Disease relevance of FAM49B

• X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene [1].
• X-ray crystallographic analysis of these particles at 3.5 A resolution shows that L1 closely resembles VP1 from polyomaviruses [2].
• Gene analysis of L1 neural cell adhesion molecule in prenatal diagnosis of hydrocephalus [3].
• A number of clinical studies have implicated the cell adhesion molecule L1 in Hirschsprung's disease [4].
• We have identified an RNA-dependent DNA polymerase activity in the microsomal fraction of human pluri-potential embryonal carcinoma cells NTera2D1, which are known to express the full length coding strand of the genomic Line-1 (L1) elements [5].

Psychiatry related information on FAM49B

• Mutations in L1 are responsible for a wide spectrum of neurologic abnormalities and mental retardation [6].
• Mutation analysis and association studies of the ubiquitin carboxy-terminal hydrolase L1 gene in Huntington's disease [7].

High impact information on FAM49B

• The LINE-1 (L1) retrotransposon, the most important human mobile element, shapes the genome in many ways [8].
• LINE-1 (L1) retrotransposition continues to impact the human genome, yet little is known about how L1 integrates into DNA [9].
• The breakpoint occurs at 9q34 within COL5A1 intron 24 and interestingly, within a LINE-1 (L1) element at Xp21 [10].
• These results suggest that HSAS is a disorder of neuronal cell migration due to disruption of L1 protein function [11].
• We conclude that this insertion results in reduced transcription of the mutant L1 gene, and leads to the lectinless phenotype [12].

Chemical compound and disease context of FAM49B

• Our in vivo migration study demonstrated the migration of L1 on C6 glioma cells that had been transfected in rat brains [13].
• Mutations in the L1 neural cell adhesion molecule, a transmembrane glycoprotein, cause a spectrum of congenital neurological syndromes, ranging from hydrocephalus to mental retardation [14].
• Binding was not tryptophan synthetase E dependent and was, in general, coincident for the HPV-16 E4 and L1 proteins [15].
• Expression of alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 mRNA in human brain: genes associated with familial Parkinson's disease [16].
• Expression studies of fusion proteins lacking the collagen and N-terminal domains produced in Escherichia coli affirmed that CL-L1 binds mannose weakly [17].

Biological context of FAM49B

• We estimate that 15% to 20% of the human genome, mainly the L1-rich regions, is already covered with contigs larger than 3 Mb [18].
• Human processed pseudogenes are copies of cellular RNAs reverse transcribed and inserted into the nuclear genome by the enzymatic machinery of L1 (LINE1) non-LTR retrotransposons [19].
• Immunoblot analysis showed that expression, proteolytic cleavage, and the glycosylation pattern of L1 protein were regulated during renal development [20].
• Its sequence, localization and biosynthesis are phylogenetically conserved: in the corresponding intron of the human L1 ribosomal protein gene a highly homologous region is found which can be released from the pre-mRNA by a mechanism similar to that described for the amphibian U16 RNA [21].
• The presence of a snoRNA inside an intron of the L1 ribosomal protein gene and the phylogenetic conservation of this gene arrangement suggest an important regulatory/functional link between these two components [21].

Anatomical context of FAM49B

• Leukocyte L1 protein and the cystic fibrosis antigen [22].
• RESULTS: We show that L1 is expressed by neural crest cells as they colonize the gut [4].
• 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].
• By contrast, L1 appeared late in the distal portion of the elongating nephron in the mesenchymally derived epithelium and decreased during postnatal development [20].
• Our results indicate that interactions between mRNAs and L1 proteins seem to occur at free cytoplasmic ribosomes [19].

Associations of FAM49B with chemical compounds

• Here we demonstrate that the sixth immunoglobulin-like domain of human L1 (L1-Ig6) can function as a heterophilic ligand for multiple members of the integrin superfamily including alphavbeta3, alphavbeta1, alpha5beta1, and alphaIIbbeta3 [23].
• This was studied by using both a bovine papillomavirus type 1 L1 cDNA expression vector and a chloramphenicol acetyltransferase expression vector containing a 5' splice site in the 3'UTR [24].
• A neuronal form of the cell adhesion molecule L1 contains a tyrosine-based signal required for sorting to the axonal growth cone [25].
• Here we report the cloning of a cDNA encoding human collectin from liver (CL-L1 (collectin liver 1)) that has typical collectin structural characteristics, consisting of an N-terminal cysteine-rich domain, a collagen-like domain, a neck domain, and a carbohydrate recognition domain [17].
• We suggest, therefore, that the mechanism of hydrolysis of nitrocefin by binuclear metallo-beta-lactamases may be atypical and that cleavage of the beta-lactam amide bond is the rate-determining step for breakdown of the majority of beta-lactam substrates by the L1 enzyme [26].

Other interactions of FAM49B

• Of the 147 genes, 19 have no prior named Unigene cluster designation, and are designated herein as L1 to L19 [27].

Analytical, diagnostic and therapeutic context of FAM49B

• In the adult CD examined by electron microscopy, L1 was not expressed on intercalated cells but was restricted to CD principal cells and to the papilla tall cells [20].
• This type of L1 preparation might be considered as a candidate for a serological test to measure antibodies to conformational virion epitopes and for a vaccine to prevent papillomavirus infection [28].
• Based on UV crosslinking and electrophoretic mobility-shift assays using purified components, we demonstrate here that the ORF1 protein encoded by mouse L1 binds nucleic acids with a strong preference for RNA and other single-stranded nucleic acids [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].
• Splicing of the regulated third intron of the L1 ribosomal protein gene of Xenopus laevis has been studied in vivo by oocyte microinjection of wild-type and mutant SP6 precursor RNAs and in vitro in the heterologous HeLa nuclear extract [31].

References