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Protein

ATP-dependent RNA helicase DDX3X

Gene

DDX3X

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.24 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi200 – 2078ATP
Nucleotide bindingi224 – 2318ATP

GO - Molecular functioni

  • ATPase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • ATP-dependent DNA helicase activity Source: UniProtKB
  • ATP-dependent RNA helicase activity Source: UniProtKB
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • CTPase activity Source: AgBase
  • DNA binding Source: UniProtKB
  • eukaryotic initiation factor 4E binding Source: UniProtKB
  • GTPase activity Source: AgBase
  • mRNA 5'-UTR binding Source: UniProtKB
  • nucleoside-triphosphatase activity Source: AgBase
  • poly(A) binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • ribosomal small subunit binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • RNA stem-loop binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • translation initiation factor binding Source: UniProtKB

GO - Biological processi

  • cellular response to arsenic-containing substance Source: UniProtKB
  • cellular response to osmotic stress Source: UniProtKB
  • chromosome segregation Source: UniProtKB
  • extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
  • innate immune response Source: UniProtKB
  • intracellular signal transduction Source: UniProtKB
  • intrinsic apoptotic signaling pathway Source: UniProtKB
  • mature ribosome assembly Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • negative regulation of protein complex assembly Source: UniProtKB
  • negative regulation of translation Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cell growth Source: UniProtKB
  • positive regulation of chemokine (C-C motif) ligand 5 production Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • positive regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
  • positive regulation of gene expression Source: AgBase
  • positive regulation of interferon-beta production Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of translation Source: UniProtKB
  • positive regulation of translational initiation Source: UniProtKB
  • positive regulation of viral genome replication Source: AgBase
  • protein localization to cytoplasmic stress granule Source: AgBase
  • response to virus Source: UniProtKB
  • RNA secondary structure unwinding Source: UniProtKB
  • stress granule assembly Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • viral process Source: UniProtKB-KW
  • Wnt signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase

Keywords - Biological processi

Apoptosis, Chromosome partition, Host-virus interaction, Immunity, Innate immunity, Ribosome biogenesis, Transcription, Transcription regulation, Translation regulation

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding, RNA-binding

Enzyme and pathway databases

BRENDAi3.6.4.13. 2681.
SIGNORiO00571.

Protein family/group databases

TCDBi1.I.1.1.3. the nuclear pore complex (npc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-dependent RNA helicase DDX3X (EC:3.6.4.13)
Alternative name(s):
DEAD box protein 3, X-chromosomal
DEAD box, X isoform
Helicase-like protein 2
Short name:
HLP2
Gene namesi
Name:DDX3X
Synonyms:DBX, DDX3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:2745. DDX3X.

Subcellular locationi

  • 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 G0 phase and in the cytoplasm during G1/S phase.

