DHX36

DEAH (Asp-Glu-Ala-His) box polypeptide 36
Identifiers
Symbols	DHX36; DDX36; G4R1; KIAA1488; MLEL1; RHAU
External IDs	OMIM: 612767 MGI: 1919412 HomoloGene: 6356 GeneCards: DHX36 Gene
EC number	3.6.4.13
Gene Ontology Molecular function • nucleotide binding • nucleic acid binding • helicase activity • protein binding • ATP binding • ATP-dependent helicase activity • hydrolase activity Cellular component • nucleus • cytoplasm Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	170506	72162
Ensembl	ENSG00000174953	ENSMUSG00000027770
UniProt	Q9H2U1	A0JLR3
RefSeq (mRNA)	NM_001114397.1	NM_028136.2
RefSeq (protein)	NP_001107869.1	NP_082412.2
Location (UCSC)	Chr 3: 153.99 – 154.04 Mb	Chr 3: 62.27 – 62.31 Mb
PubMed search	[1]	[2]

Probable ATP-dependent RNA helicase DHX36 also known as DEAH box protein 36 (DHX36) or MLE-like protein 1 (MLEL1) or G4 resolvase (G4R1) or RNA helicase associated with AU-rich elements (RHAU) is an enzyme that in humans is encoded by the DHX36 gene.^[1][2]

Structure

Structurally, RHAU is a 1008 amino acid-long modular protein. It consists of a ~440-amino acid helicase core comprising all signature motifs of the DEAH-box family of helicases with N- and C-terminal flanking regions of ~180 and ~380 amino acids, respectively. Like all the DEAH-box proteins, the helicase associated domain is located adjacent to the helicase core region and occupies 75 % of the C-terminal region.

Function

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. 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 DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division.^[1]

RHAU exhibits a unique ATP-dependent guanine-quadruplex (G4) resolvase activity and specificity for its substrate in vitro.^[3][4] RHAU 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, RHAU was also identified as the major source of tetramolecular RNA-resolving activity in HeLa cell lysates.

Previous work showed that RHAU associates with mRNAs and re-localises to stress granules (SGs) upon translational arrest induced by various environmental stresses.^[5][6] A region of the first 105 amino acid was shown to be critical for RNA binding and re-localisation to SGs.

References

1. ^ ^{a b} "Entrez Gene: DHX36 DEAH (Asp-Glu-Ala-His) box polypeptide 36". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=170506. 
2. ^ Abdelhaleem M, Maltais L, Wain H (June 2003). "The human DDX and DHX gene families of putative RNA helicases". Genomics 81 (6): 618–22. doi:10.1016/S0888-7543(03)00049-1. PMID 12782131. 
3. ^ Vaughn JP, Creacy SD, Routh ED, Joyner-Butt C, Jenkins GS, Pauli S, Nagamine Y, Akman SA (November 2005). "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. 280 (46): 38117–20. doi:10.1074/jbc.C500348200. PMID 16150737. 
4. ^ Creacy SD, Routh ED, Iwamoto F, Nagamine Y, Akman SA, Vaughn JP (December 2008). "G4 Resolvase 1 Binds Both DNA and RNA Tetramolecular Quadruplex with High Affinity and Is the Major Source of Tetramolecular Quadruplex G4-DNA and G4-RNA Resolving Activity in HeLa Cell Lysates". J. Biol. Chem. 283 (50): 34626–34. doi:10.1074/jbc.M806277200. PMC 2596407. PMID 18842585. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2596407. 
5. ^ Chalupníková K, Lattmann S, Selak N, Iwamoto F, Fujiki Y, Nagamine Y (December 2008). "Recruitment of the RNA helicase RHAU to stress granules via a unique RNA-binding domain". J. Biol. Chem. 283 (50): 35186–98. doi:10.1074/jbc.M804857200. PMID 18854321. 
6. ^ Chalupníková, Kateřina (2008). "Characterizing functional domains of the RNA helicase RHAU involved in subcellular localization and RNA interaction". http://edoc.unibas.ch/866/1/DissB_8509.pdf. ^{[unreliable medical source?]}

Further reading

• Nagase T, Kikuno R, Ishikawa K, et al. (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 Res. 7 (2): 143–50. doi:10.1093/dnares/7.2.143. PMID 10819331. 
• Fu JJ, Li LY, Lu GX (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 34 (5): 655–61. PMID 12198572. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Tran H, Schilling M, Wirbelauer C, et al. (2004). "Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU". Mol. Cell 13 (1): 101–11. doi:10.1016/S1097-2765(03)00481-7. PMID 14731398. 
• Brill LM, Salomon AR, Ficarro SB, et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Vaughn JP, Creacy SD, Routh ED, et al. (2006). "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. 280 (46): 38117–20. doi:10.1074/jbc.C500348200. PMID 16150737. 
• Brown V, Brown RA, Ozinsky A, et al. (2006). "Binding specificity of Toll-like receptor cytoplasmic domains". Eur. J. Immunol. 36 (3): 742–53. doi:10.1002/eji.200535158. PMC 2762736. PMID 16482509. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2762736. 
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948. 

External links

• Group Yoshikuni Nagamine homepage
• Group Steven Akman homepage