Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several disease loci have been mapped to the Xq21.3-Xq22 region of the human X Chromosome (Chr) including X-linked agammaglobulinemia (XLA), Fabry disease, Alport syndrome, and Pelizaeus Merzbacher disease. Upon cloning of the XLA gene, Bruton's tyrosine kinase (btk), both Fabry disease and XLA were mapped within the same 50- to 70-kb interval. In order to investigate the genomic organization of the region surrounding btk and the Fabry disease gene, alpha-galactosidase A (gla), we constructed a 6-cosmid contig spanning the region from 5' of gla to 3' of btk. Two of these cosmids spanning most of the coding sequence and the upstream region of btk and gla, U237D10 and U230D1, were sequenced by a random shotgun strategy combined with automated sequencing, resulting in 69 kb of contiguous genomic sequence. Sequencing of U237D10 showed btk to be comprised of 19 exons spanning over 35 kb. Sequencing of U230D1 showed that the 3' end of gla is 9 kb from the 5' end of btk and also demonstrated the presence of two additional genes in the region immediately 5' to btk. The surprisingly high gene density is similar to that seen previously only in the human major histocompatibility locus.
 ...
PMID:Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci. 762 84

A regional physical and transcription map involving yeast artificial chromosomes (YACs), cosmids, and cDNAs has been constructed for Xq21.3-q22 around the gene BTK (formerly atk or BPK) defective in X-linked agammaglobulinemia (XLA). With a positional cloning strategy employing direct cDNA selection, novel cDNAs were found to cluster in the region of approximately 100 kb flanking the XLA and alpha-galactosidase A loci. While these widely expressed transcripts are in the area known to contain CpG islands, a less evolutionarily conserved gene, located more than 130 kb distal of DXS178, maps to cosmid clones that could not be digested with rare-cutting restriction enzymes. The presence of transcribed sequences flanking the BTK allowed us to investigate their involvement in complex XLA phenotypes. Southern blot analysis using cDNA clones isolated from this region permitted us to exclude a contiguous deletion syndrome as an underlying defect in three patients with XLA and associated growth hormone deficiency. A single XLA patient with torsion dystonia and cosegregating X-linked deafness has been found with a deletion in the 3' part of BTK extending centromerically into the flanking expressed sequence DXS1274E. This suggests a possible involvement of the DXS1274E in this phenotype. The GenBank accession numbers for novel cDNA sequences are as follows: DXS1269E (L20773), DXS1271E (UO1923), DXS1273E (UO1925), and DXS1274E (UO1922).
 ...
PMID:Isolation of cosmid and cDNA clones in the region surrounding the BTK gene at Xq21.3-q22. 795 28

We have produced physical maps of the proximal part of Xq22, containing the Bruton's tyrosine kinase (BTK) and alpha-galactosidase A (GLA) gene loci, using long range physical mapping techniques and yeast artificial chromosomes (YACs). These maps reveal five previously unidentified CpG islands which could indicate the presence of other genes in this region.
 ...
PMID:Physical mapping in the region of the Bruton's tyrosine kinase and alpha-galactosidase A gene loci in proximal Xq22. 798 38

Xiphophorus fish have been the subject of intensive genetic research for more than 60 yr, primarily because of the availability of a number of interspecific hybrids that are malignant melanoma models with apparently simple oncogene and tumor suppressor gene determinants. The gene map of Xiphophorus is one of the most extensive among nonhuman vertebrates, with about 100 genes assigned to at least 20 independently assorting linkage groups (LGs), as well as more than 250 anonymous DNA sequence markers, providing coverage for most of the genome for genetic mapping studies. This characteristic has resulted in the mapping of a tumor suppressor locus, DIFF, which is one of two genetic determinants of melanoma formation in the best-studied hybrid melanoma, the Gordon-Kosswig melanoma model. The other gene responsible for melanoma formation in this model is a sex-linked tyrosine kinase gene related to EGFR and called Xiphophorus melanoma receptor kinase (Xmrk). The cellular oncogene homologues of the non-receptor tyrosine kinase family orthologous toyes and fyn have also been found to be overexpressed in malignant melanomas of Xiphophorus and may be involved in tumor progression. We report here the map location of a Xiphophorus yes gene, YES1, in LG VI, closest to the EGFR gene and the assignment of a fyn gene homologue to newly designated LG XV, linked to the gene for cytosolic alpha-galactosidase. We also confirmed that an EGFR-related sequence (EGFRL1) that we previously assigned to Xiphophorus LG VI by cross-hybridization to a viral erbB probe was the EGFR orthologue. Our results suggest that the presence of expressed duplicates of members of the tyrosine kinase gene family in teleost fishes may increase the potential number of targets in oncogenic cascades in fish tumor models.
 ...
PMID:Mapping of tyrosine kinase gene family members in a Xiphophorus melanoma model. 968 40