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • cytoplasmic stress granule Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • mitochondrial outer membrane Source: UniProtKB-SubCell
  • nuclear speck Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked 102 (MRX102)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. MRX102 features include mild to severe intellectual disability, hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Additionally, patients manifest variable non-neurologic features such as joint hyperlaxity, skin pigmentary abnormalities, cleft lip and/or palate, hearing and visual impairment, and precocious puberty.
See also OMIM:300958
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti214 – 2141I → T in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075731
Natural varianti233 – 2331A → V in MRX102. 1 Publication
Corresponds to variant rs796052223 [ dbSNP | Ensembl ].
VAR_075732
Natural varianti233 – 2331Missing in MRX102. 1 Publication
VAR_075733
Natural varianti235 – 2351L → P in MRX102. 1 Publication
Corresponds to variant rs796052224 [ dbSNP | Ensembl ].
VAR_075734
Natural varianti300 – 3001V → F in MRX102; loss of ATP-dependent RNA helicase activity.
VAR_075735
Natural varianti326 – 3261R → H in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075736
Natural varianti351 – 3511R → Q in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075737
Natural varianti362 – 3621R → C in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075738
Natural varianti376 – 3761R → C in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
Corresponds to variant rs796052231 [ dbSNP | Ensembl ].
VAR_075739
Natural varianti392 – 3921L → P in MRX102. 1 Publication
Corresponds to variant rs796052232 [ dbSNP | Ensembl ].
VAR_075740
Natural varianti417 – 4171Q → P in MRX102. 1 Publication
Corresponds to variant rs796052233 [ dbSNP | Ensembl ].
VAR_075741
Natural varianti475 – 4751R → G in MRX102. 1 Publication
VAR_075742
Natural varianti480 – 4801R → S in MRX102. 1 Publication
VAR_075743
Natural varianti488 – 4881R → H in MRX102. 1 Publication
Corresponds to variant rs796052235 [ dbSNP | Ensembl ].
VAR_075744
Natural varianti507 – 5071I → T in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075745
Natural varianti509 – 5091N → I in MRX102. 1 Publication
VAR_075746
Natural varianti514 – 5141I → T in MRX102. 1 Publication
Corresponds to variant rs796052226 [ dbSNP | Ensembl ].
VAR_075747
Natural varianti534 – 5341R → H in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075748
Natural varianti560 – 5601Missing in MRX102. 1 Publication
VAR_075749
Natural varianti568 – 5681P → L in MRX102. 1 Publication
VAR_075750

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi38 – 381Y → A: Impairs interaction with EIF4E. No effect on translation of HIV-1 RNA; when associated with A-43. 2 Publications
Mutagenesisi43 – 431L → A: Impairs interaction with EIF4E. Fails to induce stress granule assembly and to rescue cell viability after stress. No effect on translation of HIV-1 RNA; when associated with A-38. 2 Publications
Mutagenesisi71 – 711S → A: Reduces total phosphorylation by 60%. No effect on interaction with IKBKE. 1 Publication
Mutagenesisi82 – 832SS → AA: Reduces total phosphorylation by 50%. No effect on interaction with IKBKE. 1 Publication
Mutagenesisi84 – 852FF → AA: Abolishes interaction with VACV protein K7, IRF3 activation and IFN-beta promoter induction. 1 Publication
Mutagenesisi102 – 1021S → A: Reduces total phosphorylation by 30%. Abolishes interaction with IRF3 and fails to enhance IFNB promoter induction. No effect on interaction with IKBKE. 1 Publication
Mutagenesisi102 – 1021S → D: Interacts with IRF3 and enhances IFNB promoter induction. 1 Publication
Mutagenesisi152 – 1521S → A: Reduces total phosphorylation by 60%. No effect on interaction with IKBKE. 1 Publication
Mutagenesisi181 – 1811S → A: Greatly impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-183; A-240 and A-269. 1 Publication
Mutagenesisi183 – 1831S → A: Greatly impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-181; A-240 and A-269. 1 Publication
Mutagenesisi200 – 2001Y → A: No effect on general translation; when associated with A-207; A-230; A-347 and A-348. 1 Publication
Mutagenesisi207 – 2071Q → A: Inhibits translation of HIV-1 RNA. No effect on general translation; when associated with A-200; A-230: A-347 and A-348. 2 Publications
Mutagenesisi230 – 2301K → A: No effect on general translation; when associated with A-200; A-207; A-347 and A-348. 3 Publications
Mutagenesisi230 – 2301K → E: Abolishes ATPase activity and RNA-unwinding activity. Inhibits translation of HIV-1 RNA. 3 Publications
Mutagenesisi240 – 2401S → A: Greatly impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-181; A-183 and A-269. 1 Publication
Mutagenesisi269 – 2691S → A: Greatly impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-181; A-183 and A-240. 1 Publication
Mutagenesisi347 – 3471D → A: No effect on general translation; when associated with A-200; A-207; A-230 and A-348. 1 Publication
Mutagenesisi348 – 3481E → A: No effect on general translation; when associated with A-200; A-207; A-230 and A-347. 2 Publications
Mutagenesisi348 – 3481E → Q: Inhibits translation of HIV-1 RNA. 2 Publications
Mutagenesisi382 – 3821S → L: Abolishes ATPase activity and RNA-unwinding activity. No effect on translation of HIV-1 RNA. 2 Publications
Mutagenesisi429 – 4291S → A: Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-438; A-442; A-456 and A-520. 1 Publication
Mutagenesisi438 – 4381T → A: Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-442; A-456 and A-520. 1 Publication
Mutagenesisi442 – 4421S → A: Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-438; A-456 and A-520. 1 Publication
Mutagenesisi456 – 4561S → A: Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-438; A-442 and A-520. 1 Publication
Mutagenesisi520 – 5201S → A: Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-438; A-442 and A-456. 1 Publication

