UniProtKB entry for human CRYAA (Alpha-crystallin A chain)
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UniProt records CRYAA as cytoplasmic and stress-induced nuclear, with heat-shock-dependent residence in SC35/nuclear splicing speckles.
"Nucleus. Note=Translocates to the nucleus during heat shock and resides in sub-nuclear structures known as SC35 speckles or nuclear splicing speckles."
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay.
Role of the C-terminal extensions of alpha-crystallins. Swapping the C-terminal extension of alpha-crystallin to alphaB-crystallin results in enhanced chaperone activity.
Alteration of protein-protein interactions of congenital cataract crystallin mutants.
Cell death triggered by a novel mutation in the alphaA-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q.
Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis.
Lenticular chaperones suppress the aggregation of the cataract-causing mutant T5P gamma C-crystallin.
A novel mutation in AlphaA-crystallin (CRYAA) caused autosomal dominant congenital cataract in a large Chinese family.
HSPB7 is a SC35 speckle resident small heat shock protein.
An alphaA-crystallin gene mutation, Arg12Cys, causing inherited cataract-microcornea exhibits an altered heat-shock response.
The eye lens chaperone alpha-crystallin forms defined globular assemblies.
Temperature-dependent structural and functional properties of a mutant (F71L) αA-crystallin: molecular basis for early onset of age-related cataract.
The polydispersity of αB-crystallin is rationalized by an interconverting polyhedral architecture.
Binding determinants of the small heat shock protein, αB-crystallin: recognition of the 'IxI' motif.
A proteome-scale map of the human interactome network.
Widespread macromolecular interaction perturbations in human genetic disorders.
Mutation analysis of two families with inherited congenital cataracts.
Two novel mutations identified in ADCC families impair crystallin protein distribution and induce apoptosis in human lens epithelial cells.
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
A novel mutation in the CRYAA gene associated with congenital cataract and microphthalmia in a Chinese family.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Cloning, expression, and chaperone-like activity of human alphaA-crystallin.
Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA.
Falcon deep research for human CRYAA
Alpha-crystallin can function as a molecular chaperone.
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Horwitz reported that unfractionated alpha-crystallin (alphaA + alphaB) both suppressed aggregation of and refolded GdnHCl-denatured gamma-crystallin by circular dichroism. This is the principal primary observation behind a positive refolding assignment, but it used a mixed alphaA/alphaB preparation and a secondary-structure readout, so it does not establish autonomous alphaA foldase activity.
"alpha-Crystallin was also effective in preventing aggregation and in refolding guanidine hydrochloride-denatured gamma-crystallin, as judged by circular dichroism spectroscopy."
Small heat shock proteins are molecular chaperones.
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Jakob et al. established the family-level, ATP-independent sHSP refolding result often cited as context for sHSP refolding. The proteins named in the abstract are murine Hsp25, human Hsp27 and bovine alphaB-crystallin; alphaA-crystallin (CRYAA) is not among them, so this paper does not provide alphaA-specific refolding evidence. Note this is a 4-page JBC communication and only the abstract is cached, so this is an inference from the abstract's enumeration rather than from the full text.
"we studied the influence of murine Hsp25, human Hsp27, and bovine alpha-B-crystallin (an eye lens protein homologous to sHsps) on the unfolding and refolding of citrate synthase and alpha-glucosidase in vitro"
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The refolding promoted by these sHSPs was ATP-independent, which is why a refolding term could be assigned without invoking a nucleotide-binding domain.
"they promote the functional refolding of these proteins after urea denaturation similar to GroE and Hsp90. The interaction both with unfolding and refolding proteins seems to be ATP-independent."
The Small Ones Matter-sHsps in the Bacterial Chaperone Network.
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sHSP-client assemblies are resolved by downstream ATP-dependent Hsp70 and Hsp100 chaperones, which execute the productive refolding step; the sHSP contribution is holding clients aggregation-free.
"Formation of these assemblies facilitates subsequent Hsp70 and Hsp100 chaperone-dependent disaggregation and substrate refolding into native species"
Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases.
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Human HSPBs (the family containing CRYAA/HSPB4) act as ATP-independent holdases and cooperate in refolding that is driven by other chaperones, rather than performing the refolding themselves.
"HSPBs take part in cell homeostasis by acting as holdases, which is the ability to interact with a substrate preventing its aggregation. In addition, HSPBs cooperate in substrates refolding driven by other chaperones"
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HSPBs interact indirectly with ATP-dependent foldases such as HSP70 for the refolding process, placing the foldase step outside the sHSP itself.
"HSPBs act as ATP-independent holdases, avoiding misfolded substrates aggregation"
OpenScientist hypothesis report for CRYAA protein refolding (GO:0042026)
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The run independently concluded that CRYAA is an ATP-independent holdase that cannot be an autonomous foldase, because P02489 is a single alpha-crystallin domain protein with no nucleotide-binding or ATPase module. This agrees with the existing review.
"no nucleotide-binding site and no ATPase domain"
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The run placed the productive refolding step on downstream ATP-dependent chaperones rather than on CRYAA itself.
"the productive refolding step is executed by downstream ATP-dependent chaperones"
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The run acknowledged that the historical CD-based refolding readouts may reflect spontaneous recovery once aggregation is suppressed, which is the basis for discounting PMID:1438232 as evidence of foldase activity.
"the older assays is often an outcome measured in systems where spontaneous or residual refolding can occur once aggregation is suppressed"