Tag Content
UniProt Accession
Theoretical PI
Molecular Weight
92476 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Gene Synonyms/Alias
Grp94, Tra-1, Tra1 
Protein Name
Protein Synonyms/Alias
94 kDa glucose-regulated protein;GRP-94 Endoplasmic reticulum resident protein 99;ERp99 Heat shock protein 90 kDa beta member 1; Polymorphic tumor rejection antigen 1; Tumor rejection antigen gp96;Flags: Precursor 
Mus musculus (Mouse) 
NCBI Taxonomy ID
Chromosome Location
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Probability (GAS) of Function in Spermatogenesis
The probability was calculated by GAS algorithm, ranging from 0 to 1. The closer it is to 1, the more possibly it functions in spermatogenesis.
Temporarily unavailable 
Abstract of related literatures
1. We have isolated an expressible full-length cDNA clone encoding murine ERp99, an abundant, conserved transmembrane glycoprotein of the endoplasmic reticulum membrane. ERp99 is synthesized as a 92,475-kDa precursor containing 802 amino acids. It possesses a signal peptide of 21 amino acids which is cleaved cotranslationally. Analysis of the amino acid sequence deduced from the nucleotide sequence of the cDNA clone led us to propose a model for the orientation of ERp99 in the endoplasmic reticulum membrane. In this model, ERp99 possesses one membrane-spanning, stop transfer segment in the N-terminal region. The protein chain passes through the membrane only once, and approximately 75% of the protein remains on the cytoplasmic side of the ER membrane. Comparison of the ERp99 sequence to the sequence of other proteins revealed that ERp99 has extensive homology with the 90-kDa heat shock protein of Saccharomyces cerevisiae (hsp90) and the 83-kDa heat shock protein of Drosophila melanogaster. In addition, the N terminus of mature ERp99 is identical to that of the 94-kDa glucose regulated protein (GRP94) of mammalian cells. PMID: [3036833] 

2. The amino acid sequences of peptides isolated from murine endoplasmin showed significant homology (approximately 50%) with sequences in the heat-shock proteins 90 and 83 of yeast and Drosophila, respectively, indicating that they are related proteins. Mixed oligonucleotide probes, deduced from the peptide sequences, were used to isolate cDNAs from a murine liver cDNA library. DNA sequencing confirmed the presence of a coding sequence for one of the endoplasmin peptides, formally establishing the authenticity of the cDNA. The identity of the murine and hamster endoplasmin sequences suggests a level of sequence conservation associated with proteins that perform a structural role in cells. PMID: [3612811] 

3. We have proposed that the distinct tumor rejection antigens of chemically induced sarcomas in inbred mice belong to a family of Mr 96,000 glycoproteins (gp96). An identical 14-amino acid sequence was found at the amino terminus of gp96 from two antigenically distinct BALB/c sarcomas. Oligonucleotide probes derived from this sequence permitted isolation of 5' cDNA and genomic fragments coding for gp96. Three short exons interrupted by relatively long introns were identified at the 5' terminus of the gp96 gene. The first exon encodes a signal peptide, which is consistent with gp96 being a cell surface antigen. Southern blot analysis indicated that the gp96 family is encoded by a single gene, and 3-kilobase transcripts were detected in all normal and tumor cells tested. Nucleotide and deduced amino acid sequences from 311 base paris at the 5' terminus showed no homology with any known protein. The availability of molecular probes for the gp96 system permits analysis of the structural polymorphism of these antigens. PMID: [2438686] 

