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MT000178

UniProt Annotations

Entry Information
Gene NameDEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked
Protein Entry
UniProt ID
SpeciesHuman
Comments
Comment typeDescription
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O00571-1; Sequence=Displayed; Name=2; IsoId=O00571-2; Sequence=VSP_042830; Note=No experimental confirmation available.;
Catalytic Activity ATP + H(2)O = ADP + phosphate.
Function Multifunctional ATP-dependent RNA helicase. The ATPase activity can be stimulated by various ribo- and deoxynucleic acids indicative for a relaxed substrate specificity. In vitro can unwind partially double-stranded DNA with a preference for 5'- single-stranded DNA overhangs. Is involved in several steps of gene expression, such as transcription, mRNA maturation, mRNA export and translation. However, the exact mechanisms are not known and some functions may be specific for a subset of mRNAs. Involved in transcriptional regulation. Can enhance transcription from the CDKN1A/WAF1 promoter in a SP1-dependent manner. Found associated with the E-cadherin promoter and can down-regulate transcription from the promoter. Involved in regulation of translation initiation. Proposed to be involved in positive regulation of translation such as of cyclin E1/CCNE1 mRNA and specifically of mRNAs containing complex secondary structures in their 5'UTRs; these functions seem to require RNA helicase activity. Specifically promotes translation of a subset of viral and cellular mRNAs carrying a 5'proximal stem-loop structure in their 5'UTRs and cooperates with the eIF4F complex. Proposed to act prior to 43S ribosomal scanning and to locally destabilize these RNA structures to allow recognition of the mRNA cap or loading onto the 40S subunit. After association with 40S ribosomal subunits seems to be involved in the functional assembly of 80S ribosomes; the function seems to cover translation of mRNAs with structured and non-structured 5'UTRs and is independent of RNA helicase activity. Also proposed to inhibit cap-dependent translation by competetive interaction with EIF4E which can block the EIF4E:EIF4G complex formation. Proposed to be involved in stress response and stress granule assembly; the function is independent of RNA helicase activity and seems to involve association with EIF4E. May be involved in nuclear export of specific mRNAs but not in bulk mRNA export via interactions with XPO1 and NXF1. Also associates with polyadenylated mRNAs independently of NXF1. Associates with spliced mRNAs in an exon junction complex (EJC)-dependent manner and seems not to be directly involved in splicing. May be involved in nuclear mRNA export by association with DDX5 and regulating its nuclear location. Involved in innate immune signaling promoting the production of type I interferon (IFN-alpha and IFN-beta); proposed to act as viral RNA sensor, signaling intermediate and transcriptional coactivator. Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, plays a role of scaffolding adapter that links IKBKE and IRF3 and coordinates their activation. Also found associated with IFNB promoters; the function is independent of IRF3. Can bind to viral RNAs and via association with MAVS/IPS1 and DDX58/RIG-I is thought to induce signaling in early stages of infection. Involved in regulation of apoptosis. May be required for activation of the intrinsic but inhibit activation of the extrinsic apoptotic pathway. Acts as an antiapoptotic protein through association with GSK3A/B and BIRC2 in an apoptosis antagonizing signaling complex; activation of death receptors promotes caspase-dependent cleavage of BIRC2 and DDX3X and relieves the inhibition. May be involved in mitotic chromosome segregation. Appears to be a prime target for viral manipulations. Hepatitis B virus (HBV) polymerase and possibly vaccinia virus (VACV) protein K7 inhibit IFNB induction probably by dissociating DDX3X from TBK1 or IKBKE. Is involved in hepatitis C virus (HCV) replication; the function may involve the association with HCV core protein. HCV core protein inhibits the IPS1-dependent function in viral RNA sensing and may switch the function from a INFB inducing to a HCV replication mode. Involved in HIV-1 replication. Acts as a cofactor for XPO1-mediated nuclear export of incompletely spliced HIV-1 Rev RNAs. {ECO:0000269|PubMed:10329544, ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:16301996, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20375222, ECO:0000269|PubMed:20657822, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22034099, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23478265}.
