Human myosin-binding protein H (MyBP-H) : complete primary sequence, genomic organization, and chromosomal localization

Vertebrate striated muscle contains a set of myosin-associated proteins with discrete distributions in the A-band. Some of these proteins, including MyBP-H and MyBP-C, are characterized by a series of internal repeats (motifs) with homology to either the C2-set of the immunoglobulin superfamily or the fibronectin type III repeat. These repeats are predicted to be involved in protein-protein interactions within the myofibril. The cDNA sequence, the genomic organization, and the chromosomal localization of the human homologue of MyBP-H are presented. The 1.8-kb cDNA encodes a 52-kDa polypeptide containing two Ig-C2 and two type III repeats. The mRNA is expressed in a skeletal muscle-specific pattern. A 28-kb region of genomic sequence has been isolated that encompasses the 5' and 3' ends of the cDNA. This region includes 4.2 kb of upstream sequence with a potential promoter and 14 kb of downstream sequence containing the polyadenylation site. The chromosomal assignment was made by high resolution chromosomal in situ hybridization. This method maps the gene to chromosome 1q32.1. The repeat structure described previously in chicken MyBP-H and MyBP-C was also detected in human MyBP-H. The primary sequence of the C-terminal Ig-C2 motif and its predicted secondary structure have been extensively conserved in MyBP-H homologues and other members of the MyBP family. This Ig-C2 motif has been implicated in myosin binding.