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CRYAB (crystallin, alpha B)

Identity

Other namesAlpha(B)-crystallin
CRYA2
CTPP2
HSPB5
HspB5
HGNC (Hugo) CRYAB
LocusID (NCBI) 1410
Location 11q23.1
Location_base_pair Starts at 111779344 and ends at 111783937 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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

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.
  

External links

Nomenclature
HGNC (Hugo)CRYAB   2389
Cards
AtlasCRYABID40156ch11q23
Entrez_Gene (NCBI)CRYAB  1410  crystallin, alpha B
GeneCards (Weizmann)CRYAB
Ensembl (Hinxton)ENSG00000109846 [Gene_View]  chr11:111779344-111783937 [Contig_View]  CRYAB [Vega]
ICGC DataPortalENSG00000109846
AceView (NCBI)CRYAB
Genatlas (Paris)CRYAB
WikiGenes1410
SOURCE (Princeton)NM_001289807 NM_001289808 NM_001885
Genomic and cartography
GoldenPath (UCSC)CRYAB  -  11q23.1   chr11:111779344-111783937 -  11q22.3-q23.1   [Description]    (hg19-Feb_2009)
EnsemblCRYAB - 11q22.3-q23.1 [CytoView]
Mapping of homologs : NCBICRYAB [Mapview]
OMIM123590   613763   615184   
Gene and transcription
Genbank (Entrez)AF007162 AK295498 AK314029 AM392549 AM393027
RefSeq transcript (Entrez)NM_001289807 NM_001289808 NM_001885
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NG_009824 NG_033080 NT_033899 NW_001838042 NW_004929381
Consensus coding sequences : CCDS (NCBI)CRYAB
Cluster EST : UnigeneHs.703770 [ NCBI ]
CGAP (NCI)Hs.703770
Alternative Splicing : Fast-db (Paris)GSHG0033178
Alternative Splicing GalleryENSG00000109846
Gene ExpressionCRYAB [ NCBI-GEO ]     CRYAB [ SEEK ]   CRYAB [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP02511 (Uniprot)
NextProtP02511  [Medical]
With graphics : InterProP02511
Splice isoforms : SwissVarP02511 (Swissvar)
Domaine pattern : Prosite (Expaxy)HSP20 (PS01031)   
Domains : Interpro (EBI)a-crystallin/Hsp20_dom    Alpha-crystallin/HSP    Alpha-crystallin_B    Alpha-crystallin_N    HSP20-like_chaperone   
Related proteins : CluSTrP02511
Domain families : Pfam (Sanger)Crystallin (PF00525)    HSP20 (PF00011)   
Domain families : Pfam (NCBI)pfam00525    pfam00011   
DMDM Disease mutations1410
Blocks (Seattle)P02511
PDB (SRS)2KLR    2WJ7    2Y1Y    2Y1Z    2Y22    2YGD    3L1G    3SGM    3SGN    3SGO    3SGP    3SGR    3SGS    4M5S    4M5T   
PDB (PDBSum)2KLR    2WJ7    2Y1Y    2Y1Z    2Y22    2YGD    3L1G    3SGM    3SGN    3SGO    3SGP    3SGR    3SGS    4M5S    4M5T   
PDB (IMB)2KLR    2WJ7    2Y1Y    2Y1Z    2Y22    2YGD    3L1G    3SGM    3SGN    3SGO    3SGP    3SGR    3SGS    4M5S    4M5T   
PDB (RSDB)2KLR    2WJ7    2Y1Y    2Y1Z    2Y22    2YGD    3L1G    3SGM    3SGN    3SGO    3SGP    3SGR    3SGS    4M5S    4M5T   
Human Protein AtlasENSG00000109846
Peptide AtlasP02511
HPRD00428
IPIIPI00021369   IPI00981161   IPI00794466   IPI00981730   IPI00978451   IPI00982183   IPI00792299   IPI00981675   IPI00975518   
Protein Interaction databases
DIP (DOE-UCLA)P02511
IntAct (EBI)P02511
FunCoupENSG00000109846
BioGRIDCRYAB
IntegromeDBCRYAB
STRING (EMBL)CRYAB
Ontologies - Pathways
QuickGOP02511
Ontology : AmiGOresponse to hypoxia  lens development in camera-type eye  structural constituent of eye lens  protein binding  nucleus  cytoplasm  mitochondrion  Golgi apparatus  cytosol  plasma membrane  glucose metabolic process  protein folding  muscle contraction  tubulin complex assembly  muscle organ development  aging  microtubule binding  cell surface  negative regulation of gene expression  regulation of cell death  microtubule cytoskeleton  Z disc  negative regulation of cell growth  microtubule polymerization or depolymerization  response to estradiol  negative regulation of intracellular transport  actin filament bundle  response to hydrogen peroxide  identical protein binding  protein homodimerization activity  negative regulation of apoptotic process  negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  metal ion binding  unfolded protein binding  protein homooligomerization  stress-activated MAPK cascade  apoptotic process involved in morphogenesis  extracellular vesicular exosome  cellular response to gamma radiation  negative regulation of reactive oxygen species metabolic process  
Ontology : EGO-EBIresponse to hypoxia  lens development in camera-type eye  structural constituent of eye lens  protein binding  nucleus  cytoplasm  mitochondrion  Golgi apparatus  cytosol  plasma membrane  glucose metabolic process  protein folding  muscle contraction  tubulin complex assembly  muscle organ development  aging  microtubule binding  cell surface  negative regulation of gene expression  regulation of cell death  microtubule cytoskeleton  Z disc  negative regulation of cell growth  microtubule polymerization or depolymerization  response to estradiol  negative regulation of intracellular transport  actin filament bundle  response to hydrogen peroxide  identical protein binding  protein homodimerization activity  negative regulation of apoptotic process  negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  metal ion binding  unfolded protein binding  protein homooligomerization  stress-activated MAPK cascade  apoptotic process involved in morphogenesis  extracellular vesicular exosome  cellular response to gamma radiation  negative regulation of reactive oxygen species metabolic process  
Pathways : KEGGProtein processing in endoplasmic reticulum   
Protein Interaction DatabaseCRYAB
Wikipedia pathwaysCRYAB
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)CRYAB
SNP (GeneSNP Utah)CRYAB
SNP : HGBaseCRYAB
Genetic variants : HAPMAPCRYAB
1000_GenomesCRYAB 
ICGC programENSG00000109846 
CONAN: Copy Number AnalysisCRYAB 
Somatic Mutations in Cancer : COSMICCRYAB 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)Leiden Muscular Dystrophy pages
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Eye diseases - LOVD
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
DECIPHER (Syndromes)11:111779344-111783937
Mutations and Diseases : HGMDCRYAB
OMIM123590    613763    615184   
MedgenCRYAB
GENETestsCRYAB
Disease Genetic AssociationCRYAB
Huge Navigator CRYAB [HugePedia]  CRYAB [HugeCancerGEM]
Genomic VariantsCRYAB  CRYAB [DGVbeta]
Exome VariantCRYAB
dbVarCRYAB
ClinVarCRYAB
snp3D : Map Gene to Disease1410
General knowledge
Homologs : HomoloGeneCRYAB
Homology/Alignments : Family Browser (UCSC)CRYAB
Phylogenetic Trees/Animal Genes : TreeFamCRYAB
Chemical/Protein Interactions : CTD1410
Chemical/Pharm GKB GenePA26907
Clinical trialCRYAB
Cancer Resource (Charite)ENSG00000109846
Other databases
Probes
Litterature
PubMed240 Pubmed reference(s) in Entrez
CoreMineCRYAB
GoPubMedCRYAB
iHOPCRYAB

