Calreticulin is a multifunctional protein that acts as a
major Ca(2+)-binding (storage) protein in the lumen of the
endoplasmic reticulum. It is also found in the nucleus, suggesting
that it may have a role in transcription regulation. Calreticulin
binds to the synthetic peptide KLGFFKR, which is almost identical
to an amino acid sequence in the DNA-binding domain of the
superfamily of nuclear receptors. Calreticulin binds to antibodies
in certain sera of systemic lupus and Sjogren patients which
contain anti-Ro/SSA antibodies, it is highly conserved among
species, and it is located in the endoplasmic and sarcoplasmic
reticulum where it may bind calcium. The amino terminus of
calreticulin interacts with the DNA-binding domain of the
glucocorticoid receptor and prevents the receptor from binding to
its specific glucocorticoid response element. Calreticulin can
inhibit the binding of androgen receptor to its hormone-responsive
DNA element and can inhibit androgen receptor and retinoic acid
receptor transcriptional activities in vivo, as well as retinoic
acid-induced neuronal differentiation. Thus, calreticulin can act
as an important modulator of the regulation of gene transcription
by nuclear hormone receptors. Systemic lupus erythematosus is
associated with increased autoantibody titers against calreticulin
but calreticulin is not a Ro/SS-A antigen. Earlier papers referred
to calreticulin as an Ro/SS-A antigen but this was later disproven.
Increased autoantibody titer against human calreticulin is found in
infants with complete congenital heart block of both the IgG and
IgM classes.
