title: Protein 4.2: a complex linker.
abstract: The peripheral membrane protein, protein 4.2, is one of the most abundant protein components of the erythrocyte membrane. Protein 4.2 has an important role in red cell membrane structure, its absence due to natural mutations in humans or gene knockout in mice has a detrimental effect on membrane stability and results in hereditary spherocytosis. It is known to be a point of connection between the band 3 complex and the Rhesus protein complex, through its associations with band 3 and CD47 and also via interactions with the cytoskeletal protein ankyrin. Considering its relatively high abundance and importance in stability of the erythrocyte membrane, protein 4.2 has proved a somewhat neglected protein in recent years. In this review we will summarize our current understanding of protein 4.2, discuss its known interactions and describe the effects and implications of protein 4.2 deficiency. Based on protein 4.2's close homology with transglutaminase family proteins, we propose a new speculative "open" homology structure for protein 4.2 that may represent the active, membrane associated protein 4.2 molecule in red blood cells and also explain the dependence of protein 4.2 on band 3 binding for stability.
authors.affiliation: University of Bristol, Department of Biochemistry, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Satchwell
authors.forename: Debbie K
authors.initials: DK
authors.lastname: Shoemark
authors.forename: Richard B
authors.initials: RB
authors.lastname: Sessions
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Toye
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D051928:CD47 Antigen / Q000502:physiology; D048430:Cell Shape; D002470:Cell Survival; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000648:ultrastructure; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D013102:Spherocytes / Q000648:ultrastructure; D013103:Spherocytosis, Hereditary / Q000097:blood / Q000235:genetics; D011503:Transglutaminases / Q000737:chemistry
chemical_list: D001798:Blood Proteins; D051928:CD47 Antigen; C497894:CD47 protein, human; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C044791:erythrocyte membrane band 4.2 protein; D011503:Transglutaminases