| Written | 2009-03 | Aysegul Ilhan, Ludwig Wagner, Wolfgang Gartner |
| Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria |
| Identity |
| Other names | Alpha(B)-crystallin |
| CRYA2 | |
| CTPP2 | |
| HSPB5 | |
| HspB5 | |
| HGNC (Hugo) | CRYAB |
| LocusID (NCBI) | 1410 |
| Atlas_Id | 40156 |
| Location | 11q23.1 [Link to chromosome band 11q23] |
| Location_base_pair | Starts at 111779344 and ends at 111783937 bp from pter ( according to hg19-Feb_2009) [Mapping CRYAB.png] |
| Fusion genes (updated 2016) | CRYAB (11q23.1) / DES (2q35) | CRYAB (11q23.1) / GRK5 (10q26.11) | CRYAB (11q23.1) / UNKL (16p13.3) |
| FDXACB1 (11q23.1) / CRYAB (11q23.1) | LOC100507412 (-) / CRYAB (11q23.1) | MCTP2 (15q26.2) / CRYAB (11q23.1) | |
| PRIM2 (6p11.2) / CRYAB (11q23.1) | SUGCT (7p14.1) / CRYAB (11q23.1) | TEF (22q13.2) / CRYAB (11q23.1) | |
| DNA/RNA |
| Description | Crystallins are a highly conserved protein family consisting of three classes, alpha, beta and gamma. The alpha crystallins are divided into two groups according to their acidic as well as basic character, namely A and B. The genes encoding the alpha crystallins A and B are located at chromosome 11 and 21, respectively. The hamster alpha-B crystallin (CRYAB) gene, which is highly homologous to that of humans, was cloned at first by Quax-Jeuken and it was demonstrated that the coding region of CRYAB consists of three exons (Quax-Jeuken et al., 1985). |
| Transcription | CRYAB was primarily found to be expressed in the lens. At the mRNA level Dubin and his group were the first to detect CRYAB expression in several other tissues such as the lung, heart, skeletal muscle, kidney and to a lower extent within the brain and spleen (Dubin et al., 1989). |
| Protein |
| Description | CRYAB encodes a 175 amino acid long protein with a molecular weight of 22kDa. Although the three-dimensional structure of CRYAB has not been resolved yet, the crystal structures of closely related other members of the heat shock protein family are available. This provided the assumption that CRYAB is composed of a highly conserved "alpha crystallin core" domain consisting of about 80 to 100 residues with a beta-sandwich structure (Ghosh et al., 2005). |
| Expression | CRYAB was initially found in the vertebrate lens. Iwaki and his group demonstrated CRYAB expression within heart, skeletal muscles, striated muscle, sciatic nerve, kidney and placenta by immunohistochemistry as well as immunoblotting and northern analyses (Iwaki et al., 1990). Furthermore, CRYAB was found to be expressed in several human neoplasms. |
| Localisation | CRYAB exhibits mainly a cytosolic distribution. However, nuclear localisation with speckled intranuclear formations in various types of unstressed cells was also reported (van den et al., 2003). |
| Function | CRYAB as well as alpha-A crystallin contribute to ~35% of all vertebrate lens proteins. Therefore, it was firstly suggested that these proteins might be responsible for the refractory index of the eye and for maintaining lens transparency. However, the high abundance of CRYAB in tissues other than the lens and its high homology to heat shock proteins suggested that CRYAB might also represent a small heat shock protein with the potential to exert molecular chaperone function. This suggestion was strengthened by Klemenz et al. by showing heat shock inducability of CRYAB on the promoter level (Klemenz et al., 1991). Basing on the potential of heat shock proteins to bind to unfolded and denatured proteins, thus maintaining a less non-specific protein aggregation, a potential role of CRYAB in inclusion body formation in the course of several neurodegenerative diseases such as Alexander disease (Iwaki et al., 1993), Alzheimer's disease (Shinohara et al., 1993), Creutzfeldt-Jacob disease (Kato et al., 1992) and Parkinson's disease (Iwaki et al., 1992) has been suggested. Furthermore CRYAB was found to serve as an auto-antigen in multiple sclerosis (van Noort et al., 1995) and it was shown that small heat shock proteins such as CRYAB are involved in the promotion of prolonged survival of cancer cells by inhibiting apoptosis (Kamradt et al., 2001). |
