aryl hydrocarbon receptor repressor (AhR repressor, AhRR, AHRR, KIAA1234)

Function: - mediates dioxin toxicity - involved in regulation of cell growth & differentiation - represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT & subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes - represses CYP1A1 by binding the XRE sequence & recruiting ANKRA2, HDAC4 &/or HDAC5 - autoregulates its expression by associating with its own XRE site - interacts with ARNT, ANKRA2, HDAC4 & HDAC5 Structure: - contains 1 basic helix-loop-helix (bHLH) domain - contains 1 PAS (PER-ARNT-SIM) domain Compartment: - cytoplasm, nucleus - predominantly in nuclear compartment - first cytoplasmic, translocates into nucleus upon interaction with ARNT cytoplasm Alternative splicing: named isoforms=3 Expression: - highly expressed in testis, lung, ovary, spleen & pancreas - highly expressed in mononuclear cells (MNCs) from umbilical cord blood - isoform 3 is highly expressed in lung, kidney, spleen & thymus - down-regulated malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, & ovary - induced by 3-methylcholanthrene (3-MC) in MNCs from adults - induced by the heterodimer AHR/ARNT Polymorphism: - Ala-189 allele may be a susceptibility factor for dioxin- related male infertility - homozygosity for Ala-189 is observed in azoospermic individuals at higher frequency than in normozoospermic individuals - Ala-189 might also be associated with susceptibility to & severity of endometriosis

General

DNA-binding protein transcriptional silencer (transcriptional repressor)

Properties

SIZE: entity length = 701 aa MW = 76 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: DNA-binding motif SITE: 16-41 helix-loop-helix NAME: helix-loop-helix SITE: 17-82 FOR-BINDING-VIA: helix-loop-helix PAS domain {112-182} silencer element SITE: 551-701

Database Correlations

OMIM 606517 UniProt A9YTQ3 PFAM correlations

References

UniProt :accession A9YTQ3