Heat shock proteins are a family of proteins found in archaea, bacteria (such as those in the adjacent photo), and eukaryotes which share a heat shock domain of about 100 amino acids at the C-terminus.   There are five families of heat shock proteins encoded by plant nuclei.  Chloroplast heat shock proteins appear to be derived from duplications of those heat shock genes present in the ancestral eukaryotic nucleus rather than from horizontal gene transfer from the cyanobacterial endosymbiotic genome (Waters, 1999; Iwaki, 1997). bacteria

     The 70-kDa proteins which form the heat shock protein family (HSP70) are essential for all cells for the proper transport and folding of proteins.  It is one of the most conserved proteins known.  Giardia lamblia (pictured above), whose 16S rRNA sequences place it as a very early eukaryotic branch, have two HSP70 proteins: one contains a signal sequence associated with eukaryotic endoplasmic reticulum while the other is more similar to eubacterial proteins than to anything known from archebacteria (Gupta, 1994).

    It was once thought that proteins formed their proper three-dimensional structures on their own.  It was later shown that a group of proteins called chaperonins are known to facilitate the proper folding of a variety of proteins.  One gene family includes the bacterial proteins GroEL and GroES, the rubisco subunit binding protein of chloroplasts, and hsp60 in yeast and human cells.  These proteins are produced after heat shock and are referred to as heat shock proteins.  Vertebrates (including humans) seem to have 8-12 genes which are homologs of hsp60 in their genomes, of which most (and perhaps all but one) are nonfunctional pseudogenes (Venner, 1990).



     All organisms analyzed to date possess genes for heat shock proteins.  Although they were identified by the increase in their expression as a result of a temperature shock, some of them can be expressed as a result of other stimuli, such as the injection of denatured proteins.  Others are constitutively expressed.  They have been shown to assist in the proper folding and transport of proteins.

     There are different heat shock proteins which are grouped based on their size.  For example, the HSPA group (HSP70) have a molecular size of 70 kD.  There are two HSPA pseudogenes known.  It seems that exons of ancestral HSP70 genes may have been recruited into other proteins such as a sperm receptor on sea urchin eggs and MHC proteins (both of which are extracellular receptors).  It is possible that MHC proteins and HSPA proteins are members of the same gene superfamily (OMIM).


HSPA1A seems to offer some protection from neurodegenerative diseases.






HSPA5 functions in the ER and is also known as the immunoglobulin heavy chain binding protein.




HSPB (HSP27) proteins have sizes of about 27 kD.

HSPB1 may offer protection against neurodegenerative diseases.


HSPB3 can produce multiple transcripts, one of which is only expressed in smooth muscle.  Smooth muscle of the gastrointestinal tract is depicted below.


HSPE1 has a size of 10 kD and is a homolog of the GroES protein in E. coli.


HSPD1 has a size of 60 kD and is a homolog of GroEL in E. coli.  Mutations can cause spastic paraplegia.


HSPEA has a size of 90 kD.




The heat shock protein HSP70 was duplicated early in the eukaryotic lineage to produce HSP70 and GRP78 (Kasahara, 1996). 



eye eye

     The lens of the vertebrate eye (the lenses of a developing frog, chicken, and pig are depicted in the preceding images) produces a number of water soluble proteins called crystallins which together compose 80-90% of the protein in the lens.  There are ubiquitous crystallins which are present in all vertebrate eyes and there are taxon-specific crystallins which appear in some lineages but not in others.  Interestingly, many crystallins are identical or homologous to other genes and seem to have been included in the lens as a secondary function.  Homologs of the crystallin genes, with both one domain and two domains are known in slime molds and bacteria. Two human crystallin genes on chromosome 11 seem to have arisen from a duplication in which one is transcribed in the opposite direction as the other (Iwaki, 1997).



Ubiquitous Crystallins

     aA and aB crystallins are members of the heat shock protein superfamily.  They may prevent inappropriate protein aggregations in the lens (Venner, 1990).  The mammalian α crystalline/hsp family includes αA-and βB-crystallins, p20, hsp 27, and HSPL27 (Iwaki, 1997).

     The b/g crystallins compose the majority of lens proteins in most vertebrates and are related to microbial stress-protective proteins (Piatigorsky, 2001), mammalian AIM1 which is involved in melanoma tumorigenicity, spherulin 3a of slime molds, and the epidermis-specific EDSP of amphibians (Ray, 1997).  A βγ cyrstallin is known in sponges.  Introns in vertebrate βγ crystallins seem to have arisen after the sponge lineage separated from them (Di Maro, 2002). 