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

MalaCardsiDDX3X.
MIMi300958. phenotype.
Orphaneti99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA27216.

Chemistry

ChEMBLiCHEMBL5553.

Polymorphism and mutation databases

BioMutaiDDX3X.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources1 Publication
Chaini2 – 662661ATP-dependent RNA helicase DDX3XPRO_0000055009Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources1 Publication
Modified residuei55 – 551N6-acetyllysineBy similarity
Modified residuei82 – 821PhosphoserineCombined sources
Modified residuei86 – 861PhosphoserineCombined sources
Modified residuei90 – 901PhosphoserineCombined sources
Modified residuei102 – 1021Phosphoserine; by IKKE1 Publication
Modified residuei104 – 1041PhosphotyrosineBy similarity
Modified residuei118 – 1181N6-acetyllysineCombined sources
Modified residuei131 – 1311PhosphoserineCombined sources
Modified residuei183 – 1831PhosphoserineCombined sources
Cross-linki215 – 215Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei456 – 4561PhosphoserineBy similarity
Modified residuei594 – 5941PhosphoserineCombined sources
Modified residuei605 – 6051PhosphoserineCombined sources
Modified residuei612 – 6121PhosphoserineCombined sources

Post-translational modificationi

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.3 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO00571.
MaxQBiO00571.
PaxDbiO00571.
PeptideAtlasiO00571.
PRIDEiO00571.

2D gel databases

REPRODUCTION-2DPAGEIPI00215637.
SWISS-2DPAGEO00571.

PTM databases

iPTMnetiO00571.
PhosphoSiteiO00571.
SwissPalmiO00571.

Expressioni

Inductioni

Regulated by the cell cycle. Maximally expressed din the cytoplasm uring G1/S phase and decreased expression during G2/M phase.1 Publication

Gene expression databases

BgeeiENSG00000215301.
CleanExiHS_DDX3X.
ExpressionAtlasiO00571. baseline and differential.
GenevisibleiO00571. HS.

Organism-specific databases

HPAiHPA001648.
HPA005631.

Interactioni

Subunit structurei

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.21 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
P266643EBI-353779,EBI-9209740From a different organism.
P2795811EBI-353779,EBI-6377335From a different organism.
Q99IB89EBI-353779,EBI-6674379From a different organism.
Q9WMX24EBI-353779,EBI-6863754From a different organism.
DDX58O957862EBI-353779,EBI-995350
EIF2S1P051983EBI-353779,EBI-1056162
EIF3BP558845EBI-353779,EBI-366696
EIF3CQ996133EBI-353779,EBI-353741
EIF4G1Q046373EBI-353779,EBI-73711
IKBKEQ141644EBI-353779,EBI-307369
K7RP684676EBI-353779,EBI-8022707From a different organism.
MAVSQ7Z4344EBI-353779,EBI-995373
NCAPHQ150032EBI-353779,EBI-1046410
NXF1Q9UBU95EBI-353779,EBI-398874
PABPC1P1194010EBI-353779,EBI-81531
tatP046084EBI-353779,EBI-6164389From a different organism.
Trpm7Q923J12EBI-353779,EBI-8010314From a different organism.

