In fact, much longer examples of DAPT signal peptides are known to exhibit additional functions besides precursor targeting, for example regulation of the protein export rate as described for interleukin-15, or signal peptide accumulation in the nucleoli in the case of mouse mammary tumor virus Remprotein after release from the endoplasmic reticulum. In the present study, we introduce a structurally motivated modularization of long signal peptides into separate functional modules, and demonstrate the actual functional relevance of this concept for the long signal peptide of the integral membrane protein shrew-1 as an example. Shrew-1 was originally isolated from an epithelial-like cell line obtained from an endometriosis biopsy. It contains a cleavable N-terminal signal peptide of 43 residues, an extracellular domain, a transmembrane segment and a cytoplasmic domain. Shrew-1 is transported to the basolateral part of the plasma membrane in polarized epithelial cells and interacts with the Ecadherin mediated adherens junction complex. In nonpolarised cells, like transformed epithelial cells, shrew-1 also displays plasma membrane localization, though apparently less polarized. Shrew-1 appears to be involved in the regulation of cell invasion and motility and, in line with this, interacts with protein CD147, a known promoter of invasiveness. Based on proteome analysis by machine-learning systems, we propose a bipartite domain model of long signal peptides from single-pass integral membrane proteins. According to this model, such long signal peptides may contain two separate functional domains: an N-terminal domain and a C-terminal domain traceable by a turn-rich linker area connecting both. We denote this linker element ����transition area����. Proof-of-principle for the validity of the NtraC domain model is provided by in vitro targeting experiments with shrew-1. Analysis of long signal peptides was performed in two steps: First, potential domains were predicted using a novel machinelearning technique for turn prediction. Potential turncontaining regions were found to be predominantly located in the central Temozolomide portion of these long signals. Based on the location of this ����transition area����, long signal peptides were dissected into two parts, an N-terminal and a C-terminal fragment. Then, the resulting sequence fragments were scrutinized for potential targeting functions. The concept of this NtraC model of signal peptide organization is based on the hypothesis that the two functional modules in a long signal peptide may exhibit individually distinct tasks in the context of protein targeting. This requires a minimal peptide length, and for the present study we decided to focus only on signal peptide domains containing conventional signals with an expected average length of approximately 20 residues each. This choice is motivated by the observed average length of targeting signals coding for a single compartment.