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Information on EC 3.6.4.13 - RNA helicase and Organism(s) Mus musculus and UniProt Accession Q62167
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3.6.4.13 RNA helicaseIUBMB Comments
RNA helicases utilize the energy from ATP hydrolysis to unwind RNA. Some of them unwind RNA with a 3' to 5' polarity , other show 5' to 3' polarity . Some helicases unwind DNA as well as RNA [7,8]. May be identical with EC 3.6.4.12 (DNA helicase).
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Word Map
- 3.6.4.13
-
single-stranded
- strand
- viruses
- duplex
- fork
-
retinoic
- nucleic
- chromatin
-
acid-inducible
- mda5
- dsrnas
- ssdna
-
rna-binding
-
stall
-
werner
-
nonstructural
-
bloom
- polyproteins
-
dna-dependent
- primase
-
exonuclease
- replisome
-
spliceosome
-
hexameric
-
minichromosome
-
differentiation-associated
- dengue
-
g-quadruplexes
- eif4g
-
single-molecule
-
unwound
-
replicase
-
restart
-
ifn-stimulated
-
nonsense-mediated
- rpa
- rad51
-
holliday
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polyi:c
- flavivirus
- tfiih
- exoribonuclease
-
ifn-beta
-
d-loops
- pigmentosum
-
cap-dependent
- xeroderma
-
positive-stranded
- pre-rrnas
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overhang
- pharmacology
- medicine
- drug development
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
helicase, rig-i, rna helicase, eif4a, ddx3x, dead-box rna helicase, ns3 helicase, dead-box helicase, ddx21, rna helicase a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DEAD box RNA helicase
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (RNA helix unwinding)
RNA helicases utilize the energy from ATP hydrolysis to unwind RNA. Some of them unwind RNA with a 3' to 5' polarity [3], other show 5' to 3' polarity [8]. Some helicases unwind DNA as well as RNA [7,8]. May be identical with EC 3.6.4.12 (DNA helicase).
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
helicase DDX6 colocalizes with TRIM32 in neural stem cells and neurons and increases the activity of Let-7a. The activation of Let-7a depends on the enzyme's helicase activity
-
-
?
ATP + H2O
ADP + phosphate
the ability of RNA helicases to modulate the structure and thus availability of critical RNA molecules for processing leading to protein expression is the likely mechanism by which RNA helicases contribute to differentiation
-
-
?
ATP + H2O
ADP + phosphate
the ability of RNA helicases to modulate the structure and thus availability of critical RNA molecules for processing leading to protein expression is the likely mechanism by which RNA helicases contribute to differentiation. DDX17 is involved in mRNA splicing
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
helicase DDX6 colocalizes with TRIM32 in neural stem cells and neurons and increases the activity of Let-7a. The activation of Let-7a depends on the enzyme's helicase activity
-
-
?
ATP + H2O
ADP + phosphate
the ability of RNA helicases to modulate the structure and thus availability of critical RNA molecules for processing leading to protein expression is the likely mechanism by which RNA helicases contribute to differentiation
-
-
?
