Disease relevance of Jon99Ci

• Hepatitis C virus (HCV) nonstructural 3 (NS3) serine protease disrupts important cellular antiviral signaling pathways and plays a pivotal role in the proteolytic maturation of the HCV polyprotein precursor [1].
• Finally, a mutation called disorganization, which is located near the serine protease complex, is of considerable interest because it causes an extraordinarily wide variety of congenital defects [2].

High impact information on Jon99Ci

• This process requires serine proteolytic activity; the injection of serine protease inhibitors into the perivitelline space of wild-type embryos results in the formation of dorsalized embryos [3].
• We have found that nine dominant and four recessive mutations are caused by single amino acid substitutions at conserved sites in the putative serine protease catalytic domain [4].
• Dominant and recessive alleles of the Drosophila easter gene are point mutations at conserved sites in the serine protease catalytic domain [4].
• The molecular cloning of the gene and analysis of a complementary DNA sequence suggest that the gene encodes a serine protease which is structurally similar to proteases involved in blood clotting, peptide processing, and complement fixation pathways [5].
• CIAP1 and the serine protease HTRA2 are involved in a novel p53-dependent apoptosis pathway in mammals [6].

Biological context of Jon99Ci

• The predicted amino acid sequences of all of these were found to be homologous to the serine protease family of enzymes [7].
• Sequence analysis of portions of the genomic clone and representative cDNAs revealed the presence of two uninterrupted and complete open reading frames (SER1 and SER2) and part of a third (SER3) [7].
• Here, we present the functional characterization of the Drosophila serine protease Sp7 (CG3006) by inducible RNA interference [8].
• We have identified 44 serine protease (SP) and 13 serine protease homolog (SPH) genes in the genome of Apis mellifera [9].
• Comparative analysis of serine protease-related genes in the honey bee genome: possible involvement in embryonic development and innate immunity [9].

Anatomical context of Jon99Ci

• We show that Sp7 is constitutively expressed in blood cells during embryonic and larval stages [8].
• The serine protease prolylcarboxypeptidase (PRCP), isolated from human umbilical vein endothelial cells (HUVECs), is a plasma prekallikrein (PK) activator [10].
• Mutations that cause the malformed phenotype have already led to the identification and cloning of genes encoding transcription factors, a transmembrane serine protease presumably required for modification of the apical extracellular matrix, and components of the contractile cytoskeleton and adherens junctions [11].
• A complex of serine protease genes expressed preferentially in cytotoxic T-lymphocytes is closely linked to the T-cell receptor alpha- and delta-chain genes on mouse chromosome 14 [2].
• With this approach we have detected a novel serine protease activity with a relative mobility of 37 kDa, localized to the surface of pole cells, the germ-line precursors, in embryos between nuclear cycles 11 and 14 in development [12].

Associations of Jon99Ci with chemical compounds

• Levels of RNA from a family of putative serine protease genes are reduced in Drosophila melanogaster dunce mutants and are regulated by cyclic AMP [7].
• In an effort to identify serine proteases involved in the insect's immune response, we used a degenerate PCR approach to amplify putative serine protease gene fragments in Drosophila [13].
• The labeling is inhibited in the presence of tosylphenylalanine chloromethyl ketone and phenylmethane sulfonylfluoride but not by tosyllysine chloromethyl ketone, suggesting that a chymotrypsin-like serine protease is associated with the chromosomes [14].
• Infection also leads to an increase in the kappaB-binding activity and up-regulation of immune-related gene expression, like inducible nitric oxide synthase and Factor C, an LPS-activated serine protease [15].
• Molecular cloning of cDNA for pro-phenol-oxidase-activating factor I, a serine protease is induced by lipopolysaccharide or 1,3-beta-glucan in coleopteran insect, Holotrichia diomphalia larvae [16].

Other interactions of Jon99Ci

• To activate the pathway, we overexpressed an activated form of the EGFR (UAS-caEGFR), and an activated form of the signal transducer Raf (UAS-caRaf); we also over- or ectopically expressed the downstream homeobox transcription factor Mirror (UAS-mirr) and the ligand-activating serine protease Rhomboid (UAS-rho) [17].
• The easter gene encodes a serine protease that generates processed Spätzle, which is proposed to act as the Toll ligand [18].
• The gut-specific sequences encode a maltase, a V-ATPase subunit, a GTP binding protein, two different lectins, and a nontrypsin serine protease [19].
• Easter is the final protease in a serine protease cascade in which initial reaction steps appear not to be ventrally restricted, but where Easter activity is promoted ventrally through the action of a spatial cue at an unknown step in the pathway [20].
• Evidence of serine-protease activity closely associated with Drosophila alcohol dehydrogenase [21].

Analytical, diagnostic and therapeutic context of Jon99Ci

• Site-directed mutagenesis suggests that Gd functions as a serine protease [22].
• Recent studies have demonstrated that the zymogen form of the serine protease factor C, a major granular component of hemocyte, also exists on the hemocyte surface and functions as a biosensor for LPS [23].

References