The low-calcium response (Icr) is strongly conserved among the pathogenic Yersinia species and is observed when the pathogen is grown at 37°C in Ca2+-depleted medium. This response is characterized by a general metabolic downshift and by a specific induction of virulence-plasmid-encoded yop genes. Regulation of yop expression is exerted at transcriptional level by a temperature-regulated activator and by Ca2+-regulated negative elements. The yopN gene was shown to encode a protein (formerly also designated Yop4b) which is surface-located when Yersmia is grown at 37°C. yopN was found to be part of an operon that is induced during the low-calcium response. Insertional inactivation of the yopN gene resulted in derepressed transcription of yop genes. A hybrid plasmid containing the yopN gene under the control of the tac promoter fully restored the wild-type phenotype of the yopN mutant. Thus the surface-located YopN somehow senses the calcium concentration and transmits a signal to shut off yop transcription when the calcium concentration is high.