Structure of the human gene encoding granule membrane protein-140, a member of the selectin family of adhesion receptors for leukocytes.
GMP-140, an inducible granule membrane protein of platelets and endothelial cells, is a member of the selectin family of cell surface receptors that mediate interactions of leukocytes with the blood vessel wall. These molecules all contain an N-terminal lectin-like domain, followed by an epidermal growth factor-like domain, a variable number of consensus repeats related to those in complement-binding proteins, a transmembrane domain, and a cytoplasmic tail. Two variant cDNAs for GMP-140 have been identified, one predicting a soluble form of the molecule lacking the transmembrane domain and the other predicting a molecule containing eight instead of nine consensus repeats. Here we describe the organization of the human gene encoding GMP-140, which spans over 50 kilobase pairs and contains 17 exons. Almost all exons encode distinct structural domains, including the lectin-like domain, the epidermal growth factor-like domain, each of the nine consensus repeats, and the transmembrane region. Each of the two deletions found in the variant cDNAs is precisely encoded by an exon, suggesting that these forms of GMP-140 are derived from alternative splicing of mRNA. By using the polymerase chain reaction, transcripts encoding the putative soluble form of GMP-140 can be amplified from both platelet and endothelial cell RNA. The structure of the GMP-140 gene supports the concept that the selectins evolved as a result of exon duplication and rearrangement.
Department of Medicine, St. Francis Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City 73104.
G I
GI
Johnston
G A
GA
Bliss
P J
PJ
Newman
R P
RP
McEver
D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons; D015723:Gene Library; D005796:Genes; D006801:Humans; D007438:Introns; D007962:Leukocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D012326:RNA Splicing; D015183:Restriction Mapping; D014158:Transcription, Genetic
D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins