CLONING AND SEQUENCE-ANALYSIS OF BETA-4 CDNA - AN INTEGRIN SUBUNIT THAT CONTAINS A UNIQUE 118 KD CYTOPLASMIC DOMAIN

The α6β4 complex is a member of the integrin superfamily of adhesion receptors. A human keratinocyte lambda gt11 cDNA library was screened using a monoclonal antibody directed against the β4 subunit. Two cDNAs were selected and subsequently used to isolate a complete set of overlapping cDNA clones. The β4-subunit consists of 1778 amino acids with a 683 amino acid extracellular domain, a 23 amino acid transmembrane domain and an exceptionally long cytoplasmic domain of 1072 residues. The deduced amino-terminal sequence is in good agreement with the published amino-terminal sequence of purified β4. The extracellular domain contains five potential N-linked glycosylation sites and four cysteine-rich homologous repeat sequences. The extracellular part of the β4 subunit sequence shows 35% identity with other integrin β subunits, but is the most different among this class of molecules. The transmembrane region is poorly conserved, whereas the cytoplasmic domain shows no substantial identity in any region to the cytoplasmic tails of the known β sequences or to other protein sequences. The exceptionally long cytoplasmic domain suggests distinct interactions of the β4 subunit with cytoplasmic proteins.