Cloning and sequence analysis of human breast epithelial antigen BA46 reveals an RGD cell adhesion sequence presented on an epidermal growth factor-like domain.
The BA46 antigen of the human milk fat globule (HMFG) membrane is expressed in human breast carcinomas and has been used successfully as a target for experimental breast cancer radioimmunotherapy. To characterize this antigen further, we obtained the entire cDNA sequence and focused on its possible role in cell adhesion. The derived protein sequence of BA46 encodes a 387-residue precursor composed of a putative signal peptide, an amino-terminal epidermal growth factor (EGF)-like domain containing the cell adhesion tripeptide arginine-glycine-aspartic acid (RGD), and human factor V and factor VIII C1/C2-like domains. The EGF-like domain of BA46 is similar to the calcium-binding EGF-like domains of several coagulation factors, but the BA46 domain lacks a residue required for calcium binding and the coagulation factor domains do not include an RGD sequence. Assuming that all EGF-like domains fold into a similar structure, the RGD-containing sequence in BA46 is inserted between two antiparallel beta strands. This positioning suggests a novel function for the EGF-like domain as a scaffold for RGD presentation.
Couto
J R
JR
Cancer Research Fund of Contra Costa, Walnut Creek, CA 94596, USA.
Taylor
M R
MR
Godwin
S G
SG
Ceriani
R L
RL
Peterson
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000737:chemistry*; D001483:Base Sequence; D001779:Blood Coagulation Factors / Q000737:chemistry; D001940:Breast / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology; D002417:Cattle; D003001:Cloning, Molecular; D016384:Consensus Sequence; D017124:Conserved Sequence; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000737:chemistry*; D004848:Epithelium / Q000276:immunology; D005165:Factor V / Q000737:chemistry; D005169:Factor VIII / Q000737:chemistry; D005260:Female; D015723:Gene Library; D006801:Humans; D008894:Milk Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry*; D009842:Oligopeptides; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
D000954:Antigens, Surface; D001779:Blood Coagulation Factors; D017931:DNA Primers; C098942:MFGE8 protein, human; D008894:Milk Proteins; D018396:Mucin-1; D009842:Oligopeptides; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; C047981:arginyl-glycyl-aspartic acid; D005165:Factor V; D005169:Factor VIII