GRB10-interacting GYF protein 2 (GIGYF2)

GRB10-interacting GYF protein 2 (GIGYF2) is a large multidomain protein containing a GYF (glycine-tyrosine-phenylalanine) domain and regions rich in polyglutamine repeats. It is a key component of the 4EHP-GYF2 repressive complex, where it partners with eIF4E homologous protein (4EHP, also known as EIF4E2) to inhibit translation initiation of certain mRNAs, target them for decapping, and coordinate mRNA decay through interaction with proteins such as DDX6 and components of the microRNA-induced silencing complex (including TNRC6A/GW182 and ZNF598)[1][2]. Despite its historical name, GIGYF2 does **not interact with GRB10 in humans** due to absence of a key proline-rich motif; its main roles involve control of mRNA translation and quality control, especially in neurons, and possible regulation of tyrosine kinase receptor signaling (including IGF1R and insulin receptors)[2][1][4]. Mutations in GIGYF2 have been associated with familial Parkinson’s disease and possibly autism spectrum disorder, but the pathogenic and therapeutic significance remains controversial and under investigation[1][2][4]. GIGYF2 is broadly expressed in several tissues, with high levels in the brain, pancreas, and testis[5].

Other names

KIAA0642PERQ2TNRC15PARK11PERQ3GYF2Trinucleotide repeat-containing gene 15 proteinGYF domain containing 2PERQ amino acid-rich with GYF domain-containing protein 2

Inhibition of GIGYF2-induced Akt phosphorylation and related effects on IGF1R signaling by Ridaifen B[4]