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Protein Page:
DDX3 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
DDX3 a multifunctional DEAD box family RNA helicase with diverse cellular functions. DEAD box proteins are characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), and are involved in several steps of gene expression, such as transcription, maturation of nuclear and mitochondrial mRNA, mRNA export, translation initiation, and ribosome and spliceosome assembly. DDX3 is required for nuclear export of HIV-1 viral transcripts, possibly in a complex with the viral Rev protein and host cofactor CRM1. DDX3 is required for hepatitis C virus (HCV) RNA replication and its expression is downregulated in hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC). May function as a tumor suppressor protein. Its expression inhibits tumor cell colony formation and increases expression of the cdk inhibitor p21 Waf1/Cip1. Low DDX3 expression has been shown in HCC, and aberrant subcellular localization occurs in many squamous cell carcinomas. Reduced DDX3 expression in cultured cells causes a diminished dependence on serum for cell proliferation and changes in cyclin D1 and p21 Waf1/Cip1 expression. Associates with eIF4F to promote translation of selected mRNAs. Is phosphorylated by the mitotic cyclin dependent kinase, cyclin B/cdc2. This phosphorylation may cause a loss of DDX3 function and a concomitant repression of ribosome biogenesis and translation in mitosis. Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFN-beta induction. Involved in regulation of apoptosis. May be required for activation of the intrinsic but inhibit activation of the extrinsic apoptotic pathway. Regulated by the cell cycle. Maximally expressed in the cytoplasm during G1/S phase and decreased expression during G2/M phase. Located predominantly in nuclear speckles and, at low levels, throughout the cytoplasm. Associates with the outer side of nuclear pore complexes (NPC) and mitochondrial outer membranes. Shuttles between the nucleus and the cytoplasm in an exportin1-dependent manner. Associates with polyadenylated mRNAs in the cytoplasm and the nucleus. Predominantly located in nucleus during G0 phase and in the cytoplasm during G1/S phase. Belongs to the DEAD box helicase family, DDX3 subfamily. Two isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Translation initiation; Tumor suppressor; EC 3.6.4.13; Spliceosome; Helicase; Cell cycle regulation; EC 3.6.1.-
Cellular Component: eukaryotic translation initiation factor 3 complex; mitochondrial outer membrane; stress granule; cytoplasm; nuclear speck; nucleus
Molecular Function: ATP-dependent DNA helicase activity; protein binding; DNA binding; translation initiation factor binding; RNA binding; ATPase activity; eukaryotic initiation factor 4E binding; mRNA 5'-UTR binding; transcription factor binding; ATP binding; ATP-dependent RNA helicase activity; ribosomal small subunit binding; poly(A) binding
Biological Process: ATP catabolic process; stress granule assembly; transcription, DNA-dependent; viral reproduction; positive regulation of translation; positive regulation of apoptosis; response to virus; positive regulation of caspase activity; negative regulation of caspase activity; positive regulation of cell growth; DNA duplex unwinding; chromosome segregation; positive regulation of translational initiation; induction of apoptosis via death domain receptors; negative regulation of translation; RNA secondary structure unwinding; positive regulation of interferon-beta production; innate immune response; positive regulation of transcription from RNA polymerase II promoter; negative regulation of cell growth; negative regulation of protein complex assembly; mature ribosome assembly; negative regulation of apoptosis
Reference #:  O00571 (UniProtKB)
Alt. Names/Synonyms: ATP-dependent RNA helicase DDX3X; CAP-Rf; DBX; DDX14; DDX3; DDX3X; DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked; DEAD box protein 3, X-chromosomal; DEAD box, X isoform; DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3; DEAD/H box-3; helicase like protein 2; Helicase-like protein 2; HLP2
Gene Symbols: DDX3X
Molecular weight: 73,243 Da
Basal Isoelectric point: 6.73  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

DDX3

Protein Structure Not Found.


