Official Symbol: CRYABprovided by HGNC
Official Full Name: crystallin, alpha Bprovided by HGNC
Primary Source: HGNC:2389
See related: Ensembl:ENSG00000109846; HPRD:00428; MIM:123590
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CRYA2; CTPP2; HSPB5; CRYAB
Summary: 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. Alpha crystallins can be induced by heat shock and are members of the small heat shock protein (sHSP also known as the HSP20) family. They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead they hold them in large soluble aggregates. Post-translational modifications decrease the ability to chaperone. These heterogeneous aggregates consist of 30-40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively. 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. [provided by RefSeq]

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(minus strand) Go to reference sequence details Try our new Sequence Viewer

[Top][Help]Bibliography

GeneRIFs: Gene References Into Function What's a GeneRIF?

	1.	the motifs III and IV of betaA3-crystallin were interactive with alphaA-crystallin, and motifs II and III of betaA3-crystallin primarily interacted with alphaB-crystallin
	2.	These results supported the idea that the novel R11H mutation was responsible for the autosomal dominant nuclear congenital cataract in this pedigree.
	3.	Co-immunoprecipitation experiments rule out an interaction of alphaA(alphaB)-crystallins with PAR-1, PAR-3, and PAR-4, demonstrating that alphaA(alphaB)-crystallins are PAR-2-specific interaction proteins.
	4.	The structures of recombinant alpha-crystallins were analyzed using biophysical methods.
	5.	The large amount of HSP27, alphaB-crystallin, and HSP70 in the cytoskeletal/myofibrillar fraction after a repeated bout of exercise suggests a protective role as part of the repeated-bout effect.
	6.	Single molecule force spectroscopy of the cardiac titin N2B element: effects of the molecular chaperone alphaB-crystallin with disease-causing mutations.
	7.	immune response to CRYAB and possible involvement in multiple sclerosis and EAE [REVIEW]
	8.	study reports levels of alphaB-crystallin are slightly increased in Down syndrome(DS) brain; amounts of alphaB-crystallin phosphorylated at Ser45 & Ser59 are dramatically higher in brains of older children & young adults with DS than age-matched controls
	9.	a homozygous missense mutation in CRYAB was identified in a family with autosomal recessive juvenile cataract
	10.	The isolated alpha-crystallin domain undergoes a dimer-monomer transition over the pH range 7.5-6.8.
	11.	the differential expression patterns of alphaB-crystallin and Hsp27 indicate functional differences between these highly related proteins in placental tissues.
	12.	alphaB-crystallin as a novel mediator of chondrocyte matrix gene expression that may contribute to altered chondrocyte metabolism during the development of osteoarthritis
	13.	Expression of the alpha B-crystallin gene can be used as a prognostic indicator in human hepatocellular carcinomas.
	14.	A review summarizing the interaction of alphaB-crystallin and other sHsps with fibril-forming proteins is presented.
	15.	Abnormal assemblies and subunit exchange of CRYAB R120 mutants could be associated with destabilization of the dimeric substructure.
	16.	Hearts of mice with cardiomyocyte-restricted transgenic overexpression of CryAB and subjected to transverse aortic constriction or sham surgery show attenuated cardiac hypertrophic responses but unchanged cardiac function.
	17.	BB is the most susceptible to gamma-irradiation and that alpha B-crystallin forms a more stable aggregate than alpha A-crystallin under normal conditions.
	18.	Inhibition of the early stage of beta2m aggregation by alphaB-crystallin does not necessarily require a mechanicistic chaperon-like action implying one-to-one binding.
	19.	Elevated alphaBC-IgG indices might serve as markers of PNS inflammation and supplement currently used laboratory tests in the diagnosis of GBS.
	20.	Glial fibrillary acidic protein filaments can tolerate the incorporation of assembly-compromised GFAP-delta, but with consequences for filament organization and alphaB-crystallin association
	21.	alphaB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer.
	22.	This study suggests that residues from the NH(2)- and COOH-terminal regions in alphaB-crystallin interact with residues from the corresponding regions of another subunit.
