The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily Journal Article


Authors: Heath, J. K.; White, S. J.; Johnstone, C. N.; Catimel, B.; Simpson, R. J.; Moritz, R. L.; Tu, G. F.; Ji, H.; Whitehead, R. H.; Groenen, L. C.; Scott, A. M.; Ritter, G.; Cohen, L.; Welt, S.; Old, L. J.; Nice, E. C.; Burgess, A. W.
Article Title: The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily
Abstract: The mAb A33 detects a membrane antigen that is expressed in normal human colonic and small bowel epithelium and >95% of human colon cancers. It is absent from most other human tissues and tumor types. The murine A33 mAb has been shown to target colon cancer in clinical trials, and the therapeutic potential of a humanized antibody is currently being evaluated. Using detergent extracts of the human colon carcinoma cell lines LIM1215 and SW1222, in which the antigen is highly expressed, the molecule was purified, yielding a 43-kDa protein. The N-terminal sequence was determined and further internal peptide sequence obtained following enzymatic cleavage. Degenerate primers were used in PCRs to produce a probe to screen a LIM1215 cDNA library, yielding clones that enabled us to deduce the complete amino acid sequence of the A33 antigen and express the protein. The available data bases have been searched and reveal no overall sequence similarities with known proteins. Based on a hydrophilicity plot, the A33 protein has three distinct structural domains: an extracellular region of 213 amino acids (which, by sequence alignment of conserved residues, contains two putative immunoglobulin-like domains), a single hydrophobic transmembrane domain, and a highly polar intracellular tail containing four consecutive cysteine residues. These data indicate that the A33 antigen is a novel cell surface receptor or cell adhesion molecule in the immunoglobulin superfamily.
Keywords: signal transduction; human cell; antigen expression; animals; gene expression; immunoglobulin; cos cells; monoclonal antibody; colorectal neoplasms; cloning, molecular; membrane antigen; amino acid sequence; molecular sequence data; immunotherapy; antigens, neoplasm; membrane glycoproteins; colon cancer; carcinoma; murinae; base sequence; protein structure; multigene family; immunoglobulins; dna, complementary; receptors, cell surface; solubility; antigen purification; cdna cloning; humans; human; priority journal; article
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 94
Issue: 2
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1997-01-21
Start Page: 469
End Page: 474
Language: English
DOI: 10.1073/pnas.94.2.469
PUBMED: 9012807
PROVIDER: scopus
PMCID: PMC19536
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
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  1. Leonard Cohen
    18 Cohen
  2. Gerd Ritter
    166 Ritter
  3. Lloyd J Old
    593 Old
  4. Sydney   Welt
    98 Welt