| Homology | CRYAB exhibits a high homology of 56% to alpha-A-crystallin. Moreover, additional homologies to several other heat shock proteins were demonstrated (Wistow, 1985). |
| Mutations |
| Note | Until now, there are two known mutations within the CRYAB gene with potential impact on human pathologies. Vicart and his group found a missense mutation of R120G within the CRYAB gene, which was associated with desmin-related myopathy (Vicart et al., 1998). Furthermore a deletion mutation within exon 3, 450delA, which results in an aberrant protein, was found to be related to dominant posterior congenital cataract in humans (Berry et al., 2001). |
| Implicated in |
| Note | |
| Entity | Breast cancer |
| Note | It was reported that CRYAB expression is strongly associated with lymph node metastasis in breast cancer (Chelouche-Lev et al., 2004). This result was further supported by the high abundance of CRYAB in basal like breast carcinoma, which represents a subgroup of breast cancers with bad prognosis and high metastatic potential (Moyano et al., 2006). Furthermore, this research group demonstrated activation of the MEK/ERK pathway through CRYAB over-expression in immortalized human mammary epithelial cells, which lead to increased cell migration and invasion. This effect could be entirely suppressed using MEK/ERK inhibitors. |
| Entity | Renal cell carcinoma |
| Note | Up-regulation of CRYAB expression was found in cultured renal cell carcinoma cells as well as in tissues derived from renal cell carcinomas (Shi et al., 2004). This finding was further confirmed by another research group using protein chip and immunohistochemistry analyses (Holcakova et al., 2008). |
| Entity | Brain tumours |
| Note | Expression of CRYAB within malignant brain tumours such as astrocytomas, oligodendrogliomas and glioblastoma multiforme (GBM) was reported (Iwaki et al., 1991; Aoyama et al., 1993; Shinohara et al., 1993). Moreover, it was demonstrated that chemotherapy induces an increased expression of CRYAB in neuroblastomas (Ishiguro et al., 1997). Comparative proteomic studies on human low grade astrocytomas and GBM showed a significant higher expression of CRYAB within the GBM (Odreman et al., 2005). |
| Entity | Anaplastic thyroid carcinoma |
| Note | Mineva showed differential regulation of CRYAB and the closely related heat shock protein 27-1 (HSP27-1) within the highly malignant anaplastic thyroid carcinomas (ATC). Whereas CRYAB expression was found to be down-regulated, HSP27-1 was considerably expressed within ATC (Mineva et al., 2005). Analyses of the CRYAB promotor region including tumor associated methylation analysis as well as CRYAB promoter specific trasncription factor analysis lead to the suggestion that this might be due to tumor specific transcription factor and promoter methylation patterns. |
| Entity | Buccal squamous carcinoma |
| Note | This type of carcinoma, which is mostly seen in central and southeast Asia, is characterized by a considerably aggressive course. Chen and his group performed a proteomic assay in order to define the expression pattern of cancer-related proteins within this tumor entity. Similar to the anaplastic thyroid carcinomas, CRYAB was found to be underrepresented, whereas several other proteins involved in heat shock responses and anti-oxidative processes were up-regulated (Chen et al., 2004). |