4. The 100-kDa heat shock protein, HSP100, was purified from mouse lymphoma cells. Amino acid sequences of three peptide fragments which were obtained from the purified protein by lysylendopeptidase digestion were completely or nearly identical with those of a mouse endoplasmic reticulum protein, ERp99, of a hamster glucose-regulated protein, GRP94, and of a chicken heat shock protein, HSP108, all of which have been known to have strong homology with the 90-kDa heat shock protein, HSP90. HSP100 bound to actin filaments and an apparent Kd for the binding was determined to be 8 x 10(-7) M in 2 mM MgCl2 + 100 mM KCl. Calmodulin inhibited the binding in a Ca2+-dependent manner. Equilibrium gel filtration demonstrated that HSP100 has an ability to bind to calmodulin only in the presence of Ca2+. Moreover, HSP100 competed with HSP90 for binding to actin filaments. These results together with our previous findings that HSP90 and HSP100 have similar physicochemical properties (Koyasu, S., Nishida, E., Kadowaki, T., Matsuzaki, F., Iida, K., Harada, F., Kasuga, M., Sakai, H., and Yahara, I. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8054-8058) and HSP90 is a calmodulin-regulated actin-binding protein (Nishida, E., Koyasu, S., Sakai, H., and Yahara, I. (1986) J. Biol. Chem. 261, 16033-16036), strongly suggest that HSP100 is structurally and functionally related to HSP90. PMID: [2768254] 

5. The synthesis and cotranslational modification of GRP94, an abundant, resident protein of the endoplasmic reticulum belonging to the hsp90 family of stress proteins, has been studied in transient expression studies in COS cells. A fraction of the expressed murine GRP94 was more highly glycosylated than normal, having a greater number of endoglycosidase H (Endo H)-sensitive oligosaccharide moieties than authentic GRP94. To understand better the basis for the appearance of the hyperglycosylated form and determine the acceptor sites that were used for this extra glycosylation, we have used in vitro mutagenesis techniques to construct a set of point mutants and deletion mutants of GRP94. Analysis of the expression of wild-type GRP94 and the mutant proteins has revealed that Asn-196 is the acceptor site used in normal glycosylation of GRP94 and that hyperglycosylation is dependent upon the level of expression of the GRP94 and is occurring at acceptor sites in the carboxy-terminal region of the protein. We have shown, in addition, that Cys-117 is involved in the formation of a disulfide-bonded homodimer of GRP94. Finally, analysis of deletions made from the amino terminus of the mature protein has demonstrated that these alterations change the pattern of usage of the remaining N-glycosylation sites in the mutants. PMID: [8179819] 

6. We demonstrate the existence of a large endoplasmic reticulum (ER)-localized multiprotein complex that is comprised of the molecular chaperones BiP; GRP94; CaBP1; protein disulfide isomerase (PDI); ERdj3, a recently identified ER Hsp40 cochaperone; cyclophilin B; ERp72; GRP170; UDP-glucosyltransferase; and SDF2-L1. This complex is associated with unassembled, incompletely folded immunoglobulin heavy chains. Except for ERdj3, and to a lesser extent PDI, this complex also forms in the absence of nascent protein synthesis and is found in a variety of cell types. Cross-linking studies reveal that the majority of these chaperones are included in the complex. Our data suggest that this subset of ER chaperones forms an ER network that can bind to unfolded protein substrates instead of existing as free pools that assembled onto substrate proteins. It is noticeable that most of the components of the calnexin/calreticulin system, which include some of the most abundant chaperones inside the ER, are either not detected in this complex or only very poorly represented. This study demonstrates an organization of ER chaperones and folding enzymes that has not been previously appreciated and suggests a spatial separation of the two chaperone systems that may account for the temporal interactions observed in other studies. PMID: [12475965] 

