Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymocyte-activating molecule (THAM) was initially characterized as a developmentally regulated, dimeric cell-surface molecule capable of activating mouse thymocytes and T lymphocytes upon monoclonal antibody (mAb)-mediated cross-linking. We recently obtained structural evidence indicating that this molecule is the mouse homologue of the human T cell-activating ectoenzyme CD26 (dipeptidyl peptidase IV, DPP IV). We describe here the cloning and the characterization of THAM cDNA. Two clones (3.3 and 2.8 kilobases) were isolated. THAM-3.3 cDNA contains an open reading frame of 2,280 nucleotides that encodes a protein of 760 amino acids having a calculated size of 87,500 Da. Complete N-glycosylation at each of the nine potential sites would result in a mature 110,000-Da molecule. Protein sequence comparisons revealed a significant homology (in particular in the COOH-terminal domain) between THAM and the rat or human DPP IV or the yeast dipeptidyl aminopeptidase B molecules (92, 85, and 30% sequence identity, respectively). Structural comparison of serine proteases (i.e. acyl-amino acid hydrolase or prolyl endopeptidase) with the most conserved domain of THAM identified a stretch of 200 amino acids containing a putative catalytic triad arranged in a novel topological order (Ser-624, Asp-702, and His-734) thereby defining a subfamily of nonclassical serine proteases. Expression of THAM during thymus ontogeny was found to be mainly regulated at the transcriptional level as determined by RNase protection assay. To investigate directly some of the functions which have been ascribed to DPP IV, we transfected an ovalbumin/Aq-reactive, THAM- T hybridoma cell line with THAM-3.3 cDNA. The resultant transfectants acquired (i) DPP IV enzymatic activity that precisely paralleled the density of surface-expressed THAM; (ii) an Mr = 115,000 (reduced) and 110,000/128,000 (nonreduced) molecule that could be immunoprecipitated by the THAM-specific mAb H194-112; and (iii) the capacity of being triggered by this mAb to release interleukin-2. These data indicate that a single cDNA species can encode a multifunctional molecule (e.g. activation signal-transducing structure and ectopeptidase), the heterodimeric state of which very likely results from a differential post-translational modification of the same protein core.
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PMID:cDNA cloning for mouse thymocyte-activating molecule. A multifunctional ecto-dipeptidyl peptidase IV (CD26) included in a subgroup of serine proteases. 137 Aug 13

The dipeptidyl peptidase IV gene encodes a plasma-membrane exopeptidase that is highly expressed in small intestine, lung and kidney. In order to better understand the mechanisms responsible for this tissue-specific expression we cloned, sequenced and functionally characterized the 5'-flanking region of the human dipeptidyl peptidase IV gene. The first 500 bases of the 5'-flanking sequence constituted an unmethylated CpG island, contained several Sp1-binding sites and lacked a consensus TATA box, all characteristics of gene promoters lacking tissue-specific expression. RNase-protection analysis using both small intestinal and Caco2 cell RNA indicated that the dipeptidyl peptidase IV transcript was initiated from no fewer than six major and 12 minor start sites. The 5'-flanking sequence also exhibited functional promoter activity in transient transfection experiments. Here, various lengths of the sequence were cloned upstream of a luciferase gene and introduced into cultured cells using lipofectin. A region located between bases -150 and -109 relative to the start of translation was found to be important for high-level promoter activity in both Caco2 and HepG2 cells. Moreover, Caco2 cells and HepG2 cells, which express high levels of dipeptidyl peptidase IV activity, exhibited much higher normalized luciferase activity after transfection than did 3T3, Jurkat or COS-7 cells, which have low enzyme levels. Sodium butyrate was found to increase both enzyme activity and normalized luciferase in HepG2 cells. Thus the dipeptidyl peptidase IV promoter possesses the ability to initiate transcription in a tissue-specific fashion in spite of having the sequence characteristics of a housekeeping gene promoter.
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PMID:Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter. 748 39

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization by activation of neuronal adenosine A(1) receptors, suppressing acetylcholine release from motor neurons and excitatory neurotransmitters from central sites. It also exacerbates venom-induced hypotension by activating A(2) receptors in the vasculature. Adenosine and inosine both activate mast cell A(3) receptors, liberating vasoactive substances and increasing vascular permeability. Guanosine probably contributes to hypotension, by augmenting vascular endothelial cGMP levels via an unknown mechanism. Novel functions are suggested for toxins that act upon blood coagulation factors, including nitric oxide production, using the prey's carboxypeptidases. Leucine aminopeptidase may link venom hemorrhagic metalloproteases and endogenous chymotrypsin-like proteases with venom L-amino acid oxidase (LAO), accelerating the latter. The primary function of LAO is probably to promote prey hypotension by activating soluble guanylate cyclase in the presence of superoxide dismutase. LAO's apoptotic activity, too slow to be relevant to prey capture, is undoubtedly secondary and probably serves principally a digestive function. It is concluded that the principal function of L-type Ca(2+) channel antagonists and muscarinic toxins, in Dendroaspis venoms, and acetylcholinesterase in other elapid venoms, is to promote hypotension. Venom dipeptidyl peptidase IV-like enzymes probably also contribute to hypotension by destroying vasoconstrictive peptides such as Peptide YY, neuropeptide Y and substance P. Purines apparently bind to other toxins which then serve as molecular chaperones to deposit the bound purines at specific subsets of purine receptors. The assignment of pharmacological activities such as transient neurotransmitter suppression, histamine release and antinociception, to a variety of proteinaceous toxins, is probably erroneous. Such effects are probably due instead to purines bound to these toxins, and/or to free venom purines.
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PMID:Ophidian envenomation strategies and the role of purines. 1173 31