ATP-dependent RNA helicase A (DHX9)
The protein contains 1270 amino acids for an estimated molecular weight of 140958 Da.
Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing (PubMed:9111062, PubMed:11416126, PubMed:12711669, PubMed:15355351, PubMed:16680162, PubMed:17531811, PubMed:20669935, PubMed:21561811, PubMed:24049074, PubMed:25062910, PubMed:24990949, PubMed:28221134). Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs) (PubMed:1537828). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes (PubMed:20669935, PubMed:21561811, PubMed:24049074). Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA (PubMed:9111062, PubMed:10198287). Binds also to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A (PubMed:12711669). Plays a role in DNA replication at origins of replication and cell cycle progression (PubMed:24990949 (updated: Dec. 20, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs1049264 |
Biological Process
Alternative mRNA splicing, via spliceosome
Cellular protein-containing complex assembly
Cellular response to exogenous dsRNA
Cellular response to heat
Cellular response to tumor necrosis factor
Circadian rhythm
CRD-mediated mRNA stabilization
DNA duplex unwinding
DNA replication
DNA-templated transcription, termination
DNA-templated viral transcription
G-quadruplex DNA unwinding
Gene expression
Inflammatory response
Innate immune response
MRNA splicing, via spliceosome
MRNA transport
Osteoblast differentiation
Positive regulation of cytoplasmic translation
Positive regulation of DNA repair
Positive regulation of DNA replication
Positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity
Positive regulation of fibroblast proliferation
Positive regulation of gene silencing by miRNA
Positive regulation of inflammatory response
Positive regulation of innate immune response
Positive regulation of interferon-alpha production
Positive regulation of interferon-alpha secretion
Positive regulation of interferon-beta production
Positive regulation of interferon-beta secretion
Positive regulation of interleukin-18 production
Positive regulation of interleukin-6 production
Positive regulation of interleukin-6 secretion
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of polysome binding
Positive regulation of response to cytokine stimulus
Positive regulation of RNA export from nucleus
Positive regulation of transcription by RNA polymerase II
Positive regulation of tumor necrosis factor production
Positive regulation of tumor necrosis factor secretion
Positive regulation of type I interferon production
Positive regulation of viral transcription
Positive regulation of viral translation
Protein localization to cytoplasmic stress granule
Pyroptosis
Regulation of cytoplasmic translation
Regulation of defense response to virus by host
Regulation of mRNA processing
Regulation of transcription by RNA polymerase II
Rhythmic process
RNA processing
RNA secondary structure unwinding
RNA splicing
Small RNA loading onto RISC
Targeting of mRNA for destruction involved in RNA interference
Cellular Component
Actin cytoskeleton
Centrosome
CRD-mediated mRNA stability complex
Cytoplasm
Cytoplasmic ribonucleoprotein granule
Cytosol
Intracellular ribonucleoprotein complex
Membrane
Micro-ribonucleoprotein complex
Nuclear body
Nuclear stress granule
Nucleolus
Nucleoplasm
Nucleus
Perichromatin fibrils
Polysomal ribosome
Polysome
Protein complex
Protein-containing complex
Ribonucleoprotein complex
RISC complex
RISC-loading complex
Molecular Function
3'-5' DNA helicase activity
3'-5' DNA/RNA helicase activity
3'-5' RNA helicase activity
ATP binding
ATP-dependent 3'-5' DNA helicase activity
ATP-dependent 3'-5' DNA/RNA helicase activity
ATP-dependent 3'-5' RNA helicase activity
ATP-dependent DNA helicase activity
ATP-dependent RNA helicase activity
ATPase
Chromatin DNA binding
Core promoter binding
DNA binding
DNA helicase activity
DNA replication origin binding
Double-stranded DNA binding
Double-stranded RNA binding
Importin-alpha family protein binding
Metal ion binding
MRNA binding
Nucleoside-triphosphatase activity
Nucleoside-triphosphate diphosphatase activity
Poly(A) RNA binding
Polysome binding
Promoter-specific chromatin binding
Regulatory region RNA binding
RISC complex binding
