DegronMD - Q08211(DHX9)

FUNCTION: 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). Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1 (PubMed:11149922, PubMed:9323138, PubMed:9662397, PubMed:11038348, PubMed:11416126, PubMed:15355351, PubMed:28221134). Binds to the CDKN2A promoter (PubMed:11038348). Plays several roles in post-transcriptional regulation of gene expression (PubMed:28221134, PubMed:28355180). In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes (PubMed:11402034, PubMed:16680162, PubMed:28221134, PubMed:28355180). As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms (By similarity). Acts also as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition (PubMed:28355180). Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA (PubMed:9162007, PubMed:10924507, PubMed:11402034). Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability (PubMed:19029303). Plays a role in mRNA translation (PubMed:28355180). Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs (PubMed:22190748). Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation (PubMed:21247876). Plays also a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process (PubMed:17531811). Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection (PubMed:28636595). This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis (PubMed:28636595). Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus (PubMed:11687588). {ECO:0000250|UniProtKB:O70133, ECO:0000269|PubMed:10198287, ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:11038348, ECO:0000269|PubMed:11149922, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11416126, ECO:0000269|PubMed:11687588, ECO:0000269|PubMed:12711669, ECO:0000269|PubMed:15355351, ECO:0000269|PubMed:1537828, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:20669935, ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:21561811, ECO:0000269|PubMed:22190748, ECO:0000269|PubMed:24049074, ECO:0000269|PubMed:24990949, ECO:0000269|PubMed:25062910, ECO:0000269|PubMed:28221134, ECO:0000269|PubMed:28355180, ECO:0000269|PubMed:28636595, ECO:0000269|PubMed:9111062, ECO:0000269|PubMed:9162007, ECO:0000269|PubMed:9323138, ECO:0000269|PubMed:9662397}.; FUNCTION: (Microbial infection) Plays a role in HIV-1 replication and virion infectivity (PubMed:11096080, PubMed:19229320, PubMed:25149208, PubMed:27107641). Enhances HIV-1 transcription by facilitating the binding of RNA polymerase II holoenzyme to the proviral DNA (PubMed:11096080, PubMed:25149208). Binds (via DRBM domain 2) to the HIV-1 TAR RNA and stimulates HIV-1 transcription of transactivation response element (TAR)-containing mRNAs (PubMed:9892698, PubMed:11096080). Involved also in HIV-1 mRNA splicing and transport (PubMed:25149208). Positively regulates HIV-1 gag mRNA translation, through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Binds (via DRBM domains) to a HIV-1 double-stranded RNA region of the primer binding site (PBS)-segment of the 5'-UTR, and hence stimulates DHX9 incorporation into virions and virion infectivity (PubMed:27107641). Plays also a role as a cytosolic viral MyD88-dependent DNA and RNA sensors in plasmacytoid dendritic cells (pDCs), and hence induce antiviral innate immune responses (PubMed:20696886, PubMed:21957149). Binds (via the OB-fold region) to viral single-stranded DNA unmethylated C-phosphate-G (CpG) oligonucleotide (PubMed:20696886). {ECO:0000269|PubMed:11096080, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:20696886, ECO:0000269|PubMed:21957149, ECO:0000269|PubMed:25149208, ECO:0000269|PubMed:27107641, ECO:0000269|PubMed:9892698}. View more >>

