title: Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties.
abstract: 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.
authors.affiliation: Department of Bone Metabolism, Rhône-Poulenc Rorer Central Research, Collegeville PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Hjälm
authors.forename: E
authors.initials: E
authors.lastname: Murray
authors.forename: G
authors.initials: G
authors.lastname: Crumley
authors.forename: W
authors.initials: W
authors.lastname: Harazim
authors.forename: S
authors.initials: S
authors.lastname: Lundgren
authors.forename: I
authors.initials: I
authors.lastname: Onyango
authors.forename: B
authors.initials: B
authors.lastname: Ek
authors.forename: M
authors.initials: M
authors.lastname: Larsson
authors.forename: C
authors.initials: C
authors.lastname: Juhlin
authors.forename: P
authors.initials: P
authors.lastname: Hellman
authors.forename: H
authors.initials: H
authors.lastname: Davis
authors.forename: G
authors.initials: G
authors.lastname: Akerström
authors.forename: L
authors.initials: L
authors.lastname: Rask
authors.forename: B
authors.initials: B
authors.lastname: Morse
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018909:src Homology Domains
chemical_list: D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins