The MANSC (motif at N terminus with seven cysteines) domain is a module with a well-conserved seven cysteine motif that is present at the N terminus of higher multicellular animal membrane and extracellular proteins. It is possible that some of the cysteine residues in the MANSC domain form structurally important disulfide bridges. Five classes of proteins contain single copies of the MANSC domain:

• Proteins with unkown function containing a signal peptide and transmembrane region.
• Low-density lipoprotein receptor-related protein 11 (LRP-11) and similar proteins with signal peptide, polycystic kidney disease (PKD) domain (see <PDOC50093>), low-density lipoprotein receptor domain class A (LDLRA) (see <PDOC00929>) and transmembrane region.
• Uncharacterized proteins with signal peptide, LDLRA and transmembrane region.
• Hepatocyte growth factor activator inhibitor 1 (HAI-1) proteins with signal peptide, two tandem repeats of Kunitz domains (see <PDOC00252>), LDLRA and transmembrane region.

All of the MANSC-containing proteins contain predicted transmembrane regions and signal peptides. It has been proposed that the MANSC domain in HAI-1 might function through binding with hepatocyte growth factor activator and matriptase [1].

The profile we developed covers the entire MANSC domain.