dbPAF Protein Information


Tag Content
dbPAF ID dbPAF-0000134
Uniprot Accession O00571; DDX3X_HUMAN; A8K538; B4E3E8; O15536;
Genbank Protein ID NP_001180345.1; NP_001180346.1; NP_001347.3;
Genbank Nucleotide ID NM_001193416.2; NM_001193417.2; NM_001356.4;
Protein Name ATP-dependent RNA helicase DDX3X
Protein Synonyms/Alias DEAD box protein 3, X-chromosomal;DEAD box, X isoform;Helicase-like protein 2;HLP2;
Gene Name DDX3X
Gene Synonyms/Alias DBX;DDX3;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)
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. Appears to be a prime target for viral manipulations. Hepatitis B virus (HBV) polymerase and possibly vaccinia virus (VACV) protein K7 inhibit IFNB induction probably by dissociating DDX3X from TBK1 or IKBKE. Is involved in hepatitis C virus (HCV) replication; the function may involve the association with HCV core protein. HCV core protein inhibits the IPS1-dependent function in viral RNA sensing and may switch the function from a INFB inducing to a HCV replication mode. Involved in HIV-1 replication. Acts as a cofactor for XPO1-mediated nuclear export of incompletely spliced HIV-1 Rev RNAs.
Phosphorylation Sites
dbPAF PTMs: 80 (View all)
PositionPeptidesSourceReferences ( PMIDs )
23FAGLDLNSSDNQSGGdbPTM 3.0;HPRD 9;curated20068231; 16381945; 23193290; 18988627; 25627689; 22199227;
24AGLDLNSSDNQSGGSPhosphoSitePlus;curated22135298; 25627689; 20068231
28LNSSDNQSGGSTASKcurated25627689; 20873877
31SDNQSGGSTASKGRYcurated20873877
32DNQSGGSTASKGRYIcurated20873877
34QSGGSTASKGRYIPPcurated20873877
38STASKGRYIPPHLRNPhosphoSitePlus22135298
53REATKGFYDKDSSGWdbPTM 3.0;PhosphoSitePlus;curated20007894; 20090780; 16381945; 23193290; 22135298; 22817900
57KGFYDKDSSGWSSSKdbPTM 3.0;HPRD 9;curated20068231; 16381945; 23193290; 18988627; 20873877
58GFYDKDSSGWSSSKDdbPTM 3.0;HPRD 9;curated20068231; 16381945; 23193290; 18988627; 20873877
61DKDSSGWSSSKDKDAdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoSitePlus;curated18669648; 20068231; 16381945; 23193290; 18988627; 21081558;
62KDSSGWSSSKDKDAYdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoSitePlus;curated20068231; 16381945; 23193290; 18988627; 21081558; 22135298;
63DSSGWSSSKDKDAYSdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoSitePlus;curated20068231; 16381945; 23193290; 18988627; 21081558; 22135298;
69SSKDKDAYSSFGSRSdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;curated15592455; 16094384; 16381945; 23193290; 14729942; 15144186;
70SKDKDAYSSFGSRSDdbPTM 3.0;PhosphoSitePlus;curated15570572; 16381945; 23193290; 22135298; 25627689; 20873877;
71KDKDAYSSFGSRSDSPhosphoSitePlus;curated22135298; 25850435; 25627689; 23403867; 20873877; 24961811
74DAYSSFGSRSDSRGKdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;SysPTM 2.0;curated17287340; 16381945; 23193290; 14729942; 18988627; 22135298;
76YSSFGSRSDSRGKSSdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;SysPTM 2.0;curated17287340; 16381945; 23193290; 18988627; 22135298; 19366988;
78SFGSRSDSRGKSSFFdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;SysPTM 2.0;curated17287340; 16381945; 23193290; 18988627; 22135298; 19366988;
82RSDSRGKSSFFSDRGdbPTM 3.0;HPRD 9;PhosphoSitePlus;SysPTM 2.0;curated18669648; 16381945; 23193290; 18212344; 18988627; 22135298;
Sequence
(Fasta)
MSHVAVENAL GLDQQFAGLD LNSSDNQSGG STASKGRYIP PHLRNREATK GFYDKDSSGW 60
SSSKDKDAYS SFGSRSDSRG KSSFFSDRGS GSRGRFDDRG RSDYDGIGSR GDRSGFGKFE 120
RGGNSRWCDK SDEDDWSKPL PPSERLEQEL FSGGNTGINF EKYDDIPVEA TGNNCPPHIE 180
SFSDVEMGEI IMGNIELTRY TRPTPVQKHA IPIIKEKRDL MACAQTGSGK TAAFLLPILS 240
QIYSDGPGEA LRAMKENGRY GRRKQYPISL VLAPTRELAV QIYEEARKFS YRSRVRPCVV 300
YGGADIGQQI RDLERGCHLL VATPGRLVDM MERGKIGLDF CKYLVLDEAD RMLDMGFEPQ 360
IRRIVEQDTM PPKGVRHTMM FSATFPKEIQ MLARDFLDEY IFLAVGRVGS TSENITQKVV 420
WVEESDKRSF LLDLLNATGK DSLTLVFVET KKGADSLEDF LYHEGYACTS IHGDRSQRDR 480
EEALHQFRSG KSPILVATAV AARGLDISNV KHVINFDLPS DIEEYVHRIG RTGRVGNLGL 540
ATSFFNERNI NITKDLLDLL VEAKQEVPSW LENMAYEHHY KGSSRGRSKS SRFSGGFGAR 600
DYRQSSGASS SSFSSSRASS SRSGGGGHGS SRGFGGGGYG GFYNSDGYGG NYNSQGVDWW 660
GN 663
Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0025--Alternative splicing
KW-0053--Apoptosis
KW-0067--ATP-binding
KW-0159--Chromosome partition
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0903--Direct protein sequencing
KW-0238--DNA-binding
KW-0347--Helicase
KW-0945--Host-virus interaction
KW-0378--Hydrolase
KW-0391--Immunity
KW-0399--Innate immunity
KW-1017--Isopeptide bond
KW-0472--Membrane
KW-0496--Mitochondrion
KW-1000--Mitochondrion outer membrane
KW-0547--Nucleotide-binding
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0690--Ribosome biogenesis
KW-0694--RNA-binding
KW-0804--Transcription
KW-0805--Transcription regulation
KW-0810--Translation regulation
KW-0832--Ubl conjugation

