Alternative titles; symbols
HGNC Approved Gene Symbol: GCC2
Cytogenetic location: 2q12.3 Genomic coordinates (GRCh38): 2:108,449,206-108,509,415 (from NCBI)
By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (1997) cloned GCC2, which they designated KIAA0336. The transcript contains a repetitive element in its 3-prime end, and the deduced protein contains 1,583 amino acids. RT-PCR analysis detected high expression in placenta, kidney, and testis and moderate expression in lung, liver, and pancreas.
By searching for genes encoding proteins containing GRIP domains, followed by RT-PCR and 5-prime RACE of HeLa cell RNA, Luke et al. (2003) cloned GCC1 (607418) and GCC2, which they called GCC88 and GCC185, respectively. Both proteins contain a coiled-coil region and a C-terminal GRIP domain of about 50 amino acids. The deduced 1,583-amino acid GCC185 protein has a calculated molecular mass of 185 kD. Both endogenous and fluorescence-tagged GCC88 and GCC185 localized to the trans-Golgi network, and this localization required a functional GRIP domain. Brefeldin A treatment indicated that both GCC88 and GCC185 are peripheral membrane Golgi proteins. Western blot analysis of HeLa cell extracts detected endogenous GCC185 at an apparent molecular mass of 175 kD.
Using yeast 2-hybrid screens and other protein interaction assays, Reddy et al. (2006) showed that RAB9 (300284), but not RAB5 (RAB5A; 179512), interacted with the C-terminal 110 residues of GCC185. Depletion of GCC185 via small interfering RNA led to redistribution of mannose 6-phosphate receptors (MPRs; see 154540) from their perinuclear localization to more dispersed, vesicular structures, blocked recycling of MPRs from late endosomes to the trans-Golgi network, and increased MPR degradation. GCC185 depletion also resulted in increased secretion of the lysosomal enzyme hexosaminidase (see 606869), which is normally captured in the Golgi by MPRs for transport to prelysosomes. Reddy et al. (2006) concluded that GCC185 is a RAB9 effector required for MPR recycling and MPR function in the Golgi apparatus.
By radiation hybrid analysis, Nagase et al. (1997) mapped the GCC2 gene to chromosome 2.
By genomic sequence analysis, Ciccarelli et al. (2005) mapped the GCC2 gene near the RANBP2 gene (601181) on chromosome 2q12.3. This region underwent a complex series of duplications in primate lineages (see RGPD1; 612704).
Ciccarelli, F. D., von Mering, C., Suyama, M., Harrington, E. D., Izaurralde E., Bork, P. Complex genomic rearrangements lead to novel primate gene function. Genome Res. 15: 343-351, 2005. [PubMed: 15710750] [Full Text: https://doi.org/10.1101/gr.3266405]
Luke, M. R., Kjer-Nielsen, L., Brown, D. L., Stow, J. L., Gleeson, P. A. GRIP domain-mediated targeting of two new coiled-coil proteins, GCC88 and GCC185, to subcompartments of the trans-Golgi network. J. Biol. Chem. 278: 4216-4226, 2003. [PubMed: 12446665] [Full Text: https://doi.org/10.1074/jbc.M210387200]
Nagase, T., Ishikawa, K., Nakajima, D., Ohira, M., Seki, N., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 4: 141-150, 1997. [PubMed: 9205841] [Full Text: https://doi.org/10.1093/dnares/4.2.141]
Reddy, J. V., Burguete, A. S., Sridevi, K., Ganley, I. G., Nottingham, R. M., Pfeffer, S. R. A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling. Molec. Biol. Cell 17: 4353-4363, 2006. [PubMed: 16885419] [Full Text: https://doi.org/10.1091/mbc.e06-02-0153]