In order to identify genes that may be causally involved in replicative senescence, we have isolated several gene sequences that are overexpressed in senescent human fibroblasts by differential screening of a cDNA library derived from mRNA of a subject with Werner syndrome of premature aging (Murano, S., et al., Molec. Cell. Biol., 3905-3914, 1991). Herein, we describe the sequence and expression of one of these genes, WS3-10, which encodes a novel human cytoplasmic protein of 22.5 kilodaltons. The steady-state mRNA levels of WS3-10 mRNA were higher in WS and late-passage normal cells compared to early-passage normal cells following serum depletion and subsequent repletion. Computer analysis showed similarities between WS3-10 and certain proteins in other species, indicating that WS3-10 represents the human homolog of a smooth muscle protein involved in calcium interactions that may contribute to replicative senescence.