Disease relevance of IGKV1-16

• The L1 and L2 proteins form icosahedral capsids for progeny virion generation [1].
• The ease with which small virus-like particles may be obtained from L1 expressed in E. coli makes them attractive candidate components of a papillomavirus vaccine [2].
• Here we report two pedigrees with apparently sporadic hydrocephalus in which we demonstrated a disabling mutation in the L1 gene [3].
• A number of clinical studies have implicated the cell adhesion molecule L1 in Hirschsprung's disease [4].
• We have combined image reconstructions from electron cryomicroscopy (cryoEM) of bovine papillomavirus at 9 A resolution with coordinates from the crystal structure of small virus-like particles of the human papillomavirus type 16 L1 protein to generate an atomic model of the virion [5].

Psychiatry related information on IGKV1-16

• Immunohistochemical localization of the cell adhesion molecules Thy-1 and L1 in the human prefrontal cortex patients with schizophrenia, bipolar disorder, and depression [6].
• Thus, there was an influence of Alzheimer and non-Alzheimer dementias and neurodegeneration on L1, whereas age and neurodegeneration influenced NCAM concentrations [7].
• The proteolytic fragments of L1, but not NCAM were also elevated in patients with vascular dementia and dementia of mixed type [7].
• Interest in L1 derives from the fact that mutations in its gene lead to human genetic diseases including mental retardation [8].

High impact information on IGKV1-16

• The LINE-1 (L1) retrotransposon, the most important human mobile element, shapes the genome in many ways [9].
• Thus, our data demonstrate multiple pathways for L1 integration in cultured cells, and show that L1 is not simply an insertional mutagen, but that its retrotransposition can result in significant deletions of genomic sequence [10].
• Human L1 elements are highly abundant poly(A) (non-LTR) retrotransposons whose second open reading frame (ORF2) encodes a reverse transcriptase (RT) [11].
• Purified L1 EN protein (L1 ENp) makes 5'-PO4, 3'-OH nicks in supercoiled plasmids, shows no preference for AP sites, and preferentially cleaves sequences resembling L1 in vivo target sequences [11].
• We propose that L1 EN cleaves the target site for L1 insertion and primes reverse transcription [11].

Chemical compound and disease context of IGKV1-16

• These data suggest that M21 melanoma cells recognize and adhere to L1 through a mechanism that is primarily heterophilic and integrin dependent [12].
• These results suggest that L1cs expressed on glioma cells may play an important role in the adhesion and migration of glioma cells by homophilic binding (probably through the extracellular immunoglobulin C2 domain of L1) and that L1cs participates in tumor invasion along neuronal fibers [13].
• Stopped-flow tryptophan fluorescence under single turnover and pseudo-first-order conditions has been used to investigate the kinetic mechanism of beta-lactam hydrolysis by the Stenotrophomonas maltophilia L1 metallo-beta-lactamase [14].
• The results suggested that reactivity of MAb HPV-16.I23 to L1 protein is lost when leucine 152 of the HPV-16 L1 protein is replaced by phenylalanine [15].
• In an effort to clarify the role of this phenomenon in the regulation and carcinogenicity of HPV-16, 115 clinical samples were studied to establish the methylation patterns of the 19 CpG dinucleotides within the long control region and part of the L1 gene by bisulfite modification, PCR amplification, DNA cloning, and sequencing [16].

Biological context of IGKV1-16

• The major late promoter of adeovirus-2 is located at coordinate 16.45 and initiates synthesis of nuclear precursors that are processed into mRNAs which fall into five 3- co-terminal families, L1-L5 [17].
• L1 mRNA accumulates in the cytoplasm in the presence of cycloheximide, which blocks DNA replication and the onset of the late phase [17].
• This demonstrates that a mutation in a type V collagen gene, COL5A1, results in EDS type I, and shows the involvement of L1 sequences in a constitutional chromosomal translocation [18].
• This implies that precisely the same transcription start site is utilized for early L1 mRNA synthesis as is used during the late stage for L1-L5 late mRNA synthesis [17].
• Sequence analysis and analytical ultracentrifugation suggest that the domain arrangement is a feature of the L1 family of neural cell adhesion molecules related to hemolin [19].

Anatomical context of IGKV1-16

• RESULTS: We show that L1 is expressed by neural crest cells as they colonize the gut [4].
• The calcium binding L1 protein was found to inhibit growth of blood culture isolates of Candida spp and cerebrospinal fluid isolates of Cryptococcus neoformans [20].
• L1-deficient mice show a small but significant reduction in neural crest cell migration at early developmental stages, but the entire gastrointestinal tract is colonized [4].
• The cell adhesion molecule L1 is developmentally regulated in the renal epithelium and is involved in kidney branching morphogenesis [21].
• We show here that L1-EGFP can undergo retrotransposition in vivo and produce fluorescence in mouse testis [22].

Associations of IGKV1-16 with chemical compounds

• Our findings suggest that physiological levels of calcium will impose a hierarchy of integrin binding to L1 such that alphavbeta3 or active alphaIIbbeta3 > alphavbeta1 > alpha5beta1 [23].
• We find evidence for specific positioning of the L1 RNA with the ORF2 protein, probably mediated in part by the polyadenosine portion of L1 RNA [24].
• The L1-stimulated migration was significantly inhibited by antibody that recognizes the immunoglobulin C2-like domain of L1 [13].
• Glutathione S-transferase-Ig2 fusion proteins containing these mutations were used to evaluate their effects on L1 [25].
• Hence, there is a subset of human L1 elements in which methylation is efficiently maintained in asymmetric non-CG sites and further that this non-CG methylation may be part of a wider phenomenon involving hemi-methylation at CG dinucleotides [26].

Analytical, diagnostic and therapeutic context of IGKV1-16

• To delineate the genetic origins of such potentially pathogenic RFs, we adapted the anchored polymerase chain reaction to rapidly clone and characterize the expressed Ig V genes for the L1 and the D1 IgG RFs [27].
• We performed HPV testing of cervicovaginal lavage specimens by gene amplification using polymerase chain reaction with a consensus primer to target the L1 gene region of HPV [28].
• We have shown that mutations in the gene encoding L1 neural cell adhesion molecule result in X-linked hydrocephalus, which enables improved prenatal diagnosis and investigation of the role of this molecule in sporadic cases [3].
• We propose that distal receptor ligation events at the cell-cell interface may induce a conformational change within the L1 ectodomain that culminates in receptor multimerization and integrin recruitment via interaction with the FN3 domain [29].
• L1 exon shuffling potential has been reported in cell culture assays, and two potential L1-mediated exon shuffling events have been identified in the genome [30].

References