Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Achromobacter protease I (API) is a lysine-specific serine protease which hydrolyzes specifically the lysyl peptide bond. A gene coding for API was cloned from Achromobacter lyticus M497-1. Nucleotide sequence of the cloned DNA fragment revealed that the gene coded for a single polypeptide chain of 653 amino acids. The N-terminal 205 amino acids, including signal peptide and the threonine/serine-rich C-terminal 180 amino acids are flanking the 268 amino acid-mature protein which was identified by protein sequencing. Escherichia coli carrying a plasmid containing the cloned API gene overproduced and secreted a protein of Mr 50,000 (API') into the periplasm. This protein exhibited a distinct endopeptidase activity specific for lysyl bonds as well. The N-terminal amino acid sequence of API' was the same as mature API, suggesting that the enzyme retained the C-terminal extended peptide chain. The present experiments indicate that API, an extracellular protease produced by gram-negative bacteria, is synthesized in vivo as a precursor protein bearing long extended peptide chains at both N and C termini.
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PMID:Cloning, nucleotide sequence, and expression of Achromobacter protease I gene. 268 82

The pleiotropic activities of IL-1 have fostered a series of studies on the structure-function relationship in these proteins. In fact, the attempt to dissociate different biological functions of IL-1 should simplify its therapeutic use. About human IL-1 beta, which has been more extensively studied in this respect, enzymatic cleavage of the precursor protein to generate the mature polypeptide appears necessary for its full biological activity. The almost complete integrity of the mature IL-1 beta protein is also required for its ability to bind to the receptor and trigger cellular functions. However, by the use of monoclonal antibodies and recombinant or synthetic peptides, it has been possible to map some IL-1 beta regions important for different activities. Both N-terminal and C-terminal fragments are important for receptor binding. A domain around amino acids 187-204 is apparently involved in the hyperalgesic effects of IL-1 beta. Finally, the fragment in position 163-171 appears to be responsible for a restricted series of the IL-1 beta activities, mainly directed to the immune system, although irrelevant for inflammation-related effects and unable of binding to the IL-1R. It is thus possible, within the sequence of a cytokine, to isolate selectively active domains. This will give us new tools for new therapeutic approaches. Thus, IL-1 might be the prototype of a new generation of cytokines developed with the goal of stimulating specific biological activities without activating the cascade effects which are typical for many cytokines.
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PMID:Structure-function relationship of interleukin-1 giving new insights for its therapeutic potential. 270 51

In the amphibian intermediate pituitary gland the biosynthetic activity for production of the precursor protein proopiomelanocortin (POMC) can be physiologically manipulated; POMC synthesis is high in animals adapted to a black background and low in white-adapted animals. In order to study genes associated with POMC gene expression we applied a differential hybridization technique involving screening of a pituitary cDNA library with probes derived from RNA of inactive and physiologically activated intermediate pituitary cells of the amphibian Xenopus laevis. A differentially hybridizing Xenopus pituitary cDNA clone encoded the novel polypeptide 7B2. This Mr-21,000 secretory granule-associated protein of unknown function is shown to be highly conserved between Xenopus and human (83% amino acid sequence similarity). Conserved segments within the 7B2 structure included the N-terminal portion, three pairs of basic amino acids which are potential recognition sites for proteolytic enzymes, and three regions sharing similarity with putative GTP-binding domains. Levels of 7B2 mRNA were about 3% of POMC mRNA levels in Xenopus pituitary glands. In the intermediate pituitary the amount of both POMC and 7B2 mRNA was much higher in black-adapted toads than in white-adapted animals. These physiologically-induced changes in POMC and 7B2 mRNA levels were not found in the anterior pituitary. We conclude that the POMC and 7B2 genes are coexpressed and that modulation of the activity of these genes is tissue-specific.
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PMID:The novel pituitary polypeptide 7B2 is a highly-conserved protein coexpressed with proopiomelanocortin. 271 83

The nucleotide sequence of the mRNA coding for the precursor of mitochondrial serine:pyruvate aminotransferase of rat liver was determined from those of cDNA clones. The mRNA comprises at least 1533 nucleotides, except the poly(A) tail, and encodes a polypeptide consisting of 414 amino acid residues with a molecular mass of 45,834 Da. Comparison of the N-terminal amino acid sequence of mitochondrial serine:pyruvate aminotransferase with the nucleotide sequence of the mRNA showed that the mature form of the mitochondrial enzyme consisted of 390 amino acid residues of 43,210 Da. The amino acid composition of mitochondrial serine:pyruvate aminotransferase deduced from the nucleotide sequence of the cDNA showed good agreement with the composition determined on acid hydrolysis of the purified protein. The extra 24 amino acid residues correspond to the N-terminal extension peptide (pre-sequence) that is indispensable for the specific import of the precursor protein into mitochondria. In the extension peptide there are four basic amino acids distributed among hydrophobic amino acids and, as revealed on helical wheel analysis, the putative alpha-helical structure of the peptide was amphiphilic in nature. The secondary structures of the mature serine:pyruvate aminotransferase and three other aminotransferases of rat liver were predicted from their amino acid sequences. Their secondary structures exhibited a common feature and so we propose the specific lysine residue which binds pyridoxal phosphate as the active site of serine:pyruvate aminotransferase.
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PMID:Nucleotide sequence of the cDNA encoding the precursor for mitochondrial serine:pyruvate aminotransferase of rat liver. 282 18