ATP + H2O
ADP + phosphate
the ability of RNA helicases to modulate the structure and thus availability of critical RNA molecules for processing leading to protein expression is the likely mechanism by which RNA helicases contribute to differentiation. DDX17 is involved in mRNA splicing
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TIP5
DHX9 associates with TIP5 independently of RNA. DHX9 requires the association of TIP5 with mature pRNA to bind to rRNA genes. DHX9 binds to rRNA genes only upon ESC differentiation and its activity guides TIP5 to rRNA genes and establishes heterochromatin
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
DHX9 is expressed in both ESCs and differentiated cells, the latter showing a slight increase at mRNA and protein levels
DDX17 transcripts are abundant in rat brains in early embryonic stages and becomes downregulated in late post-natal and adults, suggesting involvement during neuronal differentiation during development of the central nervous system
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the 1 kb fragment (5' to the ATG codon) of GRTH gene contains sequences for androgen regulation of its expression in Leydig cells
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GRTH resides in the nucleus, cytoplasm and chromatoid body of round spermatids
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the expression of GRTH in testicular cells is differentially regulated by its 5' flanking sequence
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
accumulation of DHX9 in nucleoli and its association with rRNA genes only upon ESC
additional information
upon differentiation DHX9 drastically changes its position within the nucleus, and all cells show DHX9 with an exclusive localization within nucleoli and a weak signal in the rest of nucleoplasm
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-
p68 shuttles between the nucleus and the cytoplasm. The nucleocytoplasmic shuttling of p68 is mediated by two nuclear localization signal and two nuclear exporting signal sequence elements. p68 shuttles via a classical RanGTPase dependent pathway
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
mice lacking DDX3X during hematopoiesis show an altered leukocyte composition in bone marrow and spleen and a striking inability to combat infection with Listeria monocytogenes. Mice lacking DDX3X in the hematopoietic system show alterations of bone marrow and splenic cell populations. Alterations in innate immune responses result from decreased effector cell availability and function as well as a sex-dependent impairment of cytokine synthesis. Production of important cytokines such as IL12 or IFNgamma is reduced, DDX3X-deficient macrophages show reduced ability to restrict Listeria monocytogenes growth. Owing to partial redundancy with its close Y chromosomal homologue, DDX3Y, the observed effects differ between mouse sexes. DDX3Y, either alone or together with additional Y-chromosomal genes, partially compensates for the loss of the Ddx3x gene, as homozygous female cells and mice show more severe loss-of-function phenotypes
metabolism
pivotal and sex-specific role for the heterosomal isoforms of the DEAD box RNA helicase DDX3 in the immune system. Mechanism of DDX3X action, redundancy with DDX3Y, overview
physiological function
the RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity, essential contribution of a non-RLR DExD/H RNA helicase to innate immunity. Enzyme DDX3 is an interactor of the S/T kinase TBK1 which regulates the production of type I Interferons (IFN-I), contributions of DDX3X to hematopoiesis. DDX3X is critically involved in enhancing the expression of numerous antimicrobial genes. DDX3X may contribute to sex differences in immunity to pathogens and inflammatory disease. Besides its role in the regulation of the TBK1-IRF3 axis, DDX3X controls the NFkappaB signaling pathway and has a profound impact on inflammatory cytokine production. DDX3Y, either alone or together with additional Y-chromosomal genes, partially compensates for the loss of the Ddx3x gene, as homozygous female cells and mice show more severe loss-of-function phenotypes
evolution
malfunction
metabolism
physiological function
additional information
DHX9 is characterized by two copies of a double-stranded RNA binding domain (DSRM) at the N-terminus, a helicase core domain (HrpA) in the central region, and an RGG-rich region at the carboxyl terminus, which confers both RNA and DNA helicase activities
evolution
DDX5 (p68) and DDX17 (p72) belong to the large family of evolutionarily conserved DEAD box RNA helicases. The regulatory activity of DDX5 and DDX17 in transcription is conserved throughout evolution. Possible evolutionary divergence of the insulation process between drosophila and mammals
evolution
DDX5 (p68) and DDX17 (p72) belong to the large family of evolutionarily conserved DEAD box RNA helicases.The regulatory activity of DDX5 and DDX17 in transcription is conserved throughout evolution. Possible evolutionary divergence of the insulation process between drosophila and mammals
malfunction
conditional ablation of Supv3L1 in adult mice leads to premature aging phenotypes including loss of muscle mass and adipose tissue and severe skin abnormalities
malfunction
