Cytoplasmic domain of NCAM140 interacts with ubiquitin-fold modifier-conjugating enzyme-1 (Ufc1)

• A protein macroarray analysis was performed to identify novel interactions partners of NCAM.
• Ufc1 was identified as a potential interaction partner of NCAM140.
• NCAM co-localizes with Ufc1 and Ufm1 on the cell surface of neurons.
• Ufm1 increases endocytosis of NCAM.

The neural cell adhesion molecule NCAM is implicated in different neurodevelopmental processes and in synaptic plasticity in adult brain. The cytoplasmic domain of NCAM interacts with several cytoskeletal proteins and signaling molecules. To identify novel interaction partners of the cytosolic domain of NCAM a protein macroarray has been performed. We identified the ubiquitin-fold modifier-conjugating enzyme-1 (Ufc1) as an interaction partner of NCAM140. Ufc1 is one of the enzymes involved in modification of proteins with the ubiquitin-like molecule ubiquitin-fold modifier-1 (Ufm1). We also observed a partial co-localization of NCAM140 with Ufc1 and Ufm1 and increased endocytosis of NCAM140 in the presence of Ufm1 suggesting a possible ufmylation of NCAM140 and a potential novel function of Ufm1 for cell surface proteins.