title: Cellular localization and characterization of cytosolic binding partners for Gla domain-containing proteins PRRG4 and PRRG2.
abstract: The genes encoding a family of proteins termed proline-rich γ-carboxyglutamic acid (PRRG) proteins were identified and characterized more than a decade ago, but their functions remain unknown. These novel membrane proteins have an extracellular γ-carboxyglutamic acid (Gla) protein domain and cytosolic WW binding motifs. We screened WW domain arrays for cytosolic binding partners for PRRG4 and identified novel protein-protein interactions for the protein. We also uncovered a new WW binding motif in PRRG4 that is essential for these newly found protein-protein interactions. Several of the PRRG-interacting proteins we identified are essential for a variety of physiologic processes. Our findings indicate possible novel and previously unidentified functions for PRRG proteins.
authors.affiliation: From the Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Mustafa N
authors.initials: MN
authors.lastname: Yazicioglu
authors.affiliation: From the Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Luca
authors.initials: L
authors.lastname: Monaldini
authors.affiliation: From the Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Kirk
authors.initials: K
authors.lastname: Chu
authors.affiliation: From the Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Fayaz R
authors.initials: FR
authors.lastname: Khazi
authors.affiliation: From the Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Murphy
authors.affiliation: From the Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Heshu
authors.initials: H
authors.lastname: Huang
authors.affiliation: From the Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104,; the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, and.
authors.forename: Paris
authors.initials: P
authors.lastname: Margaritis
authors.affiliation: From the Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104,; the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, and; the Howard Hughes Medical Institute, Chevy Chase, Maryland 20815. Electronic address: high@email.chop.edu.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: High
mesh_terms: D020816:Amino Acid Motifs; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D008565:Membrane Proteins; C423615:PRRG4 protein, human
keywords: Cell Signaling; Cytosolic Binding Partners; Gla Domain; Membrane Proteins; Molecular Biology; Mutagenesis Site-specific; PRRG2; PRRG4; Protein Carboxylation; Vitamin K