Disease relevance of SPINK5L3

• Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis [1].
• Infection of monocytes with human immunodeficiency virus type 1(Ba-L) (HIV-1(Ba-L)) is significantly inhibited by treatment with the serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI) [2].
• Viral kinetics in patients with chronic hepatitis C treated with the serine protease inhibitor BILN 2061 [3].
• We analysed viral kinetics from a 2-day treatment with BILN 2061, a serine protease inhibitor of hepatitis C virus, in patients chronically infected with genotype 1 hepatitis C virus [3].
• Maspin, a serine protease inhibitor (serpin), can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro [4].

Psychiatry related information on SPINK5L3

• Two approaches--molecular cloning and immunochemical analysis--have identified one of the components of Alzheimer's disease amyloid deposits as the serine protease inhibitor alpha 1-antichymotrypsin [5].
• It is likely that induction of both IRF-1 and the serine protease inhibitor in response to infection by M. tuberculosis represent host defense mechanisms [6].
• Since a polymorphism in the signal peptide of the serine-protease inhibitor alpha1 antichymotrypsin (ACT) is one of the factors that may enhance amyloid formation, we studied this polymorphism in 63 CJD patients and 103 control subjects [7].

High impact information on SPINK5L3

• Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome [8].
• Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor [1].
• We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor [9].
• Serine protease inhibitor 6 protects cytotoxic T cells from self-inflicted injury by ensuring the integrity of cytotoxic granules [10].
• Expression of the serpin serine protease inhibitor 6 protects dendritic cells from cytotoxic T lymphocyte-induced apoptosis: differential modulation by T helper type 1 and type 2 cells [11].

Chemical compound and disease context of SPINK5L3

• The cleavage at the IETD downward arrowS site required a protease activity that was selectively inhibited by the peptide, Ac-IETD-CHO (acetyl-IETD-aldehyde), and other protease inhibitors, such as the cowpox viral serine protease inhibitor, CrmA, and N-alpha-tosyl-L-phenylalanine chloromethyl ketone [12].
• Engineered serine protease inhibitor prevents furin-catalyzed activation of the fusion glycoprotein and production of infectious measles virus [13].
• Suppression of TNF-alpha secretion by cyclosporin A or by a serine protease inhibitor did not suppress the HIV-1 LTR activation [14].
• The anti-HIV activity of the serine protease inhibitor rSLPI is most likely due to its interaction with a cell-surface molecule(s) other than the primary HIV-1 receptor, CD4, and may involve (i) inhibition of cell-surface serine protease(s), and/or (ii) interaction with other human-specific co-factors essential for viral entry [15].
• Chromatofocusing has been used as an analytical tool to check preparations of the enzyme ferredoxin-NADP+ oxidoreductase (EC 1.18.1.2) purified in either the presence or absence of the serine protease inhibitor phenylmethylsulfonyl fluoride from the cyanobacterium Anabaena sp. strain 7119 [16].

Biological context of SPINK5L3

• The predicted amino acid sequence also reveals extensive homology with other members of the serine protease inhibitor gene family [17].
• Plasminogen activator inhibitor-1 (PAI-1) is a member of the serine protease inhibitor (serpin) supergene family and a central regulatory protein in the blood coagulation system [18].
• The HNF-4/HNF-1alpha transactivation cascade regulates gene activity and chromatin structure of the human serine protease inhibitor gene cluster at 14q32.1 [19].
• The thiol ester linking palmitoleic acid to the polypeptide chain was shown to be sensitive to hydrolysis by hydroxylamine and also by the widely used serine-protease inhibitor phenylmethylsulfonyl fluoride [20].
• Releasates boiled immediately after platelet aggregation with 250 nM A23187 or those produced by adding A23187 in the presence of 100 microM serine protease inhibitor (p-amidinophenyl)methanesulfonyl fluoride (APMSF) are ineffective, whereas releasates boiled or mixed with APMSF after incubation for 60 min are active [21].

Anatomical context of SPINK5L3

• Here, we show that the broad spectrum, irreversible serine protease inhibitor, AEBSF, inhibits the constitutive production of A beta in five different human cell lines, both neural and nonneural [22].
• Our data indicate that normal bovine urothelium synthesizes, as its major differentiation products, two well-known proteases: tissue-type plasminogen activator and urokinase, as well as a serine protease inhibitor, PP5 [23].
• Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor of the extrinsic coagulation system, synthesized in endothelial cells, which has recently been shown to play an important role in the regulation of activated coagulation factors at the endothelial cell surface [24].
• The human serine protease inhibitor (serpin) gene cluster at 14q32.1 contains a number of genes that are specifically expressed in hepatic cells [25].
• Our group recently cloned the cDNA-encoding bomapin, a member of the serine protease inhibitor (serpin) superfamily, from a human bone marrow cDNA library (J Biol Chem 270:2675, 1995) [26].