GO - Biological processes (BP): alternative mRNA splicing, via spliceosome [GO:0000380]; cellular response to exogenous dsRNA [GO:0071360]; cellular response to tumor necrosis factor [GO:0071356]; CRD-mediated mRNA stabilization [GO:0070934]; DNA duplex unwinding [GO:0032508]; DNA replication [GO:0006260]; DNA-templated transcription, termination [GO:0006353]; DNA-templated viral transcription [GO:0039695]; G-quadruplex DNA unwinding [GO:0044806]; inflammatory response [GO:0006954]; innate immune response [GO:0045087]; mRNA transport [GO:0051028]; negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay [GO:1900152]; osteoblast differentiation [GO:0001649]; positive regulation of cytoplasmic translation [GO:2000767]; positive regulation of DNA repair [GO:0045739]; positive regulation of DNA replication [GO:0045740]; positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity [GO:2000373]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of gene silencing by miRNA [GO:2000637]; positive regulation of inflammatory response [GO:0050729]; positive regulation of innate immune response [GO:0045089]; positive regulation of interferon-alpha production [GO:0032727]; positive regulation of interferon-beta production [GO:0032728]; positive regulation of interleukin-18 production [GO:0032741]; positive regulation of interleukin-6 production [GO:0032755]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of polysome binding [GO:1905698]; positive regulation of response to cytokine stimulus [GO:0060760]; positive regulation of RNA export from nucleus [GO:0046833]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of tumor necrosis factor production [GO:0032760]; positive regulation of viral transcription [GO:0050434]; positive regulation of viral translation [GO:1904973]; protein-containing complex assembly [GO:0065003]; protein localization to cytoplasmic stress granule [GO:1903608]; pyroptosis [GO:0070269]; regulation of cytoplasmic translation [GO:2000765]; regulation of defense response to virus by host [GO:0050691]; regulation of mRNA processing [GO:0050684]; regulation of transcription by RNA polymerase II [GO:0006357]; rhythmic process [GO:0048511]; RNA secondary structure unwinding [GO:0010501]; small RNA loading onto RISC [GO:0070922]; targeting of mRNA for destruction involved in RNA interference [GO:0030423] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P95H	TCGA-B5-A11E	UCEC	TCGA	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation altering degron motif	0.7694
p.P95H	TCGA-VQ-A8PP	STAD	TCGA	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation altering degron motif	0.7694
p.P95H	DO51774	STAD	ICGC	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation altering degron motif	0.7694
p.P95H	DO41644	UCEC	ICGC	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation altering degron motif	0.7694
p.G1236E	TCGA-B5-A3FA	UCEC	TCGA	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.3056
p.G1236E	DO52402	UCEC	ICGC	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.3056
p.D1233Y	TCGA-BS-A0UF	UCEC	TCGA	DYR	CBL_MET	1233:1235	Mutation altering degron motif	0.7325
p.D1233Y	DO41488	UCEC	ICGC	DYR	CBL_MET	1233:1235	Mutation altering degron motif	0.7325
p.P334H	TCGA-EB-A44R	SKCM	TCGA	PWTSS	DEG_SPOP_SBC_1	341:345	Mutation rewiring degron network	0.1389
p.P334H	DO37754	SKCM	ICGC	PWTSS	DEG_SPOP_SBC_1	341:345	Mutation rewiring degron network	0.1389
p.P95S	TCGA-FR-A8YC	SKCM	TCGA	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation altering degron motif	0.6752
p.P95S	DO50301	SKCM	ICGC	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation altering degron motif	0.6752
p.G1224R	TCGA-GL-7773	KIRP	TCGA	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.0833
p.G1224R	DO20804	KIRP	ICGC	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.0833
p.A101S	DO229028	LICA	ICGC	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation rewiring degron network	0.25
p.S1238I	DO229022	LICA	ICGC	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.25
p.S345I	DO229027	LICA	ICGC	PWTSS	DEG_SPOP_SBC_1	341:345	Mutation altering degron motif	0.7341
p.D93Y	DO229027	LICA	ICGC	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation altering degron motif	0.6214
p.A99S	DO229006	LICA	ICGC	LTDTPDTT	DEG_SCF_FBW7_1	91:98	Mutation rewiring degron network	0.3056
p.N338S	DO50949	LICA	ICGC	PWTSS	DEG_SPOP_SBC_1	341:345	Mutation rewiring degron network	0.25
p.D1233E	DO46961	RECA	ICGC	DYR	CBL_MET	1233:1235	Mutation altering degron motif	0.6758
p.G1243R	SIDM01278	Colorectal Carcinoma	GDSC	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.1111
p.Y1241C	SIDM00323	B-Cell Non-Hodgkin's Lymphoma	GDSC	DYR	CBL_MET	1233:1235	Mutation blocking phosphorylation signal	0.6111
p.Y1241C	ACH-002313	Lymphoma	CCLE	DYR	CBL_MET	1233:1235	Mutation blocking phosphorylation signal	0.6111
p.Y1241C	TK	haematopoietic and lymphoid tissue	COSMIC	DYR	CBL_MET	1233:1235	Mutation blocking phosphorylation signal	0.6111
p.G1228D	SIDM00150	Colorectal Carcinoma	GDSC	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.1944
p.G1228D	ACH-000969	Colon/Colorectal Cancer	CCLE	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.1944
p.G1228D	KM12	large intestine	COSMIC	DYR	CBL_MET	1233:1235	Mutation rewiring degron network	0.1944

DegronMD: protein-targeted degradation, mutation and drug response to degrons

DHX9

UniProt ID: Q08211

Entrez ID: 1660

Protein name: ATP-dependent RNA helicase A (EC 3.6.4.13) (DEAH box protein 9) (DExH-box helicase 9) (Leukophysin) (LKP) (Nuclear DNA helicase II) (NDH II) (RNA helicase A)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for DHX9 in