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Protein

Probable ATP-dependent RNA helicase DDX5

Gene

DDX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as transcriptional repressor in a promoter-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms.8 Publications

Caution

Was reported to act as transcriptional coactivator for estrogen receptor ESR1; these publications have been retracted (PubMed:10409727, PubMed:11250900). The function has been questioned (PubMed:18829551).3 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei121ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi114 – 116ATP3
Nucleotide bindingi138 – 145ATP8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHelicase, Hydrolase, RNA-binding
Biological processBiological rhythms, mRNA processing, mRNA splicing, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.6.4.13 2681
ReactomeiR-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-9018519 Estrogen-dependent gene expression
SIGNORiP17844

Names & Taxonomyi

Protein namesi
Recommended name:
Probable ATP-dependent RNA helicase DDX5 (EC:3.6.4.13)
Alternative name(s):
DEAD box protein 5
RNA helicase p68
Gene namesi
Name:DDX5
Synonyms:G17P1, HELR, HLR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108654.11
HGNCiHGNC:2746 DDX5
MIMi180630 gene
neXtProtiNX_P17844

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus, Spliceosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi53K → R: Abolishes sumoylation, abolishes interaction with HDAC1, increases TP53 coactivation and promotes polyubiquitination. 2 Publications1
Mutagenesisi55E → A: Abolishes sumoylation. 1 Publication1
Mutagenesisi144K → R: Abolishes RNA helicase activity. 1 Publication1
Mutagenesisi403R → L: Binds to the tau stem-loop-containing RNA. Inhibits tau exon 10 inclusion and RNA cleavage. Does not inhibit interaction with RBM4. 1 Publication1

Organism-specific databases

DisGeNETi1655
OpenTargetsiENSG00000108654
PharmGKBiPA27228

Polymorphism and mutation databases

BioMutaiDDX5
DMDMi129383

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000549911 – 614Probable ATP-dependent RNA helicase DDX5Add BLAST614

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24PhosphoserineCombined sources1
Modified residuei32N6-acetyllysine; alternateCombined sources1
Cross-linki32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei33N6-acetyllysineCombined sources1
Modified residuei40N6-acetyllysineCombined sources1
Cross-linki45Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki53Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki53Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki53Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei236N6-acetyllysineBy similarity1
Modified residuei297PhosphotyrosineCombined sources1
Cross-linki340Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki343Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki388Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki411Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki437Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki451Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki470Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei480PhosphoserineCombined sources1
Modified residuei520PhosphoserineCombined sources1
Cross-linki523Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Arg-502 is dimethylated, probably to asymmetric dimethylarginine.
Sumoylated; sumoylation, promoted by PIAS1, promotes interaction with HDAC1 and transcriptional repression activity. Sumoylation also significantly increases stability, and reduces polyubiquitination.2 Publications
Polyubiquitinated, leading to proteasomal degradation.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP17844
MaxQBiP17844
PaxDbiP17844
PeptideAtlasiP17844
PRIDEiP17844
ProteomicsDBi53519

2D gel databases

SWISS-2DPAGEiP17844

PTM databases

iPTMnetiP17844
PhosphoSitePlusiP17844
SwissPalmiP17844

Expressioni

Gene expression databases

BgeeiENSG00000108654 Expressed in 200 organ(s), highest expression level in testis
CleanExiHS_DDX5
ExpressionAtlasiP17844 baseline and differential
GenevisibleiP17844 HS

Organism-specific databases

HPAiCAB005868
HPA020043

Interactioni

Subunit structurei

Identified in the spliceosome C complex. Interacts with RBM4; the interaction occurs in an RNA-independent manner. Interacts with AGO1 and AGO2. Interacts with ESR1, AR, EP300, CREBBP, POLR2A, TP53, RUNX2 and HDAC1. Self-associates. Interacts with DDX17. Interacts with BRDT. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852).15 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108021, 237 interactors
CORUMiP17844
DIPiDIP-29844N
IntActiP17844, 128 interactors
MINTiP17844
STRINGi9606.ENSP00000225792

Structurei

Secondary structure

1614
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP17844
SMRiP17844
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17844

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini125 – 300Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST176
Domaini328 – 475Helicase C-terminalPROSITE-ProRule annotationAdd BLAST148

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni477 – 614Transactivation domainAdd BLAST138

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi94 – 122Q motifAdd BLAST29
Motifi248 – 251DEAD box4

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0331 Eukaryota
COG0513 LUCA
GeneTreeiENSGT00930000150858
HOGENOMiHOG000268804
HOVERGENiHBG015893
InParanoidiP17844
KOiK12823
PhylomeDBiP17844
TreeFamiTF300332

