Disease relevance of ARNTL2

• The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors [1].

High impact information on ARNTL2

• Antisense overexpression of BMAL2 enhances cell proliferation [2].
• Given that BMAL1 and BMAL2 differ in their spatiotemporal distributions, such distinctions may allow intrinsic circadian clocks to modulate the amplitudes of their oscillators, while maintaining circadian periodicity [3].
• These studies revealed that alternative splicing generates BMAL2 isoforms possessing high, medium, low, or no transcriptional activity [4].
• The BMAL2 gene encodes a member of the basic helix-loop-helix PER-ARNT-SIM family of transcription factors, which control diverse physiological processes including circadian rhythms [4].
• Alternative splicing yields novel BMAL2 variants: tissue distribution and functional characterization [4].

Biological context of ARNTL2

• The chromosomal localization of the human BMAL2 gene was determined by fluorescent in situ hybridization to be localized on chromosome 12 at region p12.2-p11 [5].
• In an attempt to better understand how organisms sense environmental changes, we have characterized a novel member of the PAS superfamily, MOP9 (member of PAS superfamily), that maps to human chromosome 12p11.22-11.23 [1].
• There is a lack of correlation between the debrisoquine metabolic ratio (DMR) and either the total plasma clearance of IF (CLIF) or the AUC of the plasma NBP-alkylating activity [6].
• In endothelial cells, the heterodimer of CLIF and CLOCK upregulated the PAI-1 gene expression through E-box sites [7].
• We recently isolated a novel bHLH/PAS protein, CLIF (cycle like factor), by yeast two-hybrid screening of human umbilical endothelial cell cDNA library [7].

Anatomical context of ARNTL2

• RNA analysis revealed that expression of BMAL2 transcripts was restricted to the fetal brain and to the adult liver in human, while human BMAL1 mRNA was expressed in the brain and skeletal muscle [5].
• Importantly, MOP9 is coexpressed with CLOCK in the suprachiasmatic nucleus, the site of the master circadian oscillator in mammals [1].
• In a manner consistent with its role as a biologically relevant partner of these proteins, MOP9 is coexpressed in regions of the brain such as the thalamus, hypothalamus, and amygdala [1].

Associations of ARNTL2 with chemical compounds

• We identified four novel human BMAL2 transcripts that differ by alternative splicing within their NH2-terminal regions [4].
• Sera from 2061 patients were measured by three methods: an enzyme-linked immunosorbent assay (ELISA), an indirect immunofluorescence test with Crithidia luciliae as substrate (CLIF), and the Farr assay, a radioimmunological method based on the ammonium sulfate precipitation of immune complexes [8].

Other interactions of ARNTL2

• The overall identity of BMAL2 polypeptide to that of human BMAL1 is 49% [5].

Analytical, diagnostic and therapeutic context of ARNTL2

• Five different high-titer histone antibody-containing sera were assayed by the Crithidia luciliae indirect immunofluorescence (CLIF) technic [9].
• However, positive results should be confirmed by the CLIF test or preferably by the Farr assay, thus combining sensitivity with specificity [8].

References