Note. The amino acid positions for human gp330 cited in the text are numbered from the probable cleavage site of signal pepdidase. The sequence reported in the paper has been deposited in the GenBank data base (accession number U33837).
Cloning and Sequencing of Human gp330, a Ca2+-Binding Receptor with Potential Intracellular Signaling Properties
Article first published online: 23 JUL 2004
European Journal of Biochemistry
Volume 239, Issue 1, pages 132–137, July 1996
How to Cite
Hjälm, G., Murray, E., Crumley, G., Harazim, W., Lundgren, S., Onyango, I., Ek, B., Larsson, M., Juhlin, C., Hellman, P., Davis, H., Åkerström, G., Rask, L. and Morse, B. (1996), Cloning and Sequencing of Human gp330, a Ca2+-Binding Receptor with Potential Intracellular Signaling Properties. European Journal of Biochemistry, 239: 132–137. doi: 10.1111/j.1432-1033.1996.0132u.x
- Issue published online: 23 JUL 2004
- Article first published online: 23 JUL 2004
- (Received 18 December 1995/25 March 1996) – EJB 95 2065/2
- Heymann nephritis;
- calcium signaling;
- cysteine repeats;
- low-density-lipoprotein-receptor superfamily;
- endocytic receptor
We present here the complete primary structure of human gp330, the human variant of the principal kidney autoantigen causing Heymann membranous glomerulonephritis in rats. The deduced 4655 amino acid residues give a calculated molecular mass of 519636 Da for the mature protein and consists of a probable 25-amino-acid N-terminal signal peptide sequence, an extracellular region of 4398 amino acids, a single transmembrane-spanning domain of 23 amino acids, and an intracellular C-terminal region of 209 amino acid residues. Three types of cysteine-rich repeats characteristic of the low-density lipoprotein receptor (LDLR) superfamily are present in human gp330. In the extracellular region, there are a total of 36 LDLR ligand-binding repeats, comprising four distinct domains, 16 growth factor repeats separated by eight YWTD spacer regions, and one epidermal growth factor-like repeat. No consensus cleavage sequence for the processing endoprotease furin is detected in human gp330. The intracellular tail contains not only two copies of the F(X)NPXY coated-pit mediated internalization signal characteristic of LDLR superfamily members, but also intriguing and potentially functional motifs including several Src-homology 3 recognition motifs, one Src-homology 2 recognition motif for the p85 regulatory subunit of phosphatidylinositol 3-kinase, and additional sites for protein kinase C, casein kinase II and CAMP-/cGMP-dependent protein kinase. There is approximately 77% amino acid identity between human and rat gp330 with minor differences between the extracellular and intracellular regions. Recently gp330 has been implicated in Ca2+ regulation in the parathyroid, the placenta, and the renal tubule, but its overall physiological and pathological role still remains uncertain.