A transcription/translation system for generating poliovirus proteins in vitro has been used to assess the proteolytic activity of various polypeptides containing the virus-coded 3C region towards the poliovirus precursor protein P1. Plasmids containing a phage T7 promoter followed by either the complete poliovirus P1 sequence or various sequences containing the 3C region were used for this purpose. We showed that all except one of the 3C-containing polypeptides had a very restricted activity towards P1, generating only a small amount of VP1 and no VP0 or VP3. The only polypeptide capable of fully processing P1 into VP0, VP3 and VP1 in vitro was protein 3CD, consisting of the complete 3C and 3D sequences.
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PMID:Poliovirus protein 3CD is the active protease for processing of the precursor protein P1 in vitro. 283 99

We have isolated two overlapping cDNA clones that encompass the entire structural gene for pyruvate, orthophosphate dikinase from maize. The analysis of the nucleotide sequence has revealed that the cDNA clones include an insert of a total of 3,171 nucleotides without a poly(A) tail and encode a polypeptide that contains 947 amino acid residues and has a molecular weight of 102,673. Comparison of the N-terminal amino acid sequence of purified pyruvate, orthophosphate dikinase protein with that deduced from the nucleotide sequence shows that the mature form of pyruvate, orthophosphate dikinase in the maize chloroplast consists of 876 amino acid residues and has a molecular weight of 95,353. The amino acid composition of the deduced sequence of pyruvate, orthophosphate dikinase is in good agreement with that of the purified enzyme. The region that contains the active and regulatory sites of pyruvate, orthophosphate dikinase can be found in the deduced sequence of amino acids. We have predicted the secondary structure and calculated the hydropathy pattern of this region. The extra 71 residues at the N terminus of the deduced sequence of amino acid residues corresponds to the transit peptide which is indispensable for the transport of the precursor protein into chloroplasts. We have compared the primary structure of the pyruvate, orthophosphate dikinase transit peptide to those of other proteins and found sequences similar to the consensus sequences found in other transit peptides.
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PMID:Primary structure of maize pyruvate, orthophosphate dikinase as deduced from cDNA sequence. 284 17

An abundant 0.9 kb female-specific mRNA in Schistosoma mansoni is thought to code for an egg-shell precursor protein [Bobek et al. (1986) Proc. Natl. Acad. Sci. USA 83, 5544-5548]. This gene contains two ORFs. A recombinant plasmid was constructed that expresses a fusion protein containing a glycine- and tyrosine-rich polypeptide coded for by one of these ORFs. Antisera raised against homogenates of female, but not of male, S. mansoni recognise this fusion protein, providing direct evidence that this ORF is used by S. mansoni. In comparative Western blots of S. mansoni homogenates from males and females affinity purified antibodies that react with the fusion protein react exclusively with proteins from females, recognising a 28 kDa polypeptide and a smear of immunoreactive material probably caused by oxidative crosslinking. In immunohistology, the affinity purified antibodies react with mature vitelline cells in female schistosomes. The immunoreactive material is localised in the so-called 'vitelline droplets' that are morphologically very similar to 'shell globules', known to contain egg-shell precursors, that are found in Fasciola hepatica. In situ hybridisation shows that the eggshell precursor gene is only transcribed in immature vitelline cells and has a short half-life. Taken together, these observations provide persuasive evidence that the 0.9 kb mRNA codes for an eggshell precursor.
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PMID:Identification and localisation of the products of a putative eggshell precursor gene in the vitellarium of Schistosoma mansoni. 284 44

A purified, artificial precursor protein was used as a transport vehicle to test the tolerance of the mitochondrial protein import system. The precursor was a fusion protein consisting of mouse dihydrofolate reductase linked to a yeast mitochondrial presequence; it contained a unique cysteine as its COOH-terminal residue. This COOH-terminal cysteine was covalently coupled to either a stilbene disulfonate derivative or, with the aid of a bifunctional cross-linker, to one of the free amino groups of horse heart cytochrome c. Coupling to horse heart cytochrome c generated a mixture of branched polypeptide chains since this cytochrome lacks a free alpha-amino group. Both adducts were imported and cleaved by isolated yeast mitochondria. The mitochondrial protein import machinery can thus transport more complex structures and even highly charged "membrane-impermeant" organic molecules. This suggests that transport occurs through a hydrophilic environment.
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PMID:Mitochondria can import artificial precursor proteins containing a branched polypeptide chain or a carboxy-terminal stilbene disulfonate. 284 48

Alzheimer's disease is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles and extracellularly as amyloid plaque cores and in blood vessels. The major protein subunit (A4) of the amyloid fibril of tangles, plaques and blood vessel deposits is an insoluble, highly aggregating small polypeptide of relative molecular mass 4,500. The same polypeptide is also deposited in the brains of aged individuals with trisomy 21 (Down's syndrome). We have argued previously that the A4 protein is of neuronal origin and is the cleavage product of a larger precursor protein. To identify this precursor, we have now isolated and sequenced an apparently full-length complementary DNA clone coding for the A4 polypeptide. The predicted precursor consists of 695 residues and contains features characteristic of glycosylated cell-surface receptors. This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
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PMID:The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. 288 Dec 7

A plasmid containing the gene coding for the Saccharomyces cerevisiae F0F1 ATPase subunit 4 was isolated from a yeast genomic DNA library using the oligonucleotide probe procedure. The gene and the surrounding regions were cloned into M13 tg 130 and M13 tg 131 phage vectors. A 732-base-pair open reading frame encoding a 244-amino-acid polypeptide is described. The nucleotide sequence predicts that subunit 4 is probably derived from a precursor protein with a hydrophilic and basic 35-amino-acid leader sequence. Mature subunit 4 contains 209 amino acid residues and the predicted molecular mass is 23250 Da. This subunit presents amphiphilic behaviour with two distinct domains. A high alpha-helix content of 77% was predicted from the sequence. Subunit 4 shows homology with the b subunit of Escherichia coli ATP synthase.
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PMID:ATP4, the structural gene for yeast F0F1 ATPase subunit 4. 289 78


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