Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein Z is a vitamin K-dependent plasma protein of unknown function. Its modular structure is identical with those of factors VII, IX, X, and protein C. These proteins have an N-terminal gamma-carboxyglutamic acid (Gla)-containing module which binds six to ten Ca2+. In factors IX, X, and protein C, the adjacent epidermal growth factor (EGF)-like module binds one Ca2+ whereas the EGF-like module in protein Z does not. We have compared the Ca2+ binding properties of a fragment of protein Z comprising the Gla and N-terminal EGF-like modules (pZ-GlaEGFN) with those of intact protein Z and the isolated Gla module by measuring the Ca(2+)-induced quenching of the intrinsic protein fluorescence. The similar Ca2+ affinities of pZ-GlaEGFN and protein Z indicate that pZ-GlaEGFN has a native conformation and normal Ca2+ binding properties. A comparison of the Ca2+ binding to pZ-GlaEGFN with those to the corresponding fragments of factors IX, X, and protein C indicate that Ca2+ binding to the N-terminal EGF-like modules in the latter proteins does not influence the folding and Ca2+ binding properties of their Gla modules. Furthermore, the Ca(2+)-induced fluorescence enhancements of GlaEGF fragments from factors IX, X, and protein C appear to be caused by Ca2+ binding to the site in the EGF-like modules since it is not observed for pZ-GlaEGFN.
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PMID:Comparison of the Ca2+ binding properties of the gamma-carboxyglutamic acid-containing module of protein Z in the intact protein and in N-terminal fragments. 145 4

Methane monooxygenase (MMO) is the enzyme responsible for the conversion of methane to methanol in methanotrophic bacteria. The soluble MMO enzyme complex from Methylosinus trichosporium also oxidizes a wide range of aliphatic and aromatic compounds in a number of potentially useful biotransformations. In this study we have used heterologous DNA probes from the type X methanotroph Methylococcus capsulatus (Bath) to isolate mmo genes from the type II methanotroph M. trichosporium. We report here that the gene encoding the reductase component, Protein C of MMO, lies adjacent to the genes encoding the other components of soluble MMO in M. trichosporium but is separated by an open reading frame of unknown function, orfY. The complete nucleotide sequence of these genes is presented. Sequence analysis of mmoC indicates that the N-terminus of Protein C has significant homology with 2Fe2S ferredoxins from a wide range of organisms.
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PMID:The methane monooxygenase gene cluster of Methylosinus trichosporium: cloning and sequencing of the mmoC gene. 178 54

Protein Z is a vitamin K-dependent protein of unknown function present in normal bovine plasma at a concentration of approximately 0.1 microM. Quantitative affinity chromatographic studies using diisopropylphosphoryl (DIP)-thrombin-Affi-Gel 10 as the affinity matrix and free DIP-thrombin as the competitor demonstrated that protein Z interacts with DIP-thrombin with a dissociation constant of 0.15 +/- 0.05 microM. Binding was independent of Ca2+. Protein C and factor IX, other vitamin K-dependent clotting proteins with the same domain structure as that of protein Z, did not interact with immobilized DIP-thrombin under these conditions; and factor X interacted with an affinity 20-fold lower than that for protein Z. The Michaelis constant, Km, for hydrolysis of pyro-Glu-Pro-Arg-p-nitroanilide by thrombin was increased 1.8-fold, from 130 to 230 microM, as a result of the binding of protein Z and the Km for H-Val-Leu-Arg-p-nitroanilide 1.4-fold, from 390 to 560 microM. From these kinetic studies, a dissociation constant of 0.11 +/- 0.04 microM was calculated for the binding of protein Z to alpha-thrombin. Protein Z bound to large phospholipid vesicles (25% phosphatidylserine, 75% phosphatidylcholine) with a dissociation constant of 0.39 +/- 0.16 microM at a phospholipid to protein ratio of 82 mol of phospholipid/mol of protein Z at saturation. In the presence of protein Z thrombin associated with phospholipid vesicles, whereas thrombin did not interact with phospholipid vesicles in the absence of protein Z. These studies, therefore, demonstrate a physiologically relevant interaction between protein Z and thrombin. They also suggest a mechanism whereby thrombin is localized to an injury site by virtue of its interaction with protein Z bound to phospholipid surfaces.
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PMID:Interaction of vitamin K-dependent protein Z with thrombin. Consequences for the amidolytic activity of thrombin and the interaction of thrombin with phospholipid vesicles. 204 Jun 12

