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IID00232
UniprotO00571
ProteinATP-dependent RNA helicase DDX3X
GeneDDX3X
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
662
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 2-10 Hetero trimer : P01889
 Evidence X-RAY 4o2c C Reference
       Region 4o2c C 2-10 order
 Evidence X-RAY 4o2e C Reference
       Region 4o2e C 2-10 order
 Evidence X-RAY 4o2e F Reference
       Region 4o2e F 2-10 order
 Evidence X-RAY 4o2f C Reference
       Region 4o2f C 3-10 order
 Evidence X-RAY 4o2f F Reference
       Region 4o2f F 3-10 order
Seqdisorder 5-167
 Evidence CD Reference
       Region 5-167 disorder
Seq 71-90 Hetero pentamer : IID90010Complex
 Evidence X-RAY 3jrv C Reference
       Region 3jrv C 71-80 disorder
       Region 3jrv C 81-89 order
       Region 3jrv C 90-90 disorder
 Evidence X-RAY 3jrv D Reference
       Region 3jrv D 71-81 disorder
       Region 3jrv D 82-88 order
       Region 3jrv D 89-90 disorder
 Evidence X-RAY 3jrv E Reference
       Region 3jrv E 71-81 disorder
       Region 3jrv E 82-86 order
       Region 3jrv E 87-90 disorder
Seq 133-584 Monomer :
 Evidence X-RAY 5e7i B Reference
       Region 5e7i B 133-133 disorder
       Region 5e7i B 134-153 order
       Region 5e7i B 154-165 disorder
       Region 5e7i B 166-256 order
       Region 5e7i B 257-262 disorder
       Region 5e7i B 263-472 order
       Region 5e7i B 473-480 disorder
       Region 5e7i B 481-577 order
       Region 5e7i B 578-584 disorder
 Evidence X-RAY 5e7i A Reference
       Region 5e7i A 133-133 disorder
       Region 5e7i A 134-153 order
       Region 5e7i A 154-163 disorder
       Region 5e7i A 164-256 order
       Region 5e7i A 257-260 disorder
       Region 5e7i A 261-577 order
       Region 5e7i A 578-584 disorder
 Evidence X-RAY 5e7i C Reference
       Region 5e7i C 133-133 disorder
       Region 5e7i C 134-153 order
       Region 5e7i C 154-164 disorder
       Region 5e7i C 165-255 order
       Region 5e7i C 256-262 disorder
       Region 5e7i C 263-575 order
       Region 5e7i C 576-584 disorder
 Evidence X-RAY 5e7j A Reference
       Region 5e7j A 133-154 order
       Region 5e7j A 155-165 disorder
       Region 5e7j A 166-255 order
       Region 5e7j A 256-263 disorder
       Region 5e7j A 264-584 order
 Evidence X-RAY 5e7m A Reference
       Region 5e7m A 133-133 disorder
       Region 5e7m A 134-153 order
       Region 5e7m A 154-165 disorder
       Region 5e7m A 166-255 order
       Region 5e7m A 256-261 disorder
       Region 5e7m A 262-575 order
       Region 5e7m A 576-584 disorder
 Evidence X-RAY 2i4i A Reference
       Region 2i4i A 168-406 order
       Region 2i4i A 407-410 disorder
       Region 2i4i A 411-534 order
       Region 2i4i A 535-536 disorder
       Region 2i4i A 537-580 order
       Region 2i4i A 581-582 disorder
 Evidence X-RAY 4pxa A Reference
       Region 4pxa A 135-576 order
       Region 4pxa A 577-582 disorder
Seq 135-407 Monomer :
 Evidence X-RAY 4px9 A Reference
       Region 4px9 A 135-151 order
       Region 4px9 A 152-162 disorder
       Region 4px9 A 163-407 order
 Evidence X-RAY 4px9 B Reference
       Region 4px9 B 135-151 order
       Region 4px9 B 152-162 disorder
       Region 4px9 B 163-407 order
 Evidence X-RAY 4px9 C Reference
       Region 4px9 C 135-407 order
Seq 409-580 Monomer :
 Evidence X-RAY 2jgn A Reference
       Region 2jgn A 409-410 disorder
       Region 2jgn A 411-438 order
       Region 2jgn A 439-439 disorder
       Region 2jgn A 440-472 order
