ATP-dependent RNA helicase DDX3X (DDX3X)
The protein contains 662 amino acids for an estimated molecular weight of 73243 Da.
Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132). Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132). CDKN1A up-regulation may be cell-type specific (PubMed:18264132). Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132). Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may pl (updated: Oct. 7, 2020)
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.
- 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.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Cell differentiation
Cellular response to arsenic-containing substance
Cellular response to osmotic stress
Cellular response to virus
Chromosome segregation
DNA duplex unwinding
Extrinsic apoptotic signaling pathway via death domain receptors
Gamete generation
Innate immune response
Intracellular signal transduction
Intrinsic apoptotic signaling pathway
Lipid homeostasis
Mature ribosome assembly
Negative regulation of apoptotic process
Negative regulation of cell growth
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
Negative regulation of intrinsic apoptotic signaling pathway
Negative regulation of NIK/NF-kappaB signaling
Negative regulation of protein-containing complex assembly
Negative regulation of translation
Neutrophil degranulation
Positive regulation of apoptotic process
Positive regulation of canonical Wnt signaling pathway
Positive regulation of cell growth
Positive regulation of chemokine (C-C motif) ligand 5 production
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
Positive regulation of G1/S transition of mitotic cell cycle
Positive regulation of gene expression
Positive regulation of interferon-alpha production
Positive regulation of interferon-beta production
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of NLRP3 inflammasome complex assembly
Positive regulation of protein acetylation
Positive regulation of protein autophosphorylation
Positive regulation of protein K63-linked ubiquitination
Positive regulation of protein serine/threonine kinase activity
Positive regulation of toll-like receptor 7 signaling pathway
Positive regulation of toll-like receptor 8 signaling pathway
Positive regulation of transcription by RNA polymerase II
Positive regulation of translation
Positive regulation of translation in response to endoplasmic reticulum stress
Positive regulation of translational initiation
Positive regulation of viral genome replication
Primary miRNA processing
Protein localization to cytoplasmic stress granule
Response to virus
RNA secondary structure unwinding
Stress granule assembly
Transcription, DNA-templated
Translational initiation
Viral process
Wnt signaling pathway
Cellular Component
Cell leading edge
Centrosome
Cytoplasm
Cytoplasmic stress granule
Cytosol
Extracellular exosome
Extracellular region
Ficolin-1-rich granule lumen
Lamellipodium
Mitochondrial outer membrane
NLRP3 inflammasome complex
Nuclear speck
Nucleolus
Nucleoplasm
Nucleus
P granule
Plasma membrane
Secretory granule lumen
Molecular Function
ATP binding
ATP-dependent DNA helicase activity
ATP-dependent RNA helicase activity
ATPase
Cadherin binding
CTPase activity
DNA binding
DNA helicase activity
Eukaryotic initiation factor 4E binding
Gamma-tubulin binding
GTPase activity
MRNA 5'-UTR binding
MRNA binding
Nucleoside-triphosphatase activity
Poly(A) binding
Poly(A) RNA binding
Protein serine/threonine kinase activator activity
Ribosomal small subunit binding
RNA binding
RNA helicase activity
RNA stem-loop binding
RNA strand annealing activity
Transcription factor binding
Translation initiation factor binding
The reference OMIM entry for this protein is 300160
Dead/h box 3, x-linked; ddx3x
Ddx3
Dbx
CLONING
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. Chung et al. (1995) cloned cDNAs encoding DDX3, a member of the DEAD box protein family. Lahn and Page (1997) identified DDX3, which they called DBX, as 1 of 5 X-linked genes that have homologs located in the nonrecombining region of the Y chromosome (NRY). They determined that these 5 X-linked genes escape X inactivation. Lahn and Page (1997) postulated that these 5 genes are cases in which gene expression is maintained at comparable levels in males and females by preservation of homologous genes on both the X and the NRY, with male and female cells expressing both copies of each gene. Sequence analysis revealed that DBX shares 91% protein sequence identity with DBY (400010), the Y-linked homolog.GENE FUNCTION
A single transcript in its unspliced and spliced forms directs synthesis of all human immunodeficiency virus (HIV)-1 proteins. Although nuclear export of intron-containing cellular transcripts is restricted in mammalian cells, HIV-1 has evolved the viral Rev protein to overcome this restriction for viral transcripts. CRM1 (XPO1; 602559) is a cellular cofactor for Rev-dependent export of intron-containing HIV-1 RNA. Yedavalli et al. (2004) presented evidence that Rev/CRM1 activity uses the ATP-dependent RNA helicase DDX3. They showed that DDX3 is a nucleocytoplasmic shuttling protein that binds CRM1 and localizes to nuclear membrane pores. Knockdown of DDX3 using either antisense vector or dominant-negative mutants suppressed Rev-RRE (Rev response element) function in the export of incompletely spliced HIV-1 RNAs. Yedavalli et al. (2004) concluded that DDX3 is the human RNA helicase that functions in the CRM1 RNA export pathway analogously to the postulated role for Dbp5 (605812) in yeast mRNA export. Cruciat et al. (2013) identified the DEAD box RNA helicase DDX3 as a regulator of the Wnt (see 164820)-beta-catenin (116806) network, where it acts as a regulatory subunit of CK1-epsilon (600863): in a Wnt-dependent manner, DDX3 binds CK1-epsilon and directly stimulates its kinase activity, and promotes phosphorylation of the scaffold protein dishevelled (see 601365). DDX3 is required for Wnt-beta-catenin signaling in mammalian cells and during Xenopus and C. elegans development. Cruciat et al. (2013) concluded that their results suggested that the kinase-stimulatory function extends to other DDX and CK1 members.MAPPING
By fluorescence in situ hybridization, Park et al. (1998) mapped the DDX3X gene to Xp11.3-p11.23. ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
March 3, 2020: 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 300160 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed