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Protein Page:
DDX3 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
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: RNA-binding; Spliceosome; EC 3.6.4.13; Translation initiation; Cell cycle regulation; Helicase
Chromosomal Location of Human Ortholog: Xp11.3-p11.23
Cellular Component: eukaryotic translation initiation factor 3 complex; mitochondrial outer membrane; stress granule; cytoplasm; nuclear speck; nucleus
Molecular Function: GTPase activity; CTPase activity; RNA binding; ATPase activity; transcription factor binding; poly(A) binding; ATP-dependent DNA helicase activity; protein binding; DNA binding; translation initiation factor binding; eukaryotic initiation factor 4E binding; nucleoside-triphosphatase activity; mRNA 5'-UTR binding; ATP binding; ATP-dependent RNA helicase activity; ribosomal small subunit binding
Biological Process: stress granule assembly; positive regulation of viral genome replication; viral reproduction; positive regulation of translation; transcription, DNA-dependent; 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; RNA secondary structure unwinding; negative regulation of translation; 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


 LTP 

LTP: 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.


 HTP 

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


       human

► Hide Isoforms
 
0 1 S24-p AGLDLNSsDNQSGGS
0 1 K50 LRNREATKGFyDkDS
0 87 Y53-p REATKGFyDkDSSGW
0 1 K55-ub ATKGFyDkDSSGWss
0 1 S61-p DkDSSGWsssKDKDA
0 7 S62-p kDSSGWsssKDKDAy
0 3 S63-p DSSGWsssKDKDAys
0 610 Y69-p ssKDKDAyssFGsRs
1 31 S70-p sKDKDAyssFGsRsD
1 23 S71-p KDKDAyssFGsRsDs
1 4 S74-p DAyssFGsRsDsRGK
0 1 S76-p yssFGsRsDsRGKss
0 1 S78-p sFGsRsDsRGKssFF
0 1 K81 sRsDsRGKssFFsDr
1 5 S82-p RsDsRGKssFFsDrG
1 6 S83-p sDsRGKssFFsDrGs
1 4 S86-p RGKssFFsDrGsGsr
0 13 R88-m1 KssFFsDrGsGsrGr
0 13 S90-p sFFsDrGsGsrGrFD
0 4 S92-p FsDrGsGsrGrFDDR
0 8 R93-m1 sDrGsGsrGrFDDRG
0 1 R93 sDrGsGsRGrFDDRG
0 4 R95-m1 rGsGsrGrFDDRGrs
0 21 R101-m1 GrFDDRGrsDyDGIG
1 68 S102-p rFDDRGrsDyDGIGs
0 906 Y104-p DDRGrsDyDGIGsrG
1 8 S109-p sDyDGIGsrGDRSGF
0 10 R110-m1 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 6 S131-p NsRWCDksDEDDWSK
1 3 S152-p RLEQELFsGGNtGIN
1 0 T156-p ELFsGGNtGINFEKy
0 1 Y163-p tGINFEKyDDIPVEA
0 1 S183-p PPHIESFsDVEMGEI
2 2 T204-p LTRYTRPtPVQkHAI
0 9 K208-ub TRPtPVQkHAIPIIk
0 3 K215-ub kHAIPIIkEKRDLMA
0 12 Y243-p LPILSQIySDGPGEA
0 2 K264-ub NGRYGRRkQyPISLV
0 15 Y266-p RYGRRkQyPISLVLA
0 11 Y283-p RELAVQIyEEARKFS
0 124 Y301-p RVRPCVVyGGADIGQ
2 7 T323-p GCHLLVAtPGRLVDM
0 6 K335-ub VDMMERGkIGLDFCk
0 6 K342-ub kIGLDFCkyLVLDEA
0 2 Y343-p IGLDFCkyLVLDEAD
0 12 K373-ub EQDTMPPkGVRHTMM
0 3 S410-p LAVGRVGsTSENITQ
0 1 S429-p VEESDKRsFLLDLLN
0 2 T438-p LLDLLNAtGKDSLTL
0 2 K452-ub LVFVETKkGADsLED
0 4 S456-p ETKkGADsLEDFLyH
0 195 Y462-p DsLEDFLyHEGyACT
0 6 Y466-p DFLyHEGyACTSIHG
0 4 S492-p HQFRSGKsPILVATA
0 2 S508-p AARGLDIsNVkHVIN
0 20 K511-ub GLDIsNVkHVINFDL
0 2 S520-p VINFDLPsDIEEYVH
0 1 S543-p GNLGLATsFFNERNI
0 27 K554-ub ERNINITkDLLDLLV
0 2 S590-p SSRGRSKssrFsGGF
0 1 S591-p SRGRSKssrFsGGFG
0 9 R592-m1 RGRSKssrFsGGFGA
0 1 R592 RGRSKssRFsGGFGA
0 36 S594-p RSKssrFsGGFGARD
0 6 Y602-p GGFGARDyRQssGAS
0 5 S605-p GARDyRQssGASSSs
0 40 S606-p ARDyRQssGASSSsF
0 8 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
  DDX3 iso2  
S24 AGLDLNSSDNQSGGS
- gap
Y37 GSTASSFYDKDSSGW
K39 TASSFYDKDSSGWSS
S45 DKDSSGWSSSKDKDA
S46 KDSSGWSSSKDKDAY
S47 DSSGWSSSKDKDAYS
Y53 SSKDKDAYSSFGSRS
S54 SKDKDAYSSFGSRSD
S55 KDKDAYSSFGSRSDS
S58 DAYSSFGSRSDSRGK
S60 YSSFGSRSDSRGKSS
S62 SFGSRSDSRGKSSFF
K65 SRSDSRGKSSFFSDR
S66 RSDSRGKSSFFSDRG
S67 SDSRGKSSFFSDRGS
S70 RGKSSFFSDRGSGSR
R72 KSSFFSDRGSGSRGR
S74 SFFSDRGSGSRGRFD
S76 FSDRGSGSRGRFDDR
R77 SDRGSGSRGRFDDRG
R77 SDRGSGSRGRFDDRG
R79 RGSGSRGRFDDRGRS
R85 GRFDDRGRSDYDGIG
S86 RFDDRGRSDYDGIGS
Y88 DDRGRSDYDGIGSRG
S93 SDYDGIGSRGDRSGF
R94 DYDGIGSRGDRSGFG
R97 GIGSRGDRSGFGKFE
K102 GDRSGFGKFERGGNS
K102 GDRSGFGKFERGGNS
S109 KFERGGNSRWCDKSD
K114 GNSRWCDKSDEDDWS
S115 NSRWCDKSDEDDWSK
S136 RLEQELFSGGNTGIN
T140 ELFSGGNTGINFEKY
Y147 TGINFEKYDDIPVEA
S167 PPHIESFSDVEMGEI
T188 LTRYTRPTPVQKHAI
K192 TRPTPVQKHAIPIIK
K199 KHAIPIIKEKRDLMA
Y227 LPILSQIYSDGPGEA
K248 NGRYGRRKQYPISLV
Y250 RYGRRKQYPISLVLA
Y267 RELAVQIYEEARKFS
Y285 RVRPCVVYGGADIGQ
T307 GCHLLVATPGRLVDM
K319 VDMMERGKIGLDFCK
K326 KIGLDFCKYLVLDEA
Y327 IGLDFCKYLVLDEAD
K357 EQDTMPPKGVRHTMM
S394 LAVGRVGSTSENITQ
S413 VEESDKRSFLLDLLN
T422 LLDLLNATGKDSLTL
K436 LVFVETKKGADSLED
S440 ETKKGADSLEDFLYH
Y446 DSLEDFLYHEGYACT
Y450 DFLYHEGYACTSIHG
S476 HQFRSGKSPILVATA
S492 AARGLDISNVKHVIN
K495 GLDISNVKHVINFDL
S504 VINFDLPSDIEEYVH
S527 GNLGLATSFFNERNI
K538 ERNINITKDLLDLLV
S574 SSRGRSKSSRFSGGF
S575 SRGRSKSSRFSGGFG
R576 RGRSKSSRFSGGFGA
R576 RGRSKSSRFSGGFGA
S578 RSKSSRFSGGFGARD
Y586 GGFGARDYRQSSGAS
S589 GARDYRQSSGASSSS
S590 ARDYRQSSGASSSSF
S596 SSGASSSSFSSSRAS
S598 GASSSSFSSSRASSS
S599 ASSSSFSSSRASSSR
S600 SSSSFSSSRASSSRS
R601 SSSFSSSRASSSRSG
S603 SFSSSRASSSRSGGG
R616 GGGHGSSRGFGGGGY
  mouse