Gamma-carboxyglutamic acid is an amino acid with a dicarboxylic acid side chain. This amino acid, with unique metal binding properties, confers metal binding character to the proteins into which it is incorporated. This amino acid has been discovered in blood coagulation proteins (prothrombin, Factor X, Factor IX, and Factor VII), plasma proteins of unknown function (Protein C, Protein S, and Protein Z), and proteins from calcified tissue (osteocalcin and bone-Gla protein). It has also been observed in renal calculi, atherosclerotic plaque, and the egg chorioallantoic membrane, among other tissues. Gamma-carboxyglutamic acid is synthesized by the post-translational modification of glutamic acid residues. This reaction, catalyzed by a hepatic carboxylase, requires reduced vitamin K, oxygen, and carbon dioxide. The function of gamma-carboxyglutamic acid is uncertain. In prothrombin gamma-carboxyglutamic acid residues bound to metal ions participate as an intramolecular non-covalent bridge to maintain protein conformation. Additionally, these amino acids participate in the calcium-dependent molecular assembly of proteins on membrane surfaces through intermolecular bridges involving gamma-carboxyglutamic acid and metal ions.
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PMID:Gamma-carboxyglutamic acid. 645 61

Biological methane oxidation is carried out by methanotrophs, bacteria that utilize methane as their sole carbon and energy source. The enzyme they contain that is responsible for methane oxidation is methane monooxygenase, the most well studied being the soluble methane monooxygenase enzyme complexes from Methylococcus capsulatus (Bath) and Methylosinus trichosporium OB3b. In both organisms, the genes encoding soluble methane monooxygenase have been found to be clustered on the chromosome in the order mmoX, mmoY, mmoB, mmoZ, orfY and mmoC. These genes encode the alpha and beta subunits of Protein A, Protein B, the gamma subunit of Protein A, a protein of unknown function and Protein C respectively of the soluble methane monooxygenase complex. The complete DNA sequences of both gene clusters have been determined and they show considerable homology. Expression of soluble methane monooxygenase genes occurs under growth conditions where the copper-to-biomass ratio is low. Transcriptional regulation of the gene cluster from Methylosinus occurred at an RpoN-like promoter, 5' of the mmoX gene. mmoB and mmoC of Methylococcus have been expressed in E. coli and the proteins obtained were functionally active. Soluble methane monooxygenase mutants have been constructed by marker-exchange mutagenesis. They were found to be more stable than those generated using the suicide substrate dichloromethane. Soluble methane monooxygenase probes have been used to detect both methane monooxygenase gene-specific DNA and methanotrophs in natural environmental samples.
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PMID:Molecular genetics of methane oxidation. 776 30

Hereditary predisposition to colorectal cancer assumes two well-defined forms: familial adenomatous polyposis and hereditary nonpolyposis colon cancer. These tumors segregate as autosomal dominant conditions whose penetrance increases with age; cancer is expected to develop ultimately in as much as 50% of the offspring of affected individuals. These traits account for less than 1% and approximately 5% of all colorectal cancer, respectively. In addition, first-degree relatives of patients with common (sporadic) colorectal neoplasia are at increased risk of colorectal cancer. This relative risk averages approximately twofold but is significantly higher for relatives of younger patients (age at diagnosis, < 55 years). Familial adenomatous polyposis and a major subset of hereditary nonpolyposis colon cancer are due to loss-of-function germline mutations of genes located on chromosomes 5q and 2p, respectively. Both of these genes have been cloned recently. The gene affected in familial polyposis, APC, encodes a protein of unknown function that normally is found on the surface of maturing cells in the upper colonic crypts. The relevant gene in many hereditary nonpolyposis colon cancer kindreds is hMSH2. This gene encodes the human homologue of a bacterial protein MutS, which is part of a system known to repair base mismatches in newly replicated DNA. Loss of hMSH2 function may explain the strikingly erroneous replication of short DNA repeats (microsatellites) in colon tumors from patients with hereditary nonpolyposis colon cancer. Because this error-prone replication is found in approximately 13% of nonfamilial colon cancers, defective mismatch repair may contribute to the development of both hereditary and sporadic colon neoplasia. Molecular genetic assays to detect mutated alleles of these genes will facilitate presymptomatic identification of carriers in families with familial polyposis and hereditary nonpolyposis colon cancer. Current recommendations for surveillance of family members are presented in the light of the new genetic understanding of these diseases.
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PMID:Southwestern internal medicine conference: hereditary predisposition to colorectal cancer: new insights. 797 49

