Alternative titles; symbolsp76HGNC Approved Gene Symbol: TM9SF2Cytogenetic location: 13q32.3 Genomic coordinates (GRCh38): 13:99,501,471-99,564,047 (from NCB...
Alternative titles; symbols
HGNC Approved Gene Symbol: TM9SF2
Cytogenetic location: 13q32.3 Genomic coordinates (GRCh38): 13:99,501,471-99,564,047 (from NCBI)
▼ Cloning and Expression
Endosomes are intracellular acidic compartments that participate in the sorting of proteins in the endocytic pathway. Proteins endocytosed from the plasma membrane are transported to early endosomes by clathrin-coated vesicles and then are either transported to lysosomes via late endosomes or recycled to the cell surface. In response to the low pH of the endosomes, endocytosed proteins undergo structural changes that affect their fate. Thus, the pH of the endosome, and therefore ion-translocating proteins in the endosome membrane, are important for endosome function. Using a yeast 2-hybrid system to identify proteins that interact preferentially with the active form of RAB9 (300284), Diaz et al. (1997) isolated a partial human cDNA encoding TM9SF2. By screening a Jurkat T-cell cDNA library with a fragment of the partial TM9SF2 cDNA, Schimmoller et al. (1998) isolated a cDNA containing the full-length coding sequence of TM9SF2, which they called p76. The deduced 663-amino acid TM9SF2 protein has a calculated molecular mass of 76 kD. TM9SF2 contains a putative signal sequence, a hydrophilic N-terminal region, and 9 predicted C-terminal transmembrane domains. The authors demonstrated that TM9SF2 adopts a type I topology within the membrane, with its hydrophilic N terminus facing the lumen. TM9SF2 shares 35% amino acid sequence identity with the S. cerevisiae Emp70 protein. By indirect immunofluorescence microscopy, recombinant TM9SF2 appeared to be localized to endosomes by virtue of its apparent colocalization with transferrin receptors (190010) and some mannose 6-phosphate receptors; TM9SF2 was not detected in the plasma membrane or in the Golgi apparatus. Northern blot analysis detected an approximately 3.2-kb TM9SF2 transcript in all human tissues tested, with the highest expression in pancreas, high expression in kidney, lower expression in heart, brain, skeletal muscle, and placenta, and the lowest expression in lung and liver. Schimmoller et al. (1998) suggested that TM9SF2 functions as an endosome ion channel or small molecule transporter.
Gross (2014) mapped the TM9SF2 gene to chromosome 13q32.3 based on an alignment of the TM9SF2 sequence (GenBank BC110656) with the genomic sequence (GRCh37).