST13) is a protein that in humans is encoded by the ST13 gene.

<span class="mw-page-title-main">HSPB2</span> Protein-coding gene in the species Homo sapiens

Heat shock protein beta-2 is a protein that in humans is encoded by the HSPB2 gene.

<span class="mw-page-title-main">HSPA1L</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 1L is a protein that in humans is encoded by the HSPA1L gene on chromosome 6. As a member of the heat shock protein 70 (Hsp70) family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease.

<span class="mw-page-title-main">LDB3</span> Protein-coding gene in the species Homo sapiens

LIM domain binding 3 (LDB3), also known as Z-band alternatively spliced PDZ-motif (ZASP), is a protein which in humans is encoded by the LDB3 gene. ZASP belongs to the Enigma subfamily of proteins and stabilizes the sarcomere during contraction, through interactions with actin in cardiac and skeletal muscles. Mutations in the ZASP gene has been associated with several muscular diseases.

<span class="mw-page-title-main">HSPB6</span> Protein-coding gene in the species Homo sapiens

Heat shock protein beta-6 (HSPB6) is a protein that in humans is encoded by the HSPB6 gene.

<span class="mw-page-title-main">CRYAA</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">FourU thermometer</span> Class of non-coding RNAs in Salmonella

FourU thermometers are a class of non-coding RNA thermometers found in Salmonella. They are named 'FourU' due to the four highly conserved uridine nucleotides found directly opposite the Shine-Dalgarno sequence on hairpin II (pictured). RNA thermometers such as FourU control regulation of temperature via heat shock proteins in many prokaryotes. FourU thermometers are relatively small RNA molecules, only 57 nucleotides in length, and have a simple two-hairpin structure.

The heat shock protein Hsp20 family, also known as small heat shock proteins (sHSPs), is a family of heat shock proteins.

<span class="mw-page-title-main">Protein moonlighting</span> Proteins performing more than one function

Protein moonlighting is a phenomenon by which a protein can perform more than one function. Ancestral moonlighting proteins originally possessed a single function but through evolution, acquired additional functions. Many proteins that moonlight are enzymes; others are receptors, ion channels or chaperones. The most common primary function of moonlighting proteins is enzymatic catalysis, but these enzymes have acquired secondary non-enzymatic roles. Some examples of functions of moonlighting proteins secondary to catalysis include signal transduction, transcriptional regulation, apoptosis, motility, and structural.

<span class="mw-page-title-main">HSPB3</span> Protein-coding gene in the species Homo sapiens

Heat shock protein beta-3 (HspB3) also known as heat shock 27kDa protein 3 is a protein that in humans is encoded by the HSPB3 gene.

<span class="mw-page-title-main">HSPB7</span> Gene of the species Homo sapiens

Heat Shock Protein Family B (small) member 7 (HSPB7) in humans is a protein encoded by a gene of the same name with four exons that is located on chromosome 1p36.13.,. HSPB7 contains 170 amino acids and has a molecular weight of 18,611Da. HSPB7 is a member of human small heat shock protein (HSPB) family, which contains eleven family members of chaperone proteins. HSPB7 and its gene pair SRARP are located 5 kb apart on the opposite strands of chromosome 1p36.13.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000109846 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032060 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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. S2CID   9038111.
  6. 1 2 3 4 5 6 7 "Entrez Gene: CRYAB crystallin, alpha B".
  7. 1 2 3 4 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. 1 2 3 4 5 6 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   3990244 . PMID   24725344.
  9. ↑ Brodehl, Andreas; Gaertner-Rommel, Anna; Klauke, Bärbel; Grewe, Simon Andre; Schirmer, Ilona; Peterschröder, Andreas; Faber, Lothar; Vorgerd, Matthias; Gummert, Jan (August 2017). "The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy". Human Mutation. 38 (8): 947–952. doi: 10.1002/humu.23248 . ISSN   1098-1004. PMID   28493373. S2CID   13942559.
  10. ↑ Vicart, P.; Caron, A.; Guicheney, P.; Li, Z.; Prévost, M. C.; Faure, A.; Chateau, D.; Chapon, F.; Tomé, F. (September 1998). "A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy". Nature Genetics. 20 (1): 92–95. doi:10.1038/1765. ISSN   1061-4036. PMID   9731540. S2CID   24517435.
  11. ↑ Fichna JP, Maruszak A, Żekanowski C (November 2018). "Myofibrillar myopathy in the genomic context". Journal of Applied Genetics. 59 (4): 431–439. doi: 10.1007/s13353-018-0463-4 . PMID   30203143.
  12. ↑ Fichna JP, Potulska-Chromik A, Miszta P, Redowicz MJ, Kaminska AM, Zekanowski C, Filipek S (November 2016). "A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects αB-crystallin structure". BBA Clinical. 7: 1–7. doi:10.1016/j.bbacli.2016.11.004. PMC   5124346 . PMID   27904835.
  13. ↑ 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.
  14. ↑ 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. S2CID   13942559.
  15. ↑ 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.
  16. ↑ 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   1323258 . PMID   16395408.
  17. 1 2 3 4 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.
  18. ↑ 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.
  19. ↑ 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. doi: 10.1016/S0021-9258(18)42574-4 . PMID   1560006.
  20. ↑ Boelens WC, Croes Y, de Jong WW (January 2001). "Interaction between αB-crystallin and the human 20S proteasomal subunit C8/α7". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1544 (1–2): 311–9. doi:10.1016/S0167-4838(00)00243-0. PMID   11341940.

Further reading

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