embryonic stem cells (ESCs) depleted of DHX9 are unable to differentiate, and this phenotype is reverted by the addition of pRNA, whereas providing IGS-rRNA and pRNA mutants deficient for TIP5 binding are not sufficient. Knockdown of TIP5 does not affect DHX9 levels. NIH 3T3 cells depleted of DHX9 show a reduction in rRNA gene silencing
malfunction
the aberrant expression of DDX5 and/or DDX17 contributes to pathologies such as cancer
metabolism
analysis of lncRNA biogenesis during development and support of a model in which the state of rRNA gene chromatin is part of the regulatory network that controls exit from pluripotency and initiation of differentiation pathways. Critical role of pRNA biogenesis in the establishment of rRNA gene heterochromatin. DHX9 is required for the formation of heterochromatin at rRNA genes through processing of IGS-rRNA into pRNA
metabolism
protein and noncoding RNA partners of DDX5 and DDX17, DDX5/DDX17 and the regulation of gene insulation, overview. DDX5 and DDX17 can regulate alternative splicing through other mechanisms, via a direct effect on the local folding of their targeted transcripts or via the recruitment of RNA binding cofactors
physiological function
plays a critical role in the mitochondrial RNA surveillance and degradation machinery
physiological function
-
the protein plays a very important role in early organ development and maturation, function of the protein in transcriptional regulation and pre-mRNA splicing
physiological function
-
through its export/transport function as a component of mRNP (mRNAs that associate with ribonuclear particles) GRTH is essential to govern the structure of the chromatoid body in spermatids and to maintain systems that may participate in mRNA storage and their processing during spermatogenesis
physiological function
the balance between stem cell maintenance and neuronal differentiation depends on cell-fate determinants such as TRIM32. TRIM32 associates with the RNA-induced silencing complex and increases the activity of microRNAs such as Let-7a. The RNA helicase DDX6 is involved in microRNA regulation. Helicase DDX6 colocalizes with TRIM32 in neural stem cells and neurons and increases the activity of Let-7a. Enzyme DDX6 is necessary and sufficient for neuronal differentiation and it functions in cooperation with TRIM32
physiological function
RNA helicases DDX5 and DDX17 are multitasking proteins that regulate gene expression in different biological contexts through diverse activities. The enzymes are associated with long noncoding RNAs that are key epigenetic regulators, DDX5 and DDX17 may act through modulating the activity of various ribonucleoprotein complexes that could ensure their targeting to specific chromatin loci. Potential roles of DDX5 and DDX17 in the 3D chromatin organization with impact on gene expression at the transcriptional and post-transcriptional levels. DDX5 may also contribute to cancer development by modulating various signaling pathways. Murine Ddx5 and Ddx17 are essential for the early stages of myoblast or osteoblast differentiation through their interaction with master transcription factors Myod or Runx2, respectively. In both cases, Ddx5 is recruited to Myod and Runx2 responsive promoters, and it enhances their transcriptional activity. During myogenesis, one consequence is the induced expression of myogenic microRNAs, myogenic transcription factors (Myog or Mef2c), as well as muscle specific genes. DDX17 and DDX5 are necessary for repressing the expression of a large subset of neuronal genes in undifferentiated neuroblastoma cells, in cooperation with the REST transcription factor. DDX5 and DDX17 interact and synergize with acetyltransferases CBP (CREB-binding protein) and p300 to activate transcription, such as in the context of SMAD3-mediated transcriptional activation. DDX5 and DDX17 interact with the BRG1 chromatin remodeler. In muscle cells, DDX5 and DDX17 recruit BRG1 to MYOD target genes, increasing the chromatin accessibility for the transcription machinery, which helps coactivate MYOD-dependent transcription. DDX5 may be involved in the control of DNA methylation and/or demethylation of CpG dinucleotides, as it interacts with DNA methyltransferase 3 proteins (DNMT3A and B) as well as with thymine DNA glycosylase (TDG). DDX5 is recruited to chromatin along with both DNMT3A/B and TDG proteins at the beginning of each transcription cycle of an ERalpha-responsive promoter. During myogenic differentiation of mouse C2C12 cells, both RNA helicases and steroid nuclear receptor activator RNA (SRA)coactivate the transcription factor MyoD, and the joint overexpression of SRA and Ddx5 stimulates the MyoD-induced conversion of mouse embryonic fibroblasts in skeletal muscle cells. The SRA lncRNA can act as a multimodal scaffold for several complexes, and it can be dynamically regulated by RNA helicases
physiological function
