Heme and a five-amino-acid hemophore region form the bipartite stimulus triggering the has signaling cascade.

Bacterial cells sense the extracellular environment and adapt to that environment by activating gene regulation circuits, often by means of signaling molecules. The Serratia marcescens hemophore is a signaling molecule that acts as an extracellular heme-scavenging protein. The heme-loaded hemophore interacts with its cognate receptor (HasR), triggering transmembrane signaling and turning on transcription of hemophore-dependent heme uptake genes.

Haemophore-mediated signalling in Serratia marcescens: a new mode of regulation for an extra cytoplasmic function (ECF) sigma factor involved in haem acquisition.

Bacterial extra cytoplasmic function (ECF) sigma factors control a wide range of cell envelope activities including iron and haem uptake systems. Sigma activity is usually inhibited by membrane-bound antisigma. An extra cytoplasmic signal modulates sigma-antisigma interactions and thereby leads to the transcription of the target operon.