Table 4: Summary of IGFBP proteases and their proteolytic cleavage sites.

Proteolytic cleavage sites IGFBP proteaseReference

IGFBP-2
Met166-Gly167, Lys168-Gly169, Tyr103-Gly104, Leu152-Ala153, Arg156-Glu157, Gln165-Met166, Thr205-Met206, Arg287-Met288Unknown protease in hemofiltrate[80]
Leu3-Phe4, Lys168-Gly169, Lys181-Leu182Unknown in milk[200]
Arg164-Gln165Human kallikrein-2[201]
Leu152, Gly175-Leu176, Lys181-Leu182Matrix metalloproteinase-7[202]
Gln165-Met166PAPP-A[203]
His165-Arg166Calpain[204]

IGFBP-3
Arg97-Ala98, Lys160-Val161Plasmin[205]
Arg95-Leu96, Lys160-Val16Plasmin[206]
Arg97-Ala98, Arg206-Gly207 Thrombin[205]
Arg97-Ala98, Lys149-Lys150, Lys150-Gly151, Lys154-Asp155Serum[205]
Arg97-Ala98, Arg132-Val133, Tyr159-Lys160, Phe173-Ser174, Arg179-Glu180Seminal plasma PSA[157]
Arg97-Ala98, His131-Arg132, Tyr159-Lys160Urinary PSA[207]
Arg97-Ala98Cysteine protease from MCF-7 cells[208]
Tyr99-Leu100, Leu96-Arg97, Leu141-His142 MMP-1, MMP-2[176]
Tyr99-Leu100, Asn109-Ala110, Glu176-Ser177MMP-3[176]

IGFBP-4
Lys120-His121 Calcium-dependent serine protease from smooth muscle cells[193, 209, 210]
Met135-Lys136 PAPP-A [211, 212]

IGFBP-5
Arg138-Arg139 Serine protease from smooth muscle cells[213]
Ser143-Lys144 (secondary cleavage site), Ser143-Lys144PAPP-A2[214]
Gln142-Ser-143PAPPA[214]
Lys120-His121, Arg156-Ile157, Arg192-Ala193Thrombin[215]