Human PPFIA1 (also known as LIP.1 or Liprin α1) gene, located within CCND1-FGF4-EMS1 amplicon at human chromosome 11q13.3, encodes KIF1A-binding protein, which is implicated in trafficking of LAR subfamily PTPases and AMPA-type glutamate receptors. Human PPFIA4 (AF034801) and rat Ppfia4 (AY057064) are 5'-truncated partial cDNAs, and the complete coding sequence of PPFIA4 ortholog of any species remained to be identified. Here, we determined the complete coding sequence of human PPFIA4 gene by using bioinformatics. Exons 1-12 of PPFIA4 gene were located within human genome sequence AC096632.3, while exons 11-29 within AL451082.6. PPFIA4-MYOG locus (human chromosome 1q32.1) was paralogous to PPFIA2-LIN7A-MYF5-MYF6 locus (12q21.31), which was also paralogous to PPFIA3-LIN7B locus (19q13.41). PPFIA4 (1186 aa) showed 70.9%, 67.1%, and 61.8% total-amino-acid identity with PPFIA2, PPFIA1, and PPFIA3, respectively. PPFIA family members consist of PFIH1, PFIH2, PFIH3, PFIH4 domains and three SAM (Sterile α motif) domains. C-terminal binding domain for GRIP proteins (VRTYSC motif) was present in PPFIA1, PPFIA2 and PPFIA3, but not in PPFIA4. Bipartite nuclear localization signal was included within PFIH4 domain. PFIH2 domain was identical to ERM or Smc domain. The region spanning PFIH2-PFIH3 domains is the binding domain for KIF1A. The region spanning SAM1-SAM3 domains is the binding domain for LAR subfamily PTPases and PPFIBP (Liprin β) family proteins. This is the first report on comprehensive characterization of PPFIA4 belonging to the PPFIA family of kinesin-cargo linkers.

Related Articles