The gene coding for the beta-chain of C4b-binding protein (C4BPB) has become a pseudogene in the mouse.
C4BP beta is one of the two polypeptides that in humans compose the plasma glycoprotein C4b-binding protein (C4BP). C4BP beta binds the anticoagulant vitamin K-dependent protein S. Two, nonmutually exclusive, roles have been proposed for the C4BP-protein S interaction. It has been suggested to play a role in the control of the protein C anticoagulatory pathway. In addition, it may serve an important role in localizing C4BP to the surface of injured or activated cells. While the physiological significance of C4BP-protein S interaction is unclear, it has clinical relevance because elevated plasma levels of C4BP are associated with increased risk for thromboembolic disorders in humans, due to an inactivation of the protein C anticoagulatory pathway. Using a human C4BP beta cDNA probe, we have isolated and characterized a genomic DNA fragment that includes the murine C4BPB gene. Murine C4BPB is a single-copy gene that maps close to the C4BPA gene in chromosome 1. It contains two exons homologous to the exons coding for the SCR-1 and SCR-2 repeats of the human C4BP beta polypeptide chain. Sequence analysis of the C4BPB exons in the Mus musculus inbred strains CBA, Balb/c, and C57BL/6, in pen-bred Swiss mice, and in Mus spretus demonstrated the presence of two in-phase stop codons that are incompatible with the expression of a functional C4BP beta polypeptide. Thus, the characterization of the murine C4BPB gene documents the peculiar situation of a single-copy gene that is functional in humans but has become a pseudogene in the mouse.(ABSTRACT TRUNCATED AT 250 WORDS)
Rodríguez de Córdoba
S
S
Unidad de Inmunología, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.
Pérez-Blas
M
M
Ramos-Ruiz
R
R
Sánchez-Corral
P
P
Pardo-Manuel de Villena
F
F
Rey-Campos
J
J
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D015935:Complement C4b / Q000378:metabolism; D003169:Complement Inactivator Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D005091:Exons; D006023:Glycoproteins; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice / Q000235:genetics*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009115:Muridae; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011544:Pseudogenes; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D006023:Glycoproteins; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D015935:Complement C4b