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78 kD glucose-regulated protein; GRP 78; heat shock 70 kD protein 5; immunoglobulin heavy chain-binding protein; BiP; endoplasmic reticulum lumenal Ca(2+)-binding protein grp78 (HSPA5, GRP78)

Function: - molecular chaperone that associates with newly synthesized proteins usually in the form of aggregates - stress increases association of proteins with GRP78 - any unfolded protein that can bind GRP78 can induce the unfolded protein response pathway - probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER - interacts with DNAJC1 (via J domain) (putative) - component of an EIF2 complex at least composed of CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 & HSPA5 - part a large chaperone multiprotein complex comprising CABP1, DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PPIB, SDF2L1, UGT1A1 & very small amounts of ERP29, but not, or at very low levels, CALR nor CANX - interacts with TMEM132A Structure: belongs to the heat shock protein 70 family Compartment: - endoplasmic reticulum lumen - melanosome Expression: - glucose regulated protein, induced by glucose starvation Pathology: - seizure-related protein - autoantigen in rheumatoid arthritis - role in transmission of Covid-19 Comparative biology: - up-regulated after environmental enrichment in mice [3]

General

heat shock protein [hsp]-70 family

Properties

SIZE: entity length = 654 aa MW = 72 kD COMPARTMENT: endoplasmic reticulum MOTIF: signal sequence {1-18} Thr phosphorylation site {T166} Tyr phosphorylation site {Y466} Ser phosphorylation site {S571} ER-retention {651-654} MISC-INFO: P-ISOELECTRIC 5.2-5.3

Database Correlations

OMIM correlations UniProt P11021 Pfam PF00012 Entrez Gene 3309 Kegg hsa:3309

References

  1. Ou WJ et al Association of folding intermediates of glycoproteins with calnexin during protein maturation. Nature 364:771 1993 PMID: 8102790
  2. Arlan Richardson, AGE meeting Oct 3-6, 1990 New York, NY
  3. Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, Schultz PG, Tsien JZ, Hu Y. Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12880-4. PMID: 11070096
  4. Abrams Z New drug shows promise for fighting both COVID-19 and cancer. Keck School of Medicine USC. Keck School News. Nov 14, 2022 https://keck.usc.edu/new-drug-shows-promise-for-fighting-both-covid-19-and-cancer/ - Shin WJ, Ha DP, Machida K, Lee AS The stress-inducible ER chaperone GRP78/BiP is upregulated during SARS-CoV-2 infection and acts as a pro-viral protein. Nature Communications. 2022. 13:6551. Nov 14 PMID: 36376289 PMCID: PMC9663498 Free PMC article. https://www.nature.com/articles/s41467-022-34065-3