What are domains?
A domain is a specific region of a protein that has a distinct function and can usually function independently from other domains. A single protein can have many domains, and each domain may be present in many different proteins. Protein domains can be used to study overall protein functions and interactions. [1]
What are the domains of C4A?
Domains within the human C4A protein and its homologs were found using SMART, and the search was done under a setting that includes domains recognized by PFAM as well. The domains and their locations in the C4A protein can be seen in Figure 1 below.
More information about each of the human C4A domains (as well as protein architecture, interactions and post translational modifications) can be found by checking the "PFAM domains" box and searching "P0C0L4" on the SMART site.
The different colored shapes in Figure 1 represent different domains of the protein. The small, unlabeled pink boxes represent what are called "low complexity regions", which are areas where the SMART and PFAM programs suspect an additional domain may be. The predicted domains and motifs in the human C4A protein along with the amino acid positions and E-values of each can be seen on the SMART search and in Figure 2 below.
The different colored shapes in Figure 1 represent different domains of the protein. The small, unlabeled pink boxes represent what are called "low complexity regions", which are areas where the SMART and PFAM programs suspect an additional domain may be. The predicted domains and motifs in the human C4A protein along with the amino acid positions and E-values of each can be seen on the SMART search and in Figure 2 below.
The full names of the domains are as follows:
A2M_N: Alpha-2-macroglobulin N-terminal region
ANATO: Anaphylatoxin homologous domain
A2M: Alpha-2-macroglobulin
Thiol-ester_cl: Alpha-2-macroglobulin thiol-ester bond-forming region
A2M_comp: Complement component region of alpha-2-macroglobulin
A2M_recep: Alpha-2-macroglobulin receptor domain
C345C: Netrin C-terminal domain
Despite the vastly differing identities of homologous C4A proteins in different species (Pan troglodytes, Mus musculus, Danio rerio, and Xenopus tropicalis), the domains in these homologs are completely conserved. A comparison of the homologous protein domains is shown in Figure 3.
A2M_N: Alpha-2-macroglobulin N-terminal region
ANATO: Anaphylatoxin homologous domain
A2M: Alpha-2-macroglobulin
Thiol-ester_cl: Alpha-2-macroglobulin thiol-ester bond-forming region
A2M_comp: Complement component region of alpha-2-macroglobulin
A2M_recep: Alpha-2-macroglobulin receptor domain
C345C: Netrin C-terminal domain
Despite the vastly differing identities of homologous C4A proteins in different species (Pan troglodytes, Mus musculus, Danio rerio, and Xenopus tropicalis), the domains in these homologs are completely conserved. A comparison of the homologous protein domains is shown in Figure 3.
Discussion
SMART and PFAM together identified eight C4A protein domains that were well conserved across homologous protein sequences. This suggests that each domain plays a crucial role in the function or structure of the protein. Six of the eight are A2M family domains, which play a role in protease inhibition. A2M family domains specifically inhibit plasmin from playing a role in fibrin degradation, shown in Figure 4 below [2].