	23.	Alpha-B-crystallin was not a prognostic marker for head and neck squamous cell carcinoma.
	24.	Results describe the selective copper binding, redox silencing, and cytoprotective effects of the small heat shock proteins alphaA- and alphaB-crystallin.
	25.	alphaB-crystallin is a Bcl2L12-induced oncoprotein that enables Bcl2L12 to block the activation of both effector caspases via distinct mechanisms, thereby contributing to Glioblastoma multiforme pathogenesis and its hallmark biological properties.
	26.	mutation of lysine and glutamic acid residues in the C-terminal extension of alphaB-crystallin resulted in proteins that had improved chaperone activity against amyloid fibril forming target proteins
	27.	presence of measurable interactions between MIP26 and all crystallins, with the extent of interactions decreasing from alphaA- and alphaB-crystallin to betaB2- and gammaC-crystallin.
	28.	a cellular defense against dysregulated proteins, in the form of Hsp27 and alphaB-crystallin, might contribute to the cell cycle reentry seen in AD cells
	29.	These results suggest that the changes in the structure and function of the alpha-crystallin complex and cytotoxicity are vital factors in the pathogenesis of congenital cataract linked to the P20S mutation in the alphaB-crystallin.
	30.	This study confirmed the interactions between a low molecular weight peptide derived from betaA3/A1-crystallin found in aged and cataract lenses and alphaB-crystallin.
	31.	Synthetic bioactive peptides of alphaB crystallin interact with exposed residues in the beta strands of transthyretin and beta2-microglobulin, respectively, to modulate fibrillation.
	32.	The presence of an intact C-terminus is essential for the formation of fully integrated heteroaggregates with equal proportion of alphaA and alphaB subunits.
	33.	Q151X alphaB-crystallin is found mainly in the insoluble fraction of cell extracts from transient transfected cells, due to the formation of cytoplasmic aggregates
	34.	Data implicate alphaB-crystallin as an important regulator of tubular morphogenesis and survival of endothelial cell during tumor angiogenesis.
	35.	The interaction of Ksp-cadherin with alpha B-crystallin is important for the connection of Ksp-cadherin to the cytoskeleton and thus for maintaining tissue integrity in the kidney.
	36.	After ultraviolet ray-A-exposure, the deamidated alphaB-Asn146Asp mutant protein showed a complete loss of chaperone activity compared to WT alphaB and alphaB-Asn78Asp and alphaB-Asn78/146Asp deamidated species.
	37.	Data showed that that alphaB-crystallin interrupted alpha-synuclein aggregation at its earliest stages, most likely by binding to partially folded monomers and thereby preventing their aggregation into fibrillar structures.
	38.	Observational study of gene-disease association. (HuGE Navigator)
	39.	AlphaB-crystallin is a sensitive (81%) and specific (100%) marker for basal-like breast carcinomas.
	40.	A novel pathway regulating human myometrial contraction at labor with HSP27 and alphaB-crystallin as potential targets for future tocolytic studies.
	41.	Bivalent zinc specifically interacts with alpha-crystallin with a dissociation constant in the submillimolar range.
	42.	HMGA1 nonhistone chromatin proteins, the SWI/SNF chromatin remodeling complexes, and sequence-specific transcription factors act together to regulate the expression of the CRYAB gene.
	43.	Interactive domains in alphaB crystallin have multiple functions in stabilizing the cytoskeleton and protecting cytosolic proteins from unfolding.
	44.	Alpha-B-crystallin associates with the perinuclear Golgi in a cell cycle-dependent fashion in U373 human glioblastoma cells. It appears in the nascent Golgi immediately following cytokinesis.
	45.	characterization of the formation of amyloid fibrils by human alphaB-crystallin in detail, and also that of alphaA-crystallin and the disease-related mutant R120G alphaB-crystallin
	46.	The preservation of an Arg residue at position 120 of alphaBeta-crystallin is critical for the structural and functional integrity of the protein and each mutation results in specific changes in both structural and functional characteristics.
	47.	Transgenic mice overexpressing cardiac-specific human mutant CryAB (hR120GCryAB) recapitulate lethal human cardiomyopathy with reductive stress and dysregulation of glucose-6-phosphate dehydrogenase.
