Summary: A sulfhydryl proteinase with cysteine at the active site from ficus latex. Preferential cleavage is at tyrosine and phenylalanine residues. EC

Top Publications

  1. Belenky A, Wask Rotter E, Sommer M. Absence of protein G-Fc interaction in ficin-derived mouse IgG1 digests. J Immunoassay Immunochem. 2003;24:311-8 pubmed
  2. Bonroy K, Frederix F, Reekmans G, Dewolf E, De Palma R, Borghs G, et al. Comparison of random and oriented immobilisation of antibody fragments on mixed self-assembled monolayers. J Immunol Methods. 2006;312:167-81 pubmed
  3. Nakayama S, Watanabe T, Takahashi K, Hoshino M, Yoshida M. Comparative study on the active sites of ficin and papain by the spin labeling method. J Biochem. 1987;102:531-5 pubmed
  4. Nakamura S, Iwanaga S, Suzuki T. On the activation of bovine plasma factor XIII. Amino acid sequence of the peptide released by thrombin and the terminal residues of the subunit polypeptides. J Biochem. 1975;78:1247-66 pubmed
    ..4.21.8], urokinase [EC], trypsin [EC], ficin [EC], papain [EC], and bromelain [EC]. Among these enzymes, only bromelain and trypsin showed clear activating effects. ..
  5. Richter G, Schwarz H, Dorner F, Turecek P. Activation and inactivation of human factor X by proteases derived from Ficus carica. Br J Haematol. 2002;119:1042-51 pubmed
    ..The cleavage pattern of FXa degradation products in the light chain was influenced by Ca2+ and Mn2+. These data suggest the haemostatic potency of Ficus proteases is based on activation of human coagulation factor X. ..
  6. Coblentz W, Fritz J, Cochran R, Rooney W, Bolsen K. Protein degradation in response to spontaneous heating in alfalfa hay by in situ and ficin methods. J Dairy Sci. 1997;80:700-13 pubmed
    ..Increases in degradation rates concurrent with conservation and minimal heating appear to be especially important considerations when results of the ficin assay are being interpreted. ..
  7. Gorodkiewicz E, Breczko J, Sankiewicz A. Surface Plasmon Resonance Imaging biosensor for cystatin determination based on the application of bromelain, ficin and chymopapain. Folia Histochem Cytobiol. 2012;50:130-6 pubmed publisher
    ..6 ?g/ml and the detection limit is equal to 0.1 ?g/ml. In order to demonstrate the sensor potential, cystatin was determined in blood plasma, urine and saliva, showing good agreement with the data reported in the literature. ..
  8. Davenport R, Judd W, Dake L. Persistence of cefotetan on red blood cells. Transfusion. 2004;44:849-52 pubmed
    ..The minimum necessary concentration for RBC binding is low compared to an estimated plasma concentration of 240 micromol/L from a single i.v. dose of 1 g. ..
  9. Takahashi M, Tezuka T, Towatari T, Katunuma N. Properties and nature of a cysteine proteinase inhibitor located in keratohyalin granules of rat epidermis. FEBS Lett. 1990;267:261-4 pubmed
    ..Therefore it is highly probable that HSP is a cystatin-alpha derivative or a very similar proteinase inhibitor belonging to a family of cystatins. ..

More Information


  1. Andrew S, Titus J. Fragmentation of immunoglobulin G. Curr Protoc Cell Biol. 2003;Chapter 16:Unit 16.4 pubmed publisher
    ..This unit also describes alternative methods for preparing F(ab')(2) fragments. ..
  2. Devaraj K, Kumar P, Prakash V. Purification, characterization, and solvent-induced thermal stabilization of ficin from Ficus carica. J Agric Food Chem. 2008;56:11417-23 pubmed publisher
    ..However, the maximum stabilization effect was observed in terms of thermal stabilization by the co-solvent trehalose...