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Sites Implicated In
cell growth, altered: T204‑p, T323‑p
translation, altered: T204‑p, T323‑p
enzymatic activity, inhibited: T204‑p, T323‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 S24-p AGLDLNSsDNQSGGS
0 86 Y53-p REATKGFyDkDSSGW
0 1 K55-ub ATKGFyDkDSSGWss
0 1 S61-p DkDSSGWsssKDKDA
0 7 S62-p kDSSGWsssKDKDAy
0 3 S63-p DSSGWsssKDKDAys
0 607 Y69-p ssKDKDAyssFGsRs
1 30 S70-p sKDKDAyssFGsRsD
1 20 S71-p KDKDAyssFGsRsDs
1 3 S74-p DAyssFGsRsDsRGK
0 1 S76-p yssFGsRsDsRGKss
0 1 S78-p sFGsRsDsRGKssFF
0 1 K81 sRsDsRGKssFFsDr
1 4 S82-p RsDsRGKssFFsDrG
1 5 S83-p sDsRGKssFFsDrGs
1 3 S86-p RGKssFFsDrGsGsr
0 13 R88-m1 KssFFsDrGsGsrGr
0 8 S90-p sFFsDrGsGsrGrFD
0 3 S92-p FsDrGsGsrGrFDDR
0 8 R93-m1 sDrGsGsrGrFDDRG
0 1 R93 sDrGsGsRGrFDDRG
0 4 R95-m1 rGsGsrGrFDDRGRs
0 21 R101 GrFDDRGRsDyDGIG
1 66 S102-p rFDDRGRsDyDGIGs
0 901 Y104-p DDRGRsDyDGIGsRG
1 8 S109-p sDyDGIGsRGDRSGF
0 10 R110 DyDGIGsRGDRSGFG
0 1 R113 GIGsRGDRSGFGkFE
1 11 K118-ac GDRSGFGkFERGGNs
0 2 K118-ub GDRSGFGkFERGGNs
0 1 S125-p kFERGGNsRWCDksD
0 1 K130-ac GNsRWCDksDEDDWS
0 3 S131-p NsRWCDksDEDDWSK
1 2 S152-p RLEQELFsGGNtGIN
1 0 T156-p ELFsGGNtGINFEKy
0 1 Y163-p tGINFEKyDDIPVEA
0 1 S183-p PPHIESFsDVEMGEI
2 1 T204-p LTRYTRPtPVQkHAI
0 9 K208-ub TRPtPVQkHAIPIIk
0 3 K215-ub kHAIPIIkEKRDLMA
0 12 Y243-p LPILSQIySDGPGEA
0 2 K264-ub NGRYGRRkQyPISLV
0 14 Y266-p RYGRRkQyPISLVLA
0 11 Y283-p RELAVQIyEEARKFS
0 124 Y301-p RVRPCVVyGGADIGQ
2 6 T323-p GCHLLVAtPGRLVDM
0 6 K335-ub VDMMERGkIGLDFCk
0 7 K342-ub kIGLDFCkyLVLDEA
0 1 Y343-p IGLDFCkyLVLDEAD
0 12 K373-ub EQDTMPPkGVRHTMM
0 1 S410-p LAVGRVGsTSENITQ
0 1 S429-p VEESDKRsFLLDLLN
0 2 T438-p LLDLLNAtGKDSLTL
0 2 K452-ub LVFVETKkGADsLED
0 3 S456-p ETKkGADsLEDFLyH
0 194 Y462-p DsLEDFLyHEGyACT
0 6 Y466-p DFLyHEGyACTSIHG
0 3 S492-p HQFRSGKsPILVATA
0 2 S508-p AARGLDIsNVkHVIN
0 20 K511-ub GLDIsNVkHVINFDL
0 1 S543-p GNLGLATsFFNERNI
0 28 K554-ub ERNINITkDLLDLLV