RNA helicases DDX5 and DDX17 are multitasking proteins that regulate gene expression in different biological contexts through diverse activities. The enzymes are associated with long noncoding RNAs that are key epigenetic regulators, DDX5 and DDX17 may act through modulating the activity of various ribonucleoprotein complexes that could ensure their targeting to specific chromatin loci. Potential roles of DDX5 and DDX17 in the 3D chromatin organization with impact on gene expression at the transcriptional and post-transcriptional levels. Murine Ddx5 and Ddx17 are essential for the early stages of myoblast or osteoblast differentiation through their interaction with master transcription factors Myod or Runx2, respectively. In both cases, Ddx5 is recruited to Myod and Runx2 responsive promoters, and it enhances their transcriptional activity. During myogenesis, one consequence is the induced expression of myogenic microRNAs, myogenic transcription factors (Myog or Mef2c), as well as muscle specific genes. DDX17 and DDX5 are necessary for repressing the expression of a large subset of neuronal genes in undifferentiated neuroblastoma cells, in cooperation with the REST transcription factor. DDX5 and DDX17 interact and synergize with acetyltransferases CBP (CREB-binding protein) and p300 to activate transcription, such as in the context of SMAD3-mediated transcriptional activation. DDX5 and DDX17 interact with the BRG1 chromatin remodeler. In muscle cells, DDX5 and DDX17 recruit BRG1 to MYOD target genes, increasing the chromatin accessibility for the transcription machinery, which helps coactivate MYOD-dependent transcription. During myogenic differentiation of mouse C2C12 cells, both RNA helicases and steroid nuclear receptor activator RNA (SRA) coactivate the transcription factor MyoD, and the joint overexpression of SRA and Ddx5 stimulates the MyoD-induced conversion of mouse embryonic fibroblasts in skeletal muscle cells. The SRA lncRNA can act as a multimodal scaffold for several complexes, and it can be dynamically regulated by RNA helicases
physiological function
rRNA genes undergo chromatin changes during mouse embryonic stem cell (ESC) differentiation. The establishment of heterochromatin at rRNA genes depends on the processing of IGS-rRNA into pRNA. The RNA helicase DHX9 is a regulator of pRNA processing. DHX9 binds to rRNA genes only upon ESC differentiation and its activity guides TIP5 to rRNA genes and establishes heterochromatin. The production of mature pRNA is essential since it guides the repressor TIP5 to rRNA genes. The processing of IGS-rRNA into pRNA is impaired in embryonic stem cells (ESCs) and activated only upon differentiation. IGS-rRNA abolishes the process of guiding of repressor TIP5 to rRNA genes. The RNA helicase DHX9 associates with IGS-rRNA and TIP5. DHX9 is required for the formation of heterochromatin at rRNA genes through processing of IGS-rRNA into pRNA. DHX9 requires the association of TIP5 with mature pRNA to bind to rRNA genes
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DDX3X_MOUSE
662
0
73101
Swiss-Prot
other Location (Reliability: 1)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
helicase activity of DDX5 is regulated by phosphorylation and calmodulin binding
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
generation of Ddx3xfl/fl mice, analysis of DDX3X and DDX3Y activity in fibroblasts from gene-targeted mice. Mouse embryonic fibroblasts (MEFs) derived from female Ddx3xfl/fl CreERT2 mice are treated with 4-OHT to delete Ddx3x. Innate immunity of DDX3X-deficient cells and of Ddx3xfl/y Vav-iCre mice is analyzed, overview. Mice lacking DDX3X in hematopoietic cells have reduced numbers of lymphocytes and natural killer cells. Mice lacking DDX3X in the hematopoietic system produce reduced amounts of serum IL-12 and IFNgamma after Listeria monocytogenes infection compromising the immune response of macrophages
additional information
trageting of the enzyme DDX6 with shRNA in N2a cells. Construction of a mutant DDX6 that contains a point mutation within the DEAD box motif II of DDX6 and thus lacks helicase activity, but is still able to coimmunoprecipitate TRIM32
additional information
plasmids and siRNAs are transfected in HEK-293T cells using calcium phosphate protocol. NIH 3T3 mouse fibroblasts, U2OS, and murine embryonic stem cells are transfected with the siRNA, siRNA-mediated depletions and synthetic RNA levels are monitored by quantitative RT-PCR expression analysis 3-4 days post transfection
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of the DEADbox mitif II mutant enzyme in N2a cells leading to reduced Let-7a activity
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
furing development, expression of Supv3L1 begins at the blastocyst stage, becomes widespread and strong in all fetal tissues and cell types, and continues during postnatal growth. Supv3L1 is an developmentally regulated gene, which continues to be expressed in all mature tissues, particularly the rapidly proliferating cells of testes, but also in the brain and sensory organs
GRTH gene expression is transcriptionally upregulated by human chorionic gonadotropin (hCG) via second messenger (cAMP) and androgen in Leydig cells. The expression of GRTH in testicular cells is differentially regulated by its 5' flanking sequence. The 1 kb fragment of GRTH gene (5' to the ATG codon) contains sequences for androgen regulation of its expression in Leydig cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
DDX4 can serve as a useful and highly specific biomarker for the diagnosis of germ cell tumors
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Abdelhaleem, M.
