Structure and organization of genes for the predominant seminal plasma proteins semenogelin I, semenogelin II and beta-microseminoprotein

Detta är en avhandling från Clinical Chemistry, Malmö

Sammanfattning: In man, the predominant proteins in the seminal plasma include semenogelin I, semenogelin II and b-microseminoprotein (MSP). Semenogelin I and II are both synthesized in the seminal vesicles and are the backbone of the gel formed upon semen coagulation. MSP is synthesized in the prostate, but its role has not yet been defined. The genes and cDNA of semenogelin I and II and of MSP were cloned and characterized . A cDNA encoding human MSP was isolated from a prostate cDNA library. The nucleotide sequence was found to be identical to that of prostatic secretory protein of 94 amino acids. Using the cloned cDNA as probe, transcripts of 0.6 kb were detected in human prostate, trachea, bronchi, lung, and gastric mucosa A human genomic clone was isolated, encompassing exons 2, 3, and 4 of the MSP gene. These exons were 106 bp, 106 bp, and 240 bp long respectively, interrupted by introns of 1 and 5.2 kb. The gene is present at one copy per genome and is located on chromosome 10. The human semenogelin I and II genes were isolated. The transcription units of the two genes, 2.7 kb and 3.1 kb respectively, are separated by 11.5 kb of intergenic DNA. Both genes are composed of three-exon transcriptional units with nucleotide sequence similarity ranging from 80% in introns to close to 90% in exons. In both genes exon 1 codes for the signal peptide, exon 2 for the secreted protein, and exon 3 contains non-coding nucleotides only. In contrast to the majority of highly expressed human genes, codons in the second exon of the semenogelin genes prefer A and T bases in the third position instead of G and C. The location of the human semenogelin locus was assigned to chromosome 20q12.q-13.1. The rhesus monkey semenogelin II gene was cloned and consists of three exons of 97, 2086 and 124 bp organized in the same way as the human semenogelin II gene. Due to the larger size of the second exon the translation product from the rhesus monkey gene is 124 amino acid residues longer than its human counterpart. Old World monkeys probably carry semenogelin I genes of the same size as in man, while the semenogelin II gene has evolved to yield proteins that are extended by 120 amino acid residues from man to rhesus monkey to baboon. Semenogelin genes are also present in New World monkeys. The semenogelin genes, and genes related to them, have undergone very rapid evolution and all encode substrates for the enzyme transglutaminase. Hence they constitute a novel gene family: the REST gene family (rapidly evolving substrates for transglutaminase). The gene of the protease inhibitor SKALP/elafin fulfilled all criteria of being a REST gene. The gene for secretory leukocyte protease inhibitor is probably also a member.

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