	48.	Administration of recombinant CRYAB ameliorated EAE; thus, the immune response against a negative regulator of inflammation, CRYAB, in multiple sclerosis, would exacerbate inflammation and demyelination.
	49.	The exposed side chains of Glu-78, Lys-82, and His-83 in the interactive beta3 sequence of the alpha crystallin core domain in alphaB crystallin are important for chaperone function.
	50.	The CRYAB sequences that interacted with FGF-2, NGF-beta, VEGF, insulin, and beta-catenin overlapped with sequences that selectively interact with partially unfolded proteins, suggesting a common function for CRYAB in chaperone activity
	51.	alphaB-crystallin competes efficiently for Abeta monomer-monomer interactions.
	52.	Involvement of the residues in the 73-92 region of alphaB-crystallin in substrate protein binding and chaperone-like action.
	53.	role of CRYA2 in protein conformational diseases, particularly in Alzheimer's disease
	54.	The regions of alpha B crystallin most affected by interaction with ATP are near putative substrate binding regions and in the C-terminal extension, as identified by hydrogen-deuterium exchange.
	55.	alpha B-crystallin is the dominant target antigen for serum autoantibodies in both multiple sclerosis patients and healthy controls
	56.	Arg157His mutation of alphaB crystallin may be involved in the pathogenesis of dilated cardiomyopathy via impaired accommodation to the heart-specific N2B domain of titin/connectin.
	57.	CRYAB is a nuclear speckle component in unstressed cells in tissue culture.
	58.	Autoreactive alpha B-crystallin-specific T helper type 1 (Th1) cells may have the potential to contribute to the pathogenesis of multiple sclerosis.
	59.	alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3.
	60.	the involvement of alphaB-crystallin in the ubiquitin/proteasome pathway in a phosphorylation- and cell cycle-dependent manner
	61.	This study identified a second novel mutation in CRYAB at the evolutionarily conserved residue Pro20 in the N-terminal region of alphaB-crystallin.
	62.	results presented here clearly establish the beta4-beta8 groove as the ATP interactive region in alphaB crystallin, and are in contrast to the existing paradigm that classifies small heat-shock proteins as ATP-independent chaperones.
	63.	alpha-crystallin B, glyceraldehyde phosphate dehydrogenase (GAPDH), and alpha-enolase identified as significantly S-glutathionylated in Alzheimer's disease infeior parietal lobule
	64.	alphaB-crystallin bound in the position of the N2B region of titin, but not to PEVK region
	65.	Of the 24 genes regulated during osteoblastic differentiation, only one, the alpha B crystalline gene, showed evidence of linkage.
	66.	These findings indicate that alpha B-crystallin is a novel negative regulator of myogenic apoptosis that directly links the differentiation program to apoptosis resistance.
	67.	Phosphorylation of alphaB-crystallin alters chaperone function through loss of dimeric substructure
	68.	isothermal titration calorimetric analysis of hydrophobicity and the chaperone-like function of alphaA- and alphaB-crystallin
	69.	Identification of protein domains of alphaB crystallin that are needed for chaperone activity.
	70.	the protective effect of alphaB-crystallin requires synthesis of the endogenous heat shock proteins
	71.	structure activity relationship
	72.	Alpha B-crystallin is a major chaperone in multiple system atrophy. A role for this protein in the formation of inclusion bodies in glial cells is suggested.
	73.	the SRLFDQFFG sequence region contributes to the oligomer dynamics in addition to the higher order assembly and structural stability, and is one of the critical motifs in structure-function regulation of alpha A- and alpha B-crystallin
	74.	alphaB-crystallin has a phosphorylation-dependent role in the ubiquitination of a component of SC35 speckles
	75.	A truncating mutation in the C-terminal region of alphaB-crystallin was determined in 2 patients with adult-onset myofibrillar myopathy; the region is crucial for the solubilization and chaperone functions of the molecule.
	76.	High stability of alphaB-crystallin assemblies in urea & thiocyanate in relationship with variable quaternary structure. Changes in inner radius as well as the thickness & dispersion of protein shell, account for preservation of chaperone-like activity.
