Human Erythrocyte Membrane Protein 4.2 is Palmitoylated

Protein 4.2 is a major protein of the human erythrocyte membrane. It has previously been shown to be N‐myristoylated. After labeling of intact human erythrocytes with [³H]palmitic acid, radioactivity was found to be associated with protein 4.2 by immunoprecipitation of peripheral membrane proteins extracted at pH 11 from ghosts with anti‐(4.2) sera, followed by SDS/PAGE and fluorography. The fatty acid linked to protein 4.2 was identified as palmitic acid after hydrolysis of protein and thin‐layer chromatography of the fatty acid extracted in the organic phase. Protein 4.2 could be depalmitoylated with hydroxylamine, suggesting a thioester linkage. Depalmitoylated protein 4.2 showed significantly decreased binding to protein‐4.2‐depleted membranes, compared to native protein 4.2.