Myosin-binding-protein C (MyBP-C) is a myosin-associated protein of unknown function found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. Using a cDNA clone encoding the fast-type isoform of chicken MyBP-C, we screened a human fetal muscle cDNA library and isolated clones encoding the full-length human fast-type isoform of MyBP-C. cDNA clones encoding the slow-type isoform of human MyBP-C, were also isolated and fully sequenced. Northern-blot analysis demonstrated skeletal muscle-specific expression of these gene products. Using human/hamster somatic-cell hybrids, we were able to map the slow-type MyBP-C to human chromosome 12, and the fast-type MyBP-C to chromosome 19. The cDNA for human fast-type MyBP-C encodes a polypeptide of 1142 amino acids with an expected molecular mass of 128.1 kDa. Comparison of this cDNA with other members of the MyBP family reveals extensive primary-sequence conservation. Each MyBP-C contains seven immunoglobulin C2 motifs and three fibronectin type-III repeats in the arrangement C2-C2-C2-C2-C2-III-III-C2-III-C2. Regions of high identity shared by the chicken and the two human proteins are not restricted to the immunoglobulin and fibronectin motifs. Sequence comparison of all three proteins has allowed us to map a highly conserved region between the first and second C2 motifs, the only large spacer sequence present between motifs in these proteins.
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PMID:Complete sequence of human fast-type and slow-type muscle myosin-binding-protein C (MyBP-C). Differential expression, conserved domain structure and chromosome assignment. 837

Defects in the APC gene are inarguably linked to the progression of colon cancers that arise both sporadically and through the transmission of germline mutations. Genetic evidence from humans and mouse models suggest that APC is a classic tumor suppressor in that both alleles likely require inactivation for tumor growth to ensue. Nearly all of the mutations, germline and somatic, result in premature termination of the single polypeptide chain, normally consisting of 2843 amino acids. Several definable motifs have now been mapped to the linear amino acid sequence of the APC polypeptide. These include an oligomerization domain, armadillo repeats, binding sites for beta-catenin, the human discs large protein, microtubules, and other proteins of unknown function. Inactivation of APC in cancer is likely due to loss of function(s) normally associated with the deleted protein structure.
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PMID:The adenomatous polyposis coli (APC) tumor suppressor. 919 22

Members of the Ikaros multigene family of zinc finger proteins are expressed in a tissue-specific manner and most are critical determinants in the development of both the B and T lymphocytes as well as NK and dendritic APC lineages. A PCR amplification strategy that is based on regions of shared sequence identity in Ikaros multigene family members found in mammals and several other vertebrates has led to the recovery of cDNAs that represent the orthologues of Ikaros, Aiolos, Helios, and Eos in Raja eglanteria (clearnose skate), a cartilaginous fish that is representative of an early divergence event in the phylogenetic diversification of the vertebrates. The tissue-specific patterns of expression for at least two of the four Ikaros family members in skate resemble the patterns observed in mammals, i.e., in hematopoietic tissues. Prominent expression of Ikaros in skate also is found in the lymphoid Leydig organ and epigonal tissues, which are unique to cartilaginous fish. An Ikaros-related gene has been identified in Petromyzon marinus (sea lamprey), a jawless vertebrate species, in which neither Ig nor TCRs have been identified. In addition to establishing a high degree of evolutionary conservation of the Ikaros multigene family from cartilaginous fish through mammals, these studies define a possible link between factors that regulate the differentiation of immune-type cells in the jawed vertebrates and related factors of unknown function in jawless vertebrates.
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PMID:Members of the Ikaros gene family are present in early representative vertebrates. 1086 Oct 66

A probe based on the sequence of the gene encoding selenoprotein A of glycine reductase of Clostridium sticklandii was used to obtain clones of adjacent DNA that encoded the other components of glycine reductase, proteins B and C, in addition to thioredoxin and thioredoxin reductase. The genes of the thioredoxin system and the glycine reductase were shown to be transcribed together, confirming an operon structure. In addition, a gene (grdX) encoding a 13.7-kDa protein of unknown function seemed to be associated with the reductase genes. Four potential promoters were identified by mapping the 5'-end of the mRNAs. The sequence of promoter P1 was shown to be similar to the sigma70 promoter consensus sequence. The other three promoters were similar to each other, but not to known promoter consensus sequences. The transcripts starting at each of the four promoters were terminated to about 80% at a predicted loop structure downstream of grdB; the remaining transcripts continued through this structure and covered the genes encoding both subunits of protein C and bmpA, a gene that was also expressed monocistronically.
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PMID:Molecular analysis of the grd operon coding for genes of the glycine reductase and of the thioredoxin system from Clostridium sticklandii. 1127 25


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