Interpro

IPR011545--DEAD/DEAH_box_helicase_dom
IPR014001--Helicase_ATP-bd
IPR001650--Helicase_C
IPR027417--P-loop_NTPase
IPR000629--RNA-helicase_DEAD-box_CS
IPR014014--RNA_helicase_DEAD_Q_motif

PROSITE

PS00039--DEAD_ATP_HELICASE
PS51192--HELICASE_ATP_BIND_1
PS51194--HELICASE_CTER
PS51195--Q_MOTIF

Pfam

PF00270--DEAD
PF00271--Helicase_C

Gene Ontology

GO:0005737--C:cytoplasm
GO:0010494--C:cytoplasmic stress granule
GO:0070062--C:extracellular exosome
GO:0005741--C:mitochondrial outer membrane
GO:0016607--C:nuclear speck
GO:0005634--C:nucleus
GO:0005524--F:ATP binding
GO:0004003--F:ATP-dependent DNA helicase activity
GO:0004004--F:ATP-dependent RNA helicase activity
GO:0016887--F:ATPase activity
GO:0043273--F:CTPase activity
GO:0003677--F:DNA binding
GO:0008190--F:eukaryotic initiation factor 4E binding
GO:0003924--F:GTPase activity
GO:0048027--F:mRNA 5'-UTR binding
GO:0017111--F:nucleoside-triphosphatase activity
GO:0008143--F:poly(A) binding
GO:0044822--F:poly(A) RNA binding
GO:0043024--F:ribosomal small subunit binding
GO:0003723--F:RNA binding
GO:0035613--F:RNA stem-loop binding
GO:0008134--F:transcription factor binding
GO:0031369--F:translation initiation factor binding
GO:0071243--P:cellular response to arsenic-containing substance
GO:0071470--P:cellular response to osmotic stress
GO:0007059--P:chromosome segregation
GO:0032508--P:DNA duplex unwinding
GO:0008625--P:extrinsic apoptotic signaling pathway via death domain receptors
GO:0045087--P:innate immune response
GO:0035556--P:intracellular signal transduction
GO:0097193--P:intrinsic apoptotic signaling pathway
GO:0042256--P:mature ribosome assembly
GO:0043066--P:negative regulation of apoptotic process
GO:0030308--P:negative regulation of cell growth
GO:0043154--P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:2001243--P:negative regulation of intrinsic apoptotic signaling pathway
GO:0031333--P:negative regulation of protein complex assembly
GO:0017148--P:negative regulation of translation
GO:0043065--P:positive regulation of apoptotic process
GO:0030307--P:positive regulation of cell growth
GO:0071651--P:positive regulation of chemokine (C-C motif) ligand 5 production
GO:0043280--P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:1900087--P:positive regulation of G1/S transition of mitotic cell cycle
GO:0010628--P:positive regulation of gene expression
GO:0032728--P:positive regulation of interferon-beta production
GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter
GO:0045727--P:positive regulation of translation
GO:0045948--P:positive regulation of translational initiation
GO:0045070--P:positive regulation of viral genome replication
GO:0009615--P:response to virus
GO:0010501--P:RNA secondary structure unwinding
GO:0034063--P:stress granule assembly
GO:0006351--P:transcription, DNA-templated
GO:0006413--P:translational initiation
GO:0016032--P:viral process