Q62167 (DDX3X_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-dependent RNA helicase DDX3X
EC=3.6.4.13

Alternative name(s):
D1Pas1-related sequence 2
DEAD box RNA helicase DEAD3
Short name=mDEAD3
DEAD box protein 3, X-chromosomal
Embryonic RNA helicase

Gene names

Name:	Ddx3x
Synonyms:	D1Pas1-rs2, Ddx3, Dead3, Erh

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	662 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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 IFN-beta induction. Also found associated with IFN-beta 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.
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	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. 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 By similarity.
Subcellular location	Nucleus speckle By similarity. Cytoplasm By similarity. Mitochondrion outer membrane By similarity. 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 By similarity.
Tissue specificity	Developmentally regulated.
Developmental stage	Expressed in oocytes. Ubiquitously found in 9 days post-conception embryo, at later stages it is restricted to brain and kidney.
Post-translational modification	Phosphorylated by TBK1; the phosphorylation is required to synergize with TBK1 in IFN-beta induction. Probably also phosphorylated by IKBKE By similarity.
Sequence similarities	Belongs to the DEAD box helicase family. DDX3/DED1 subfamily. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.

Ontologies

Keywords
Biological process	Apoptosis Chromosome partition Immunity Innate immunity Ribosome biogenesis Transcription Transcription regulation Translation regulation
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion outer membrane Nucleus
Ligand	ATP-binding DNA-binding Nucleotide-binding RNA-binding
Molecular function	Helicase Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	RNA secondary structure unwinding Inferred from sequence or structural similarity. Source: UniProtKB cellular response to arsenic-containing substance Inferred from sequence or structural similarity. Source: UniProtKB cellular response to osmotic stress Inferred from sequence or structural similarity. Source: UniProtKB chromosome segregation Inferred from sequence or structural similarity. Source: UniProtKB extrinsic apoptotic signaling pathway via death domain receptors Inferred from sequence or structural similarity. Source: UniProtKB innate immune response Inferred from sequence or structural similarity. Source: UniProtKB intracellular protein kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB intrinsic apoptotic signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB mature ribosome assembly Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of intrinsic apoptotic signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein complex assembly Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of translation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of G1/S transition of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of translational initiation Inferred from sequence or structural similarity. Source: UniProtKB response to virus Inferred from sequence or structural similarity. Source: UniProtKB stress granule assembly Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasmic stress granule Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent DNA helicase activity Inferred from sequence or structural similarity. Source: UniProtKB ATP-dependent RNA helicase activity Inferred from sequence or structural similarity. Source: UniProtKB DNA binding Inferred from sequence or structural similarity. Source: UniProtKB RNA stem-loop binding Inferred from sequence or structural similarity. Source: UniProtKB eukaryotic initiation factor 4E binding Inferred from sequence or structural similarity. Source: UniProtKB mRNA 5'-UTR binding Inferred from sequence or structural similarity. Source: UniProtKB poly(A) RNA binding Inferred from sequence or structural similarity. Source: UniProtKB ribosomal small subunit binding Inferred from sequence or structural similarity. Source: UniProtKB transcription factor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.3
	Chain	2 – 662	661	ATP-dependent RNA helicase DDX3X		PRO_0000055010
Regions
	Domain	211 – 403	193	Helicase ATP-binding
	Domain	414 – 575	162	Helicase C-terminal
	Nucleotide binding	200 – 207	8	ATP By similarity
	Nucleotide binding	224 – 231	8	ATP By similarity
	Region	2 – 139	138	Required for TBK1 and IKBKE-depenedent IFN-beta activation By similarity
	Region	2 – 100	99	Interaction with EIF4E By similarity
	Region	100 – 662	563	Interaction with GSK3B By similarity
	Region	250 – 259	10	Involved in stimulation of ATPase activity by DNA and RNA, nucleic acid binding and unwinding By similarity
	Region	260 – 517	258	Necessary for interaction with XPO1 By similarity
	Motif	180 – 208	29	Q motif
	Motif	347 – 350	4	DEAD box
	Compositional bias	582 – 662	81	Gly/Ser-rich
	Compositional bias	609 – 616	8	Poly-Ser
