Clusterin, N-terminal (IPR016014)

Short name: Clusterin_N

Domain relationships



Clusterin is a vertebrate glycoprotein [PMID: 1585460], the exact function of which is not yet clear. Clusterin expression is complex, appearing as different forms in different cell compartments. One set of proteins is directed for secretion, and other clusterin species are expressed in the cytoplasm and nucleus. The secretory form of the clusterin protein (sCLU) is targeted to the ER by an initial leader peptide. This ~60kDa pre-sCLU protein is further glycosylated and proteolytically cleaved into alpha- and beta-subunits, held together by disulphide bonds. External sCLU is an 80kDa protein and may act as a molecular chaperone, scavenging denatured proteins outside cells following specific stress-induced injury such as heat shock. sCLU possesses nonspecific binding activity to hydrophobic domains of various proteins in vitro [PMID: 12551933].

A specific nuclear form of CLU (nCLU) acts as a pro-death signal, inhibiting cell growth and survival. The nCLU protein has two coiled-coil domains, one at its N terminus that is unable to bind Ku70, and a C-terminal coiled-coil domain that is uniquely able to associate with Ku70 and is minimally required for cell death.

Clusterin is synthesized as a precursor polypeptide of about 400 amino acids which is post-translationally cleaved to form two subunits of about 200 amino acids each. The two subunits are linked by five disulphide bonds to form an antiparallel ladder-like structure [PMID: 1491011]. In each of the mature subunits the five cysteines that are involved in disulphide bonds are clustered in domains of about 30 amino acids located in the central part of the subunits.

This entry represents the N-terminal domain of the clusterin precursor.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.