Murine sex-limited protein: complete cDNA sequence and comparison with murine fourth complement component

Area of Science:

• Immunogenetics
• Molecular Biology

Background:

• Murine sex-limited protein (Slp) is a structural homolog of murine complement component 4 (C4).
• Slp lacks C4 activity and its function remains unknown.
• The genes for C4 and Slp are located in the S region of the murine major histocompatibility complex.

Purpose of the Study:

• To sequence the complete protein-coding region of murine Slp.
• To elucidate the structural basis for Slp's lack of C4 activity.
• To explore the evolutionary potential of the Slp gene.

Main Methods:

• Sequencing of a cDNA clone spanning the entire protein-coding region of Slp from the B10.WR mouse strain.
• Comparison of the Slp sequence with the previously reported murine C4 sequence.

Main Results:

• The Slp sequence revealed a 1735 amino acid open reading frame for prepro-Slp.
• Slp exhibits 96% nucleotide and 94% amino acid identity to murine C4.
• A three amino acid deletion near the Cls cleavage site in Slp was identified, likely conferring resistance to proteolysis and thus inactivity.
• Sequence variations suggest the transcription of at least two distinct Slp genes in B10.WR mice.

Conclusions:

• The identified deletion explains Slp's lack of C4 activity.
• Slp may represent a gene in evolutionary transition, potentially evolving towards a pseudogene or a novel functional gene.