RNA helicases: regulators of differentiation
Clin. Biochem.
38
499-503
2005
Homo sapiens (O00571), Homo sapiens (O15523), Homo sapiens (Q9NQI0), Homo sapiens (Q9UHL0), Homo sapiens, Mus musculus (Q501J6), Mus musculus (Q61656), Mus musculus (Q9QY15), Rattus norvegicus (Q9QY16)
Sato, H.; Tsai-Morris, C.H.; Dufau, M.L.
Relevance of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) in the structural integrity of the chromatoid body during spermatogenesis
Biochim. Biophys. Acta
1803
534-543
2010
Mus musculus
Wang, H.; Gao, X.; Huang, Y.; Yang, J.; Liu, Z.R.
P68 RNA helicase is a nucleocytoplasmic shuttling protein
Cell Res.
19
1388-1400
2009
Mus musculus
Tsai-Morris, C.H.; Sheng, Y.; Gutti, R.; Li, J.; Pickel, J.; Dufau, M.L.
Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) gene: cell-specific expression and transcriptional regulation by androgen in transgenic mouse testis
J. Cell. Biochem.
109
1142-1147
2010
Mus musculus
Paul, E.; Kielbasinski, M.; Sedivy, J.M.; Murga-Zamalloa, C.; Khanna, H.; Klysik, J.E.
Widespread expression of the Supv3L1 mitochondrial RNA helicase in the mouse
Transgenic Res.
19
691-701
2010
Mus musculus (Q80YD1), Mus musculus
Nicklas, S.; Okawa, S.; Hillje, A.L.; Gonzalez-Cano, L.; Del Sol, A.; Schwamborn, J.C.
The RNA helicase DDX6 regulates cell-fate specification in neural stem cells via miRNAs
Nucleic Acids Res.
43
2638-2654
2015
Mus musculus (P54823)
Giraud, G.; Terrone, S.; Bourgeois, C.F.
Functions of DEAD box RNA helicases DDX5 and DDX17 in chromatin organization and transcriptional regulation
BMB Rep.
51
613-622
2018
Drosophila melanogaster, Drosophila melanogaster (P19109), Homo sapiens (P17844), Homo sapiens (Q92841), Mus musculus (Q501J6), Mus musculus (Q61656)
Leone, S.; Baer, D.; Slabber, C.F.; Dalcher, D.; Santoro, R.
The RNA helicase DHX9 establishes nucleolar heterochromatin, and this activity is required for embryonic stem cell differentiation
EMBO Rep.
18
1248-1262
2017
Mus musculus (O70133)
Szappanos, D.; Tschismarov, R.; Perlot, T.; Westermayer, S.; Fischer, K.; Platanitis, E.; Kallinger, F.; Novatchkova, M.; Lassnig, C.; Mueller, M.; Sexl, V.; Bennett, K.L.; Foong-Sobis, M.; Penninger, J.M.; Decker, T.
The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity
PLoS Pathog.
14
e1007397
2018
Mus musculus (Q62167)
EXTERNAL LINKS (specific for EC-Number 3.6.4.13)
Transporter Classification Database (TCDB): 1.I.1.1.3, 1.G.3.1.7, 3.A.18.1.1, 1.A.53.1.5, 1.A.85.1.6, 1.A.53.1.7, 1.G.3.1.2, 1.G.3.1.1, 3.A.22.1.1, 1.A.53.1.11, 1.A.53.1.6
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