HSPA5 (GRP78)
HSP70 family

Author: Gianpiero Pescarmona
Date: 07/11/2011

Description

DEFINITION

Binding immunoglobulin protein (BiP) also known as 78 kDa glucose-regulated protein (GRP-78) or heat shock 70 kDa protein 5 is a Heat Shock Protein and belongs to the family of the HSP70. It is a molecular chaperone located in the lumen of the endoplasmic reticulum (ER). Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER.

  • Subunit structure: Interacts with DNAJC1 (via J domain) By similarity. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Part a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with TMEM132A and TRIM21. May form a complex with ERLEC1, OS9, SEL1L and SYVN1.

THE GENE

DatabaseLink
WikigenesHSPA5
GeneCards"URL":
Your Favorite Gene Sigma"URL":

CHEMICAL STRUCTURE AND IMAGES

When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage

SYNTHESIS AND TURNOVER

mRNA synthesis

  • Oncostatin M up-regulates the ER chaperone Grp78/BiP in liver cells. 2010 Biochem Pharmacol. 2010 Dec 15;80(12):2066-73. Epub 2010 Jul 30.
    OSM, a cytokine of the IL-6-type cytokine family, regulates inflammatory processes (like the acute phase response), tissue remodeling, angiogenesis, cell differentiation and proliferation. Inflammation is discussed to favor carcinogenesis and the inflammatory cytokine OSM was lately described to up-regulate HIF-1α, whose up-regulation is also observed in many cancers. In this study we demonstrate that OSM, and to a lesser degree IL-6, induces the expression of Grp78/BiP, an ER chaperone associated with tumor development and poor prognosis in cancer. In contrast, IFN-γ or TNF-α had no effect on Grp78 expression. The up-regulation seems to be specific to liver cells, as it occurs in hepatocytes and hepatoma cells but not in prostate, melanoma, breast or kidney cells. OSM does not lead to up-regulation of Grp94, enhanced XBP-1 mRNA splicing or phosphorylation of eIF2α, indicating that it is not associated to a general ER stress response. Analysis of the underlying mechanism showed that Grp78 is up-regulated by transcriptional processes which are to the greater part, though not completely, dependent on MEK/Erk activation.
    protein synthesis
  • Exposure of astrocytes to hypoxia/reoxygenation enhances expression of glucose-regulated protein 78 facilitating astrocyte release of the neuroprotective cytokine interleukin 6. 1996 J Neurochem. 1996 Mar;66(3):973-9.
    Astrocytes exposed to hypoxia (H) or hypoxia/ reoxygenation (H/R) maintain cell viability and display changes in protein biosynthesis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of metabolically labeled astrocytes exposed to H showed induction of an approximately 78-kDa polypeptide that demonstrated sequence identity with glucose-regulated protein (GRP) 78. Cell lysates from H/R astrocytes displayed induction of neuroprotective interleukin (IL) 6, which was present in a high-molecular-weight complex also containing GRP78, suggesting that GRP78 might be functioning as a chaperone during cellular stress consequent on H/R. Introduction of antisense oligonucleotide to GRP78 into astrocytes prevented expression of the protein and suppressed H/R-induced astrocyte release of IL-6 by approximately 50%. These data indicate that modulation of astrocyte properties during oxygen deprivation results, in part, from intracellular glucose depletion and subsequent expression of GRP78, which sustains generation of neuroprotective IL-6 under the stress of H/R.

post-translational modifications
degradation

CELLULAR FUNCTIONS

GRP78 functions

cellular localization,
biological function

  • Enzymes
DatabaseLink
BRENDA - The Comprehensive Enzyme Information System"URL":
KEGG Pathways"URL":
Human Metabolome Database"URL":
  • Cell signaling and Ligand transport
  • Structural proteins

REGULATION

In cells starved of glucose the synthesis of several proteins, called glucose-regulated proteins (GRPs), is markedly increased.
They include:

  • GRP78
  • GRP94

Its synthesis is markedly induced under conditions that lead to the accumulation of unfolded polypeptides in the ER.

DIAGNOSTIC USE

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