The sodium dependent imino transporter 1 (SIT1, Slc6a20) is a Na⁺- and Cl^- dependent co-transporter of imino- and neutral amino acids that localizes at the luminal membrane of renal proximal tubule cells and small intestine enterocytes. We have previously shown that the expression of the mouse ortholog of SIT1 is decreased in the kidney of Collectrin knock out mice. Collectrin was shown previously to be necessary for the expression of B⁰AT1 (Slc6a19) in kidney proximal tubule and to increase the function of B⁰AT1 when co-expressed in Xenopus oocytes. The type I transmembrane glycoprotein Collectrin is expressed mostly in the kidney, and structurally it is homologuous to the membrane anchor region of Angiotensin Converting Enzyme 2 (ACE2), an important player of the Renin-Angiotensin-Aldosteron-System (RAAS). In contrast to the situation observed in kidney, it is not Collectrin but ACE2 that was shown to be necessary for the expression of B⁰AT1 in small intestine, where Collectrin is almost absent. The aim of the present study is to characterize the function of the human ortholog of SIT1 and to analyze its interaction with the tissue-specific accessory proteins Collectrin and ACE2. Co-expression of human Collectrin or ACE2 with human SIT1 in Xenopus laevis oocytes induced a transport of the imino acid proline that was 2 - 3-fold higher, when compared to the oocytes expressing the transporter alone. This increased uptake is probably due to a higher number and/or transport rate of SIT1 expressed at the cell surface, as suggested by analogy to observations made for B⁰AT1 and also by the fact that the maximal transport rate of L-Pro was increased (V_max hSIT1 alone: 4.3  1.6 pmol/h/oocyte, V_max hSIT1 + hColl: 32.6 10.6 pmol/h/oocyte, V_max hSIT1 + hACE2: 15.7 3.2 pmol/h/oocyte), whereas the apparent affinity.for L-Pro was not significantly changed (K_0.5 hSIT1 alone: 0.16 0.13 mM, K_0.5 hSIT1 + hColl: 0.17 0.12 mM, K_0.5 hSIT1 + hACE2: 0.08 0.04 mM). These preliminary results suggest that Collectrin and ACE2 are also accessory proteins of the human imino acid transporter, hSIT1, in kidney and small intestine, respectively.