TXN and plasma cell myeloma: To further investigate whether HAI-2 exhibits a role in suppressing the proteolytic activity of matriptase, we performed an in vitro proteolytic activity assay, using the recombinant proteins of active matriptase protease domain (Trx-MTX PD, the protease domain of matriptase carrying the amino acid sequence from the residue 615 to 854 which was conjugated with an N-terminal thioredoxin tag) purified from an E. coli expression system (Supplementary Figure S3), an artificial substrate (Boc-Gln-Ala-Arg-AMC) for matriptase, and recombinant HAI-2 proteins purified from mouse myeloma cells.