Correlation of gene and protein structure of rat and human lipocortin I.
Lipocortins (annexins) are a family of calcium-dependent phospholipid-binding proteins with phospholipase A2 inhibitory activity. The characteristic primary structure of members of this family consists of a core structure of four or eight repeated domains, which have been implicated in calcium-dependent phospholipid binding. In two lipocortins (I and II) a short amino-terminal sequence distinct from the core structure has potential regulatory functions which are dependent on its phosphorylation state. We have isolated the rat and the human lipocortin I genes and found that they both consist of 13 exons with a striking conservation of their exon-intron structure and their promoter and amino acid sequences. Both lipocortin I genes are at least 19 kbp in length with exons ranging from 57 to 123 bp interrupted by introns as large as 5 kbp. Each of the four repeat units of lipocortin I are encoded by two consecutive exons while individual exons code for the highly conserved putative calcium-binding domains. The promoter sequences in the rat and in human genes are highly conserved and contain nucleotide sequences characterized as enhancer sequences in other genes. The structure of the lipocortin I gene lends support to the hypothesis that the lipocortin genes arose by a duplication of a single domain.
Kovacic
R T
RT
Biogen Inc., Cambridge, Massachusetts 02142.
Tizard
R
R
Cate
R L
RL
Frey
A Z
AZ
Wallner
B P
BP
D000595:Amino Acid Sequence; D000818:Animals; D017302:Annexins; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons; D005796:Genes; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D013329:Structure-Activity Relationship
D017302:Annexins; D002135:Calcium-Binding Proteins