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| | Schematic representation of the GPA33 protein, indicating the position of the Ig-like V-type and Ig-like C2-type domain in the extracellular region and the polycysteine residue ('CCCC' motif). |
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| Description | 319 amino acids; 43 kDa protein. The A33 glycoprotein is a member of the immunoglobulin superfamily and contains three distinct structural domains: a 213 amino acid extracellular region containing two immunoglobulin-like domains (a C2-type domain and a v-type domain), a 23 amino acid hydrophobic transmembrane domain, and a 62 amino acid highly polar intracellular tail containing four consecutive cysteine residues (Heath et al., 1997). Post translational modification includes N-glycosylation (containing approximately 8 kDa of N-linked carbohydrate), and S-palmitoylation. The S-palmitoylation may be involved in regulating the internalization process initiated by binding of the monoclonal antibody A33 to the A33 antigen. There is no evidence of O-glycosylation, sialylation or glycophosphatidylinositol (Ritter et al., 1997). |
| Expression | GPA33 demonstrates a rare tissue-specific expression pattern. GPA33 is a cell surface differentiation antigen that is constitutively expressed on the basolateral surfaces of normal human and mouse colon and small bowel epithelium. GPA33 is homogeneously expressed in over 95% of both human primary and metastatic colon cancers, and in 55% of gastric carcinomas, although absent in normal stomach epithelium (Welt et al., 1990). |
| Localisation | Membrane; single-pass type 1 membrane protein. |
| Function | Unknown; the protein structure is consistent with a putative role of GPA33 in cell-cell recognition and signaling (Heath et al., 1997). A33 may play a role in relaying information between intestinal epithelial cells and the gut immune system (Lee et al., 2007). |
| Homology | The two Ig-like domains are well conserved between humans, chimpanzee, dog, mouse and rat, whereas chicken and zebrafish retain only the Ig-like V-like domain. The overall GPA33 protein similarity between humans and various species are: chimpanzee (Pan troglodytes) 97%, domestic dog (Canis lupus familiaris) 75%, mouse (Mus musculus) 66%, rat (Rattus norvegicus) 68%, domestic chicken (Gallus gallus) 44%, and zebrafish (Danio rerio) 35%. |
| Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. |
| Welt S, Divigi CR, Real FX, Yeh SD, Garin-Chesa P, Finstad CL, Sakamoto J, Choen A, Sigurdson ER, Kemeny N, Carswell EA, Oettgen HF, Old LJ. |
| J Clin Oncol 1990; 8(11): 1894-1906. |
| PMID 2230877 |
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| Phase I/II study of iodine 131-labeled monoclonal antibody A33 in patients with advanced colon cancer. |
| Welt S, Divgi CR, Kemeny N, Finn RD, Scott AM, Graham M, Germain JS, Richards EC, Larson SM, Oettgen HF, Old LJ. |
| J Clin Oncol 1994; 12(8): 1561-1571. |
| PMID 8040668 |
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| Enhancement of radiation dose to the nucleus by vesicular internalization of iodine-125-labeled A33 monoclonal antibody. |
| Daghighian F, Barendswaard E, Welt S, Humm J, Scott A, Willingham MC, McGuffie E, Old LJ, Larson SM. |
| J Nucl Med. 1996; 37(6): 1052-1057. |
| PMID 8683300 |
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| The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily. |
| Heath JK, White SJ, Johnstone CN, Catimel B, Simpson RJ, Moritz RL, Tu GF, Ji H, Whitehead RH, Groenen LC, Scott AM, Ritter G, Cohen L, Welt S, Old LJ, Nice EC, Burgess AW. |
| Proc Natl Acad Sci USA 1997; 94(2): 469-474. |
| PMID 9012807 |
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| Characterization of posttranslational modifications of human A33 antigen, a novel palmitoylated surface glycoprotein of human gastrointestinal epithelium. |
| Ritter G, Cohen LS, Nice EC, Catimel B, Burgess AW, Moritz RL, Ji H, Heath JK, White SJ, Welt S, Old LJ, Simpson RJ. |
| Biochem Biophys Res Commun. 1997; 236(3): 682-686. |
| PMID 9245713 |
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| Phase I trial of 131I-huA33 in patients with advanced colorectal carcinoma. |
| Chong G, Lee FT, Hopkins W, Tebbutt N, Cebon JS, Mountain AJ, Chappell B, Papenfuss A, Schleyer P, U P, Murphy R, Wirth V, Smyth FE, Potasz N, Poon A, Davis ID, Saunder T, O'keefe GJ, Burgess AW, Hoffman EW, Old LJ, Scott AM. |
| Clin Cancer Res. 2005; 11(13): 4818-4826. |
| PMID 16000579 |
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| A phase I trial of humanized monoclonal antibody A33 in patients with colorectal carcinoma: biodistribution, pharmacokinetics, and quantitative tumor uptake. |
| Scott AM, Lee FT, Jones R, Hopkins W, MacGregor D, Cebon JS, Hannah A, Chong G, U P, Papenfuss A, Rigopoulos A, Sturrock S, Murphy R, Wirth V, Murone C, Smyth FE, Knight S, Welt S, Ritter G, Richards E, Nice EC, Burgess AW, Old LJ. |
| Clin Cancer Res. 2005; 11(13): 4810-4817. |
| PMID 16000578 |
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| Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. |
| Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC, Yonekura AR, Heath JK, Turley SJ. |
| Nat Immunol. 2007; 8(2): 181-190. |
| PMID 17195844 |
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