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • eukaryotic initiation factor 4E binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • translation initiation factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108020. 158 interactions.
DIPiDIP-27551N.
IntActiO00571. 111 interactions.
MINTiMINT-8395017.
STRINGi9606.ENSP00000382840.

Chemistry

BindingDBiO00571.

Structurei

Secondary structure

1
662
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi136 – 1383Combined sources
Helixi144 – 1518Combined sources
Beta strandi161 – 1633Combined sources
Beta strandi168 – 1725Combined sources
Helixi182 – 1843Combined sources
Helixi189 – 19810Combined sources
Helixi205 – 21511Combined sources
Beta strandi220 – 2234Combined sources
Helixi230 – 24516Combined sources
Helixi249 – 2568Combined sources
Beta strandi261 – 2633Combined sources
Beta strandi268 – 2725Combined sources
Helixi276 – 29015Combined sources
Beta strandi297 – 3004Combined sources
Beta strandi302 – 3043Combined sources
Helixi306 – 3138Combined sources
Beta strandi318 – 3225Combined sources
Helixi324 – 3329Combined sources
Beta strandi343 – 3486Combined sources
Helixi349 – 3546Combined sources
Helixi358 – 3658Combined sources
Beta strandi367 – 3693Combined sources
Beta strandi376 – 3838Combined sources
Helixi387 – 39610Combined sources
Beta strandi401 – 4055Combined sources
Turni411 – 4144Combined sources
Beta strandi415 – 4217Combined sources
Helixi424 – 4263Combined sources
Helixi427 – 43711Combined sources
Beta strandi444 – 4496Combined sources
Helixi451 – 46313Combined sources
Beta strandi468 – 4714Combined sources
Beta strandi473 – 4753Combined sources
Helixi477 – 4804Combined sources
Helixi482 – 4887Combined sources
Beta strandi491 – 4988Combined sources
Turni499 – 5013Combined sources
Turni502 – 5043Combined sources
Beta strandi509 – 5179Combined sources
Helixi522 – 5298Combined sources
Beta strandi535 – 5373Combined sources
Beta strandi539 – 5457Combined sources
Helixi547 – 5526Combined sources
Helixi553 – 56210Combined sources
Helixi569 – 5757Combined sources
Helixi578 – 5803Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I4IX-ray2.20A168-582[»]
2JGNX-ray1.91A/B/C409-580[»]
3JRVX-ray1.60C/D/E71-90[»]
4O2CX-ray1.80C2-10[»]
4O2EX-ray1.98C/F2-10[»]
4O2FX-ray1.90C/F3-10[»]
4PX9X-ray2.31A/B/C135-407[»]
4PXAX-ray3.20A135-582[»]
5E7IX-ray2.22A/B/C133-584[»]
5E7JX-ray2.23A133-584[»]
5E7MX-ray2.30A133-584[»]
ProteinModelPortaliO00571.
SMRiO00571. Positions 135-576.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00571.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini211 – 403193Helicase ATP-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini414 – 575162Helicase C-terminalPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 139138Required for TBK1 and IKBKE-dependent IFN-beta activationAdd
BLAST
Regioni2 – 10099Interaction with EIF4EAdd
BLAST
Regioni81 – 9010Required for interaction with VACV protein K7
Regioni100 – 662563Interaction with GSK3BAdd
BLAST
Regioni100 – 11011Required for interaction with IKBKEAdd
BLAST
Regioni250 – 25910Involved in stimulation of ATPase activity by DNA and RNA, nucleic acid binding and unwinding and HIV-1 replication
Regioni260 – 517258Necessary for interaction with XPO1Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi180 – 20829Q motifAdd
BLAST
Motifi347 – 3504DEAD box

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi582 – 66281Gly/Ser-richAdd
BLAST