0 1 S590-p SSRGRSKssrFsGGF
0 1 S591-p SRGRSKssrFsGGFG
0 9 R592-m1 RGRSKssrFsGGFGA
0 1 R592 RGRSKssRFsGGFGA
0 26 S594-p RSKssrFsGGFGARD
0 6 Y602-p GGFGARDyRQssGAS
0 4 S605-p GARDyRQssGASSSs
0 36 S606-p ARDyRQssGASSSsF
0 7 S612-p ssGASSSsFsssrAs
0 2 S614-p GASSSsFsssrAsSS
0 2 S615-p ASSSsFsssrAsSSR
0 1 S616-p SSSsFsssrAsSSRS
0 5 R617-m1 SSsFsssrAsSSRSG
0 1 S619-p sFsssrAsSSRSGGG
0 17 R632-m1 GGGHGSSrGFGGGGY
  mouse

 
S24 AGLDLNSSDNQSGGS
Y53-p REATKGFyDKDSSGW
K55 ATKGFyDKDSSGWSs
S61 DKDSSGWSsSKDKDA
S62-p KDSSGWSsSKDKDAy
S63 DSSGWSsSKDKDAys
Y69-p sSKDKDAyssFGsRG
S70-p SKDKDAyssFGsRGD
S71-p KDKDAyssFGsRGDS
S74-p DAyssFGsRGDSRGk
G76 yssFGsRGDSRGkss
S78 sFGsRGDSRGkssFF
K81-ub sRGDSRGkssFFGDr
S82-p RGDSRGkssFFGDrG
S83-p GDSRGkssFFGDrGs
G86 RGkssFFGDrGsGsr
R88-m1 kssFFGDrGsGsrGr
S90-p sFFGDrGsGsrGrFD
S92-p FGDrGsGsrGrFDDR
R93-m1 GDrGsGsrGrFDDRG
R93-m2 GDrGsGsrGrFDDRG
R95-m1 rGsGsrGrFDDRGrG
R101-m1 GrFDDRGrGDyDGIG
G102 rFDDRGrGDyDGIGG
Y104-p DDRGrGDyDGIGGrG
G109 GDyDGIGGrGDrSGF
R110-m1 DyDGIGGrGDrSGFG
R113-m1 GIGGrGDrSGFGkFE
K118 GDrSGFGKFERGGNS
K118-ub GDrSGFGkFERGGNS
S125 kFERGGNSRWCDKsD
K130 GNSRWCDKsDEDDWS
S131-p NSRWCDKsDEDDWSK
S152 RLEQELFSGGNTGIN
T156 ELFSGGNTGINFEKY
Y163 TGINFEKYDDIPVEA
S183 PPHIESFSDVEMGEI
T204 LTRYTRPTPVQKHAI
K208 TRPTPVQKHAIPIIk
K215-ub KHAIPIIkEKRDLMA
Y243-p LPILSQIyADGPGEA
K264-ub NGRYGRRkQYPISLV
Y266 RYGRRkQYPISLVLA
Y283-p RELAVQIyEEARKFS
Y301-p RVRPCVVyGGAEIGQ
T323 GCHLLVATPGRLVDM
K335-ub VDMMERGkIGLDFCK
K342 kIGLDFCKYLVLDEA
Y343 IGLDFCKYLVLDEAD
K373 EQDTMPPKGVRHTMM
S410-p LAVGRVGsTSENITQ
S429 VEEIDKRSFLLDLLN
T438 LLDLLNATGKDSLTL
K452 LVFVETKKGADsLED
S456-p ETKKGADsLEDFLyH
Y462-p DsLEDFLyHEGyACT
Y466-p DFLyHEGyACTSIHG
S492 HQFRSGKSPILVATA
S508 AARGLDISNVkHVIN
K511-ub GLDISNVkHVINFDL
S543 GNLGLATSFFNERNI
K554-ub ERNINITkDLLDLLV
S590 SSRGRSKSSrFsGGF
S591 SRGRSKSSrFsGGFG
R592-m1 RGRSKSSrFsGGFGA
R592-m2 RGRSKSSrFsGGFGA
S594-p RSKSSrFsGGFGARD
