Alternative titles; symbols
HGNC Approved Gene Symbol: GOLGB1
Cytogenetic location: 3q13.33 Genomic coordinates (GRCh38): 3:121,663,201-121,749,966 (from NCBI)
The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Linstedt and Hauri (1993) searched for proteins involved in forming intercisternal cross-bridges that may mediate stacking. They generated antibodies to a Golgi-marker-enriched membrane fraction, and found that one antibody was Golgi-specific. The antibody stained Golgi specifically in several human tissues, as well as in rat, hamster, mouse, and chicken cells. On Western blots, the antibody recognized a 400-kD protein, called 'giantin' because of its large size. Giantin is not extracted from the membrane by high salt, urea, alkaline carbonate, or Triton X-100 (nonionic detergent) treatment, suggesting that it is an integral component of the Golgi membrane that is associated with the cytoskeleton. Protease digestion experiments suggest that giantin has a large (at least 350 kD) cytoplasmic domain. Linstedt and Hauri (1993) suggested that giantin may participate in forming intercisternal cross-bridges of the Golgi complex.
Seelig et al. (1994) isolated giantin cDNA by using serum from a Sjogren syndrome (270150) patient with scleroderma that contained anti-Golgi autoantibodies to screen a HeLa cell cDNA expression library. The gene is transcribed as an approximately 10-kb mRNA that encodes a predicted 3,259-amino acid protein, which they designated 'macrogolgin' because of its large size. The predicted pI is 4.77, and the protein contains a high fraction of alpha-helical domains with heptad repeats that can form coiled-coils. On Western blots, the antibodies recognize 320- and 380-kD proteins. Anti-macrogolgin antibodies were found in 11% of HIV-positive patients.
Using Golgi-specific autoantibodies from a chronic rheumatoid arthritis patient to screen a pancreatic carcinoma cell cDNA expression library, Sohda et al. (1994) independently cloned the same gene. The gene they cloned, designated GCP372 (Golgi complex-associated protein, 372-kD) encodes a predicted 3,225-amino acid protein that migrates as an approximately 360-kD protein on SDS-PAGE.
Gross (2014) mapped the GOLGB1 gene to chromosome 3q13.33 based on an alignment of the GOLGB1 sequence (GenBank AB593126) with the genomic sequence (GRCh37).
By chemical mutagenesis and whole-exome sequencing, Lan et al. (2016) identified mice with a spontaneous loss-of-function mutation in the Golgb1 gene. Using CRISPR/Cas9-mediated genome editing, they generated mice with additional Golgb1 loss-of-function mutations. Loss of Golgb1 function resulted in cleft palate and failure of palatal shelf elevation that was detectable in midterm embryos. Prior to the developmental stage of palatal shelf elevation, mutant embryos exhibited increased cell density, reduced hyaluronan accumulation, and impaired protein glycosylation in palatal mesenchyme. Lan et al. (2016) concluded that the ubiquitously expressed Golgb1 protein has specific functions in protein glycosylation and tissue morphogenesis.
Gross, M. B. Personal Communication. Baltimore, Md. 4/17/2014.
Lan, Y., Zhang, N., Liu, H., Xu, J., Jiang, R. Golgb1 regulates protein glycosylation and is crucial for mammalian palate development. Development 143: 2344-2355, 2016. [PubMed: 27226319] [Full Text: https://doi.org/10.1242/dev.134577]
Linstedt, A. D., Hauri, H.-P. Giantin, a novel conserved Golgi membrane protein containing a cytoplasmic domain of at least 350 kDa. Molec. Biol. Cell 4: 679-693, 1993. [PubMed: 7691276] [Full Text: https://doi.org/10.1091/mbc.4.7.679]
Seelig, H. P., Schranz, P., Schroter, H., Wiemann, C., Renz, M. Macrogolgin--a new 376 kD Golgi complex outer membrane protein as target of antibodies in patients with rheumatic diseases and HIV infections. J. Autoimmun. 7: 67-91, 1994. [PubMed: 8198703] [Full Text: https://doi.org/10.1006/jaut.1994.1006]
Sohda, M., Misumi, Y., Fujiwara, T., Nishioka, M., Ikehara, Y. Molecular cloning and sequence analysis of a human 372-kDa protein localized in the Golgi complex. Biochem. Biophys. Res. Commun. 205: 1399-1408, 1994. [PubMed: 7802676] [Full Text: https://doi.org/10.1006/bbrc.1994.2821]