7. The RNA-binding protein CUGBP1 regulates translation of proteins in a variety of biological processes. In this study, we show that aging liver increases CUGBP1 translational activities by induction of a high molecular weight protein-protein complex of CUGBP1. The complex contains CUGBP1, subunits alpha, beta, and gamma of the initiation translation factor eIF2, and four proteins of the endoplasmic reticulum, eR90, CRT, eR60, and Grp78. The induction of the CUGBP1-eIF2 complex in old livers is associated with the elevation of protein levels of CUGBP1 and with the hyper-phosphorylation of CUGBP1 by a cyclin D3-cdk4 kinase, activity of which is increased with age. We have examined the role of the elevation of CUGBP1 and the role of cyclin D3-cdk4-mediated phosphorylation of CUGBP1 in the formation of the CUGBP1-eIF2 complex by using CUGBP1 transgenic mice and young animals expressing high levels of cyclin D3 after injection with cyclin D3 plasmid. These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein. Consistent with these observations, the purified CUGBP1-eIF2 complex binds to the 5' region of C/EBPbeta mRNA and significantly increases translation of the three isoforms of C/EBPbeta in a cell-free translation system, in cultured cells, and in the liver. Thus, these studies demonstrated that age-mediated induction of the CUGBP1-eIF2 complex changes translation of C/EBPbeta in old livers. PMID: [16931514] 

8. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1; previously known as p43) is a multifunctional protein that was initially found in multitRNA synthetase complex. In the present study, screening of the AIMP1-binding proteins revealed that AIMP1 can form a molecular complex with heat shock protein gp96. AIMP1 enhances gp96 dimerization and the interaction between gp96 and KDEL receptor-1 (KDELR-1), which mediates the retrieval of KDEL-containing proteins from Golgi to the endoplasmic reticulum (ER). The interaction between gp96 and KDELR-1 was reduced in AIMP1-deficient cells, and this disturbed ER retention of gp96 and increased its cell surface localization. Moreover, this localization of gp96 at the cell surface was suppressed by its interaction with AIMP1 and enhanced by the depletion of endogenous AIMP1. In addition, AIMP1-deficient mice showed dendritic cell activation attributable to increased gp96 surface presentation and lupus-like autoimmune phenotypes. These results suggest that AIMP1 acts as a regulator of the ER retention of gp96 and provide a new perspective of the regulatory mechanism underlying immune stimulation by gp96. PMID: [17525271] 

9. A system which consisted of multidimensional liquid chromatography (Yin-yang MDLC) coupled with mass spectrometry was used for the identification of peptides and phosphopeptides. The multidimensional liquid chromatography combines the strong-cation exchange (SCX), strong-anion exchange (SAX), and reverse-phase methods for the separation. Protein digests were first loaded on an SCX column. The flow-through peptides from SCX were collected and further loaded on an SAX column. Both columns were eluted by offline pH steps, and the collected fractions were identified by reverse-phase liquid chromatography tandem mass spectrometry. Comprehensive peptide identification was achieved by the Yin-yang MDLC-MS/MS for a 1 mg mouse liver. In total, 14 105 unique peptides were identified with high confidence, including 13 256 unmodified peptides and 849 phosphopeptides with 809 phosphorylated sites. The SCX and SAX in the Yin-Yang system displayed complementary features of binding and separation for peptides. When coupled with reverse-phase liquid chromatography mass spectrometry, the SAX-based method can detect more extremely acidic (pI < 4.0) and phosphorylated peptides, while the SCX-based method detects more relatively basic peptides (pI > 4.0). In total, 134 groups of phosphorylated peptide isoforms were obtained, with common peptide sequences but different phosphorylated states. This unbiased profiling of protein expression and phosphorylation provides a powerful approach to probe protein dynamics, without using any prefractionation and chemical derivation. PMID: [17203969] 

10. Although the classification of cell types often relies on the identification of cell surface proteins as differentiation markers, flow cytometry requires suitable antibodies and currently permits detection of only up to a dozen differentiation markers in a single measurement. We use multiplexed mass-spectrometric identification of several hundred N-linked glycosylation sites specifically from cell surface-exposed glycoproteins to phenotype cells without antibodies in an unbiased fashion and without a priori knowledge. We apply our cell surface-capturing (CSC) technology, which covalently labels extracellular glycan moieties on live cells, to the detection and relative quantitative comparison of the cell surface N-glycoproteomes of T and B cells, as well as to monitor changes in the abundance of cell surface N-glycoprotein markers during T-cell activation and the controlled differentiation of embryonic stem cells into the neural lineage. A snapshot view of the cell surface N-glycoproteins will enable detection of panels of N-glycoproteins as potential differentiation markers that are currently not accessible by other means. PMID: [19349973] 

