DHX36

DHX36
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2N16, 2N21
Identifiers
Aliases	DHX36, DDX36, G4R1, MLEL1, RHAU, DEAH-box helicase 36
External IDs	OMIM: 612767; MGI: 1919412; HomoloGene: 6356; GeneCards: DHX36; OMA:DHX36 - orthologs
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3|3 E1 Start 62,468,013 bp End 62,507,004 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm lower lobe of lung pancreatic ductal cell caput epididymis trigeminal ganglion pons external globus pallidus corpus epididymis superficial temporal artery spinal ganglia Top expressed in ventromedial nucleus lateral septal nucleus Rostral migratory stream mammillary body lateral hypothalamus lateral geniculate nucleus maxillary prominence anterior amygdaloid area human fetus cerebellar vermis More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding DNA binding ATP-dependent activity, acting on DNA helicase activity G-quadruplex RNA binding histone deacetylase binding G-quadruplex DNA binding protein binding nucleic acid binding double-stranded RNA binding hydrolase activity ATP binding telomerase RNA binding RNA binding single-stranded DNA binding magnesium ion binding RNA polymerase II cis-regulatory region sequence-specific DNA binding mRNA 3'-UTR binding DNA helicase activity 3'-5' RNA helicase activity mRNA 3'-UTR AU-rich region binding metal ion binding mRNA 5'-UTR binding pre-miRNA binding Cellular component chromosome telomere extracellular exosome cytosol nucleus cytoplasm mitochondrion cytoplasmic stress granule nuclear speck axon dendrite cell projection perikaryon Biological process RNA processing regulation of transcription, DNA-templated ossification response to exogenous dsRNA response to virus transcription, DNA-templated positive regulation of telomere maintenance RNA secondary structure unwinding positive regulation of type I interferon production positive regulation of transcription by RNA polymerase II telomerase RNA stabilization immune system process positive regulation of myeloid dendritic cell cytokine production regulation of transcription by RNA polymerase III regulation of translation multicellular organism development spermatogenesis positive regulation of gene expression negative regulation of translation cell differentiation positive regulation of mRNA 3'-end processing DNA duplex unwinding cellular response to heat cellular response to UV positive regulation of I-kappaB kinase/NF-kappaB signaling regulation of mRNA stability G-quadruplex DNA unwinding innate immune response regulation of embryonic development defense response to virus positive regulation of cardioblast differentiation positive regulation of transcription initiation from RNA polymerase II promoter positive regulation of dendritic spine morphogenesis 3'-UTR-mediated mRNA destabilization positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay positive regulation of hematopoietic progenitor cell differentiation cellular response to arsenite ion positive regulation of telomere maintenance via telomere lengthening positive regulation of intracellular mRNA localization positive regulation of cytoplasmic translation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 170506 72162 Ensembl n/a ENSMUSG00000027770 UniProt Q9H2U1 Q8VHK9 RefSeq (mRNA) NM_020865 NM_001114397 NM_028136 RefSeq (protein) NP_001107869 NP_065916 NP_082412 Location (UCSC) n/a Chr 3: 62.47 – 62.51 Mb PubMed search
Wikidata
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Probable ATP-dependent RNA helicase DHX36 also known as DEAH box protein 36 (DHX36) or MLE-like protein 1 (MLEL1) or G4 resolvase 1 (G4R1) or RNA helicase associated with AU-rich elements (RHAU) is an enzyme that in humans is encoded by the DHX36 gene.

Structure

Structurally, DHX36 is a 1008 amino acid-long modular protein that has been crystallized in a complex with a DNA G-quadruplex. It consists of a ~440-amino acid helicase core comprising all signature motifs of the DEAH/RHA family of helicases with N- and C-terminal flanking regions of ~180 and ~380 amino acids, respectively. Part of the N-terminal flanking region forms an alpha-helix called the DHX36-specific motif, which recognizes the 5'-most G-quadruplex quartet. The OB-fold domain binds to the 3'-most G-tract sugar-phosphate backbone. Like all the DEAH/RHA helicases, the helicase associated domain is located adjacent to the helicase core region and occupies 75% of the C-terminal region.

Function

DEAH/RHA proteins are RNA and DNA helicases typically characterized by low processivity translocation on substrates and the capability to bind/unwind non-canonical nucleic acid secondary structures. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAH/RHA protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division.

DHX36 exhibits a unique ATP-dependent guanine-quadruplex (G4) resolvase activity and specificity for its substrate in vitro. DHX36 displays repetitive unwinding activity as a function of the thermal stability of the G-quadruplex substrate, characteristic of a number of other G-quadruplex resolvases such as the BLM/WRN helicases. DHX36 binds G4-nucleic acid with sub-nanomolar affinity and unwinds G4 structures much more efficiently than double-stranded nucleic acid. Consistent with these biochemical observations, DHX36 was also identified as the major source of tetramolecular RNA-resolving activity in HeLa cell lysates.

Previous work showed that DHX36 associates with mRNAs and re-localises to stress granules (SGs) upon translational arrest induced by various environmental stresses. A region of the first 105 amino acid was shown to be critical for RNA binding and re-localisation to SGs.

Further reading

• Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O (April 2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (2): 143–50. doi:10.1093/dnares/7.2.143. PMID 10819331.
• Fu JJ, Li LY, Lu GX (September 2002). "Molecular cloning and characterization of human DDX36 and mouse Ddx36 genes, new members of the DEAD/H box superfamily". Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao Acta Biochimica et Biophysica Sinica. 34 (5): 655–61. PMID 12198572.
• Tran H, Schilling M, Wirbelauer C, Hess D, Nagamine Y (January 2004). "Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU". Molecular Cell. 13 (1): 101–11. doi:10.1016/S1097-2765(03)00481-7. PMID 14731398.
• Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC (May 2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Analytical Chemistry. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186.
• Brown V, Brown RA, Ozinsky A, Hesselberth JR, Fields S (March 2006). "Binding specificity of Toll-like receptor cytoplasmic domains". European Journal of Immunology. 36 (3): 742–53. doi:10.1002/eji.200535158. PMC 2762736. PMID 16482509.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

External links

• Group Yoshikuni Nagamine homepage
• Group Steven Akman homepage