  3. Saitoh E, Minaguchi K, Ishibashi O. Production and characterization of two variants of human cystatin SA encoded by two alleles at the CST2 locus of the type 2 cystatin gene family. Arch Biochem Biophys. 1998;352:199-206 pubmed
    ..Our data supply evidence indicating that the amino acid sequence of the first hairpin loop of the cystatin superfamily is important in the inhibition of papain, ficin, cathepsin C, cathepsin H, and cathepsin K. ..
  4. Hirota Y, Yang M, Araki S, Yoshihara K, Furusawa S, Yasuda M, et al. Enhancing effects of chicken egg white derivatives on the phagocytic response in the dog. J Vet Med Sci. 1995;57:825-9 pubmed
    ..These results suggest that EWD has an enhancing effect on phagocytosis of MNC and PMN, which may be mediated through active humoral substances produced by EWD-stimulated MNC. ..
  5. Himmelspach M, Richter G, Muhr E, Varadi K, Turecek P, Dorner F, et al. A fully recombinant partial prothrombin complex effectively bypasses fVIII in vitro and in vivo. Thromb Haemost. 2002;88:1003-11 pubmed
    ..In the Wessler test, rfII/rfXa showed no thrombogenicity. These data show that a well-defined, particularly safe and efficacious agent with fVIII bypassing activity can be generated from recombinant fII and fXa. ..
  6. Mazda T, Makino K, Yabe R, Nakata K, Fujisawa K, Ohshima H. Use of standardized protease enzymes for antibody screening of blood donor samples with the microplate system AutoAnalyzer. Transfus Med. 1995;5:43-50 pubmed
  7. Williams L, Domen R. Vancomycin-induced red cell aggregation. Transfusion. 1989;29:23-6 pubmed
    ..The mechanism(s) through which vancomycin enhances aggregation may be related to its polycationic properties and to its direct protein binding to the RBC membrane, although other nonimmunologic mechanisms may be operative. ..
  8. Ogasawara K, Mazda T. Differences in substrate specificities for cysteine proteinases used in blood group serology, and the use of bromelain in a two-phase inhibitor technique. Vox Sang. 1989;57:72-6 pubmed
    ..This method improved upon the one-stage bromelain technique in terms of sensitivity, freedom from false positive reactions and it compared well with the two-phase papain inhibitor technique. ..
  9. Gleisner J, Liener I. Chemical modification of the histidine residue located at the active site of ficin. Biochim Biophys Acta. 1973;317:482-91 pubmed
    ..S. and Lowe, G. (1970), Biochem. J. 117, 341). During the course of these studies a very sensitive assay for measuring the activity of ficin was developed which employs p-nitrophenyl-N-alpha-carbobenzoxy-L-citrullinate as the substrate. ..
  10. Reddy V, Lerner E. Plant cysteine proteases that evoke itch activate protease-activated receptors. Br J Dermatol. 2010;163:532-5 pubmed publisher
    ..Bromelain, ficin and papain function as signalling molecules and activate protease-activated receptors. Activation of these receptors is the likely mechanism by which these proteases evoke itch. ..
  11. Devaraj K, Kumar P, Prakash V. Characterization of acid-induced molten globule like state of ficin. Int J Biol Macromol. 2009;45:248-54 pubmed publisher
    ..Ficin at pH 1.4 retained about approximately 74% secondary structure with a substantial loss of tertiary structure. The acid-induced state was found to have a compact shape as measured by Stokes radius on size exclusion chromatography. ..
  12. Sekizaki H, Toyota E, Fuchise T, Zhou S, Noguchi Y, Horita K. Application of several types of substrates to ficin-catalyzed peptide synthesis. Amino Acids. 2008;34:149-53 pubmed
    ..It used a condensation of N-Boc-Ala-OpGu and Ala-pNA as a model reaction. The products were obtained in 72-96% yield using 10 different substrates, within a few minutes of reaction time. ..
  13. Anderson K, Heath E. The relationship between rat major acute phase protein and the kininogens. J Biol Chem. 1985;260:12065-71 pubmed
  14. Isemura S, Saitoh E. Inhibitory activities of partially degraded salivary cystatins. Int J Biochem. 1994;26:825-31 pubmed
    ..2. Cystatin SN still retained the inhibitory activity for ficin after reduction and carboxymethylation, although the inhibition constant increased. ..
