The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone. GRP78 is a member of the 70 kDa heat shock family of proteins involved in correcting and clearing misfolded proteins in the ER. In response to cellular stress, GRP78 escapes from the ER and moves to the plasma membrane where it (a) functions as a receptor for many ligands, and (b) behaves as an autoantigen for autoantibodies that contribute to human disease and cancer. Cell surface GRP78 (csGRP78) associates with the major histocompatibility complex class I (MHC-I), and is the port of entry for several viruses, including the predictive binding of the novel SARS-CoV-2. Furthermore, csGRP78 is found in association with partners as diverse as the teratocarcinoma-derived growth factor 1 (Cripto), the melanocortin-4 receptor (MC4R) and the DnaJ-like protein MTJ-1. CsGRP78 also serves as a receptor for a large variety of ligands including activated α₂-macroglobulin (α₂M*), plasminogen kringle 5 (K5), microplasminogen, the voltage-dependent anion channel (VDAC), tissue factor (TF), and the prostate apoptosis response-4 protein (Par-4). In this review, we discuss the mechanisms involved in the translocation of GRP78 from the ER to the cell surface, and the role of secreted GRP78 and its autoantibodies in cancer and neurological disorders.

中文翻译：

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葡萄糖调节蛋白 (GRP78) 是病毒侵袭、癌症和神经系统疾病的重要细胞表面受体

78 kDa 葡萄糖调节蛋白 (GRP78) 是一种内质网 (ER) 驻留分子伴侣。GRP78 是 70 kDa 热休克蛋白家族的成员，参与纠正和清除 ER 中错误折叠的蛋白。响应细胞应激，GRP78从ER逃逸并移至质膜，在其中它（a）充当许多配体的受体，（b）充当有助于人类疾病和癌症的自身抗体的自身抗原。细胞表面 GRP78 (csGRP78) 与主要组织相容性复合体 I 类 (MHC-I) 相关，并且是多种病毒的入口，包括新型 SARS-CoV-2 的预测性结合。此外，发现 csGRP78 与畸胎癌衍生生长因子 1 (Cripto) 等多种多样的伙伴有关，黑皮质素 4 受体 (MC4R) 和 DnaJ 样蛋白 MTJ-1。CsGRP78 还可作为多种配体的受体，包括活化的 α_{2 -}巨球蛋白 (α ₂ M*)、纤溶酶原 kringle 5 (K5)、微纤溶酶原、电压依赖性阴离子通道 (VDAC)、组织因子 (TF) 和前列腺细胞凋亡反应 4 蛋白 (Par-4)。在这篇综述中，我们讨论了 GRP78 从内质网易位到细胞表面的机制，以及分泌的 GRP78 及其自身抗体在癌症和神经系统疾病中的作用。