Sequence similaritiesi

Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0335. Eukaryota.
ENOG410XNTI. LUCA.
GeneTreeiENSGT00770000120531.
HOVERGENiHBG015893.
InParanoidiO00571.
KOiK11594.
PhylomeDBiO00571.
TreeFamiTF300364.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR011545. DEAD/DEAH_box_helicase_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR000629. RNA-helicase_DEAD-box_CS.
IPR014014. RNA_helicase_DEAD_Q_motif.
[Graphical view]
PfamiPF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS00039. DEAD_ATP_HELICASE. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51195. Q_MOTIF. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00571-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSHVAVENAL GLDQQFAGLD LNSSDNQSGG STASKGRYIP PHLRNREATK
60 70 80 90 100
GFYDKDSSGW SSSKDKDAYS SFGSRSDSRG KSSFFSDRGS GSRGRFDDRG
110 120 130 140 150
RSDYDGIGSR GDRSGFGKFE RGGNSRWCDK SDEDDWSKPL PPSERLEQEL
160 170 180 190 200
FSGGNTGINF EKYDDIPVEA TGNNCPPHIE SFSDVEMGEI IMGNIELTRY
210 220 230 240 250
TRPTPVQKHA IPIIKEKRDL MACAQTGSGK TAAFLLPILS QIYSDGPGEA
260 270 280 290 300
LRAMKENGRY GRRKQYPISL VLAPTRELAV QIYEEARKFS YRSRVRPCVV
310 320 330 340 350
YGGADIGQQI RDLERGCHLL VATPGRLVDM MERGKIGLDF CKYLVLDEAD
360 370 380 390 400
RMLDMGFEPQ IRRIVEQDTM PPKGVRHTMM FSATFPKEIQ MLARDFLDEY
410 420 430 440 450
IFLAVGRVGS TSENITQKVV WVEESDKRSF LLDLLNATGK DSLTLVFVET
460 470 480 490 500
KKGADSLEDF LYHEGYACTS IHGDRSQRDR EEALHQFRSG KSPILVATAV
510 520 530 540 550
AARGLDISNV KHVINFDLPS DIEEYVHRIG RTGRVGNLGL ATSFFNERNI
560 570 580 590 600
NITKDLLDLL VEAKQEVPSW LENMAYEHHY KGSSRGRSKS SRFSGGFGAR
610 620 630 640 650
DYRQSSGASS SSFSSSRASS SRSGGGGHGS SRGFGGGGYG GFYNSDGYGG
660
NYNSQGVDWW GN
Length:662
Mass (Da):73,243
Last modified:January 23, 2007 - v3
Checksum:i7074D2B8A6EBBF09
GO
Isoform 2 (identifier: O00571-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     35-51: KGRYIPPHLRNREATKG → S

Note: No experimental confirmation available.
Show »
Length:646
Mass (Da):71,355
Checksum:iA8E9EB966FC6C617
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti50 – 501K → R in AAC51830 (PubMed:9381176).Curated
Sequence conflicti50 – 501K → R in AAC51829 (PubMed:9381176).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti214 – 2141I → T in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075731
Natural varianti233 – 2331A → V in MRX102. 1 Publication
Corresponds to variant rs796052223 [ dbSNP | Ensembl ].
VAR_075732
Natural varianti233 – 2331Missing in MRX102. 1 Publication
VAR_075733
Natural varianti235 – 2351L → P in MRX102. 1 Publication
Corresponds to variant rs796052224 [ dbSNP | Ensembl ].
VAR_075734
Natural varianti294 – 2941R → T in a breast cancer sample; somatic mutation. 1 Publication
VAR_035839
Natural varianti300 – 3001V → F in MRX102; loss of ATP-dependent RNA helicase activity.
VAR_075735
Natural varianti326 – 3261R → H in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075736
Natural varianti351 – 3511R → Q in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075737
Natural varianti362 – 3621R → C in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075738
Natural varianti376 – 3761R → C in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
Corresponds to variant rs796052231 [ dbSNP | Ensembl ].
VAR_075739
Natural varianti392 – 3921L → P in MRX102. 1 Publication
Corresponds to variant rs796052232 [ dbSNP | Ensembl ].
VAR_075740
Natural varianti417 – 4171Q → P in MRX102. 1 Publication
Corresponds to variant rs796052233 [ dbSNP | Ensembl ].
VAR_075741
Natural varianti475 – 4751R → G in MRX102. 1 Publication
VAR_075742
Natural varianti480 – 4801R → S in MRX102. 1 Publication
VAR_075743
Natural varianti488 – 4881R → H in MRX102. 1 Publication
Corresponds to variant rs796052235 [ dbSNP | Ensembl ].
VAR_075744
Natural varianti507 – 5071I → T in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075745
Natural varianti509 – 5091N → I in MRX102. 1 Publication
VAR_075746
Natural varianti514 – 5141I → T in MRX102. 1 Publication
Corresponds to variant rs796052226 [ dbSNP | Ensembl ].
VAR_075747
Natural varianti534 – 5341R → H in MRX102; loss of ATP-dependent RNA helicase activity. 1 Publication
VAR_075748
Natural varianti560 – 5601Missing in MRX102. 1 Publication
VAR_075749
Natural varianti568 – 5681P → L in MRX102. 1 Publication
VAR_075750

