The endoplasmic reticulum calcium-binding protein of 55 kDa is a novel EF- hand protein retained in the endoplasmic reticulum by a carboxyl-terminal His-Asp-Glu-Leu motif

K. Weis, G. Griffiths, A. I. Lamond

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Abstract

We have identified a new human Ca2+-binding protein that is specifically localized in the endoplasmic reticulum (ER). The protein is termed ERC-55, i.e. ER calcium-binding protein of 55 kDa. ERC-55 is a single copy gene and is encoded by an approximately 1900-base mRNA, which shows a ubiquitous expression pattern. The ERC-55 protein comprises an amino-terminal signal sequence followed by six copies of the EF-hand Ca2+ binding motif. Ca2+ binding was demonstrated directly for recombinant ERC-55 using the 45Ca2+ overlay technique. The carboxyl-terminal sequence His-Asp-Glu-Leu (HDEL) is required for retention of ERC-55 in the ER. Deletion of HDEL results in slow secretion into the medium. In pulse-chase experiments, approximately 50% of the HDEL deletion mutant is secreted, whereas no detectable secretion is observed with the wild-type protein. This represents the first example of an endogenous human protein that is retained in the ER by an HDEL rather than Lys-Asp-Glu-Leu (KDEL) carboxyl-terminal tetrapeptide. Comparative sequence analysis indicates that ERC-55, together with the recently identified protein reticulocalbin (Ozawa and Muramatsu, 1993), constitute a new subfamily of the EF-hand superfamily of Ca2+-binding proteins that are specifically located in the ER.

Original languageEnglish
Pages (from-to)19142-19150
Number of pages9
JournalJournal of Biological Chemistry
Volume269
Issue number29
Publication statusPublished - 22 Jul 1994

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