HSPA5
GeneName
HSPA5
Summary
HSPA5, commonly known as GRP78 or BiP, is a 72 kDa heat shock protein that primarily resides in the endoplasmic reticulum (ER) and plays a crucial role as a molecular chaperone. It is involved in the proper folding of proteins, the response to ER stress, and the maintenance of protein homeostasis. HSPA5 binds to misfolded proteins, facilitating their refolding or degradation, and is also implicated in various cellular processes including cell migration and apoptosis regulation. Its expression is observed in multiple tissues, particularly under stress conditions, and it can also be found in extracellular exosomes, indicating its potential role in cell communication and signalling.
Importance
HSPA5 is relevant to: - The unfolded protein response, which is critical for maintaining cellular homeostasis under stress conditions. - Cancer biology, where its overexpression is associated with tumour progression and resistance to therapy. - Neurodegenerative diseases, as it is involved in the management of protein misfolding and aggregation. - Metabolic disorders, given its role in the cellular response to glucose starvation and regulation of insulin signalling.
Top Products
For researchers investigating HSPA5, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-GRP78 BiP antibody (ab21685), which has garnered 791 citations, highlighting its reliability in the field. This antibody is particularly effective for Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). In addition, we offer the recombinant monoclonal antibody, Anti-GRP78 BiP antibody [EPR4041(2)] (ab108615). This product has been validated for use in WB, IHC, and flow cytometry (FC), making it a versatile option for various experimental needs. With 103 citations, it is also gaining recognition among researchers. The recombinant nature of this antibody ensures batch-to-batch consistency, which is essential for reproducible results in your studies. The Recombinant Human BIP Protein ELISA Kit (ab287939) is an excellent option for researchers looking to measure HSPA5 levels in their samples.
Abcam Product Citation Summary
The data indicates a significant focus on the role of HSPA5 in various biological contexts, particularly related to endoplasmic reticulum stress and apoptosis across multiple species, including humans and rodents. The studies employ Western blotting as the primary application for detecting HSPA5, highlighting its relevance in understanding cellular stress responses and disease mechanisms.
Abcam Product Citation Table
Domain
The interdomain linker regulates the chaperone activity by mediating the formation of homooligomers. Homooligomers are formed by engagement of the interdomain linker of one HSPA5/BiP molecule as a typical substrate of an adjacent HSPA5/BiP molecule. HSPA5/BiP oligomerization inactivates participating HSPA5/BiP protomers. HSPA5/BiP oligomers probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell. When the levels of unfolded proteins rise, cells can rapidly break up these oligomers to make active monomers.
Function
Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:11907036, PubMed:19538957). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Also binds and inactivates EIF2AK3/PERK in unstressed cells (PubMed:11907036). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1 and EIF2AK3/PERK, allowing their homodimerization and subsequent activation (PubMed:11907036). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (PubMed:26045166).
(Microbial infection) Plays an important role in viral binding to the host cell membrane and entry for several flaviruses such as Dengue virus, Zika virus and Japanese encephalitis virus (PubMed:15098107, PubMed:28053106, PubMed:33432092). Acts as a component of the cellular receptor for Dengue virus serotype 2/DENV-2 on human liver cells (PubMed:15098107).
(Microbial infection) Acts as a receptor for CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi (PubMed:20484814, PubMed:24355926, PubMed:32487760). Acts as a receptor for R.delemar CotH3 in nasal epithelial cells, which may be an early step in rhinoorbital/cerebral mucormycosis (RCM) disease progression (PubMed:32487760).
Involvement in disease
Autoantigen in rheumatoid arthritis.
Post-translational modifications
AMPylated by FICD (PubMed:25601083). In unstressed cells, AMPylation at Thr-518 by FICD inactivates the chaperome activity: AMPylated form is locked in a relatively inert state and only weakly stimulated by J domain-containing proteins (By similarity). In response to endoplasmic reticulum stress, de-AMPylation by the same protein, FICD, restores the chaperone activity (By similarity).
Sequence Similarities
Belongs to the heat shock protein 70 family.
Cellular localization
- Endoplasmic reticulum lumen
- Melanosome
- Cytoplasm
- Cell surface
- Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:12643545). Localizes to the cell surface of epithelial cells in response to high levels of free iron (PubMed:20484814, PubMed:24355926, PubMed:27159390).
Alternative names
GRP78, HSPA5, Endoplasmic reticulum chaperone BiP, 78 kDa glucose-regulated protein, Binding-immunoglobulin protein, Heat shock protein 70 family protein 5, Heat shock protein family A member 5, Immunoglobulin heavy chain-binding protein, GRP-78, BiP, HSP70 family protein 5