  15. Bjork I, Pol E, Raub Segall E, Abrahamson M, Rowan A, Mort J. Differential changes in the association and dissociation rate constants for binding of cystatins to target proteinases occurring on N-terminal truncation of the inhibitors indicate that the interaction mechanism varies with different enzymes. Biochem J. 1994;299 ( Pt 1):219-25 pubmed
    ..This behaviour indicates that the contribution of the N-terminal segment of the two inhibitors to the interaction mechanism varies with the target proteinase as a result of structural differences in the active-site region of the enzyme. ..
  16. Patel M, Kayani I, Mellor G, Sreedharan S, Templeton W, Thomas E, et al. Variation in the P2-S2 stereochemical selectivity towards the enantiomeric N-acetylphenylalanylglycine 4-nitroanilides among the cysteine proteinases papain, ficin and actinidin. Biochem J. 1992;281 ( Pt 2):553-9 pubmed
    ..Km for the four reactions involving papain (Pap) and actinidin (Act) with the L- and D-enantiomeric substrates: Pap-L much greater than Act-L greater than Pap-D much greater than Act-D.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  17. Tsimba Chitsva F, Bishop S, Kezeor K. Warm autoadsorption with enzyme-treated red blood cells. Immunohematology. 2012;28:88-90 pubmed
    ..The adsorption process can be enhanced by enzyme pretreatment of autologous RBCs. ..
  18. Pedersen J, Kaplan H, Wedeck L, Murphy R, LoBue J, Pincus M. Octapeptide segments from the amino terminus of glycophorin A contain the antigenic determinants of the M and N blood groups systems. J Lab Clin Med. 1990;116:527-34 pubmed
  19. Beck M, Freihaut B, Henry R, Pierce S, Bayer W. A serum haemagglutinating property dependent upon polycarboxyl groups. Br J Haematol. 1975;29:149-56 pubmed
    ..Experimental evidence is presented indicating that it is free polycarboxyl groups that potentiate agglutination and that any metal ion, such as calcium, capable of chelating with these groups will prove to be inhibitory. ..
  20. Etem M, Laird Fryer B, Holub M, Hedl J, Symington D, Figueroa D. Allogeneic adsorptions: a comparison of the traditional method with a modified PEG adsorption method. Immunohematology. 2010;26:104-8 pubmed
    ..As expected, reductions in the number of adsorptions and adsorbing time were observed. The modified-PEG adsorption is an improved method that may replace the current unenhanced method. ..
  21. Reid J, Hussain S, Sreedharan S, Bailey T, Pinitglang S, Thomas E, et al. Variation in aspects of cysteine proteinase catalytic mechanism deduced by spectroscopic observation of dithioester intermediates, kinetic analysis and molecular dynamics simulations. Biochem J. 2001;357:343-52 pubmed
    ..The cavity then undergoes large scale movements (over 4.8 A) in a highly correlated manner, thus controlling the motions of the methanol molecule. The changes in this cavity that release the methanol might be those deduced kinetically. ..
  22. Schopper S, Kahraman A, Leuenberger P, Feng Y, Piazza I, Muller O, et al. Measuring protein structural changes on a proteome-wide scale using limited proteolysis-coupled mass spectrometry. Nat Protoc. 2017;12:2391-2410 pubmed publisher
    ..Scientists with basic biochemistry training can implement the sample preparation steps. MS measurement and data analysis require a background in proteomics...
  23. Blanchard D, Bernard D, Loirat M, Frioux Y, Guimbretiere J, Guimbretiere L. [Characterization of murine monoclonal antibodies against fetal erythrocytes]. Rev Fr Transfus Hemobiol. 1992;35:239-54 pubmed
    ..The antibody NaM46-4A8 (IgG class) is specific for an antigenic structure expressed on fetal cells and accessible only after papain, ficin, bromelin and endo-beta galactosidase treatment. The antigen was not identified. ..
