COMPLETE SEQUENCE OF HUMAN FAST-TYPE AND SLOW-TYPE MUSCLE MYOSIN-BINDING-PROTEIN-C (MYBP-C) - DIFFERENTIAL EXPRESSION, CONSERVED DOMAIN-STRUCTURE AND CHROMOSOME ASSIGNMENT

Myosin-binding-protein C (MyBP-C) is a myosin-associated protein of un known function found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. Using a cDNA clone encoding the fast-type is oform of chicken MyBP-C, we screened a human fetal muscle cDNA library and isolated clones encoding the full-length human fast-type isoform of MyBP-C. cDNA clones encoding the slow-type isoform of human MyBP-C, were also isolated and fully sequenced. Northern-blot analysis demons trated skeletal muscle-specific expression of these gene products. Usi ng human/hamster somatic-cell hybrids, we were able to map the slow-ty pe MyBP-C to human chromosome 12, and the fast-type MyBP-C to chromoso me 19. The cDNA for human fast-type MyBP-C encodes a polypeptide of 11 42 amino acids with an expected molecular mass of 128.1 kDa. Compariso n of this cDNA with other members of the MyBP family reveals extensive primary-sequence conservation. Each MyBP-C contains seven immunoglobu lin C2 motifs and three fibronectin type-III repeats in the arrangemen t C2-C2-C2-C2-C2-III-III-C2-III-C2. Regions of high identity shared by the chicken and the two human proteins are not restricted to the immu noglobulin and fibronectin motifs. Sequence comparison of all three pr oteins has allowed us to map a highly conserved region between the fir st and second C2 motifs, the only large spacer sequence present betwee n motifs in these proteins.