Mammalian lens crystallins are divided into alpha, beta, and gamma families. 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 (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. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. 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. Defects in this gene cause autosomal dominant congenital cataract (ADCC). [provided by RefSeq, Jan 2014]
Function:
May contribute to the transparency and refractive index of the lens.
Subunit:
Heteropolymer composed of three CRYAA and one CRYAB subunits. Inter-subunit bridging via zinc ions enhances stability,which is crucial as there is no protein turn over in the lens. Can also form homodimers and higher homooligomers. Age-dependent SLCterminal truncation affects oligomerization.
Subcellular Location:
Cytoplasm. Nucleus. Translocates to the nucleus during heat shock and resides in sub-nuclear structures known as SC35 speckles or nuclear splicing speckles.
Tissue Specificity:
Expressed in eye lens.
Post-translational modifications:
O-glycosylated; contains N-acetylglucosamine side chains.
Deamidation of Asn-101 in lens occurs mostly during the first 30 years of age, followed by a small additional amount of deamidation (approximately 5%) during the next approximately 38 years, resulting in a maximum of approximately 50% deamidation during the lifetime of the individual.
Phosphorylation on Ser-122 seems to be developmentally regulated. Absent in the first months of life, it appears during the first 12 years of human lifetime. The relative amount of phosphorylated form versus unphosphorylated form does not change over the lifetime of the individual.
DISEASE:
Defects in CRYAA are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Cataract is the most common treatable cause of visual disability in childhood.
Similarity:
Belongs to the small heat shock protein (HSP20) family.
SWISS:
P02489
Gene ID:
1409
Database links:
Entrez Gene: 281718 Cow
Entrez Gene: 1409 Human
Entrez Gene: 12954 Mouse
Entrez Gene: 100009294 Rabbit
Entrez Gene: 24273 Rat
Omim: 123580 Human
SwissProt: P02470 Cow
SwissProt: P02498 Elephant
SwissProt: P68281 Guinea pig
SwissProt: P02497 Hamster
SwissProt: P02478 Horse
SwissProt: P02489 Human
SwissProt: P24622 Mouse
SwissProt: P02475 Pig
SwissProt: P02493 Rabbit
SwissProt: P24623 Rat
SwissProt: P02488 Rhesus monkey
Unigene: 116885 Human
Unigene: 1228 Mouse
Unigene: 127769 Rat
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