Chaperone-like Activity of Calnuc Prevents Amyloid Aggregation.

Calnuc is a ubiquitously expressed protein of the EF-hand Ca-binding superfamily. Previous studies have implicated it in Ca-sensitive physiological processes, whereas details of its function and involvement in human diseases are lacking. Drawing upon the sequence homology of calnuc with calreticulin, we propose it functions as a molecular chaperone-like protein.

Serine protease activity of calnuc: regulation by Zn2+ and G proteins.

The functions of calnuc, a novel Ca(2+)-binding protein with multiple structural domains and diverse interacting partners, are yet unknown. We demonstrate unknown facets of calnuc, which is a serine protease in which Ser-378 of GXSXG motif, Asp-328 of DTG motif, and His-339 form the "catalytic triad," locating the enzyme active site in the C-terminal region. Analogous to the active site of Zn(2+) carboxypeptidases, calnuc has two high affinity (K(d) ∼ 20 nm), well conserved Zn(2+)-binding sites near its N terminus, although it is inactive as a peptidase.

Calnuc: Emerging roles in calcium signaling and human diseases.

Calnuc is a recently discovered multidomain protein with EF-hand calcium binding sites. Several studies have reported various interacting partners for calnuc and, therefore, also different sites of localization in the cell. It interacts with important molecules such as DNA, G protein, COX, and amyloid precursor protein among others in addition to being involved in stress response and trafficking.

Ion-binding properties of Calnuc, Ca2+ versus Mg2+--Calnuc adopts additional and unusual Ca2+-binding sites upon interaction with G-protein.

Calnuc is a novel, highly modular, EF-hand containing, Ca(2+)-binding, Golgi resident protein whose functions are not clear. Using amino acid sequences, we demonstrate that Calnuc is a highly conserved protein among various organisms, from Ciona intestinalis to humans. Maximum homology among all sequences is found in the region that binds to G-proteins.