It make be linked to the YabA initiation control protein which functions as the chromosomal replication initiation control in bacteria. The PspA/IM30 family is a negative regulator of sigma54 transcription initiation factor in bacteria. FYVE domain consists of Fab-1, YGL023, Vps27, and EEA1 proteins. Within the FYVE domain there are Zinc finger binding sites that interact with phosphatidylinositol-3-phosphate, to bring target proteins to membrane lipids. The proline rich motif in the FYVE domain of RUFY2 has been shown to have binding activity with the SH3 domain of EPHA3 (Etk) in signal transduction pathways. RUFY2 possibly has 6 phosphorylation sites and are located mainly in the DUF972 region. RUFY2 also has 6 protein kinase C phosphorylation sites that are located mainly within the FYVE domain. RUFY2 has 4 paralogs: RUFY3, RUFY1, RUNDC3A, RUNDC3B. There are 60 orthologs of RUFY2 that have been identified including mammals, some birds, reptiles and fish. RUFY2 is highly conserved among its orthologs but is not present in plants, bacteria, archea or protist. The following table lists the homologs of RUFY2. Certain neurodegenerative diseases such as Alzheimer's have been found to have defective endosomal trafficking. Therefore, the involvement of RUFY2 protein domains, RUN and FYVE, may possibly play a role in neurodegenerative diseases such as Alzheimer's. RUFY2 protein has been shown to mainly be expressed in the brain, lung, and testes while microarray expression shows RUFY2 ubiquitous expression.