InterPro domain: IPR019402

This entry includes Frag1, DRAM and Sfk1 proteins. Frag1 (FGF receptor activating protein 1, also known as post-GPI attachment to proteins factor 2) is a protein that is conserved from fungi to humans. There are four potential iso-prenylation sites throughout the peptide, CILW (x2), CIIW and CIGL. Frag1 is a membrane-spanning protein that is ubiquitously expressed in adult tissues suggesting an important cellular function [ 1 ]. DRAM is a family of proteins conserved from nematodes to humans with six hydrophobic transmembrane regions and an endoplasmic reticulum signal peptide. It is a lysosomal protein that induces macro-autophagy as an effector of p53-mediated death, where p53 is the tumour-suppressor gene that is frequently mutated in cancer. Expression of DRAM is stress-induced [ 2 ]. DRAM-3 (also known as modulator of macroautophagy TMEM150B) has been shown to be a modulator of both macroautophagy and cell survival under starvation conditions [ 3 ]. This region is also part of a family of small plasma membrane proteins, referred to as Sfk1, that may act together with or upstream of Stt4p to generate normal levels of the essential phospholipid PI4P, thus allowing proper localisation of Stt4p to the actin cytoskeleton [ 4 , 5 ].

1. Human FRAG1 encodes a novel membrane-spanning protein that localizes to chromosome 11p15.5, a region of frequent loss of heterozygosity in cancer. Genomics 62, 59-66
2. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 126, 121-34
3. DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose. Cell Death Differ. 22, 1714-26
4. A small molecule suppressor of FK506 that targets the mitochondria and modulates ionic balance in Saccharomyces cerevisiae. Chem. Biol. 10, 521-31
5. Stt4 PI 4-kinase localizes to the plasma membrane and functions in the Pkc1-mediated MAP kinase cascade. Dev. Cell 2, 593-605