Protein: Aryl hydrocarbon receptor (Q8R4S2)
Organism: Mus spretus (Western Mediterranean mouse) (Algerian mouse)
Function: Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer. Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation. Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists. Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands. Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1. The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription
Subcellular location: Cytoplasm. Nucleus. Note=Initially cytoplasmic; upon binding with ligand and interaction with a HSP90, it translocates to the nucleus
Sequence: MSSGANITYASRKRRKPVQKTVKPIPAEGIKSNPSKRHRDRLNTELDRLASLLPFPQDVINKLDKLSVLRLSVSYLRAKSFFDVALKSTPADRNGGQDQCRAQIRDWQNLQEGEFLLQALNGFVLVVTADALVFYASSTIQDYLGFQQSDVIHQSVYELIHTEDRAEFQRQLHWALNPSQCTDSAQGVDEAHGPPQAAVYYTPDQLPPENASFMERCFRCRLRCLLDNSSGFLAMNFQGRLKYLHGQNKKGKDGALLPPQLALFAIATPLQPPSILEIRTKNFIFRTKHKLDFTPIGCDAKGQLILGYTEVELCTRGSGYQFIHAADMLHCAESHIRMIKTGESGMTVFRLLAKHSRWRWVQSNARLIYRNGRPDYIIATQRPLTDEEGREHLQKRSMSLPFMFATGEAVLYEISSPFSPIMDPLPIRTKSNTSRKDWAPQSTPSKDSFHPSSLMSALIQQDESIYLCPPSSPAPLDSHFLMGSVSKCGSWQDSFAATGSEAALKHEQIGHAQDVNLALSGGPSELFPDNKNNDLYSIMRDLGIDFEDIRSMQNEEFFRTDSTAAAAGEVDFKDIDITDEILTYVQDSLNNSTLLNSACQQQPVTQHLSCMLQERLQLEQQQQLQQPPPQALEPQQQLCQMVCPQQDLGPKHTQINGTFASWNPTPPVSFNCPQQELKHYQIFSSLQGTAQEFPYKPEVDSVPYTQNFAPCNQPLLPEHSKSVQLDFPGRDFEPSLHPTTSNLDFVSCLQVPENQSHGINSQSAMVSPQAYYAGAMSMYQCQPGPQRTPVDQTQYGSEIPGSQAFLSKVQSRGVFNETYSSDLSSIGHAAQTTGHLHHLAEARPLPDITPGGFL
InterPro domains: - IPR036638: Helix-loop-helix DNA-binding domain superfamily (homologous_superfamily) [30-80]
- IPR035965: PAS domain superfamily (homologous_superfamily) [120-386]
- IPR033348: Aryl hydrocarbon receptor, basic helix-loop-helix domain (domain) [27-87]
- IPR013767: PAS fold (domain) [112-184]
- IPR011598: Myc-type, basic helix-loop-helix (bHLH) domain (domain) [26-87]
- IPR000014: PAS domain (domain) [109-384]
- IPR013655: PAS fold-3 (domain) [297-380]
- IPR001610: PAC motif (repeat) [346-387]
- IPR039091: Aryl hydrocarbon receptor/Aryl hydrocarbon receptor repressor (family) [6-806]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0060089 (molecular transducer activity), GO:0005488 (binding), GO:0140110 (transcription regulator activity), GO:0003700 (DNA-binding transcription factor activity), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0038023 (signaling receptor activity), GO:0005515 (protein binding), GO:0008134 (transcription factor binding), GO:0004879 (nuclear receptor activity), GO:0051087 (chaperone binding), GO:0042802 (identical protein binding), GO:0003676 (nucleic acid binding), GO:0031072 (heat shock protein binding), GO:0098531 (ligand-activated transcription factor activity), GO:0005102 (signaling receptor binding), GO:0046983 (protein dimerization activity), GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0051879 (Hsp90 protein binding), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0046982 (protein heterodimerization activity), GO:0140297 (DNA-binding transcription factor binding), GO:0042803 (protein homodimerization activity), GO:0003677 (DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0000976 (transcription cis-regulatory region binding), GO:0061629 (RNA polymerase II-specific DNA-binding transcription factor binding), GO:0003690 (double-stranded DNA binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0042221 (response to chemical), GO:0048522 (positive regulation of cellular process), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0009410 (response to xenobiotic stimulus), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0010033 (response to organic substance), GO:0009891 (positive regulation of biosynthetic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0014070 (response to organic cyclic compound), GO:0051252 (regulation of RNA metabolic process), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0010468 (regulation of gene expression), GO:1902680 (positive regulation of RNA biosynthetic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0045893 (positive regulation of DNA-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)