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ARNTL

The protein encoded by this gene is a basic helix-loop-helix protein that forms a heterodimer with CLOCK. This heterodimer binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Defects in this gene have been linked to infertility, problems with gluconeogenesis and lipogenesis, and altered sleep patterns. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]
Protein class

Transcription factors

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Excitatory neurons)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Low cell line specificity

Interaction

Component of the circadian clock oscillator which includes the CRY1/2 proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER1/2/3 proteins (By similarity). Forms a heterodimer with CLOCK (PubMed:9616112, PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and ARNTL/BMAL1 (By similarity). Part of a nuclear complex which also includes RACK1 and PRKCA; RACK1 and PRKCA are recruited to the complex in a circadian manner (By similarity). Interacts with NPAS2 (By similarity). Interacts with EZH2 (By similarity). Interacts with SUMO3 (By similarity). Interacts with SIRT1 (By similarity). Interacts with AHR (PubMed:9079689). Interacts with ID1, ID2 and ID3 (By similarity). Interacts with DDX4 (By similarity). Interacts with OGT (By similarity). Interacts with EED and SUZ12 (By similarity). Interacts with MTA1 (By similarity). Interacts with CIART (PubMed:24385426). Interacts with HSP90 (PubMed:9079689). Interacts with KAT2B and EP300 (PubMed:14645221). Interacts with BHLHE40/DEC1 and BHLHE41/DEC2 (By similarity). Interacts with RELB and the interaction is enhanced in the presence of CLOCK (By similarity). Interacts with PER1, PER2, CRY1 and CRY2 and this interaction requires a translocation to the nucleus (By similarity). Interaction of the CLOCK-ARNTL/BMAL1 heterodimer with PER or CRY inhibits transcription activation (By similarity). Interaction of the CLOCK-ARNTL/BMAL1 with CRY1 is independent of DNA but with PER2 is off DNA (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer interacts with GSK3B (By similarity). Interacts with KDM5A (PubMed:21960634). Interacts with KMT2A; in a circadian manner (By similarity). Interacts with UBE3A (PubMed:24728990). Interacts with PRKCG (By similarity). Interacts with MAGEL2 (By similarity). Interacts with NCOA2 (By similarity). Interacts with THRAP3 (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer interacts with PASD1 (PubMed:25936801). Interacts with PASD1 (PubMed:25936801). Interacts with USP9X (PubMed:29626158). Interacts with PIWIL2 (via PIWI domain) (PubMed:28903391). Interacts with HDAC3 (By similarity). Interacts with HNF4A (PubMed:30530698).

Molecular function

Activator, DNA-binding

More Types Infomation

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