       Region 2jgn A 473-480 disorder
       Region 2jgn A 481-499 order
       Region 2jgn A 500-505 disorder
       Region 2jgn A 506-576 order
       Region 2jgn A 577-580 disorder
 Evidence X-RAY 2jgn B Reference
       Region 2jgn B 409-439 order
       Region 2jgn B 440-441 disorder
       Region 2jgn B 442-501 order
       Region 2jgn B 502-506 disorder
       Region 2jgn B 507-576 order
       Region 2jgn B 577-580 disorder
 Evidence X-RAY 2jgn C Reference
       Region 2jgn C 409-411 disorder
       Region 2jgn C 412-436 order
       Region 2jgn C 437-437 disorder
       Region 2jgn C 438-439 order
       Region 2jgn C 440-441 disorder
       Region 2jgn C 442-476 order
       Region 2jgn C 477-479 disorder
       Region 2jgn C 480-575 order
       Region 2jgn C 576-580 disorder
SeqProS verified 81-89 Hetero pentamer : IID90010Complex
       Region 3jrv C 81-89 order
       Region 3jrv D 82-88 order
       Region 5-167 disorder
Seqphosphorylation
    612-612 Phosphoserine
    605-605 Phosphoserine
    594-594 Phosphoserine
    543-543 Phosphoserine; by CSNK1E and TBK1; in vitro
    542-542 Phosphothreonine; by TBK1; in vitro
    520-520 Phosphoserine; by TBK1; in vitro
    470-470 Phosphoserine; by CSNK1E; in vitro
    469-469 Phosphothreonine; by CSNK1E; in vitro
    456-456 Phosphoserine; by TBK1; in vitro
    438-438 Phosphothreonine; by TBK1; in vitro
    442-442 Phosphoserine; by TBK1; in vitro
    429-429 Phosphoserine; by CSNK1E and TBK1; in vitro
    269-269 Phosphoserine; by TBK1; in vitro
    240-240 Phosphoserine; by TBK1; in vitro
    183-183 Phosphoserine; by TBK1
    181-181 Phosphoserine; by TBK1; in vitro
    131-131 Phosphoserine
    104-104 Phosphotyrosine
    102-102 Phosphoserine; by IKKE
    90-90 Phosphoserine
    86-86 Phosphoserine
    82-82 Phosphoserine
    612-612 Phosphoserine
    605-605 Phosphoserine
    594-594 Phosphoserine
    543-543 Phosphoserine; by CSNK1E and TBK1; in vitro
    542-542 Phosphothreonine; by TBK1; in vitro
    520-520 Phosphoserine; by TBK1; in vitro
    470-470 Phosphoserine; by CSNK1E; in vitro
    469-469 Phosphothreonine; by CSNK1E; in vitro
    456-456 Phosphoserine; by TBK1; in vitro
    442-442 Phosphoserine; by TBK1; in vitro
    438-438 Phosphothreonine; by TBK1; in vitro
    429-429 Phosphoserine; by CSNK1E and TBK1; in vitro
    269-269 Phosphoserine; by TBK1; in vitro
    240-240 Phosphoserine; by TBK1; in vitro
    183-183 Phosphoserine; by TBK1
    181-181 Phosphoserine; by TBK1; in vitro
    131-131 Phosphoserine
    104-104 Phosphotyrosine
    102-102 Phosphoserine; by IKKE
    90-90 Phosphoserine
    86-86 Phosphoserine
    82-82 Phosphoserine
Seqacetylation
    118-118 N6-acetyllysine
    55-55 N6-acetyllysine
    2-2 N-acetylserine
    118-118 N6-acetyllysine
    55-55 N6-acetyllysine
    2-2 N-acetylserine
 
Prediction
NeProc
Disorder 1-147,254-257,579-662
Order 148-248,262-578
ProS 1-25,36-46,57-147,595-605,610-662
AlphaFold
Disorder 1-37,40-41,44-133,153-163,226-227,253-262,409-411,500-508,535-536,579-662
Order 38-39,42-43,134-152,164-225,228-252,263-408,412-499,509-534,537-578
Pfam Hmmer
PF00270 204-392 7.7e-71
PF00271 460-536 1.3e-37
SEG 54-67 ,70-106 ,581-598 ,600-656
Function
Function in SwissProt
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. Is an allosteric activator of CSNK1E, it stimulates CSNK1E-mediated phosphorylation of DVL2 and is involved in the positive regulation of canonical Wnt signaling (PubMed:23413191).(Microbial infection) 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.