Alternative titles; symbols
HGNC Approved Gene Symbol: LY6G6F
Cytogenetic location: 6p21.33 Genomic coordinates (GRCh38): 6:31,706,866-31,710,679 (from NCBI)
The human G6f protein is a type I transmembrane protein belonging to the immunoglobin (Ig) superfamily, which is composed of cell surface proteins involved in the immune system and cellular recognition (de Vet et al., 2003).
By nested PCR using human genomic sequence and mouse ESTs, de Vet et al. (2003) cloned human C6ORF21, which they called G6F. The deduced 297-amino acid protein contains a putative leader peptide, an extracellular region, a transmembrane segment, and a cytoplasmic tail with a tyrosine phosphorylation site. The N-terminal half of the extracellular region shares homology with V-type Ig domains of other proteins and contains 2 conserved cysteine residues capable of forming a disulfide bond. SDS-PAGE under nonreducing conditions yielded a 60-kD protein, which is twice the calculated molecular mass of G6f protein, suggesting that G6f forms a disulfide-linked dimer. Glycosidase treatment confirmed N-glycosylation of G6f, consistent with observation of a putative N-glycosylation site at amino acids 88 to 90. Immunofluorescence in COS-7 cells localized G6f to the cell surface.
Using GST pull-down and coimmunoprecipitation assays of wildtype and mutant constructs, de Vet et al. (2003) showed that G6f interacted with the SH2 domains of GRB2 (108355) and GRB7 (601522). Phosphorylation of tyr281 of G6F was required for binding to both proteins, and dominant-negative mutants of the SH2 domains of GRB2 and GRB7 resulted in absent and strongly reduced binding, respectively. By antibody crosslinking in human myelogenous leukemia cells expressing G6f, they observed that G6f increased phosphorylation of p42 MAPK (MAPK1; 176948) and p44 MAPK (MAPK3; 601795), which was not observed with Y281F-mutant Gf6. De Vet et al. (2003) concluded that G6f can couple with the Ras-MAPK signaling pathway and that this coupling requires phosphorylation of G6f at tyr281.
De Vet et al. (2003) determined that the C6ORF21 gene contains 6 exons.
De Vet et al. (2003) noted that the C6ORF21 gene maps to the MHC class III region on chromosome 6p21.
de Vet, E. C. J. M., Aguado, B., Campbell, R. D. Adaptor signalling proteins Grb2 and Grb7 are recruited by human G6f, a novel member of the immunoglobulin superfamily encoded in the MHC. Biochem. J. 375: 207-213, 2003. [PubMed: 12852788] [Full Text: https://doi.org/10.1042/BJ20030293]