	77.	SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1.
	78.	alpha-synuclein and alphaB-crystallin interact readily with each other and affect each other's properties, in particular alpha-synuclein fibril formation and alphaB-crystallin chaperone action
	79.	presence of WT-alphaB in the alpha-crystallin heteroaggregate leads to packing-induced structural changes which influences the oligomerization and modulate chaperone activity
	80.	Using a cross-linker, close proximity of C termini of alpha B and alpha C crystallins was demonstrated.
	81.	These data indicate that the altered tertiary and/or quaternary structures and the dominant negative effect of D140N mutant alphaB-crystallin underlie the molecular mechanism of cataractogenesis of this pedigree.
	82.	Proper orientation of residues contributing to RS-1 and RS-2 sites in alphaB-crystallin is important for homooligomerization and optimal subunit interaction with alphaA-crystallin.
	83.	The results established the beta3-beta8-beta9 surface of the alpha crystallin core domain as an interface for complex assembly and chaperone activity.
	84.	data show paradoxical effects of the deletion and substitution of R56 and imply that the chaperone function of human alphaB-crystallin is dictated not only by the positive charge on R56 but also by the conformational change that it bestows on the protein
	85.	suppression of dithiothreitol-induced aggregation of abrin by alpha B-crystallin
	86.	HSP27 and alphaB-crystallin are increased, phosphorylated and localized in aggresomes when proteasome activity is inhibited
	87.	Our results suggest that a variety of oligomers composed of different proportions of different sHSPs may form in cell types expressing multiple sHSPs.
	88.	The results indicate that Hsp27 promotes stability of alpha B-crystallin.
	89.	accumulation and abnormal modification of alpha-crystallins might be implicated in the pathogenic mechanism of anterior polar cataracts.
	90.	results indicate only slight decreased efficiency and increased distance between two probes for the R116C alphaA and R120G alphaB mutations despite conformational changes
	91.	We propose that increased AbetaPP is a stressor increasing alphaBC expression in s-IBM muscle fibers. Determining the consequences of alphaBC association with Abeta oligomers could have clinical therapeutic relevance.
	92.	alpha A-crystallin is more stable to gamma irradiation than alpha B-crystallin
	93.	CRYAB was expressed in vivo in lungs containing metastasized MDA-MB-435 cells but not in normal lung tissue of athymic mice, suggesting that it is an important cellular protein that is down regulated through BRMS1 mediated metastasis suppression.
	94.	HSF4 binds to alphaB-crystallin, Hsp70, and Hsp82 promoters and has a role in interacting with the canonical heat shock element of the alphaB-crystallin gene
	95.	CRYAB shows increased transcript levels in Alzheimer's disease brains.
	96.	The peripheral response towards the myelin antigen alpha B-crystallin is neither quantitatively nor qualitatively peculiar to multiple sclerosis (MS) and is not a prerequisite for MS induction in this Sardininan population.
	97.	Alpha B-crystallin peptide 1-16, generated as a remnant epitope following digestion with natural gelatinase B, provokes a significant T cell response in alpha B-crystallin knockout mice.
	98.	The role of CRYAB in the reactivation of denaturant-inactivated G6PD is reported.
	99.	alphaB-crystallin is a novel oncoprotein expressed in basal-like breast carcinomas that independently predicts shorter survival.
	100.	role of pH, Ca2+, and ATP in regulating the subunit dynamics of alphaB crystallin was investigated; a model for the relationship between the subunit dynamics and chaperone activity of alphaB crystallin was established
	101.	interactive domains in the N- and C-termini of human alphaB crystallin are important for the recognition, selection, and solubility of unfolding substrate proteins
	102.	establish the importance of residues 60-71 in oligomerization of alphaB-crystallin and subunit interaction between alphaB- and alphaA-crystallins
	103.	Studies with synchronized human glioblastoma cell line U373MG suggest association of aB-crystallin with cell cycle-dependent Golgi reorganization.
	104.	mutation causes dominant congenital posterior polar cataract