| Entity | Head and neck cancer |
| Note | In consistence with findings of breast cancer research, a high extent of CRYAB expression was found to be a strong predictive marker for short survival rates of patients suffering from head and neck cancer (Chin et al., 2005). However, an investigation of head and neck squamous cell carcinoma did not reveal a significant association between patient survival and CRYAB expression (Boslooper et al., 2008). |
| Entity | Hepatocellular carcinoma |
| Note | The CRYAB gene was found to be highly expressed in a subgroup of hepatocellular carcinomas, which was associated with declined survival rates (Tang et al., 2009). It was suggested that CRYAB might serve as a prognostic marker within hepatocellular carcinomas. |
| Bibliography |
| Expression of alpha B-crystallin in human brain tumors. |
| Aoyama A, Steiger RH, Frohli E, Schafer R, von Deimling A, Wiestler OD, Klemenz R. |
| Int J Cancer. 1993 Nov 11;55(5):760-4. |
| PMID 8244572 |
| Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. |
| Berry V, Francis P, Reddy MA, Collyer D, Vithana E, MacKay I, Dawson G, Carey AH, Moore A, Bhattacharya SS, Quinlan RA. |
| Am J Hum Genet. 2001 Nov;69(5):1141-5. Epub 2001 Sep 27. |
| PMID 11577372 |
| The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma. |
| Boslooper K, King-Yin Lam A, Gao J, Weinstein S, Johnson N. |
| Pathology. 2008 Aug;40(5):500-4. |
| PMID 18604737 |
| alphaB-crystallin as a marker of lymph node involvement in breast carcinoma. |
| Chelouche-Lev D, Kluger HM, Berger AJ, Rimm DL, Price JE. |
| Cancer. 2004 Jun 15;100(12):2543-8. |
| PMID 15197794 |
| Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis. |
| Chen J, He QY, Yuen AP, Chiu JF. |
| Proteomics. 2004 Aug;4(8):2465-75. |
| PMID 15274141 |
| Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer. |
| Chin D, Boyle GM, Williams RM, Ferguson K, Pandeya N, Pedley J, Campbell CM, Theile DR, Parsons PG, Coman WB. |
| Laryngoscope. 2005 Jul;115(7):1239-42. |
| PMID 15995513 |
| Expression of the murine alpha B-crystallin gene is not restricted to the lens. |
| Dubin RA, Wawrousek EF, Piatigorsky J. |
| Mol Cell Biol. 1989 Mar;9(3):1083-91. |
| PMID 2725488 |
| Interactive domains for chaperone activity in the small heat shock protein, human alphaB crystallin. |
| Ghosh JG, Estrada MR, Clark JI. |
| Biochemistry. 2005 Nov 15;44(45):14854-69. |
| PMID 16274233 |
| Identification of alphaB-crystallin, a biomarker of renal cell carcinoma by SELDI-TOF MS. |
| Holcakova J, Hernychova L, Bouchal P, Brozkova K, Zaloudik J, Valik D, Nenutil R, Vojtesek B. |
| Int J Biol Markers. 2008 Jan-Mar;23(1):48-53. |
| PMID 18409151 |
| Chemotherapy-induced expression of alpha B-crystallin in neuroblastoma. |
| Ishiguro Y, Kato K, Akatsuka H, Iwata H, Nagaya M. |
| Med Pediatr Oncol. 1997 Jul;29(1):11-5. |
| PMID 9142199 |
| Alpha B-crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers. |
| Iwaki T, Iwaki A, Tateishi J, Sakaki Y, Goldman JE. |
| Am J Pathol. 1993 Aug;143(2):487-95. |
| PMID 8393618 |
| Cellular distribution of alpha B-crystallin in non-lenticular tissues. |
| Iwaki T, Kume-Iwaki A, Goldman JE. |
| J Histochem Cytochem. 1990 Jan;38(1):31-9. |
| PMID 2294148 |
| Accumulation of alpha B-crystallin in central nervous system glia and neurons in pathologic conditions. |
| Iwaki T, Wisniewski T, Iwaki A, Corbin E, Tomokane N, Tateishi J, Goldman JE. |
| Am J Pathol. 1992 Feb;140(2):345-56. |
| PMID 1739128 |
| The small heat shock protein alpha B-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. |