Induction Regulated by the cell cycle. Maximally expressed din the cytoplasm uring G1/S phase and decreased expression during G2/M phase. {ECO:0000269|PubMed:22034099}.
Interaction P26664:- (xeno); NbExp=3; IntAct=EBI-353779, EBI-9209740; P27958:- (xeno); NbExp=11; IntAct=EBI-353779, EBI-6377335; Q99IB8:- (xeno); NbExp=9; IntAct=EBI-353779, EBI-6674379; O95786:DDX58; NbExp=2; IntAct=EBI-353779, EBI-995350; P05198:EIF2S1; NbExp=3; IntAct=EBI-353779, EBI-1056162; P55884:EIF3B; NbExp=5; IntAct=EBI-353779, EBI-366696; Q99613:EIF3C; NbExp=3; IntAct=EBI-353779, EBI-353741; Q04637:EIF4G1; NbExp=3; IntAct=EBI-353779, EBI-73711; Q14164:IKBKE; NbExp=4; IntAct=EBI-353779, EBI-307369; P68467:K7R (xeno); NbExp=6; IntAct=EBI-353779, EBI-8022707; Q7Z434:MAVS; NbExp=4; IntAct=EBI-353779, EBI-995373; Q15003:NCAPH; NbExp=2; IntAct=EBI-353779, EBI-1046410; Q9UBU9:NXF1; NbExp=5; IntAct=EBI-353779, EBI-398874; P11940:PABPC1; NbExp=10; IntAct=EBI-353779, EBI-81531;
Ptm Phosphorylated by TBK1; the phosphorylation is required to synergize with TBK1 in IFNB induction. Phosphorylated by IKBKE at Ser-102 after ssRNA viral infection; enhances the induction of INFB promoter by IRF3. The cytoplasmic form is highly phosphorylated in the G1/S phase and much lower phosphorylated in G2/M. {ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:22034099, ECO:0000269|PubMed:23478265}.
Similarity Belongs to the DEAD box helicase family. DDX3/DED1 subfamily. {ECO:0000305}.
Similarity Contains 1 helicase ATP-binding domain. {ECO:0000255|PROSITE-ProRule:PRU00541}.
Similarity Contains 1 helicase C-terminal domain. {ECO:0000255|PROSITE-ProRule:PRU00542}.
Subcellular Location Nucleus speckle. Cytoplasm. Mitochondrion outer membrane. Note=Located predominantly in nuclear speckles and, at low levels, throughout the cytoplasm. Located to the outer side of nuclear pore complexes (NPC). Shuttles between the nucleus and the cytoplasm in a XPO1 and may be also in a NFX1-dependent manner. Associated with polyadenylated mRNAs in the cytoplasm and the nucleus. Predominantly located in nucleus during G(0) phase and in the cytoplasm during G1/S phase.
Subunit Interacts with XPO1, TDRD3, PABPC1, NXF1, EIF3C, MAVS, DDX58 and NCAPH. Interacts with DDX5; the interaction is regulated by the phosphorylation status of both proteins. Interacts with EIF4E; DDX3X competes with EIF4G1/EIF4G3 for interaction with EIF4E. Interacts with IKBKE; the interaction is direct, found to be induced upon virus infection. Interacts (when phosphorylated at Ser-102) with IRF3; the interaction allows the phosphorylation and activation of IRF3 by IKBKE. Interacts with TBK1. Associates with the eukaryotic translation initiation factor 3 (eIF-3) complex. Associates with the 40S ribosome. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Interacts with HCV core protein. Interacts with vaccinia virus (VACV) protein K7. Found in a complex with HIV-1 Rev and XPO1. Interacts (when phosphorylated at Ser-102) with IRF3; the interaction allows the phosphorylation and activation of IRF3 by IKBKE. {ECO:0000269|PubMed:10329544, ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17631897, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18632687, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19913487, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20375222, ECO:0000269|PubMed:20657822, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22034099, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23478265}.