Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation.
The isolation and characterization of a human functional GRP78 gene and a processed pseudogene are described. We present the complete primary structure of the human GRP78 gene, which spans over 5 kb and consists of eight exons. Sequence comparisons reveal that the GRP78 gene shares unusual homology among the human, rat, and hamster in the protein-coding and 3' untranslated regions. In addition, short domains highly conserved with HSP70 isolated from human, Drosophila, Xenopus, yeast, and E. coli DNA are identified within the hydrophobic regions of GRP78. The intronless pseudogene resembles that of a processed gene. It is flanked by a short direct repeat and is embedded within an AT-rich genomic region. The highly active promoter from the functional human GRP78 gene contains a TATA box, five CCAAT sequences, and two potential binding sites for the transcriptional factor Sp1. It consists of a distal domain that enhances basal level expression and a proximal domain essential for responses to calcium ionophore and for a temperature-sensitive mutation which induce the GRP78 gene. Both domains are highly conserved between the rat and the human GRP78 promoters.
Ting
J
J
Department of Biochemistry, University of Southern California School of Medicine, Los Angeles 90033.
Lee
A S
AS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004262:DNA Restriction Enzymes; D000091342:Endoplasmic Reticulum Chaperone BiP; D005091:Exons; D005786:Gene Expression Regulation; D005796:Genes; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011544:Pseudogenes; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D008565:Membrane Proteins; C018551:glucose-regulated proteins; D004262:DNA Restriction Enzymes