| Kamradt MC, Chen F, Cryns VL. |
| J Biol Chem. 2001 May 11;276(19):16059-63. Epub 2001 Mar 23. |
| PMID 11274139 |
| Ultrastructural and immunohistochemical studies on ballooned cortical neurons in Creutzfeldt-Jakob disease: expression of alpha B-crystallin, ubiquitin and stress-response protein 27. |
| Kato S, Hirano A, Umahara T, Llena JF, Herz F, Ohama E. |
| Acta Neuropathol. 1992;84(4):443-8. |
| PMID 1332365 |
| Alpha B-crystallin is a small heat shock protein. |
| Klemenz R, Frohli E, Steiger RH, Schafer R, Aoyama A. |
| Proc Natl Acad Sci U S A. 1991 May 1;88(9):3652-6. |
| PMID 2023914 |
| Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing. |
| Mineva I, Gartner W, Hauser P, Kainz A, Loffler M, Wolf G, Oberbauer R, Weissel M, Wagner L. |
| Cell Stress Chaperones. 2005 Autumn;10(3):171-84. |
| PMID 16184762 |
| AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer. |
| 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. |
| J Clin Invest. 2006 Jan;116(1):261-70. |
| PMID 16395408 |
| Proteomic studies on low- and high-grade human brain astrocytomas. |
| Odreman F, Vindigni M, Gonzales ML, Niccolini B, Candiano G, Zanotti B, Skrap M, Pizzolitto S, Stanta G, Vindigni A. |
| J Proteome Res. 2005 May-Jun;4(3):698-708. |
| PMID 15952716 |
| Complete structure of the alpha B-crystallin gene: conservation of the exon-intron distribution in the two nonlinked alpha-crystallin genes. |
| Quax-Jeuken Y, Quax W, van Rens G, Khan PM, Bloemendal H. |
| Proc Natl Acad Sci U S A. 1985 Sep;82(17):5819-23. |
| PMID 3862098 |
| Differential protein profiling in renal-cell carcinoma. |
| Shi T, Dong F, Liou LS, Duan ZH, Novick AC, DiDonato JA. |
| Mol Carcinog. 2004 May;40(1):47-61. |
| PMID 15108329 |
| Alpha B crystallin and HSP28 are enhanced in the cerebral cortex of patients with Alzheimer's disease. |
| Shinohara H, Inaguma Y, Goto S, Inagaki T, Kato K. |
| J Neurol Sci. 1993 Nov;119(2):203-8. |
| PMID 8277336 |
| Expression and prognostic significance of the alpha B-crystallin gene in human hepatocellular carcinoma. |
| Tang Q, Liu YF, Zhu XJ, Li YH, Zhu J, Zhang JP, Feng ZQ, Guan XH. |
| Hum Pathol. 2009 Mar;40(3):300-5. Epub 2008 Nov 7. |
| PMID 18992912 |
| A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. |
| Vicart P, Caron A, Guicheney P, Li Z, Prevost MC, Faure A, Chateau D, Chapon F, Tome F, Dupret JM, Paulin D, Fardeau M. |
| Nat Genet. 1998 Sep;20(1):92-5. |
| PMID 9731540 |
| Domain structure and evolution in alpha-crystallins and small heat-shock proteins. |
| Wistow G. |
| FEBS Lett. 1985 Feb 11;181(1):1-6. |
| PMID PMID: |
| The small heat-shock protein alpha B-crystallin as candidate autoantigen in multiple sclerosis. |
| van Noort JM, van Sechel AC, Bajramovic JJ, el Ouagmiri M, Polman CH, Lassmann H, Ravid R. |
| Nature. 1995 Jun 29;375(6534):798-801. |
| PMID 7596414 |
| Nuclear speckle localisation of the small heat shock protein alpha B-crystallin and its inhibition by the R120G cardiomyopathy-linked mutation. |
| van den IJssel P, Wheelock R, Prescott A, Russell P, Quinlan RA. |
| Exp Cell Res. 2003 Jul 15;287(2):249-61. |
| PMID 12837281 |
| Citation |
| This paper should be referenced as such : |
| Ilhan, A ; Wagner, L ; Gartner, W |
| CRYAB (crystallin, alpha B) |
| Atlas Genet Cytogenet Oncol Haematol. 2010;14(2):108-110. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/CRYABID40156ch11q23.html |
| External links |
| REVIEW articles | automatic search in PubMed |
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| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Sep 28 15:57:48 CEST 2016 |
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