  24. Solves P, de la Rubia J, Arriaga F, Cervera J, Arnao M, Carpio N, et al. [Immunohematologic study and transfusion approach to patients with public antibodies]. Sangre (Barc). 1997;42:25-9 pubmed
    ..Regarding the transfusional management, autologous transfusion, crossmatch with blood from direct relatives and cryopreservation of compatible blood are the most adequate attitudes to cover future needs. ..
  25. Monter B, Herzog B, Stehle P, Furst P. Kinetically controlled synthesis of dipeptides using ficin as biocatalyst. Biotechnol Appl Biochem. 1991;14:183-91 pubmed
    ..Application of short-chain peptides has been advocated recently in clinical nutrition. Ficin-catalyzed peptide synthesis might be an attractive biotechnological approach for the synthesis of suitable dipeptides in this respect. ..
  26. Andrade R, Hagen K, Swanson P, Wick M. The use of proteolysis with ficin, for immunostaining of paraffin sections. A study of lymphoid, mesenchymal, and epithelial determinants in human tissues. Am J Clin Pathol. 1988;90:33-9 pubmed
    ..With this proviso, however, ficin appeared to be the best general enhancer for antigens known to require vigorous digestion (e.g., keratin; F8RAG) for optimal reactivity in paraffin sections. ..
  27. Kojima S, Suzuki N, Shimura N, Kubodera A, Kubota K, Yamaguchi T, et al. Comparative study of intact A7 MoAb and F(ab')2 fragments for radioimmunoimaging of human colon cancer in nude mice. Nucl Med Biol. 1993;20:243-8 pubmed
    ..In addition, the tumor image obtained at an early time using 131I-F(ab')2 was much superior in quality to that with intact 131I-A7 MoAb. The use of F(ab')2 fragments may be effective for tumor diagnosis and therapy. ..
  28. Saito A, Sinohara H. Various forms of rabbit plasma alpha-1-antiproteinase. Biochem Mol Biol Int. 1998;46:27-34 pubmed
    ..Multiple forms of alpha-1-antiproteinase in the rabbit plasma implicate the unknown functions other than the inhibition of neutrophil elastase. ..
  29. Janvier D, Lam Y, Lopez I, Elakredar L, Bierling P. A major target for warm immunoglobulin G autoantibodies: the third external loop of Band 3. Transfusion. 2013;53:1948-55 pubmed publisher
    ..We describe the first cases of warm IgG autoantibodies specific for the third loop of Band 3. This external loop also appears as a major target in patients with warm antibody AIHA. ..
  30. Andrew S, Titus J. Fragmentation of immunoglobulin G. Curr Protoc Immunol. 2001;Chapter 2:Unit 2.8 pubmed publisher
    ..Alternative methods of fragmentation to F(ab')(2) include use of papain that is preactivated with cysteine and use of the enzyme ficin. These alternate methods are particularly useful for mouse IgG(1) antibodies. ..
  31. Zou Y, Bian M, Yiang Z, Lian L, Liu W, Xu X. Comparison of four methods to generate immunoreactive fragments of a murine monoclonal antibody OC859 against human ovarian epithelial cancer antigen. Chin Med Sci J. 1995;10:78-81 pubmed
    ..These results suggested that the fragmentation of OC859 with ficin gave a higher yield of superior immunoreactive fragments. ..
  32. Chiang C, Chang Y, Chang C, Sung H. Characterization of a chitosanase isolated from a commercial ficin preparation. J Agric Food Chem. 2005;53:7579-85 pubmed
    ..The end products of the hydrolysis catalyzed by this enzyme were low molecular weight chitosan polymers and oligomers (11.2-0.7 kDa). ..
  33. Raiger Iustman L, Castilla V, Meich V, Mersich S. Effects of reducing, oxidizing and alkylating agents on early steps of Junin virus multiplication. Arch Virol. 1998;143:1425-32 pubmed
    ..Also enzymatic treatment of cell monolayers and addition of concanavalin A to cultures prior to infection suggest that cellular glycoproteins are involved in virus attachment...