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei35 – 5117KGRYI…EATKG → S in isoform 2. 1 PublicationVSP_042830Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U50553 mRNA. Translation: AAB95637.1.
AF061337 mRNA. Translation: AAC34298.1.
AF000983 mRNA. Translation: AAC51830.1.
AF000982 mRNA. Translation: AAC51829.1.
AK291153 mRNA. Translation: BAF83842.1.
AK304689 mRNA. Translation: BAG65460.1.
AL391647 Genomic DNA. Translation: CAI41416.1.
Z93015 Genomic DNA. No translation available.
CH471141 Genomic DNA. Translation: EAW59402.1.
CH471141 Genomic DNA. Translation: EAW59403.1.
CH471141 Genomic DNA. Translation: EAW59404.1.
CH471141 Genomic DNA. Translation: EAW59405.1.
BC011819 mRNA. Translation: AAH11819.1.
CCDSiCCDS43931.1. [O00571-1]
CCDS55404.1. [O00571-2]
RefSeqiNP_001180345.1. NM_001193416.2.
NP_001180346.1. NM_001193417.2. [O00571-2]
NP_001347.3. NM_001356.4. [O00571-1]
UniGeneiHs.728563.
Hs.743263.

Genome annotation databases

EnsembliENST00000399959; ENSP00000382840; ENSG00000215301. [O00571-1]
ENST00000457138; ENSP00000392494; ENSG00000215301. [O00571-2]
ENST00000478993; ENSP00000478443; ENSG00000215301. [O00571-1]
ENST00000629496; ENSP00000487224; ENSG00000215301. [O00571-1]
ENST00000629785; ENSP00000486516; ENSG00000215301. [O00571-1]
ENST00000630255; ENSP00000486720; ENSG00000215301. [O00571-1]
GeneIDi1654.
KEGGihsa:1654.
UCSCiuc004dfe.4. human. [O00571-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U50553 mRNA. Translation: AAB95637.1.
AF061337 mRNA. Translation: AAC34298.1.
AF000983 mRNA. Translation: AAC51830.1.
AF000982 mRNA. Translation: AAC51829.1.
AK291153 mRNA. Translation: BAF83842.1.
AK304689 mRNA. Translation: BAG65460.1.
AL391647 Genomic DNA. Translation: CAI41416.1.
Z93015 Genomic DNA. No translation available.
CH471141 Genomic DNA. Translation: EAW59402.1.
CH471141 Genomic DNA. Translation: EAW59403.1.
CH471141 Genomic DNA. Translation: EAW59404.1.
CH471141 Genomic DNA. Translation: EAW59405.1.
BC011819 mRNA. Translation: AAH11819.1.
CCDSiCCDS43931.1. [O00571-1]
CCDS55404.1. [O00571-2]
RefSeqiNP_001180345.1. NM_001193416.2.
NP_001180346.1. NM_001193417.2. [O00571-2]
NP_001347.3. NM_001356.4. [O00571-1]
UniGeneiHs.728563.
Hs.743263.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I4IX-ray2.20A168-582[»]
2JGNX-ray1.91A/B/C409-580[»]
3JRVX-ray1.60C/D/E71-90[»]
4O2CX-ray1.80C2-10[»]
4O2EX-ray1.98C/F2-10[»]
4O2FX-ray1.90C/F3-10[»]
4PX9X-ray2.31A/B/C135-407[»]
4PXAX-ray3.20A135-582[»]
5E7IX-ray2.22A/B/C133-584[»]
5E7JX-ray2.23A133-584[»]
5E7MX-ray2.30A133-584[»]
ProteinModelPortaliO00571.
SMRiO00571. Positions 135-576.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108020. 158 interactions.
DIPiDIP-27551N.
IntActiO00571. 111 interactions.
MINTiMINT-8395017.
STRINGi9606.ENSP00000382840.

