Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structure of the human leukocyte-common antigen-related molecule (LAR) protein tyrosine phosphatase gene was elucidated using phage and cosmid genomic DNA clones. The LAR gene is composed of 33 exons spanning over 85 kilobase pairs. Exon 2 encodes the signal sequence and the first four amino acids in the mature LAR protein. The three immunoglobulin-like domains are encoded by exons 3-7, and the eight fibronectin type III (Fn-III) domains by exons 8-17. Exons 18-22 encode the juxta-membrane and transmembrane domains, and exons 23-33 encode the two conserved tyrosine phosphatase domains and the entire 3'-untranslated region. Exon 1, which presumably encodes the 5'-untranslated sequence, has not been identified. Reverse transcription-polymerase chain reaction analysis revealed the alternative splicing of a mini-exon (exon 13) in the Fn-III domain 5 of human LAR and other related genes (rat LAR, rat PTP sigma, and human PTP delta). RNase protection analysis showed that the human LAR mRNA in which exon 13 is spliced-out is the major mRNA species in all cell lines examined. Reverse transcription-polymerase chain reaction analysis revealed further alternative splicing of LAR mRNA involving the Fn-III domains 4, 5, 6, and 7 in various combinations. These findings will facilitate the understanding of the physiological functions of the LAR extracellular domain.
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PMID:Genomic organization of the human LAR protein tyrosine phosphatase gene and alternative splicing in the extracellular fibronectin type-III domains. 792 8

RT-PCR was used to examine the expression of LAR (encoding the leukocyte-common antigen-related protein tyrosine phosphatase) in normal human colon mucosa, and colon polyps and tumors. Although the LAR protein was not detected in the colon in a previous immunohistochemical study, amplification of a region of LAR between the most membrane proximal (eighth) fibronectin type-III (FN-III) repeat and the transmembrane domain demonstrated LAR expression in all samples, but showed no difference in expression within matched samples from each patient examined. An additional minor fragment amplified in all reactions was consistently observed in colon and various cell line samples using this and two other LAR-specific sets of primers. Cloning and sequencing of the fragment identified it as deriving from a novel alternatively spliced form of LAR containing a retained intron of 85 bp. This intron encodes an additional 13 amino acids followed by an in-frame stop codon, thus its retention is predicted to give rise to a secreted LAR extracellular region isoform(s). LAR transcripts containing the intron were detected by RNase protection assay of colon samples and were present in most human tissues examined by Northern analysis. A protein in colon tumor extract was recognized by antiserum raised to the intron-encoded sequence. Soluble isoforms of the LAR extracellular immunoglobulin (Ig)-like/FN-III repeat-containing region could have a biological function distinct from those isoforms localized at the cell surface and/or coupled to intracellular phosphatase activity.
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PMID:Novel alternative splicing predicts a secreted extracellular isoform of the human receptor-like protein tyrosine phosphatase LAR. 891 69