  34. Fadýloğlu S. Immobilization and characterization of ficin. Nahrung. 2001;45:143-6 pubmed
    ..Syneresis in teleme reduced from 70% to 60% depending on immobilization. Both acidity and bitter taste of teleme produced from free ficin was due to extensive protein hydrolysis by proteolytic fractions. ..
  35. Leach M, AuBuchon J. Use of enzyme treatment to enhance reactivity of HLA and platelet-specific antibodies in solid-phase RBC adherence assays. Transfusion. 2002;42:476-80 pubmed
    ..Only occasional false-positive results after enzyme pretreatment were observed. The use of enzyme pretreatment of SPRCA screening strips can provide information that is useful in selecting appropriate units for transfusion. ..
  36. Issitt P, Combs M, Bredehoeft S, Campbell M, Heimer M, Joyner L, et al. Lack of clinical significance of "enzyme-only" red cell alloantibodies. Transfusion. 1993;33:284-93 pubmed
    ..These data support a belief, generally held in the United States but not necessarily elsewhere, that the use of protease-treated red cells for routine pretransfusion tests creates far more work than the accrued benefits justify. ..
  37. Mohr T, Desser L. Plant proteolytic enzyme papain abrogates angiogenic activation of human umbilical vein endothelial cells (HUVEC) in vitro. BMC Complement Altern Med. 2013;13:231 pubmed publisher
    ..These findings indicate that plant proteolytic enzymes may have potential as preventive and therapeutic agents against angiogenesis related human diseases. ..
  38. Azarkan M, Matagne A, Wattiez R, Bolle L, Vandenameele J, Baeyens Volant D. Selective and reversible thiol-pegylation, an effective approach for purification and characterization of five fully active ficin (iso)forms from Ficus carica latex. Phytochemistry. 2011;72:1718-31 pubmed publisher
    ..Enzymatic activity of the five ficin forms was completely inhibited by specific cysteine and cysteine/serine proteases inhibitors but was unaffected by specific serine, aspartic and metallo proteases inhibitors. ..
  39. Mariani M, Camagna M, Tarditi L, Seccamani E. A new enzymatic method to obtain high-yield F(ab)2 suitable for clinical use from mouse IgGl. Mol Immunol. 1991;28:69-77 pubmed
    ..The digestion procedure gave a uniform result for all five different MAbs and was easily scaled up to produce hundreds of milligrams of F(ab)2. ..
  40. Ohtsubo S, Kobayashi H, Noro W, Taniguchi M, Saitoh E. Molecular cloning and characterization of oryzacystatin-III, a novel member of phytocystatin in rice (Oryza sativa L. japonica). J Agric Food Chem. 2005;53:5218-24 pubmed publisher
    ..These data suggest that the above three inhibitors may play unique physiological roles in the regulations of rice cysteine proteinases...
  41. Hänsler M, Ullmann G, Jakubke H. The application of papain, ficin and clostripain in kinetically controlled peptide synthesis in frozen aqueous solutions. J Pept Sci. 1995;1:283-7 pubmed
    ..Enzyme-catalysed peptide syntheses were carried out under optimized reaction conditions (temperature, amino component concentration and pH before freezing) using the condensation of Bz-Arg-OEt and H-Leu-NH2 as a model reaction. ..
  42. Alsenz J, Schulz T, Lambris J, Sim R, Dierich M. Structural and functional analysis of the complement component factor H with the use of different enzymes and monoclonal antibodies to factor H. Biochem J. 1985;232:841-50 pubmed
    ..The 38 kDa tryptic fragment of Factor H is the N-terminal end of the Factor H molecule, as determined by N-terminal sequence analysis. A model is presented of the substructure of Factor H. ..
  43. Zivy M, Granier F. Peptide mapping of polypeptides separated by two-dimensional electrophoresis: protease digestion directly on the two-dimensional gel followed by electrophoresis in reverse direction. Electrophoresis. 1988;9:339-43 pubmed
    ..The method allows proteolytic patterns of numerous polypeptides to be visualized simply and quickly. Among proteins of wheat leaves, 31 groups of related polypeptides were found according to the similarity of their proteolytic patterns. ..
