InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ddx3x

Summary

InnateDB Protein

IDBP-133081.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Ddx3x

Protein Name

DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked

Synonyms

D1Pas1-rs2; Ddx3; Fin14;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000000804

InnateDB Gene

IDBG-133079 (Ddx3x)

Protein Structure

UniProt Annotation

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 (By similarity). {ECO:0000250}.

Subcellular Localization

Nucleus speckle {ECO:0000250}. Cytoplasm {ECO:0000250}. Mitochondrion outer membrane {ECO:0000250}. 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 (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Developmentally regulated.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 21 experimentally validated interaction(s) in this database.
They are also associated with 117 interaction(s) predicted by orthology.

Experimentally validated
Total	21 [view]
Protein-Protein	19 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	117 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003676	nucleic acid binding
GO:0003677	DNA binding
GO:0003723	RNA binding
GO:0004003	ATP-dependent DNA helicase activity
GO:0004004	ATP-dependent RNA helicase activity
GO:0004386	helicase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008134	transcription factor binding
GO:0008143	poly(A) binding
GO:0008190	eukaryotic initiation factor 4E binding
GO:0016887	ATPase activity
GO:0031369	translation initiation factor binding
GO:0035613	RNA stem-loop binding
GO:0043024	ribosomal small subunit binding
GO:0048027	mRNA 5'-UTR binding

Biological Process

GO:0006200	ATP catabolic process
GO:0006351	transcription, DNA-templated
GO:0007059	chromosome segregation
GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors
GO:0009615	response to virus
GO:0010501	RNA secondary structure unwinding
GO:0017148	negative regulation of translation
GO:0030307	positive regulation of cell growth
GO:0031333	negative regulation of protein complex assembly
GO:0032508	DNA duplex unwinding
GO:0034063	stress granule assembly
GO:0035556	intracellular signal transduction
GO:0042256	mature ribosome assembly
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043154	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043280	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045087	innate immune response
GO:0045727	positive regulation of translation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0045948	positive regulation of translational initiation
GO:0071243	cellular response to arsenic-containing substance
GO:0071470	cellular response to osmotic stress
GO:0097193	intrinsic apoptotic signaling pathway
GO:1900087	positive regulation of G1/S transition of mitotic cell cycle
GO:2001243	negative regulation of intrinsic apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005741	mitochondrial outer membrane
GO:0005852	eukaryotic translation initiation factor 3 complex
GO:0010494	cytoplasmic stress granule
GO:0016607	nuclear speck
GO:0022627	cytosolic small ribosomal subunit

Protein Structure and Domains

PDB ID

MGI:103064

InterPro

IPR001650 Helicase, C-terminal
IPR011545 DNA/RNA helicase, DEAD/DEAH box type, N-terminal
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR014014 RNA helicase, DEAD-box type, Q motif
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00271
PF00270

PRINTS

PIRSF

SMART

SM00490
SM00487

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q62167