The primary structure of the VLA-2/collagen receptor alpha 2 subunit (platelet GPIa): homology to other integrins and the presence of a possible collagen-binding domain.
VLA-2 (also called gpIa/IIa on platelets) is a collagen receptor with a unique alpha subunit and a beta subunit common to other adhesion receptors in the VLA/integrin family. Multiple cDNA clones for the human VLA-2 alpha 2 subunit have been selected from a lambda gtll library by specific antibody screening. The 5,374-bp nucleotide sequence encoded for 1,181 amino acids, including a signal peptide of 29 amino acids followed by a long extracellular domain (1,103 amino acids), a transmembrane domain, and a short cytoplasmic segment (22 amino acids). Direct sequencing of purified alpha 2 protein confirmed the identity of the 15 NH2-terminal amino acids. Overall, the alpha 2 amino acid sequence was 18-25% similar to the sequences known for other integrin alpha subunits. In particular, the alpha 2 sequence matched other integrin alpha chains in (a) the positions of 17 of its 20 cysteine residues; (b) the presence of three metal-binding domains of the general structure DXDXDGXXD; and (c) the transmembrane domain sequence. In addition, the alpha 2 sequence has a 191-amino acid insert (called the I-domain), previously found only in leukocyte integrins of the beta 2 integrin family. The alpha 2 I-domain was 23-41% similar to domains in cartilage matrix protein and von Willebrand factor, which are perhaps associated with collagen binding. The NH2-terminal sequence reported here for alpha 2 does not match the previously reported alpha 2 NH2-terminal sequence (Takada, Y., J. L. Strominger, and M. E. Hemler. 1987. Proc. Natl. Acad. Sci. USA. 84:3239-3243). Resolution of this discrepancy suggests that there may be another VLA heterodimer that resembles VLA-2 in size but has a different amino acid sequence.
Takada
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Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Hemler
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ME
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D007158:Immunologic Techniques; D016023:Integrins; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D038981:Receptors, Collagen; D016029:Receptors, Very Late Antigen; D013329:Structure-Activity Relationship
D000943:Antigens, Differentiation; D016023:Integrins; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D038981:Receptors, Collagen; D016029:Receptors, Very Late Antigen; D004247:DNA