CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-014404
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 ATP-dependent RNA helicase DDX3X 
Protein Synonyms/Alias
 D1Pas1-related sequence 2; DEAD box RNA helicase DEAD3; mDEAD3; DEAD box protein 3, X-chromosomal; Embryonic RNA helicase 
Gene Name
 Ddx3x 
Gene Synonyms/Alias
 D1Pas1-rs2; Ddx3; Dead3; Erh 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
50LRNREATKGFYDKDSacetylation[1]
55ATKGFYDKDSSGWSSacetylation[2, 3]
130GNSRWCDKSDEDDWSacetylation[3]
Reference
 [1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405]
 [2] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [3] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337] 
Functional Description
 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). 
Sequence Annotation
 DOMAIN 211 403 Helicase ATP-binding.
 DOMAIN 414 575 Helicase C-terminal.
 NP_BIND 200 207 ATP (By similarity).
 NP_BIND 224 231 ATP (By similarity).
 REGION 2 139 Required for TBK1 and IKBKE-depenedent
 REGION 2 100 Interaction with EIF4E (By similarity).
 REGION 100 662 Interaction with GSK3B (By similarity).
 REGION 250 259 Involved in stimulation of ATPase
 REGION 260 517 Necessary for interaction with XPO1 (By
 MOTIF 180 208 Q motif.
 MOTIF 347 350 DEAD box.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 69 69 Phosphotyrosine (By similarity).
 MOD_RES 74 74 Phosphoserine.
 MOD_RES 78 78 Phosphoserine (By similarity).
 MOD_RES 104 104 Phosphotyrosine (By similarity).
 MOD_RES 118 118 N6-acetyllysine (By similarity).
 MOD_RES 125 125 Phosphoserine (By similarity).
 MOD_RES 131 131 Phosphoserine (By similarity).
 MOD_RES 283 283 Phosphotyrosine (By similarity).
 MOD_RES 343 343 Phosphotyrosine (By similarity).
 MOD_RES 466 466 Phosphotyrosine (By similarity).
 MOD_RES 590 590 Phosphoserine (By similarity).
 MOD_RES 594 594 Phosphoserine.
 MOD_RES 612 612 Phosphoserine (By similarity).  
Keyword
 Acetylation; Apoptosis; ATP-binding; Chromosome partition; Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; Helicase; Hydrolase; Immunity; Innate immunity; Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Ribosome biogenesis; RNA-binding; Transcription; Transcription regulation; Translation regulation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 662 AA 
Protein Sequence
MSHVAVENAL GLDQQFAGLD LNSSDNQSGG STASKGRYIP PHLRNREATK GFYDKDSSGW 60
SSSKDKDAYS SFGSRGDSRG KSSFFGDRGS GSRGRFDDRG RGDYDGIGGR GDRSGFGKFE 120
RGGNSRWCDK SDEDDWSKPL PPSERLEQEL FSGGNTGINF EKYDDIPVEA TGNNCPPHIE 180
SFSDVEMGEI IMGNIELTRY TRPTPVQKHA IPIIKEKRDL MACAQTGSGK TAAFLLPILS 240
QIYADGPGEA LRAMKENGRY GRRKQYPISL VLAPTRELAV QIYEEARKFS YRSRVRPCVV 300
YGGAEIGQQI RDLERGCHLL VATPGRLVDM MERGKIGLDF CKYLVLDEAD RMLDMGFEPQ 360
IRRIVEQDTM PPKGVRHTMM FSATFPKEIQ MLARDFLDEY IFLAVGRVGS TSENITQKVV 420
WVEEIDKRSF LLDLLNATGK DSLTLVFVET KKGADSLEDF LYHEGYACTS IHGDRSQRDR 480
EEALHQFRSG KSPILVATAV AARGLDISNV KHVINFDLPS DIEEYVHRIG RTGRVGNLGL 540
ATSFFNERNI NITKDLLDLL VEAKQEVPSW LENMAFEHHY KGSSRGRSKS SRFSGGFGAR 600
DYRQSSGASS SSFSSSRASS SRSGGGGHGG SRGFGGGGYG GFYNSDGYGG NYNSQGVDWW 660
GN 662 
Gene Ontology
 GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
 GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
 GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004003; F:ATP-dependent DNA helicase activity; ISS:UniProtKB.
 GO:0004004; F:ATP-dependent RNA helicase activity; ISS:UniProtKB.
 GO:0003677; F:DNA binding; ISS:UniProtKB.
 GO:0008190; F:eukaryotic initiation factor 4E binding; ISS:UniProtKB.
 GO:0048027; F:mRNA 5'-UTR binding; ISS:UniProtKB.
 GO:0008143; F:poly(A) RNA binding; ISS:UniProtKB.
 GO:0043024; F:ribosomal small subunit binding; ISS:UniProtKB.
 GO:0035613; F:RNA stem-loop binding; ISS:UniProtKB.
 GO:0008134; F:transcription factor binding; ISS:UniProtKB.
 GO:0071243; P:cellular response to arsenic-containing substance; ISS:UniProtKB.
 GO:0071470; P:cellular response to osmotic stress; ISS:UniProtKB.
 GO:0007059; P:chromosome segregation; ISS:UniProtKB.
 GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISS:UniProtKB.
 GO:0045087; P:innate immune response; ISS:UniProtKB.
 GO:0007243; P:intracellular protein kinase cascade; ISS:UniProtKB.
 GO:0097193; P:intrinsic apoptotic signaling pathway; ISS:UniProtKB.
 GO:0042256; P:mature ribosome assembly; ISS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
 GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
 GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
 GO:0031333; P:negative regulation of protein complex assembly; ISS:UniProtKB.
 GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
 GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
 GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB.
 GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
 GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
 GO:0045948; P:positive regulation of translational initiation; ISS:UniProtKB.
 GO:0009615; P:response to virus; ISS:UniProtKB.
 GO:0010501; P:RNA secondary structure unwinding; ISS:UniProtKB.
 GO:0034063; P:stress granule assembly; ISS:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
 IPR014001; Helicase_ATP-bd.
 IPR001650; Helicase_C.
 IPR027417; P-loop_NTPase.
 IPR000629; RNA-helicase_DEAD-box_CS.
 IPR014014; RNA_helicase_DEAD_Q_motif. 
Pfam
 PF00270; DEAD
 PF00271; Helicase_C 
SMART
 SM00487; DEXDc
 SM00490; HELICc 
PROSITE
 PS00039; DEAD_ATP_HELICASE
 PS51192; HELICASE_ATP_BIND_1
 PS51194; HELICASE_CTER
 PS51195; Q_MOTIF 
PRINTS