Taxon-Specific Crystallins

     Of roughly 11 known taxon-specific crystallins, virtually all are enzymes which have other functions in cells such as a-enolase, lactate dehydrogenase B, and oxidoreductases. 

     In diurnal geckos, i-crystallin is a member of lipid binding proteins and is identical/closely related to cellular retinol-binding protein type I (CRBP I) which functions in the movement of retinoid.  This protein, which may compose 12% of the gecko lens, offers protection from ultraviolet light.  While most geckos are nocturnal, this ultraviolet light protection is important in geckos which have become diurnal since the eyelids of geckos are fused and they are unable to adjust the size of their pupils.  This provides an interesting example of how one lineage adopted an existing protein for a new function (Werten, 2000).


     Invertebrates also possess lens crystallins which have been recruited from other cellular roles.  J3-crystallin is one of three major lens proteins in jellyfish and it is homologous to vertebrate saposins which are involved with lysosomal lipid interactions.  Some invertebrates have incorporated enzymes (seemingly enzymatically inactive) into the lens such as glutathione S-transferase-related S-crystallins and aldehyde dehydrogenase-related W-crystallin (mollusks).  Drosocrystallin from Drosophila is expressed in the brain as well as in the eye (Piatigorsky, 2001).





It seems that the ancestor of the βγ crystallin family was a molecule with a single domain which formed homodimers.  Subsequent duplication and fusion events produced the 2 domain proteins of the βγ crystallin family (Clout, 2000).  The beta family of crystallins includes 4 acidic and 3 basic members.  Mutations in CRYBA1, CRYBB1, and CRYBB2 can cause cataracts. CRYBP1 is a pseudogene.








 Members of the gamma crystallin family are expressed only in the lens and are high molecular weight monomeric proteins.  At least six of the seven genes are located on chromosome 2.  Mutations in CRYGA, GB, GC, and GD can cause cataracts.  Mutations in CRYGEP1, which is a pseudogene, can also cause cataracts.  CRYGE and CRYGF are pseudogenes and CRYGG is a fragment.








     Alpha crystallins are composed of two subunits, A and B, which are small heat shock proteins.  Blind mole rats possess α-β-crystallins which are expressed in the eye and a number of other tissues.  The eye and heart both express identical genes (Avivi, 2001a).  In humans, mutations in both α genes can cause cataracts.



CRYAB is expressed not only in the eye, but also in the myocardium and kidney.  Mutations cause it to be induced in the brains of patients who suffer from a variety of disorders including Alzheimers, Parkinsons, and Huntingdon disease.  It is an autoantigen involved in multiple sclerosis.




CRYZ is the same gene as quinone reductase.

CRYZL1 is expressed in the lens and throughout the body.


CRYM is expressed in neural tissue (such as the cerebrum below), muscle, the kidney, and the ear.  It is thought to be a NADP regulated thyroid hormone binding protein in humans although it was first discovered as a crystallin in the eyes of Australian marsupials.



ε crystalline composes up to 23% of the lens proteins in crocodiles and some birds.  It is identical to lactose dehydrogenase β.  δ cryatallin is known in both birds and reptiles.  It is identical or very similar to arginosuccinate lyase.  λ crystalline is related to the enzyme hydroxyacyl CoA dehydrogenase and is found in rabbits and hares only.  μ crystallin is found in some marsupials.

η crystalline in elephant shrews composes 10% of the lens proteins in some genera and 25% in others.  ζ crystallin, found in some rodents, is related to alcohol dehydrogenase.  τ crystalline is the enzyme enolase.  While the protein functions as an enzyme in glycolysis, it serves as a structural tau crystalline protein in the lens.  It is found in lampreys, some gnathosotme fish, reptiles, birds and some mammals (such as ungulates). (De Jong, Wilfried, from Szalay, 1993; Suzuki, 2003).


     A crystallin gene in Drosophila melanogaster is homologous to cuticular proteins in other insects (including other Drosophila species).  As in vertebrates, it appears that invertebrates can modify the function of existing genes to create crystallins (Janssens, 1999).  Squid crystallins are unrelated to those of vertebrates but, like those of vertebrates, are derived from genes which originally had another function (Harris, 1997).