Recombinant Human ATP-dependent DNA/RNA helicase DHX36 (DHX36), partial

Function

Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:16150737, PubMed:18854321, PubMed:20472641, PubMed:21586581). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:14731398, PubMed:18279852, PubMed:21993297, PubMed:22238380, PubMed:25579584). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-DNA and G4-RNA) (PubMed:16150737, PubMed:18842585, PubMed:20472641, PubMed:21586581, PubMed:24369427, PubMed:26195789). Plays a role in genomic integrity (PubMed:22238380). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (PubMed:20472641, PubMed:21149580, PubMed:21846770, PubMed:22238380, PubMed:24151078, PubMed:25579584). Plays a role in transcriptional regulation (PubMed:21586581, PubMed:21993297). Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:21993297). Plays a role in post-transcriptional regulation (PubMed:27940037). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (PubMed:27940037). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (PubMed:24369427, PubMed:26489465). Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression (PubMed:24369427). Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively (PubMed:26489465). Also binds to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (PubMed:14731398, PubMed:18279852). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (PubMed:14731398). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (By similarity). Required for early embryonic development and hematopoiesis. Involved in the regulation of cardioblast differentiation and proliferation during heart development. Involved in spermatogonia differentiation. May play a role in ossification (By similarity)

Subcellular Location

Nucleus; Cytoplasm

Tissue Specificity

Highly expressed in testis

Subunit

Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without dsRNA poly(I:C) ligand stimulation (By similarity). Interacts (via C-terminus) with TICAM1 (via TIR domain) (By similarity). Interacts (via C-terminus) with DDX21; this interaction serves as bridges to TICAM1 (By similarity). Interacts with TERT; this interaction is dependent on the ability of DHX36 to bind to the G-quadruplex RNA (G4-RNA) structure present in the telomerase RNA template component (TERC) (PubMed:21846770). Interacts with DKC1; this interaction is dependent on the ability of DHX36 to bind to the G4-RNA structure present in TERC (PubMed:21846770). Interacts with PARN; this interaction stimulates PARN to enhance uPA mRNA decay (PubMed:14731398). Interacts with EXOSC3; this interaction occurs in a RNase-insensitive manner (PubMed:14731398). Interacts with EXOSC10; this interaction occurs in a RNase-insensitive manner (PubMed:14731398). Interacts with ILF3; this interaction occurs in a RNA-dependent manner (PubMed:14731398). Interacts with ELAVL1; this interaction occurs in an RNA-dependent manner (PubMed:14731398, PubMed:26489465). Interacts with DDX5; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with DDX17; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with HDAC1; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with HDAC3; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with HDAC4 (By similarity). Interacts with AGO1 (PubMed:17932509). Interacts with AGO2 (PubMed:17932509). Interacts with ERCC6 (PubMed:26030138)

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• Vaughn J.P. et al. The DEXH protein product of the DHX36 gene is the major source of tetramolecular quadruplex G4-DNA resolving activity in HeLa cell lysates. — J. Biol. Chem. (2005)