	Compositional bias	624 – 630	7	Poly-Gly
	Compositional bias	633 – 641	9	Poly-Gly
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.3
	Modified residue	69	1	Phosphotyrosine By similarity
	Modified residue	74	1	Phosphoserine Ref.5
	Modified residue	78	1	Phosphoserine By similarity
	Modified residue	104	1	Phosphotyrosine By similarity
	Modified residue	118	1	N6-acetyllysine By similarity
	Modified residue	125	1	Phosphoserine By similarity
	Modified residue	131	1	Phosphoserine By similarity
	Modified residue	343	1	Phosphotyrosine By similarity
	Modified residue	590	1	Phosphoserine By similarity
	Modified residue	594	1	Phosphoserine Ref.6
	Modified residue	612	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q62167 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 216515CB00324017	FASTA	662	73,101
	10 20 30 40 50 60 MSHVAVENAL GLDQQFAGLD LNSSDNQSGG STASKGRYIP PHLRNREATK GFYDKDSSGW 70 80 90 100 110 120 SSSKDKDAYS SFGSRGDSRG KSSFFGDRGS GSRGRFDDRG RGDYDGIGGR GDRSGFGKFE 130 140 150 160 170 180 RGGNSRWCDK SDEDDWSKPL PPSERLEQEL FSGGNTGINF EKYDDIPVEA TGNNCPPHIE 190 200 210 220 230 240 SFSDVEMGEI IMGNIELTRY TRPTPVQKHA IPIIKEKRDL MACAQTGSGK TAAFLLPILS 250 260 270 280 290 300 QIYADGPGEA LRAMKENGRY GRRKQYPISL VLAPTRELAV QIYEEARKFS YRSRVRPCVV 310 320 330 340 350 360 YGGAEIGQQI RDLERGCHLL VATPGRLVDM MERGKIGLDF CKYLVLDEAD RMLDMGFEPQ 370 380 390 400 410 420 IRRIVEQDTM PPKGVRHTMM FSATFPKEIQ MLARDFLDEY IFLAVGRVGS TSENITQKVV 430 440 450 460 470 480 WVEEIDKRSF LLDLLNATGK DSLTLVFVET KKGADSLEDF LYHEGYACTS IHGDRSQRDR 490 500 510 520 530 540 EEALHQFRSG KSPILVATAV AARGLDISNV KHVINFDLPS DIEEYVHRIG RTGRVGNLGL 550 560 570 580 590 600 ATSFFNERNI NITKDLLDLL VEAKQEVPSW LENMAFEHHY KGSSRGRSKS SRFSGGFGAR 610 620 630 640 650 660 DYRQSSGASS SSFSSSRASS SRSGGGGHGG SRGFGGGGYG GFYNSDGYGG NYNSQGVDWW GN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The embryonic RNA helicase gene (ERH): a new member of the DEAD box family of RNA helicases." Sowden J.C., Putt W., Morrison K., Beddington R., Edwards Y. Biochem. J. 308:839-846(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6 and DBA.
[2]	"Mouse erythroid cells express multiple putative RNA helicase genes exhibiting high sequence conservation from yeast to mammals." Gee S.L., Conboy J.G. Gene 140:171-177(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Erythroleukemia.
[3]	"An N-acetylated natural ligand of human histocompatibility leukocyte antigen (HLA)-B39. Classical major histocompatibility complex class I proteins bind peptides with a blocked NH(2) terminus in vivo." Yaguee J., Alvarez I., Rognan D., Ramos M., Vazquez J., Lopez de Castro J.A. J. Exp. Med. 191:2083-2092(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-10, ACETYLATION AT SER-2.
[4]	Lubec G., Klug S. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 535-548, MASS SPECTROMETRY. Tissue: Hippocampus.
[5]	"Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line." Shu H., Chen S., Bi Q., Mumby M., Brekken D.L. Mol. Cell. Proteomics 3:279-286(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[6]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-594, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z38117 mRNA. Translation: CAA86261.1. L25126 mRNA. Translation: AAA53630.1.
IPI	IPI00230035.
PIR	I84741.
RefSeq	NP_034158.1. NM_010028.3.
UniGene	Mm.289662.
3D structure databases
ProteinModelPortal	Q62167.
SMR	Q62167. Positions 139-580.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q62167. 2 interactions.
MINT	MINT-1870173.
PTM databases
PhosphoSite	Q62167.
2D gel databases
REPRODUCTION-2DPAGE	Q62167.
Proteomic databases
PaxDb	Q62167.
PRIDE	Q62167.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000000804; ENSMUSP00000000804; ENSMUSG00000000787.
GeneID	13205.
KEGG	mmu:13205.
Organism-specific databases
CTD	1654.
MGI	MGI:103064. Ddx3x.
Phylogenomic databases
eggNOG	COG0513.
GeneTree	ENSGT00620000087942.
HOGENOM	HOG000268804.
HOVERGEN	HBG015893.
InParanoid	Q62167.
KO	K11594.
OrthoDB	EOG47D9FV.
Gene expression databases
ArrayExpress	Q62167.
Bgee	Q62167.
CleanEx	MM_ERH.
Genevestigator	Q62167.
GermOnline	ENSMUSG00000000787. Mus musculus.
Family and domain databases
InterPro	IPR011545. DNA/RNA_helicase_DEAD/DEAH_N. IPR014001. Helicase_ATP-bd. IPR001650. Helicase_C. IPR000629. RNA-helicase_DEAD-box_CS. IPR014014. RNA_helicase_DEAD_Q_motif. [Graphical view]
Pfam	PF00270. DEAD. 1 hit. PF00271. Helicase_C. 1 hit. [Graphical view]
SMART	SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. [Graphical view]
PROSITE	PS00039. DEAD_ATP_HELICASE. 1 hit. PS51192. HELICASE_ATP_BIND_1. 1 hit. PS51194. HELICASE_CTER. 1 hit. PS51195. Q_MOTIF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	DDX3X. mouse.
NextBio	283364.
SOURCE	Search...

Entry information

Entry name

DDX3X_MOUSE

Accession

Primary (citable) accession number: Q62167
Secondary accession number(s): O09060, O09143

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 121 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program