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Description

Triple functional domain protein (UniProt: O75962, also known as EC: 2.7.11.1, PTPRF-interacting protein, TRIO) is encoded by the TRIO gene (Gene ID: 7204) in human. TRIO is a complex protein that is widely expressed in human tissue, with highest levels reported in heart, skeletal muscle, and brain. Five isoforms of TRIO have been reported that are produced by alternative splicing. It contains three catalytic domains, two tandem Dbl Homology (DH) and pleckstrin homology (PH) domains, and a serine/Threonine kinase domain. The DH-PH module is involved in guanine nucleotide exchange and the activation of the small GTPases of the Rho family. The DH1-PH1 domain (GEF1) is reported to activate the Rho G and Rac1, whereas DH2-PH2 (GEF2) is involved in the activation of RhoA. TRIO is involved in coordinating actin remodeling, which is necessary for cell migration and growth. In developing hippocampal neurons it limits dendrite formation, without affecting the establishment of axon polarity. After dendrites are formed, it is reported to be involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors at CA1 excitatory synapses. Mutations in TRIO gene have been linked to mental retardation and microcephaly. (Ref.: Debant, A. et al. (1996). Proc. Natl. Acad. Sci, USA. 93(11), 5466-71, Bellanger, JM. Et al. (2000). Nat. Cell Biol. 2(12), 888-92).