======= DDX17 =======
== Gene Information ==
* **Official Symbol**: DDX17
* **Official Name**: DEAD-box helicase 17
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=10521|10521]]
* **UniProt**: [[https://www.uniprot.org/uniprot/Q92841|Q92841]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=DDX17&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DDX17|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/608469|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: 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 splicesosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an ATPase activated by a variety of RNA species, but not by dsDNA. This protein, and that encoded by DDX5 gene, are more closely related to each other than to any other member of the DEAD box family. This gene can encode multiple isoforms due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) start codon. [provided by RefSeq, Apr 2011].
* **UniProt Summary**: As an RNA helicase, unwinds RNA and alters RNA structures through ATP binding and hydrolysis. Involved in multiple cellular processes, including pre-mRNA splicing, alternative splicing, ribosomal RNA processing and miRNA processing, as well as transcription regulation. Regulates the alternative splicing of exons exhibiting specific features (PubMed:12138182, PubMed:23022728, PubMed:24910439, PubMed:22266867). For instance, promotes the inclusion of AC-rich alternative exons in CD44 transcripts (PubMed:12138182). This function requires the RNA helicase activity (PubMed:12138182, PubMed:23022728, PubMed:24910439, PubMed:22266867). Affects NFAT5 and histone macro-H2A.1/H2AFY alternative splicing in a CDK9- dependent manner (PubMed:26209609, PubMed:22266867). In NFAT5, promotes the introduction of alternative exon 4, which contains 2 stop codons and may target NFAT5 exon 4-containing transcripts to nonsense-mediated mRNA decay, leading to the down-regulation of NFAT5 protein (PubMed:22266867). Affects splicing of mediators of steroid hormone signaling pathway, including kinases that phosphorylates ESR1, such as CDK2, MAPK1 and GSK3B, and transcriptional regulators, such as CREBBP, MED1, NCOR1 and NCOR2. By affecting GSK3B splicing, participates in ESR1 and AR stabilization (PubMed:24275493). In myoblasts and epithelial cells, cooperates with HNRNPH1 to control the splicing of specific subsets of exons (PubMed:24910439). In addition to binding mature mRNAs, also interacts with certain pri-microRNAs, including MIR663/miR-663a, MIR99B/miR-99b, and MIR6087/miR-6087 (PubMed:25126784). Binds pri-microRNAs on the 3' segment flanking the stem loop via the 5'-[ACG]CAUC[ACU]-3' consensus sequence (PubMed:24581491). Required for the production of subsets of microRNAs, including MIR21 and MIR125B1 (PubMed:24581491, PubMed:27478153). May be involved not only in microRNA primary transcript processing, but also stabilization (By similarity). Participates in MYC down-regulation at high cell density through the production of MYC-targeting microRNAs (PubMed:24581491). Along with DDX5, may be involved in the processing of the 32S intermediate into the mature 28S ribosomal RNA (PubMed:17485482). Promoter-specific transcription regulator, functioning as a coactivator or corepressor depending on the context of the promoter and the transcriptional complex in which it exists (PubMed:15298701). Enhances NFAT5 transcriptional activity (PubMed:22266867). Synergizes with TP53 in the activation of the MDM2 promoter; this activity requires acetylation on lysine residues (PubMed:17226766, PubMed:20663877, PubMed:19995069). May also coactivate MDM2 transcription through a TP53-independent pathway (PubMed:17226766). Coactivates MMP7 transcription (PubMed:17226766). Along with CTNNB1, coactivates MYC, JUN, FOSL1 and cyclin D1/CCND1 transcription (PubMed:17699760). Alone or in combination with DDX5 and/or SRA1 non-coding RNA, plays a critical role in promoting the assembly of proteins required for the formation of the transcription initiation complex and chromatin remodeling leading to coactivation of MYOD1-dependent transcription. This helicase-independent activity is required for skeletal muscle cells to properly differentiate into myotubes (PubMed:17011493, PubMed:24910439). During epithelial-to- mesenchymal transition, coregulates SMAD-dependent transcriptional activity, directly controlling key effectors of differentiation, including miRNAs which in turn directly repress its expression (PubMed:24910439). Plays a role in estrogen