The Per-Arnt-Sim (PAS) domain was identified as a 270 amino acid motif that mediates associations between various PAS family transcription factors. Several PAS domain family members have been identified including AhR, Arnt 1, and single-minded proteins (SIM1 and SIM2). The aromatic (aryl) hydrocarbon receptor, AhR, is a ligand dependent transcription factor that interacts with specific DNA sequences termed xenobiotic responsive elements (XREs) to activate several genes including CYP1A1, glutathione S-transferase Ya subunit and DT-diaphorase. The Ah receptor nuclear translocator protein 1 (Arnt 1) is required for ligand-dependent nuclear translocation of the Ah receptor and is also necessary for Ah receptor binding to the XRE element. Both SIM1 and SIM2 inhibit AhR/Arnt dimerization, thus inhibiting transcriptional activation. The SIM genes are thought to be involved in the directing and regionalization of tissues during development and the SIM2 gene, which is located on chromosome 21, is a candidate for the gene responsible for Down syndrome.
Function:
Transcriptional factor that may have pleiotropic effects during embryogenesis and in the adult.
Subunit:
Efficient DNA binding requires dimerization with another bHLH protein. Heterodimer of SIM1 and ARNT.
Subcellular Location:
Nucleus.
Similarity:
Contains 1 basic helix-loop-helix (bHLH) domain.
Contains 1 PAC (PAS-associated SLCterminal) domain.
Contains 2 PAS (PER-ARNT-SIM) domains.
Contains 1 Single-minded SLCterminal domain.
SWISS:
P81133
Gene ID:
6492
Database links:
Entrez Gene: 6492 Human
Entrez Gene: 20464 Mouse
Entrez Gene: 309888 Rat
Omim: 603128 Human
SwissProt: P81133 Human
SwissProt: Q61045 Mouse
Unigene: 520293 Human
Unigene: 4774 Mouse
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