  44. Barrett A, Davies M, Grubb A. The place of human gamma-trace (cystatin C) amongst the cysteine proteinase inhibitors. Biochem Biophys Res Commun. 1984;120:631-6 pubmed
    ..The inhibition constants of cystatin C, taken together with its widespread distribution in human tissues and extracellular fluids, suggest that a physiological function could well be the regulation of cysteine proteinase activity. ..
  45. Zare H, Moosavi Movahedi A, Salami M, Sheibani N, Khajeh K, Habibi Rezaei M. Autolysis control and structural changes of purified ficin from Iranian fig latex with synthetic inhibitors. Int J Biol Macromol. 2016;84:464-71 pubmed publisher
    ..The ficin structural changes with two synthetic inhibitors were associated with secondary structural changes related to decreased alpha-helix and increased beta sheet and random coil conformations, contributing to its aggregation. ..
  46. Ahmed A, Shamsi A, Bano B. Purification and biochemical characterization of phytocystatin from Brassica alba. J Mol Recognit. 2016;29:223-31 pubmed publisher
    ..6?×?10(-7) ?M) and bromelain (K(i)?=?7.7?×?10(-7) ?M respectively). CD spectral analysis shows that it possesses 17.11% alpha helical content...
  47. Yao J, Xiao Y, Zuo Q, Zhang Y, Tao T, Lin C. Effectiveness of cysteine proteases on protein/pigment film removal. Arch Oral Biol. 2013;58:1618-26 pubmed publisher
    ..This study indicates the potential application of the CPs for tooth stain removal and suggests that these enzymes are worthy of further investigation for use in oral healthcare. ..
  48. Bjork I, Ylinenjärvi K. Interaction between chicken cystatin and the cysteine proteinases actinidin, chymopapain A, and ficin. Biochemistry. 1990;29:1770-6 pubmed
    ..6 X 10(-7) s-1 for ficin to 1.1 X 10(-2) s-1 for actinidin, reflecting substantial differences between the enzymes in the nature of the interactions with the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  49. Huber K, Patel P, Zhang L, Evans H, Westwell A, Fischer P, et al. 2-[(1-methylpropyl)dithio]-1H-imidazole inhibits tubulin polymerization through cysteine oxidation. Mol Cancer Ther. 2008;7:143-51 pubmed publisher
    ..These findings show that modulation of targets other than thioredoxin contribute to the effects of IV-2 on proliferating cells. ..
  50. Bjork I, Brieditis I, Abrahamson M. Probing the functional role of the N-terminal region of cystatins by equilibrium and kinetic studies of the binding of Gly-11 variants of recombinant human cystatin C to target proteinases. Biochem J. 1995;306 ( Pt 2):513-8 pubmed
  51. Ishihara M, Shiroma T, Taira T, Tawata S. Purification and characterization of extracellular cysteine protease inhibitor, ECPI-2, from Chlorella sp. J Biosci Bioeng. 2006;101:166-71 pubmed
    ..The alpha-chymotrypsin hydrolysis product from ECPI-2 was further separated into six fractions by gel filtration. From these results, it is suggested that ECPI-2 has several reactive sites for papain. ..
  52. Saitoh E, Isemura S, Chiba A, Oka S, Odani S. A novel cysteine protease inhibitor with lectin activity from the epidermis of the Japanese eel Anguilla japonica. Comp Biochem Physiol B Biochem Mol Biol. 2005;141:103-9 pubmed
    ..Combined with the data on amino acid and sequence analysis, Eel-CPI-1 is identical to the eel lectin, AJL-2. This is the first report describing a cysteine protease inhibitor with lectin activity. ..
  53. Roe M, Chase L, Sniffen C. Comparison of in vitro techniques to the in situ technique for estimation of ruminal degradation of protein. J Dairy Sci. 1991;74:1632-40 pubmed