RNA binding
RNA helicase activity
RNA polymerase binding
RNA polymerase II cis-regulatory region sequence-specific DNA binding
RNA polymerase II complex binding
RNA polymerase II transcription coactivator activity
RNA polymerase II transcription cofactor activity
RNA polymerase II transcription factor binding
RNA stem-loop binding
Sequence-specific mRNA binding
Single-stranded 3'-5' DNA helicase activity
Single-stranded DNA binding
Single-stranded RNA binding
SiRNA binding
Transcription coactivator activity
Transcription coregulator activity
Triplex DNA binding
The reference OMIM entry for this protein is 603115
Deah box polypeptide 9; dhx9
Dead/h box 9; ddx9
Rna helicase a
Nuclear dna helicase ii; ndhii
CLONING
RNA helicases play important roles in transcription, RNA processing, translation, and RNA replication. DEAD box proteins are putative RNA helicases that have a characteristic Asp-Glu-Ala-Asp (DEAD) box as 1 of 8 highly conserved sequence motifs. See 600396. The Drosophila 'maleless' (MLE) RNA helicase is thought to act as a regulator of X-linked gene expression. Lee and Hurwitz (1992) isolated and characterized human RNA helicase A, an abundant 130-kD nuclear enzyme of HeLa cells that unwinds double-stranded RNA in a 3-prime to 5-prime direction. By screening a HeLa cell expression library with antibodies against RNA helicase A, Lee and Hurwitz (1993) identified cDNAs encoding the enzyme. The predicted 1,279-amino acid protein shares sequence homology with the Drosophila MLE protein and other members of the DEAH subfamily of RNA helicases. The amino acid sequences of MLE and RNA helicase A are 49% identical, and antibodies against MLE recognize RNA helicase A. Northern blot analysis of HeLa cell RNA revealed RNA helicase A expression as a 4.2-kb transcript. Lee et al. (1998) isolated mouse RNA helicase A cDNAs. The predicted mouse and human proteins share 87% identity. Zhang et al. (1995) identified bovine nuclear DNA helicase II (NDHII) as the homolog of human RNA helicase A. Bovine NDHII unwinds both DNA and RNA. Zhang and Grosse (1997) demonstrated that recombinant human RNA helicase A, or NDHII, also unwinds both double-stranded RNA and double-stranded DNA in an ATP-dependent manner. They reported that the protein contains 2 copies of a double-stranded RNA-binding domain at its N terminus, a DEIH helicase core, and a C-terminal RGG box nucleic acid-binding domain. By analysis of mutant proteins, Zhang and Grosse (1997) found that the RNA-binding domains and RGG box influence and regulate RNA helicase A activity. They suggested a model in which RNA helicase A participates in melting of DNA:RNA hybrids, such as those that occur during transcription. Leukophysin (LKP) is a 28-kD protein present in granulated CD8 (see 186910)-positive and CD4 (186940)-positive cytotoxic T lymphocytes and in the U937 monocytic cell line. By immunoscreening a U937 cDNA library, Abdelhaleem et al. (1996) obtained a cDNA encoding LKP. Immunofluorescence microscopy demonstrated the presence of LKP in granzyme A (140050)-negative granules. The deduced 235-amino acid protein contains multiple N-myristoylation sites, a potential N-linked glycosylation site, a potential O-linked glycosylation site, and 6 potential phosphorylation sites. LKP lacks typical RNA-binding domains but is identical to the C terminus of DDX9. Abdelhaleem et al. (1996) concluded that LKP is a component of granule membranes and is most likely a splice variant of DDX9.GENE FUNCTION
Using an affinity purification approach, Robb and Rana (2007) found that RHA associated with small interfering RNA (siRNA), AGO2 (EIF2C2; 606229), TRBP (TARBP2; 605053), and DICER (606241) in the RNA-induced silencing complex (RISC) in human cell lines. RHA specifically interacted with active RISC, and depletion of RHA in cells before programming with siRNA or short hairpin RNA reduced gene silencing due to decreased RISC formation. RHA depletion also reduced recruitment of siRNA to intracellular AGO2, supporting a role for RHA in RISC loading.MAPPING
Lee et al. (1998) stated that the RNA helicase A gene maps to human chromosome 1q25. By analysis of an interspecific back ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603115 was added.