Peptidase S8 family domain in Protein convertases. Protein convertases, whose members include furins and kexins, are members of the peptidase S8 or Subtilase clan of proteases. They have an Asp/His/Ser catalytic triad that is not homologous to trypsin. Kexins are involved in the activation of peptide hormones, growth factors, and viral proteins. Furin cleaves cell surface vasoactive peptides and proteins involved in cardiovascular tissue remodeling in the TGN, at cell surface, or in endosomes but rarely in the ER. Furin also plays a key role in blood pressure regulation though the activation of transforming growth factor (TGF)-beta. High specificity is seen for cleavage after dibasic (Lys-Arg or Arg-Arg) or multiple basic residues in protein convertases. There is also strong sequence conservation.

Peptidase S8 family domain, uncharacterized subfamily 15. This family is a member of the Peptidases S8 or Subtilases serine endo- and exo-peptidase clan. They have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

Peptidase S8 family domain in Autotransporter serine proteases. Autotransporter serine proteases belong to Peptidase S8 or Subtilase family. Subtilases, or subtilisin-like serine proteases, have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure (an example of convergent evolution). Autotransporters are a superfamily of outer membrane/secreted proteins of gram-negative bacteria. The presence of these subtilisin-like domains in these autotransporters are may enable them to be auto-catalytic and may also serve to allow them to act as a maturation protease cleaving other outer membrane proteins at the cell surface.

Proprotein convertase P-domain. A unique feature of the eukaryotic subtilisin-like proprotein convertases is the presence of an additional highly conserved sequence of approximately 150 residues (P domain) located immediately downstream of the catalytic domain.

Peptidase S8 family domain in Subtilisin proteins. This group is composed of many different subtilisins: Pro-TK-subtilisin, subtilisin Carlsberg, serine protease Pb92 subtilisin, and BPN subtilisins just to name a few. Pro-TK-subtilisin is a serine protease from the hyperthermophilic archaeon Thermococcus kodakaraensis and consists of a signal peptide, a propeptide, and a mature domain. TK-subtilisin is matured from pro-TK-subtilisin upon autoprocessing and degradation of the propeptide. Unlike other subtilisins though, the folding of the unprocessed form of pro-TK-subtilisin is induced by Ca2+ binding which is almost completed prior to autoprocessing. Ca2+ is required for activity unlike the bacterial subtilisins. The propeptide is not required for folding of the mature domain unlike the bacterial subtilases because of the stability produced from Ca2+ binding. Subtilisin Carlsberg is extremely similar in structure to subtilisin BPN'/Novo thought it has a 30% difference in amino acid sequence. The substrate binding regions are also similar and 2 possible Ca2+ binding sites have been identified recently. Subtilisin Carlsberg possesses the highest commercial importance as a proteolytic additive for detergents. Serine protease Pb92, the serine protease from the alkalophilic Bacillus strain PB92, also contains two calcium ions and the overall folding of the polypeptide chain closely resembles that of the subtilisins. Members of the peptidases S8 and S35 clan include endopeptidases, exopeptidases and also a tripeptidyl-peptidase. The S8 family has an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The S53 family contains a catalytic triad Glu/Asp/Ser. The stability of these enzymes may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

ChainA, Furin [Homo sapiens],6YD4_A Chain A, Furin [Homo sapiens],6YD7_A Chain A, Furin [Homo sapiens],7O1U_A Chain A, Furin [Homo sapiens],7O1W_A Chain A, Furin [Homo sapiens],7O1Y_A Chain A, Furin [Homo sapiens],7O20_A Chain A, Furin [Homo sapiens],7O22_A Chain A, Furin [Homo sapiens],7QXY_A Chain A, Furin [Homo sapiens],7QXZ_A Chain A, Furin [Homo sapiens],7QY0_A Chain A, Furin [Homo sapiens],7QY1_A Chain A, Furin [Homo sapiens],7QY2_A Chain A, Furin [Homo sapiens]