Chemistry

BindingDBiO00571.
ChEMBLiCHEMBL5553.

Protein family/group databases

TCDBi1.I.1.1.3. the nuclear pore complex (npc) family.

PTM databases

iPTMnetiO00571.
PhosphoSiteiO00571.
SwissPalmiO00571.

Polymorphism and mutation databases

BioMutaiDDX3X.

2D gel databases

REPRODUCTION-2DPAGEIPI00215637.
SWISS-2DPAGEO00571.

Proteomic databases

EPDiO00571.
MaxQBiO00571.
PaxDbiO00571.
PeptideAtlasiO00571.
PRIDEiO00571.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000399959; ENSP00000382840; ENSG00000215301. [O00571-1]
ENST00000457138; ENSP00000392494; ENSG00000215301. [O00571-2]
ENST00000478993; ENSP00000478443; ENSG00000215301. [O00571-1]
ENST00000629496; ENSP00000487224; ENSG00000215301. [O00571-1]
ENST00000629785; ENSP00000486516; ENSG00000215301. [O00571-1]
ENST00000630255; ENSP00000486720; ENSG00000215301. [O00571-1]
GeneIDi1654.
KEGGihsa:1654.
UCSCiuc004dfe.4. human. [O00571-1]

Organism-specific databases

CTDi1654.
GeneCardsiDDX3X.
HGNCiHGNC:2745. DDX3X.
HPAiHPA001648.
HPA005631.
MalaCardsiDDX3X.
MIMi300160. gene.
300958. phenotype.
neXtProtiNX_O00571.
Orphaneti99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA27216.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0335. Eukaryota.
ENOG410XNTI. LUCA.
GeneTreeiENSGT00770000120531.
HOVERGENiHBG015893.
InParanoidiO00571.
KOiK11594.
PhylomeDBiO00571.
TreeFamiTF300364.

Enzyme and pathway databases

BRENDAi3.6.4.13. 2681.
SIGNORiO00571.

Miscellaneous databases

ChiTaRSiDDX3X. human.
EvolutionaryTraceiO00571.
GeneWikiiDDX3X.
GenomeRNAii1654.
PROiO00571.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000215301.
CleanExiHS_DDX3X.
ExpressionAtlasiO00571. baseline and differential.
GenevisibleiO00571. HS.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR011545. DEAD/DEAH_box_helicase_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR000629. RNA-helicase_DEAD-box_CS.
IPR014014. RNA_helicase_DEAD_Q_motif.
[Graphical view]
PfamiPF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS00039. DEAD_ATP_HELICASE. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51195. Q_MOTIF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDDX3X_HUMAN
AccessioniPrimary (citable) accession number: O00571
Secondary accession number(s): A8K538, B4E3E8, O15536
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 190 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.