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Nucleic Acids Research, 1986, Vol. 14, No. 21 8427-8446
© 1986


Articles

Human epidermal growth factor precursor: cDNA sequence, expression in vitro and gene organization

Graeme I. Bell*, Noel M. Fong, Michelle M. Stempien, Mary Anne Wormsted, Daniel Caput, Lailing Ku, Mickey S. Urdea, Leslie B. Rall and Ray Sanchez-Pescador

Chiron Corporation 4560 Horton Street, Emeryville, CA 94608, USA

Received July 30, 1986. Revised September 29, 1986. Accepted September 29, 1986.

Complementary DNA clones encoding the human kidney epidermal growth factor (EGF) precursor have been isolated and sequenced. They predict the sequence of a 1,207 amino acid protein which contains EGF flanked by polypeptide segments of 970 and 184 residues at its NH2– and COOH-termini, respectively. The structural organization of the human EGF precursor is similar to that previously described for the mouse protein and there is 66% identity between the two sequences. Transfection of COS-7 cells with the human EGF precursor cDNA linked to the SV40 early promoter indicate that it can be synthesized as a membrane protein with its NH2-terminus external to the cell surface. The human EGF precursor gene is {small tilde}110 kilobase pairs and has 24 exons. Its exon-intron organization revealed that various domains of the EGF precursor are encoded by individual exons. Moreover, 15 of the 24 exons encode protein segments that are homologous to sequences in other proteins. Eron duplication and shuffling appear to have played an important role in determining the present structure of this protein.


*Present address: The University of Chicago, Howard Hughes Medical Institute, 920 E. 58th St., Chicago, IL 60637, USA


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