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PITP Evolutionary Analysis

Dr. Marilyn Yoder and Dr. Gerald J. Wyckoff

Phosphatidylinositol transfer proteins (PITP) are monomeric proteins that bind and transfer inositol lipids between membrane compartments. These lipids provide a source of second messengers and act as signaling molecules. PITPs are found in a wide variety of metazoan organisms and are a diverse family of proteins, with both soluble and membrane-associated forms. This presented unique challenges to global alignment; instead, a cladogram of conserved sequence motifs in 60 PITP family proteins from 26 species was created. You can view the complete motif dataset here

Three previously determined functional divisions of PITP proteins were supported by our cladistic analysis; Class I, Class IIB and Class IIA. Class I, the soluble PITPs, appear to be the ancestral form. Class IIB proteins, historically named rdgB.'s, are derived from Class I proteins. Class IIA, membrane associated proteins with N-terminal PITP-like domains, are derived from class IIB proteins.

Our analysis of PITP proteins utilizing a phylogenetic approach focused on conserved regions allowed for a detailed analysis of the possible functional roles of these conserved domains and the construction of testable hypotheses regarding PITP function and it.s role in cell signalling.


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