Bibliography

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PMID 3862098
 
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PMID PMID:
 
Expression of the murine alpha B-crystallin gene is not restricted to the lens.
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Mol Cell Biol. 1989 Mar;9(3):1083-91.
PMID 2725488
 
Cellular distribution of alpha B-crystallin in non-lenticular tissues.
Iwaki T, Kume-Iwaki A, Goldman JE.
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PMID 2294148
 
Preferential expression of alpha B-crystallin in astrocytic elements of neuroectodermal tumors.
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PMID 1655207
 
Alpha B-crystallin is a small heat shock protein.
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PMID 2023914
 
Accumulation of alpha B-crystallin in central nervous system glia and neurons in pathologic conditions.
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PMID 1739128
 
Ultrastructural and immunohistochemical studies on ballooned cortical neurons in Creutzfeldt-Jakob disease: expression of alpha B-crystallin, ubiquitin and stress-response protein 27.
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Alpha B-crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers.
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PMID 8393618
 
Alpha B crystallin and HSP28 are enhanced in the cerebral cortex of patients with Alzheimer's disease.
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PMID 8277336
 
The small heat-shock protein alpha B-crystallin as candidate autoantigen in multiple sclerosis.
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Nature. 1995 Jun 29;375(6534):798-801.
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Chemotherapy-induced expression of alpha B-crystallin in neuroblastoma.
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PMID 9142199
 
A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy.
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Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans.
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PMID 11577372
 
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.
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PMID 11274139
 
Nuclear speckle localisation of the small heat shock protein alpha B-crystallin and its inhibition by the R120G cardiomyopathy-linked mutation.
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alphaB-crystallin as a marker of lymph node involvement in breast carcinoma.
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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
 
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, a new independent marker for poor prognosis in head and neck cancer.
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Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing.
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PMID 16184762
 
Proteomic studies on low- and high-grade human brain astrocytomas.
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AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer.
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The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma.
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PMID 18604737
 
Identification of alphaB-crystallin, a biomarker of renal cell carcinoma by SELDI-TOF MS.
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PMID 18992912
 
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Contributor(s)

Written03-2009Aysegul Ilhan, Ludwig Wagner, Wolfgang Gartner
Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria

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):-.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/CRYABID40156ch11q23.html

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indexed on : Sat Nov 8 16:45:12 CET 2014

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