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Molecular chaperone that functions in the processing andtransport of secreted proteins. When associated with CNPY3,required for proper folding of Toll-like receptors. Functions inendoplasmic reticulum associated degradation (ERAD). Has ATPaseactivity (By similarity). 
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Subcellular Location
Endoplasmic reticulum lumen. Melanosome (Bysimilarity). 
Tissue Specificity
Gene Ontology
GO IDGO termEvidence
GO:0005829 C:cytosol IEA:Compara.
GO:0005783 C:endoplasmic reticulum IDA:MGI.
GO:0005788 C:endoplasmic reticulum lumen IEA:UniProtKB-SubCell.
GO:0005789 C:endoplasmic reticulum membrane IEA:Compara.
GO:0042470 C:melanosome IEA:UniProtKB-SubCell.
GO:0005792 C:microsome IEA:Compara.
GO:0030496 C:midbody IEA:Compara.
GO:0048471 C:perinuclear region of cytoplasm IEA:Compara.
GO:0044459 C:plasma membrane part IDA:MGI.
GO:0005524 F:ATP binding IEA:UniProtKB-KW.
GO:0003723 F:RNA binding IEA:Compara.
GO:0046790 F:virion binding IEA:Compara.
GO:0031247 P:actin rod assembly ISO:MGI.
GO:0006916 P:anti-apoptosis IEA:Compara.
GO:0071318 P:cellular response to ATP ISO:MGI.
GO:0030433 P:ER-associated protein catabolic process ISS:UniProtKB.
GO:0006457 P:protein folding IEA:InterPro.
GO:0043666 P:regulation of phosphoprotein phosphatase activity ISO:MGI.
GO:0001666 P:response to hypoxia IEA:Compara.
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IPR003594;    ATPase-like_ATP-bd.
IPR015566;    Endoplasmin.
IPR019805;    Heat_shock_protein_90_CS.
IPR001404;    Hsp90.
IPR020575;    Hsp90_N.
IPR020568;    Ribosomal_S5_D2-typ_fold.
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PF00183;    HSP90;    1.
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SM00387;    HATPase_c;    1.
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PS00014;    ER_TARGET;    1.
PS00298;    HSP90;    1.
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PR00775;    HEATSHOCK90.;   
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Created Date
Record Type
GAS predicted 
Sequence Annotation
SIGNAL        1     21       Potential.
CHAIN        22    802       Endoplasmin.
MOTIF       799    802       Prevents secretion from ER.
BINDING     107    107       ATP (By similarity).
BINDING     149    149       ATP (By similarity).
BINDING     162    162       ATP (By similarity).
BINDING     168    168       ATP (By similarity).
BINDING     199    199       ATP; via amide nitrogen (By similarity).
BINDING     448    448       ATP (By similarity).
MOD_RES     306    306       Phosphoserine.
MOD_RES     677    677       Phosphotyrosine (By similarity).
CARBOHYD     62     62       N-linked (GlcNAc...) (Potential).
CARBOHYD    107    107       N-linked (GlcNAc...) (Potential).
CARBOHYD    217    217       N-linked (GlcNAc...).
CARBOHYD    445    445       N-linked (GlcNAc...) (Potential).
CARBOHYD    481    481       N-linked (GlcNAc...) (Potential).
CARBOHYD    502    502       N-linked (GlcNAc...) (Potential).
DISULFID    138    138       Interchain.
MUTAGEN     103    103       E->A: Loss of CNPY3-binding.
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Nucleotide Sequence
Length: 2759 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 802 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
Gene Symbol Ref Databases
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String database  
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