CD109 contains an α2M-like thioester, but its chemical reactivity likely resembles that of complement.

(A) The CD109 thioester most closely resembles that of other α2M proteins. Although CD109 bears 45% to 50% overall sequence similarity with other vertebrate and invertebrate α2M proteins, it shares particularly high similarity in the region of the thioester. An alignment of a 50 aa stretch flanking the CD109 thioester and the corresponding regions of the 18 most closely related proteins is shown. Notably, this group does not contain complement proteins. Numbers refer to the corresponding aa coordinates. MUG, murinoglobulin; α1I3, α1-inhibitor III; α1M, α1-macroglobulin; PZP, pregnancy zone protein; OvoM, ovomacroglobulin. Black shading, aa identity; gray shading, aa similarity; no shading, unrelated. (Carp α2M-1, GenBank accession no. [GB no.] AB026128; Carp α2M-2, GB no. AB026129; Carp α2M-3, GB no. AB026130; C elegans ZK337, GB no. Z82090; Limulus α2M, GB no. D83196; Chicken OvoM, GB no. X78801; Guinea Pig α2M, GB no. D84338; Guinea Pig MUG, GB no.D84339; Human PZP, GB no. X54380; Human α2M, GB no. M11313; Lamprey α2M, GB no. D13567; Mouse MUG2, GB no. M65238; Mouse MUG1, GB no.M65736; Mouse α2M, GB no. NM_007376; Rat α1I3, GB no. J03552; Rat α2M, GB no. J02635; Rat α1M, GB no. M84000; XenopusEndodermin, GB no. L63543.) (B) The CD109 thioester reactivity-defining hexapeptide most resembles that of complement proteins. A 20 aa stretch encompassing the CD109 regulatory hexapeptide is aligned with the corresponding regions of human complement C3 and C4b and those of the 2 other α2M-family proteins—α2M and PZP. Although the α2M hexapeptide ends in an LLN triplet, that of CD109, C3, and C4b ends in VIH. Numbers refer to the corresponding aa coordinates. (Human PZP, GB no. X54380; Human α2M, GB no. M11313; Human C3, GB no. K02765; Human C4B, GB no. K02404.)