and testosterone signaling pathway at several levels. Mediates the use of alternative promoters in estrogen-responsive genes and regulates transcription and splicing of a large number of steroid hormone target genes (PubMed:24275493, PubMed:20406972, PubMed:20663877, PubMed:19995069). Contrary to splicing regulation activity, transcriptional coregulation of the estrogen receptor ESR1 is helicase-independent (PubMed:19718048, PubMed:24275493). Plays a role in innate immunity. Specifically restricts bunyavirus infection, including Rift Valley fever virus (RVFV) or La Crosse virus (LACV), but not vesicular stomatitis virus (VSV), in an interferon- and DROSHA-independent manner (PubMed:25126784). Binds to RVFV RNA, likely via structured viral RNA elements (PubMed:25126784). Promotes mRNA degradation mediated by the antiviral zinc-finger protein ZC3HAV1, in an ATPase-dependent manner (PubMed:18334637). {ECO:0000250|UniProtKB:Q501J6, ECO:0000269|PubMed:12138182, ECO:0000269|PubMed:15298701, ECO:0000269|PubMed:17011493, ECO:0000269|PubMed:17226766, ECO:0000269|PubMed:17485482, ECO:0000269|PubMed:17699760, ECO:0000269|PubMed:18334637, ECO:0000269|PubMed:19718048, ECO:0000269|PubMed:19995069, ECO:0000269|PubMed:20406972, ECO:0000269|PubMed:20663877, ECO:0000269|PubMed:22266867, ECO:0000269|PubMed:23022728, ECO:0000269|PubMed:24275493, ECO:0000269|PubMed:24581491, ECO:0000269|PubMed:24910439, ECO:0000269|PubMed:25126784, ECO:0000269|PubMed:26209609, ECO:0000269|PubMed:27478153, ECO:0000305}.
|DEAD|
|Helicase C|
|RNA-dependent ATPase activity|
|alternative mRNA splicing, via spliceosome|
|regulation of skeletal muscle cell differentiation|
|intracellular estrogen receptor signaling pathway|
|miRNA metabolic process|
|myoblast differentiation|
|androgen receptor signaling pathway|
|regulation of skeletal muscle tissue development|
|RNA helicase activity|
|regulation of alternative mRNA splicing, via spliceosome|
|intracellular steroid hormone receptor signaling pathway|
|epithelial to mesenchymal transition|
|gene silencing by RNA|
|regulation of mRNA splicing, via spliceosome|
|steroid hormone mediated signaling pathway|
|regulation of striated muscle tissue development|
|regulation of muscle tissue development|
|regulation of muscle organ development|
|regulation of RNA splicing|
|regulation of mRNA processing|
|gene silencing|
|ribonucleoprotein complex|
|mesenchymal cell differentiation|
|intracellular receptor signaling pathway|
|hormone-mediated signaling pathway|
|cellular response to steroid hormone stimulus|
|defense response to virus|
|rRNA processing|
|mesenchyme development|
|rRNA metabolic process|
|response to virus|
|transcription coactivator activity|
|RNA splicing, via transesterification reactions with bulged adenosine as nucleophile|
|mRNA splicing, via spliceosome|
|ribosome biogenesis|
|RNA splicing, via transesterification reactions|
|response to steroid hormone|
|regulation of mRNA metabolic process|
|ncRNA processing|
|RNA splicing|
|nuclear speck|
|ribonucleoprotein complex biogenesis|
|ncRNA metabolic process|
|muscle structure development|
|mRNA processing|
|cellular response to lipid|
|cellular response to organic cyclic compound|
|cellular response to hormone stimulus|
|mRNA metabolic process|
|response to lipid|
|nucleolus|
|RNA processing|
|response to hormone|
|response to organic cyclic compound|
|defense response to other organism|
|immune effector process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|RNA binding|
|response to endogenous stimulus|
|ATP binding|
|positive regulation of transcription, DNA-templated|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|RNA metabolic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|tissue development|
|regulation of cell differentiation|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|membrane|
|gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp357|Dorsomorphin 5μM R07 exp357]]|1.7|
|[[:results:exp211|AICAR 240μM R05 exp211]]|1.78|
|[[:results:exp107|UMK57 0.6μM R03 exp107]]|1.8|
|[[:results:exp135|MS023 7μM R03 exp135]]|1.85|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|1.95|
|[[:results:exp360|Genistein 15μM R07 exp360]]|2.1|
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|2.26|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 1/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|1/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 3996
* **Expression level (log2 read counts)**: 9.94
{{:chemogenomics:nalm6 dist.png?nolink |}}