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[Top][Help]Interactions

Description ..........
Product	Interactant	Other Gene	Complex	Source	Pubs
HalphaB-crystallin interacts with Bax.
NP_001876.1		BAX		BIND	PubMed
HalphaB-crystallin interacts with Bcl-Xs.
NP_001876.1	NP_001182.1	BCL2L1		BIND	PubMed

NP_001876.1	Citrate synthase	CS		HPRD	PubMed

NP_001876.1	NP_001531.1	HSPB1		HPRD	PubMed

NP_001876.1	Proteasome subunit, alpha type 3	PSMA3		HPRD	PubMed
Affinity Capture-MS
BioGRID:107800	BioGRID:107127	BMPR2		BioGRID	PubMed
Affinity Capture-Western; Two-hybrid
BioGRID:107800	BioGRID:107799	CRYAA		BioGRID	PubMed
Two-hybrid
BioGRID:107800	BioGRID:107800	CRYAB		BioGRID	PubMed
Affinity Capture-Western; Two-hybrid
BioGRID:107800	BioGRID:107805	CRYBB2		BioGRID	PubMed
Affinity Capture-Western; Two-hybrid
BioGRID:107800	BioGRID:107810	CRYGC		BioGRID	PubMed
Reconstituted Complex
BioGRID:107800	BioGRID:107818	CS		BioGRID	PubMed
Affinity Capture-Western; Co-purification; Reconstituted Complex; Two-hybrid
BioGRID:107800	BioGRID:109547	HSPB1		BioGRID	PubMed
Two-hybrid
BioGRID:107800	BioGRID:109548	HSPB2		BioGRID	PubMed
Affinity Capture-Western; Co-fractionation; Two-hybrid
BioGRID:107800	BioGRID:111657	PSMA3		BioGRID	PubMed

[Top][Help]General gene information

Markers

D11S2244E(e-PCR): Links: UniSTS:32037

GDB:197835(e-PCR): Links: UniSTS:155957

D11S3407(e-PCR): Links: UniSTS:152648

CRYA2(e-PCR): Links: UniSTS:43082

PMC123035P1(e-PCR): Links: UniSTS:270427

SHGC-31520(e-PCR): Links: UniSTS:12481

RH17897(e-PCR): Links: UniSTS:18881

Phenotypes

Cataract, posterior polar 2: MIM: 123590
Myopathy, cardioskeletal, desmin-related, with cataract: MIM: 608810

Genotypes

See CRYAB SNP Genotype Report

See CRYAB SNP Geneview Report

See CRYAB SNP Variation Viewer Report

Homology

Homologs of the CRYAB gene The CRYAB gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, and mosquito.

