A superfamily is defined structurally, and not functionally, or on sequence similarity.
In IMGT, two superfamilies are defined:
- the immunoglobulin superfamily (IgSF)
- the major histocompatibility superfamily (MhSF).
A protein belongs to the IgSF if the amino acid chain includes at least one domain with an "Ig fold". In IMGT, these domains are described:
- for IG and TR, as V-DOMAIN and C-DOMAIN,
- for proteins other than IG and TR, as V-LIKE-DOMAIN and C-LIKE-DOMAIN.
Any protein with, at least, a V-DOMAIN, C-DOMAIN, V-LIKE-DOMAIN or C-LIKE-DOMAIN belongs to the IgSF.
A protein belongs to the MhSF if it includes two groove (G) domains. Each G domain comprises a helix and a beta sheet of four strands that form half of the cleft. In IMGT, these domains are described:
- for MH, as G-DOMAIN,
- for proteins other than MH, as G-LIKE-DOMAIN.
Any protein with, at least, a G-DOMAIN or a G-LIKE-DOMAIN belongs to the MhSF.
The MH1 and MH2 chains belong both to the MhSF, by their G-DOMAIN,
and to the IgSF, by their C-LIKE-DOMAIN.
The RPI-MH1Like chains belong both to the MhSF, by their G-LIKE-DOMAIN, and to the IgSF, if the C-LIKE-DOMAIN is present.
For examples: Human CD1A, Mouse CD1D1.