X-raystructure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba [Homo sapiens],4OMC_B X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba [Homo sapiens],4OMC_C X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba [Homo sapiens],4OMC_D X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba [Homo sapiens],4OMC_E X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba [Homo sapiens],4OMC_F X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba [Homo sapiens],4OMD_A X-ray structure of human furin in complex with the competitive inhibitor Phac-RVR-Amba [Homo sapiens],4OMD_B X-ray structure of human furin in complex with the competitive inhibitor Phac-RVR-Amba [Homo sapiens],4OMD_C X-ray structure of human furin in complex with the competitive inhibitor Phac-RVR-Amba [Homo sapiens],4OMD_D X-ray structure of human furin in complex with the competitive inhibitor Phac-RVR-Amba [Homo sapiens],4OMD_E X-ray structure of human furin in complex with the competitive inhibitor Phac-RVR-Amba [Homo sapiens],4OMD_F X-ray structure of human furin in complex with the competitive inhibitor Phac-RVR-Amba [Homo sapiens],4RYD_A X-ray structure of human furin in complex with the competitive inhibitor para-guanidinomethyl-Phac-R-Tle-R-Amba [Homo sapiens],4RYD_B X-ray structure of human furin in complex with the competitive inhibitor para-guanidinomethyl-Phac-R-Tle-R-Amba [Homo sapiens],4RYD_C X-ray structure of human furin in complex with the competitive inhibitor para-guanidinomethyl-Phac-R-Tle-R-Amba [Homo sapiens],4RYD_D X-ray structure of human furin in complex with the competitive inhibitor para-guanidinomethyl-Phac-R-Tle-R-Amba [Homo sapiens],4RYD_E X-ray structure of human furin in complex with the competitive inhibitor para-guanidinomethyl-Phac-R-Tle-R-Amba [Homo sapiens],4RYD_F X-ray structure of human furin in complex with the competitive inhibitor para-guanidinomethyl-Phac-R-Tle-R-Amba [Homo sapiens],5JMO_A X-ray structure of furin in complex with the inhibitory antibody Nb14 [Homo sapiens],5JMO_B X-ray structure of furin in complex with the inhibitory antibody Nb14 [Homo sapiens],5JXG_A Structure of the unliganded form of the proprotein convertase furin. [Homo sapiens],5JXH_A Structure the proprotein convertase furin in complex with meta-guanidinomethyl-Phac-RVR-Amba at 2.0 Angstrom resolution. [Homo sapiens],5JXI_A Structure of the unliganded form of the proprotein convertase furin in presence of EDTA. [Homo sapiens],5JXJ_A Structure of the proprotein convertase furin complexed to meta-guanidinomethyl-Phac-RVR-Amba in presence of EDTA [Homo sapiens],5MIM_A Xray structure of human furin bound with the 2,5-dideoxystreptamine derived small molecule inhibitor 1n [Homo sapiens],6EQV_A X-ray structure of the proprotein convertase furin bound with the competitive inhibitor Phac-Cit-Val-Arg-Amba [Homo sapiens],6EQW_A X-ray structure of the proprotein convertase furin bound with the competitive inhibitor 4-aminomethyl-phenylacetyl-Arg-Val-Arg-Amba [Homo sapiens],6EQX_A X-ray structure of the proprotein convertase furin bound with the competitive inhibitor Arg-Arg-Arg-Val-Arg-Amba [Homo sapiens],6HLB_A X-ray structure of furin in complex with the cyclic peptide c[succinyl-Phe-2-Nal-(Arg)4-Lys]-Arg-4-Amba [Homo sapiens],6HLD_A X-ray structure of furin in complex with the cyclic peptide c[succinyl-Phe-2-Nal-(Arg)3-Lys]-Lys-4-Amba [Homo sapiens],6HLE_A X-ray structure of furin in complex with the P6-P2-cyclized peptide H-Lys-Arg-Arg-Tle-Lys-4-Amba [Homo sapiens],6HZA_A X-ray structure of furin in complex with the cyclic peptide c[glutaryl-Arg-Arg-Lys]-Arg-4-Amba [Homo sapiens],6HZB_A X-ray structure of furin in complex with the cyclic inhibitor c[glutaryl-Arg-Arg-Lys]-Lys-4-Amba [Homo sapiens],6HZC_A X-ray structure of furin in complex with the cyclic inhibitor c[glutaryl-BVK-Lys-Arg-Arg-Tle-Lys]-4-Amba [Homo sapiens],6HZD_A X-ray structure of furin in complex with the cyclic inhibitor c[glutaryl-Arg-Arg-Arg-Lys]-Arg-4-Amba [Homo sapiens],6YD2_A Chain A, Furin [Homo sapiens]

Crystalstructure of unglycosylated apo human furin @1.89A [Homo sapiens]

ChainA, Furin [Homo sapiens]

CrystalStructure Of The Proprotein Convertase Furin [Mus musculus],1P8J_B Crystal Structure Of The Proprotein Convertase Furin [Mus musculus],1P8J_C Crystal Structure Of The Proprotein Convertase Furin [Mus musculus],1P8J_D Crystal Structure Of The Proprotein Convertase Furin [Mus musculus],1P8J_E Crystal Structure Of The Proprotein Convertase Furin [Mus musculus],1P8J_F Crystal Structure Of The Proprotein Convertase Furin [Mus musculus],1P8J_G Crystal Structure Of The Proprotein Convertase Furin [Mus musculus],1P8J_H Crystal Structure Of The Proprotein Convertase Furin [Mus musculus]

Furin OS=Rattus norvegicus OX=10116 GN=Furin PE=1 SV=1

Furin OS=Bos taurus OX=9913 GN=FURIN PE=1 SV=1

Furin OS=Homo sapiens OX=9606 GN=FURIN PE=1 SV=2

Furin-1 OS=Xenopus laevis OX=8355 GN=furin PE=2 SV=1

Furin OS=Mus musculus OX=10090 GN=Furin PE=1 SV=2