Cell surface glycoproteins of 96,000 Da (GP96) elicit tumor-specific immunity to mouse tumors from which they are
isolated. The sequence of these genes show homology to heat shock protein HSP90, endoplasmic reticular protein ERP99,
and glucose-regulated protein GRP94.
By screening a human teratocarcinoma cDNA library with mouse gp96, a cDNA encoding
TRA1, also called GP96 was isolated. Sequence analysis predicted that the 803-amino acid protein, which is 96% homologous to
the mouse sequence, contains a 21-amino acid signal peptide and 5 potential N-linked glycosylation sites. Northern blot
analysis detected a 2.8-kb GP96 transcript in all tumor cell lines tested.
Using a mouse system, Binder et al. (2000) determined that the receptor for GP96 is CD91 (A2MR, or LRP1; OMIM 107770) and
that A2M (OMIM 103950), a protein found in blood, inhibits GP96 binding to CD91.
NCBI Summary:
HSP90 proteins are highly conserved molecular chaperones that have key roles in signal transduction, protein folding, protein degradation, and morphologic evolution. HSP90 proteins normally associate with other cochaperones and play important roles in folding newly synthesized proteins or stabilizing and refolding denatured proteins after stress. HSP90B1 is an endoplasmic reticulum HSP90 protein. Other HSP90 proteins are found in cytosol (see HSP90AA1; MIM 140571) and mitochondria (TRAP1; MIM 606219) (Chen et al., 2005 [PubMed 16269234]).[supplied by OMIM]
General function
Ligand, Cytokine
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Taft RA, et al 2002 reported the identification of genes encoding mouse oocyte secretory and
transmembrane proteins by a signal sequence trap.
A block in the road to fertility: autoantibodies to heat-shock protein 90-beta in human ovarian autoimmunity. Pires ES et al. OBJECTIVE: To report autoantibodies to human heat-shock protein 90-beta (HSP90beta) in sera of women with infertility. DESIGN: Prospective, controlled observations. SETTING: Major urban infertility referral center and research institution. PATIENT(S): Fifty women with premature ovarian failure, 65 infertile women enrolled in the in vitro fertilization-embryo transfer program, and 60 normally menstruating fertile women as controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Identification and complete characterization of a 90-kd protein, the most immunodominant autoantigen. RESULT(S): Our previous studies employing a novel blocking demonstrated several cellular and molecular ovarian antigenic targets using patient's serum. Of all these antigens, the 90-kd protein designated as EP90 was found to be conserved across species, was serine-threonine phosphorylated, and was expressed from the primordial stage to the graafian-stage ooplasm of the oocytes during follicular development. Using high-throughput proteomic technologies like liquid chromatography/mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF), and tandem mass spectrometry analysis revealed the identity of this protein to be HSP90beta. Commercially available recombinant protein immunoreacted with the sera from patients with antiovarian antibodies against the 90-kd antigen. In parallel, using monoclonal antibody to human HSP90, we found that it reacts with the eluted protein from a crude ovarian extract. CONCLUSION(S): This is the first report to show the presence of ovarian autoantibodies to human HSP90 in sera of women with infertility. This protein could be involved in human ovarian autoimmunity and thereby be a causative factor in early ovarian failure.
At all stages of follicular
development, oocytes interact with surrounding granulosa cells and promote their
differentiation into the types of cells that support further oocyte growth and
developmental competence. These interactions suggest the existence of an
oocyte-granulosa cell regulatory loop that includes both secreted proteins and cell
surface receptors on both cell types. Factors involved in the regulatory loop will
therefore contain a signal sequence, which can be used to identify them through a
signal sequence trap (SST). A screen of an oocyte SST library identified three
classes of oocyte-expressed sequences: known mouse genes, sequences homologous
to known mammalian genes, and novel sequences of unknown function. Many of the
recovered genes may have roles in the oocyte-granulosa cell regulatory loop. For
several of the known mouse genes, new roles in follicular development are implied
by identification of their expression, for the first time, in the oocyte.
TUMOR REJECTION ANTIGEN 1; TRA1 was found by the SST screen.