Common evolutionary origin of alpha 2-macroglobulin and complement components C3 and C4.
A comparison of the sequence of the subunit of human alpha 2-macroglobulin (alpha 2M; 1451 amino acid residues) with that of murine complement component pro-C3 (1639 amino acid residues) reveals eight extended regions of sequence similarity. These regions contain between 19% and 31% identically placed residues and account for 75% and 67%, respectively, of the polypeptide chains of alpha 2M and pro-C3. Published sequence data for complement component C4 show that segments of this protein match well with corresponding stretches in alpha 2M and pro-C3. It is proposed that alpha 2M, C3 and C4, which all contain a unique activatable beta-cysteinyl-gamma-glutamyl thiol ester, have a common evolutionary origin and are homologous proteins. Several larger regions of low sequence similarity indicate the presence of structural domains in each of these proteins that specifically modify an underlying common gross structure. The quartets of basic residues in pro-C3 and pro-C4, at which cleavage takes place to produce the mature subunits of these proteins, and most of the residues forming the anaphylatoxin peptides of C3 and C4 (C3a and C4a) are absent in alpha 2M. In addition, C3 and C4 contain large portions, which extend beyond the COOH terminus of alpha 2M.
Sottrup-Jensen
L
L
Stepanik
T M
TM
Kristensen
T
T
Lønblad
P B
PB
Jones
C M
CM
Wierzbicki
D M
DM
Magnusson
S
S
Domdey
H
H
Wetsel
R A
RA
Lundwall
A
A
D000595:Amino Acid Sequence; D005075:Biological Evolution; D003176:Complement C3 / Q000235:genetics*; D003181:Complement C4 / Q000235:genetics*; D006801:Humans; D011498:Protein Precursors / Q000235:genetics; D000511:alpha-Macroglobulins / Q000235:genetics*
D003176:Complement C3; D003181:Complement C4; D011498:Protein Precursors; D000511:alpha-Macroglobulins