GP-2/THP gene family encodes self-binding glycosylphosphatidylinositol-anchored proteins in apical secretory compartments of pancreas and kidney.
A family of homologous genes is shown to encode GP-2, the major glycosylphosphatidylinositol (GPI)-linked glycoprotein of pancreatic zymogen granule membranes, and Tamm-Horsfall protein (THP), a GPI-linked glycoprotein associated with apical vesicles in kidney thick ascending limb of Henle (TALH) cells. The C-terminal regions of GP-2 (Asp54-Phe530) and THP (Asp175-His644) from rat show 53% identity, 86% similarity, and 26 conserved cysteine residues including one epidermal growth factor motif. The unique N-terminal domain of rat THP (unique-THP, Pro29-Gln174) shows four conserved epidermal growth factor motifs, three in tandem and one in reverse orientation. GP-2 homologues are observed in a wide variety of epithelial cells, several of which contain highly regulated secretory processes. GP-2 released from zymogen granule membranes with phosphatidylinositol phospholipase C reacts with anti-cross-reactive determinant antibody (anti-CRD), confirming the GPI nature of the pancreatic homologue. In contrast, GP-2 and THP, released endogenously from pancreas and kidney, respectively, do not react with anti-cross-reactive determinant antibody, suggesting alternative enzymatic mechanisms for their physiological release. Globular domains of GP-2 and THP, but not albumin, show pH- and ion-dependent self-association in vitro. The GP-2/THP family appears to represent a newly discovered class of GPI-anchored proteins, which may utilize pH- and ion-dependent self-association mechanisms for establishing membrane (micro)domains targeted to intracellular secretory compartments.
Fukuoka
S
S
Laboratory of Cell and Molecular Biology, Charles A. Dana Research Institute, Thorndike Laboratory, Boston, MA 02215.
Freedman
S D
SD
Yu
H
H
Sukhatme
V P
VP
Scheele
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004285:Dogs; D015870:Gene Expression; D006017:Glycolipids / Q000378:metabolism; D017261:Glycosylphosphatidylinositols; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000378:metabolism*; D005810:Multigene Family; D009994:Osmolar Concentration; D010179:Pancreas / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015183:Restriction Mapping; D016415:Sequence Alignment; D058949:Uromodulin
D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009088:Mucoproteins; D010716:Phosphatidylinositols; D012333:RNA, Messenger; C548612:UMOD protein, human; C548614:Umod protein, rat; D058949:Uromodulin; C072961:glycoprotein-2, pancreas; D004247:DNA