Y602 GGFGARDYRQSsGAS
S605 GARDYRQSsGASSSs
S606-p ARDYRQSsGASSSsF
S612-p SsGASSSsFSSSrAS
S614 GASSSsFSSSrASSS
S615 ASSSsFSSSrASSSR
S616 SSSsFSSSrASSSRS
R617-m1 SSsFSSSrASSSRSG
S619 sFSSSrASSSRSGGG
R632-m1 GGGHGGSrGFGGGGY
  rat

 
S24 AGLDLNSSDNQTGGS
Y53 REATKGFYDKDSSGW
K55 ATKGFYDKDSSGWSS
S61 DKDSSGWSSSKDKDA
S62 KDSSGWSSSKDKDAy
S63 DSSGWSSSKDKDAyS
Y69-p SSKDKDAySSFGSRG
S70 SKDKDAySSFGSRGD
S71 KDKDAySSFGSRGDS
S74 DAySSFGSRGDSRGK
G76 ySSFGSRGDSRGKSS
S78 SFGSRGDSRGKSSFF
K81 SRGDSRGKSSFFGDr
S82 RGDSRGKSSFFGDrG
S83 GDSRGKSSFFGDrGS
G86 RGKSSFFGDrGSGSr
R88-m1 KSSFFGDrGSGSrGR
S90 SFFGDrGSGSrGRFD
S92 FGDrGSGSrGRFDDR
R93-m1 GDrGSGSrGRFDDRG
R93 GDrGSGSRGRFDDRG
R95 rGSGSrGRFDDRGrG
R101-m1 GRFDDRGrGDYDGIG
G102 RFDDRGrGDYDGIGG
Y104 DDRGrGDYDGIGGRG
G109 GDYDGIGGRGDRSGF
R110 DYDGIGGRGDRSGFG
R113 GIGGRGDRSGFGKFE
K118 GDRSGFGKFERGGNS
K118 GDRSGFGKFERGGNS
S125 KFERGGNSRWCDKSD
K130 GNSRWCDKSDEDDWS
S131 NSRWCDKSDEDDWSK
S152 RLEQELFSGGNTGIN
T156 ELFSGGNTGINFEKY
Y163 TGINFEKYDDIPVEA
S183 PPHIESFSDVEMGEI
T204 LTRYTRPTPVQkHAI
K208-ub TRPTPVQkHAIPIIk
K215-ub kHAIPIIkEKRDLMA
Y243-p LPILSQIyADGPGEA
K264 NGRYGRRKQYPISLV
Y266 RYGRRKQYPISLVLA
Y283-p RELAVQIyEEARKFS
Y301-p RVRPCVVyGGAEIGQ
T323 GCHLLVATPGRLVDM
K335 VDMMERGKIGLDFCK
K342 KIGLDFCKYLVLDEA
Y343 IGLDFCKYLVLDEAD
K373-ub EQDTMPPkGVRHTMM
S410 LAVGRVGSTSENITQ
S429 VEEIDKRSFLLDLLN
T438 LLDLLNATGKDSLTL
K452 LVFVETKKGADSLED
S456 ETKKGADSLEDFLyH
Y462-p DSLEDFLyHEGyACT
Y466-p DFLyHEGyACTSIHG
S492 HQFRSGKSPILVATA
S508 AARGLDISNVkHVIN
K511-ub GLDISNVkHVINFDL
S543 GNLGLATSFFNERNI
K554-ub ERNINITkDLLDLLV
S590 SSRGRSKSSRFSGGF
S591 SRGRSKSSRFSGGFG
R592 RGRSKSSRFSGGFGA
R592 RGRSKSSRFSGGFGA
S594 RSKSSRFSGGFGARD
Y602 GGFGARDYRQSSGAS
S605 GARDYRQSSGASSSS
S606 ARDYRQSSGASSSSF
S612 SSGASSSSFSSSRAS
S614 GASSSSFSSSRASSS
S615 ASSSSFSSSRASSSR
S616 SSSSFSSSRASSSRS
R617 SSSFSSSRASSSRSG
S619 SFSSSRASSSRSGGG
R632-m1 GGGHGSSrGFGGGGY
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