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)

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder with multisystemic manifestations caused by heterozygosity for a partial deletion of chromosome band 7q11.23. The breakpoints cluster within regions located approximately 1 cM either side of the elastin (ELN) locus. We have characterized a duplicated region near the common deletion breakpoints, which includes a transcribed gene. The centromeric (C) and telomeric (T) copies are almost identical in the duplicated 3[prime] portions but diverge at their 5[prime]-ends. C-specific 4.3 kb mRNA and T-specific 5.4 kb mRNA are widely expressed in embryonic and adult tissues. The telomeric gene gives rise to several alternatively spliced forms and is deleted in all WBS individuals who have documented ELN deletions. Database searches revealed that this gene encodes BAP-135, a protein phosphorylated by Bruton's tyrosine kinase in B cells, as well as the multifunctional transcription factor TFII-I, hence the gene name GTF2I. The centromeric gene is not deleted in WBS and appears to be a partially truncated expressed pseudogene with no protein product (gene name GTF2IP1). Both loci map to different genomic clone contigs that also contain other deleted and non-deleted loci. A probe from the shared region recognizes a >3 Mb Not I junction fragment that is unique to individuals with the WBS deletion. Therefore, the duplicated region containing GTF2I and GTF2IP1 respectively is located close to the deletion breakpoints and may predispose to unequal meiotic recombination between chromosome 7 homologs and/or to intrachromosomal rearrangements. Hemizygosity for GTF2I may also contribute to the WBS phenotype.
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PMID:A duplicated gene in the breakpoint regions of the 7q11.23 Williams-Beuren syndrome deletion encodes the initiator binding protein TFII-I and BAP-135, a phosphorylation target of BTK. 946 87

We have cloned and characterized Gtf2i, the mouse homolog of human GTF2I (general transcription factor II-I), which encodes BAP-135, a target for Bruton's tyrosine kinase. GTF2I represents the telomeric and functional copy of a duplicated gene flanking the 2-Mb Williams-Beuren syndrome (WBS) common deletion at 7q11.23. GTF2I is deleted in WBS, while a truncated centromeric pseudogene (GTF2IP1) is not deleted. In mouse, there appears to be only a single locus, Gtf2i, which we mapped to mouse chromosome 5 in a region of conserved mouse-human synteny. Gtf2i is 87.7% identical to GTF2I at the nucleotide and 97% at the amino acid level and generates several alternatively spliced transcripts. The gene is widely expressed in adult tissues and equally in all areas of the brain. Gtf2i transcript is detectable in ES cells by RT-PCR and on Northern blots of tissues from 7-dpc embryos. A ubiquitous expression pattern is seen by Northern and tissue in situ hybridization studies of 14-dpc embryos.
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PMID:A mouse single-copy gene, Gtf2i, the homolog of human GTF2I, that is duplicated in the Williams-Beuren syndrome deletion region. 952 69