Associations of SPINK5L3 with chemical compounds

• Protein C inhibitor (PCI) is a nonspecific, heparin-binding serpin (serine protease inhibitor) that inactivates many plasmatic and extravascular serine proteases by forming stable 1:1 complexes [27].
• In normal plasma, the serine protease inhibitor alpha 1-antitrypsin (alpha 1-AT) plays little or no role in the control of plasma kallikrein or activated Factor XII fragment (Factor XIIf), this function being performed by Cl-inhibitor [28].
• Heparin stimulates the activity of antithrombin, a serine-protease inhibitor [29].
• In contrast, neither cystatin, a cysteine protease inhibitor, nor aprotinin, a serine protease inhibitor that does not inhibit thrombin, blocked the synapse reduction [30].
• Hydroxylamine has been shown previously to dissociate covalently coupled serine protease-inhibitor complexes [31].

Physical interactions of SPINK5L3

• A serine protease inhibitor prevents endoplasmic reticulum stress-induced cleavage but not transport of the membrane-bound transcription factor ATF6 [32].
• TSG-6 protein forms a stable complex with components of the serine protease inhibitor, inter-alpha-inhibitor (I alpha I) [33].
• TF/FVIIa treated by a serine protease inhibitor and the complex of TF and inactivated FVIIa (DEGR-FVIIa) did not stimulate SMC migration [34].
• In serum, PSA is predominantly complexed to a liver-derived serine protease inhibitor, alpha-1-antichymotrypsin (ACT) [35].
• The serine protease inhibitor protein C inhibitor is present in semen at a relatively high concentration and forms in vivo complexes with two plasminogen activators also present in semen, urokinase-type and tissue-type plasminogen activators [36].

Co-localisations of SPINK5L3

• The serine protease inhibitor alpha 1-antichymotrypsin (ACT) consistently colocalizes with amyloid deposits of Alzheimer's disease (AD) and may contribute to the generation of amyloid proteins and/or physically affect fibril assembly [37].

Regulatory relationships of SPINK5L3

• GH-induced transcription of the serine protease inhibitor 2.1 gene required the same C-terminal 52-amino acid domain of the receptor as for Ca2+ signaling [38].
• Apoptosis by mutant or wt p53 was significantly inhibited by the serine protease inhibitor AEBSF but not by the inactive analog AEBSA [39].
• Plasma uPA is inhibited by the serine protease inhibitor protein C inhibitor (PCI) by the insertion of PCI's reactive site loop into the active site of the protease [40].
• RESULTS: The activation of MMP-2 could be induced by the LPS of A. actinomycetemcomitans in HPDL cells and could be inhibited by a serine protease inhibitor [41].
• The serine protease inhibitor aprotinin inhibited this activation of MMPs by plasminogen and plasmin [42].

Other interactions of SPINK5L3

• Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor found in fluids lining mucosal surfaces [43].
• In the present study we report on mutations in the serine protease inhibitor, Kazal type 1 (SPINK1) gene in north Indian patients with TCP [44].
• Since its reported discovery in 1994, maspin (mammary serine protease inhibitor) has been characterized as a class II tumor suppressor by its ability to promote apoptosis and inhibit cell invasion [45].
• Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor [46].
• Recent reports indicate that human orthologs of murine squamous cell carcinoma antigen-2 (SCCA-2/serpinb3a), a serine protease-inhibitor, are overexpressed in the airways of asthmatic patients [47].

Analytical, diagnostic and therapeutic context of SPINK5L3

• Restoration of serine protease-inhibitor interaction by protein engineering [48].
• This first cellular phenotype resulting from a gene knock-down in cnidarians suggests that the Kazal1 serine-protease-inhibitor activity is required to prevent excessive autophagy in intact hydra and to exert a cytoprotective function to survive the amputation stress [49].
• In addition, Western blot analysis of two-dimensional gel electrophoresis identified alpha-fibrinogen precursor, beta-fibrinogen precursor, fibrinogen gamma-B chain precursor, hemopexin, vitamin D binding protein, and serine protease inhibitor as proteins with a reduced reaction to anti-Amadori antibody upon intensive insulin treatment [50].
• We have studied the thermodynamics of binding of the Kazal serine protease inhibitor, turkey ovomucoid third domain (OMTKY3), to the serine protease subtilisin Carlsberg using isothermal titration calorimetry and have determined the crystal structure of the complex at very high resolution (1.1A) [51].
• Residues in the active site loop of the serine protease inhibitor, chymotrypsin inhibitor 2, thought to play an important role in loop stability and inhibitory activity, have been investigated by site-directed mutagenesis [52].

References