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.
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne, Victoria, Australia. heath@licre.ludwig.edu.au
authors.forename: J K
authors.initials: JK
authors.lastname: Heath
authors.forename: S J
authors.initials: SJ
authors.lastname: White
authors.forename: C N
authors.initials: CN
authors.lastname: Johnstone
authors.forename: B
authors.initials: B
authors.lastname: Catimel
authors.forename: R J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: R L
authors.initials: RL
authors.lastname: Moritz
authors.forename: G F
authors.initials: GF
authors.lastname: Tu
authors.forename: H
authors.initials: H
authors.lastname: Ji
authors.forename: R H
authors.initials: RH
authors.lastname: Whitehead
authors.forename: L C
authors.initials: LC
authors.lastname: Groenen
authors.forename: A M
authors.initials: AM
authors.lastname: Scott
authors.forename: G
authors.initials: G
authors.lastname: Ritter
authors.forename: L
authors.initials: L
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Welt
authors.forename: L J
authors.initials: LJ
authors.lastname: Old
authors.forename: E C
authors.initials: EC
authors.lastname: Nice
authors.forename: A W
authors.initials: AW
authors.lastname: Burgess
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D019556:COS Cells; D002277:Carcinoma / Q000737:chemistry / Q000276:immunology; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D012995:Solubility
chemical_list: D000951:Antigens, Neoplasm; D018076:DNA, Complementary; C104258:GPA33 protein, human; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface