Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein (apo) B mRNA editing consists of a C-->U conversion involving the first base of the codon CAA, encoding Gln 2153, to UAA, a stop codon. Editing occurs in the intestine only in most mammals, and in both the liver and intestine in a few mammalian species including mouse. We have cloned the cDNA for the mouse apoB mRNA editing protein, apobec1. Expression of mouse apobec1 cDNA in HepG2 cells results in the editing of the intracellular apoB mRNA. The cDNA predicts a 229-amino acid protein showing 92, 66, and 70% identity to the rat, rabbit, and human proteins, respectively. Based on the estimated values of divergence of apobec1 sequences in terms of the numbers of synonymous and non-synonymous suhstitutions per site, we found that apobec1 is a fairly rapidly evolving protein. Sequence comparison among mammalian apobec1 sequences has permitted the identification of seven conserved regions that may be functionally important for editing activity. We present a phylogenetic tree relating apobec1 sequences to double-stranded RNA adenosine deaminase and other nucleotide/nucleoside deaminases. Northern blot analysis indicates that apobec1 mRNA exists in two different sizes, a approximately 2.2-kilobase (kb) form in small intestine and a approximately 2.4-kb form in liver, spleen, kidney, lung, muscle, and heart. To study the molecular basis for the different sized apobec1 mRNAs, we cloned the apobec1 gene and characterized its exon-intron organization together with the sequences expressed in the hepatic and intestinal mRNA. The mouse apobec1 gene contains 8 exons and spans approximately 25 kb, and is located in chromosome 6. The major hepatic mRNA contains all 8 exons, whereas the major small intestinal mRNA misses the first 3 exons and its transcription is initiated in exon 4. The intestinal mRNA also contains at its 5' end a unique 102-nucleotide piece that is absent in the liver mRNA. We also identified two alternatively spliced hepatic apobec1 mRNAs with different acceptor sites in exon 4. Transient expression studies using promoter-reporter gene constructs in HeLa, Hepa, and Caco-2 cells indicate that the 5'-flanking sequences of the liver mRNA (i.e. upstream of exon 1) have predominantly hepatic promoter activity and the 5'-flanking sequences of the major small intestine mRNA (i.e. upstream of exon 4) have preferential intestinal promoter activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alternative mRNA splicing and differential promoter utilization determine tissue-specific expression of the apolipoprotein B mRNA-editing protein (Apobec1) gene in mice. Structure and evolution of Apobec1 and related nucleoside/nucleotide deaminases. 776 98

The amino acid sequence of MG160, a membrane sialoglycoprotein of the medial cisternae of the rat Golgi apparatus, is more than 90% identical with CFR, a fibroblast growth factor (FGF) binding protein of chicken membranes, and with ESL-1, a ligand for E-selectin of plasma membranes of myeloid cells; furthermore, MG160, isolated by immunoaffinity chromatography from rat brain membranes, binds to basic FGF. The gene for MG160 has been assigned to human chromosome 16q22-23. To characterize this protein further in the human, its cDNA was cloned and sequenced. The protein has a large luminal domain composed of an initial proline-glutamine-rich segment, encoded by an uninterrupted exonic sequence of several CAG-CAA repeats. Expansion of CAG repeats has been implicated in the etiology of several neurodegenerative diseases. The proline-glutamine-rich segment is followed by 16 cysteine-rich repeats that contain five potential asparagine-linked glycosylation sites, which are conserved in the human, rat, mouse, and chicken. The large intralumenal domain of the protein is followed by a single transmembrane domain and a 13-amino-acid cytoplasmic carboxy-terminal tail, which is identical to that in the chicken, rat, and mouse. The overall amino acid identifies between MG160, CFR, and ESL-1 range from 88% to 95%. In several human fetal and adult tissues, three mRNA transcripts for MG160 of 10 kb, 5 kb, and 3.8 kb were identified by Northern blot analysis of poly(A)-selected mRNAs. These transcripts may represent alternatively spliced mRNAs of the protein or mRNAs encoding closely related proteins of the Golgi apparatus and/or plasma membranes.
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PMID:Cloning and sequence analysis of the human MG160, a fibroblast growth factor and E-selectin binding membrane sialoglycoprotein of the Golgi apparatus. 898 26

The cystatin superfamily of cysteine protease inhibitors consists of three major families, including the stefins, cystatins and kininogens. However, the recent identification of several genes that possess sequence similarity with the cystatins but have different gene or protein structures indicates that several new cystatin families or subgroups of families might exist. We previously identified the cystatin-related epididymal spermatogenic (Cres) gene, which is related to the family 2 cystatins but exhibits highly tissue-specific expression in the reproductive tract. In the studies presented here, an analysis of gene structure as well as chromosomal mapping studies suggest that the Cres gene might represent a new subgroup within the family 2 cystatins. Although the Cres gene possesses an additional exon encoding 5' untranslated sequences, its coding exons are similar in size to the three coding exons of the cystatin family 2 genes, and the Cres exon/intron splice junctions occur in identical locations as in the cystatin C gene. Furthermore, chromosomal mapping studies show that the Cres gene co-segregates with the cystatin C gene on mouse chromosome 2. Similar to the cystatin family 2 proteins, the Cres protein possesses the type A and B disulphide loops that are necessary for cystatin folding. Interestingly, Cres protein also possesses half of a type C disulphide loop. Although probably related to the cystatin genes, the Cres gene is distinct in that its promoter contains consensus motifs typical of regulated genes. Finally, reverse transcriptase-mediated PCR studies and the identification of new Cres cDNA clones indicate that the Cres mRNA is alternatively spliced, resulting in two Cres mRNAs that might be involved in the regulation of Cres function.
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PMID:Structure, alternative splicing and chromosomal localization of the cystatin-related epididymal spermatogenic gene. 1022 62