Map Viewer (Mouse, Rat)

Gene Ontology Provided by GOA

Function	Evidence
cytoskeletal protein binding	IEA
microtubule binding	IEA
structural constituent of eye lens	IEA
unfolded protein binding	IPI	PubMed

Process	Evidence
aging	IEA
anti-apoptosis	IDA	PubMed
camera-type eye development	IEA
glucose metabolic process	IEA
microtubule polymerization or depolymerization	IEA
muscle contraction	TAS	PubMed
muscle organ development	IEA
negative regulation of cell growth	IEA
negative regulation of intracellular transport	IDA	PubMed
oxygen and reactive oxygen species metabolic process	IEA
protein folding	NAS	PubMed
protein homooligomerization	IDA	PubMed
response to estradiol stimulus	IEA
response to heat	IEA
response to hydrogen peroxide	IEA
stress-activated MAPK cascade	IEA

Component	Evidence
Golgi apparatus	IEA
Z disc	IEA
actin filament bundle	IEA
cell surface	IEA
contractile fiber	IEA
cytoplasm	IDA	PubMed
insoluble fraction	IEA
microtubule cytoskeleton	IEA
plasma membrane	IEA
soluble fraction	IEA

[Top][Help]General protein information

Preferred Names: crystallin, alpha B

Names: crystallin, alpha B; alpha B crystallin; alpha crystallin B chain; heat-shock 20 kD like-protein

[Top][Help]NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

Genomic

NG_009824.1 RefSeqGene

Range

5000..8123

Download

GenBank FASTA Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001885.1 → NP_001876.1 crystallin, alpha B

Source sequence(s)

S45630

Consensus CDS

CCDS8351.1

UniProtKB/Swiss-Prot

P02511

Conserved Domains (3) summary

COG0071
Location:40 – 161
Blast Score: 124

IbpA; Molecular chaperone (small heat shock protein) [Posttranslational modification, protein turnover, chaperones]

cd06498
Location:67 – 150
Blast Score: 409

ACD_alphaB-crystallin_HspB5; Alpha-crystallin domain found in the small heat shock protein (sHsp) alphaB-crystallin (HspB5, 20kDa). sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers...

pfam00525
Location:1 – 54
Blast Score: 220

Crystallin; Alpha crystallin A chain, N terminal

RefSeqs of Annotated Genomes: Build 37.1

The following sections contain reference sequences that belong to a specific genome build. Explain

Genome Reference Consortium Human Build 37 (GRCh37), Primary_Assembly

Genomic

NC_000011.9

Range

111779349..111782472, complement

Download

GenBank FASTA Sequence Viewer (Graphics)
NT_033899.8

Range

15341765..15344888, complement

Download

GenBank FASTA Sequence Viewer (Graphics)

Alternate assembly (Celera)

Genomic

AC_000054.1

Range

108932557..108935680, complement

Download

GenBank FASTA Sequence Viewer (Graphics)
NW_925173.1

Range

21801457..21804580, complement

Download

GenBank FASTA Sequence Viewer (Graphics)

Alternate assembly (HuRef)

Genomic

AC_000143.1

Range

107703256..107706379

Download

GenBank FASTA Sequence Viewer (Graphics)
NW_001838042.2

Range

8980629..8983752

Download

GenBank FASTA Sequence Viewer (Graphics)

[Top][Help]Related Sequences

Nucleotide		Protein
genomic	AP000907.6 (10241..13364)	None
genomic	CH471065.1	EAW67162.1
		EAW67163.1
		EAW67164.1
		EAW67165.1
		EAW67166.1
		EAW67167.1
genomic	EF444955.1	ACA05949.1
genomic	M28638.1	AAA52104.1
mRNA	AF007162.1	AAC19161.1
mRNA	AK295498.1	BAG58418.1
mRNA	AK314029.1	BAG36739.1
mRNA	BC007008.1	AAH07008.1
mRNA	BT006770.1	AAP35416.1
mRNA	FJ876064.1	ACP18852.1
mRNA	M24906.1	AAA60267.1
mRNA	S45630.1	AAB23453.1
other-genetic	AM392549.1	CAL37427.1
other-genetic	AM393027.1	CAL37905.1
other-genetic	DQ892517.2	ABM83443.1
other-genetic	DQ895729.2	ABM86655.1