Alternative titles; symbols
HGNC Approved Gene Symbol: GP2
Cytogenetic location: 16p12.3 Genomic coordinates (GRCh38): 16:20,309,574-20,327,513 (from NCBI)
The enzyme and zymogen forms of digestive enzymes are stored in secretory zymogen granules (ZGs) in the exocrine pancreas. Since peptide hormones and cholinergic agents enhance release of ZG contents into the apical medium, ZGs constitute an important storage compartment in the regulated secretory pathway. The process of zymogen storage captures large quantities of cellular membranes destined for targeting to the apical plasma membrane. Fukuoka et al. (1991) isolated dog cDNAs encoding GP2, a 75-kD protein that represents the major protein in ZG membranes. They found that GP2 is a GPI (glycosylphosphatidylinositol)-linked membrane protein released from the membrane of mature zymogen granules by an enzymatic mechanism. Fukuoka et al. (1992) noted that the protein sequences of C-terminal regions of rat GP2 and Tamm-Horsfall protein (UMOD; 191845) share 53% identity. They reported that both proteins engage in pH- and ion-dependent self-association/sorting events, which may play an important role in assembly of vesicular compartments targeted to apical plasma membranes via regulated exocytosis. Wong and Lowe (1996) reported that the sequence of the predicted 530-amino acid human protein shares 72% and 67% identity with sequences of dog and rat, respectively.
Yang et al. (2004) identified a domain with 8 conserved cysteines, which they designated the D8C domain, in GP2 and several other proteins. The D8C domain is about 130 amino acids long, and the 8 cysteines are predicted to form 4 pairs of disulfide bridges. The secondary structure is composed mainly of beta strands. In GP2, the D8C domain is located between the N-terminal signal sequence and the zona pellucida (ZP) domain in the C-terminal half of the protein.
Hase et al. (2009) reported that GP2, specifically expressed on the apical plasma membrane of M cells among enterocytes, serves as a transcytotic receptor for mucosal antigens. Recombinant GP2 protein selectively bound a subset of commensal and pathogenic enterobacteria, including E. coli and S. enterica serovar Typhimurium (S. Typhimurium), by recognizing FimH, a component of type I pili on the bacterial outer membrane. Consistently, these bacteria were colocalized with endogenous GP2 on the apical plasma membrane as well as in cytoplasmic vesicles in M cells. Moreover, deficiency of bacterial FimH or host GP2 led to defects in transcytosis of type-I-piliated bacteria through M cells, resulting in an attenuation of antigen-specific immune responses in Peyer patches. Hase et al. (2009) concluded that GP2 is therefore a previously unrecognized transcytotic receptor on M cells for type-I-piliated bacteria and is a prerequisite for the mucosal immune response to these bacteria.
By fluorescence in situ hybridization, Fukuoka et al. (1997) mapped the GP2 gene to human chromosome 9q21.11-q21.2. However, Gross (2011) mapped the GP2 gene to chromosome 16p12.3 based on an alignment of the GP2 sequence (GenBank AB035541) with the genomic sequence (GRCh37).
Fukuoka, S.-I., Freedman, S. D., Scheele, G. A. A single gene encodes membrane-bound and free forms of GP-2, the major glycoprotein in pancreatic secretory (zymogen) granule membranes. Proc. Nat. Acad. Sci. 88: 2898-2902, 1991. [PubMed: 2011597] [Full Text: https://doi.org/10.1073/pnas.88.7.2898]
Fukuoka, S.-I., Freedman, S. D., Yu, H., Sukhatme, V. P., Scheele, G. A. GP-2/THP gene family encodes self-binding glycosylphosphatidylinositol-anchored proteins in apical secretory compartments of pancreas and kidney. Proc. Nat. Acad. Sci. 89: 1189-1193, 1992. Note: Erratum: Proc. Nat. Acad. Sci. 89: 3669 only, 1992. [PubMed: 1531535] [Full Text: https://doi.org/10.1073/pnas.89.4.1189]
Fukuoka, S.-I., Suzuki, M., Okabayashi, K., Takahashi, E. Assignment of pancreatic zymogen granule membrane protein GP2 (GP2) to human chromosome band 9q21.11 to q21.2 by in situ hybridization. Cytogenet. Cell Genet. 79: 231-232, 1997. [PubMed: 9605860] [Full Text: https://doi.org/10.1159/000134730]
Gross, M. B. Personal Communication. Baltimore, Md. 2/25/2011.
Hase, K., Kawano, K., Nochi, T., Pontes, G. S., Fukuda, S., Ebisawa, M., Kadokura, K., Tobe, T., Fujimura, Y., Kawano, S., Yabashi, A., Waguri, S., and 10 others. Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response. Nature 462: 226-230, 2009. [PubMed: 19907495] [Full Text: https://doi.org/10.1038/nature08529]
Wong, S. M. E., Lowe, A. W. Sequence of the cDNA encoding human GP-2, the major membrane protein in the secretory granule of the exocrine pancreas. Gene 171: 311-312, 1996. [PubMed: 8666297] [Full Text: https://doi.org/10.1016/0378-1119(96)00065-0]
Yang, H., Wu, C., Zhao, S., Guo, J. Identification and characterization of D8C, a novel domain present in liver-specific LZP, uromodulin and glycoprotein 2, mutated in familial juvenile hyperuricaemic nephropathy. FEBS Lett. 578: 236-238, 2004. [PubMed: 15589826] [Full Text: https://doi.org/10.1016/j.febslet.2004.10.092]