 
S24 AGLDLNSSDNQSGGS
K50 LRNREATKGFyDKDS
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
S520-p VINFDLPsDIEEYVH
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
K50-ac LRNREATkGFYDKDS
Y53 REATkGFYDKDSSGW
K55 ATkGFYDKDSSGWSS
S61 DKDSSGWSSSKDKDA
S62 KDSSGWSSSKDKDAy
S63 DSSGWSSSKDKDAyS
Y69-p SSKDKDAySsFGSRG
S70 SKDKDAySsFGSRGD
S71-p KDKDAySsFGSRGDS
S74 DAySsFGSRGDSRGK
G76 ySsFGSRGDSRGKSS
S78 sFGSRGDSRGKSSFF
K81 SRGDSRGKSSFFGDr
S82 RGDSRGKSSFFGDrG
S83 GDSRGKSSFFGDrGs
G86 RGKSSFFGDrGsGSr
R88-m1 KSSFFGDrGsGSrGR
S90-p 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
S520 VINFDLPSDIEEYVH
S543 GNLGLATSFFNERNI
K554-ub ERNINITkDLLDLLV
S590 SSRGRSKSSRFsGGF
S591 SRGRSKSSRFsGGFG
R592 RGRSKSSRFsGGFGA
R592 RGRSKSSRFsGGFGA
S594-p 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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