Family and domain databases

CDDicd00079 HELICc, 1 hit
InterProiView protein in InterPro
IPR033488 DDX5
IPR011545 DEAD/DEAH_box_helicase_dom
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
IPR012587 P68_rpt
IPR000629 RNA-helicase_DEAD-box_CS
IPR014014 RNA_helicase_DEAD_Q_motif
PANTHERiPTHR24031:SF404 PTHR24031:SF404, 1 hit
PfamiView protein in Pfam
PF00270 DEAD, 1 hit
PF00271 Helicase_C, 1 hit
PF08061 P68HR, 2 hits
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00490 HELICc, 1 hit
SM01414 P68HR, 2 hits
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00039 DEAD_ATP_HELICASE, 1 hit
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit
PS51195 Q_MOTIF, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 16 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P17844-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSGYSSDRDR GRDRGFGAPR FGGSRAGPLS GKKFGNPGEK LVKKKWNLDE
60 70 80 90 100
LPKFEKNFYQ EHPDLARRTA QEVETYRRSK EITVRGHNCP KPVLNFYEAN
110 120 130 140 150
FPANVMDVIA RQNFTEPTAI QAQGWPVALS GLDMVGVAQT GSGKTLSYLL
160 170 180 190 200
PAIVHINHQP FLERGDGPIC LVLAPTRELA QQVQQVAAEY CRACRLKSTC
210 220 230 240 250
IYGGAPKGPQ IRDLERGVEI CIATPGRLID FLECGKTNLR RTTYLVLDEA
260 270 280 290 300
DRMLDMGFEP QIRKIVDQIR PDRQTLMWSA TWPKEVRQLA EDFLKDYIHI
310 320 330 340 350
NIGALELSAN HNILQIVDVC HDVEKDEKLI RLMEEIMSEK ENKTIVFVET
360 370 380 390 400
KRRCDELTRK MRRDGWPAMG IHGDKSQQER DWVLNEFKHG KAPILIATDV
410 420 430 440 450
ASRGLDVEDV KFVINYDYPN SSEDYIHRIG RTARSTKTGT AYTFFTPNNI
460 470 480 490 500
KQVSDLISVL REANQAINPK LLQLVEDRGS GRSRGRGGMK DDRRDRYSAG
510 520 530 540 550
KRGGFNTFRD RENYDRGYSS LLKRDFGAKT QNGVYSAANY TNGSFGSNFV
560 570 580 590 600
SAGIQTSFRT GNPTGTYQNG YDSTQQYGSN VPNMHNGMNQ QAYAYPATAA
610
APMIGYPMPT GYSQ
Length:614
Mass (Da):69,148
Last modified:August 1, 1990 - v1
Checksum:i84DF684FD6871594
GO
Isoform 2 (identifier: P17844-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     85-163: Missing.

Note: No experimental confirmation available.
Show »
Length:535
Mass (Da):60,563
Checksum:iA665AD0571ABC456
GO

Computationally mapped potential isoform sequencesi

There are 16 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KTA4J3KTA4_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
614Annotation score:
J3QSF1J3QSF1_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
153Annotation score:
J3QRQ7J3QRQ7_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
212Annotation score:
J3KRZ1J3KRZ1_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
166Annotation score:
J3QLG9J3QLG9_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
46Annotation score:
J3QR62J3QR62_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
52Annotation score:
J3QRN5J3QRN5_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
65Annotation score:
J3KTQ4J3KTQ4_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
181Annotation score:
J3KRX8J3KRX8_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
120Annotation score:
J3QS97J3QS97_HUMAN
Probable ATP-dependent RNA helicase...
DDX5
31Annotation score:
There are more potential isoformsShow all

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029241480S → A. Corresponds to variant dbSNP:rs1140409Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05615485 – 163Missing in isoform 2. 1 PublicationAdd BLAST79

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52104 mRNA Translation: CAA36324.1
AF015812 Genomic DNA Translation: AAB84094.1
BT006943 mRNA Translation: AAP35589.1
AK297192 mRNA Translation: BAG59680.1
AB451257 mRNA Translation: BAG70071.1
AC009994 Genomic DNA No translation available.
CH471109 Genomic DNA Translation: EAW94202.1
CH471109 Genomic DNA Translation: EAW94203.1
BC016027 mRNA Translation: AAH16027.1
X15729 mRNA Translation: CAA33751.1
AJ010931 Genomic DNA Translation: CAA09408.1
CCDSiCCDS11659.1 [P17844-1]
PIRiJC1087
RefSeqiNP_001307524.1, NM_001320595.1 [P17844-1]
NP_001307525.1, NM_001320596.1 [P17844-1]
NP_004387.1, NM_004396.4 [P17844-1]
UniGeneiHs.279806

Genome annotation databases

EnsembliENST00000225792; ENSP00000225792; ENSG00000108654 [P17844-1]
ENST00000450599; ENSP00000403085; ENSG00000108654 [P17844-2]
GeneIDi1655
KEGGihsa:1655
UCSCiuc002jek.3 human [P17844-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52104 mRNA Translation: CAA36324.1
AF015812 Genomic DNA Translation: AAB84094.1
BT006943 mRNA Translation: AAP35589.1
AK297192 mRNA Translation: BAG59680.1
AB451257 mRNA Translation: BAG70071.1
AC009994 Genomic DNA No translation available.
CH471109 Genomic DNA Translation: EAW94202.1
CH471109 Genomic DNA Translation: EAW94203.1
BC016027 mRNA Translation: AAH16027.1
X15729 mRNA Translation: CAA33751.1
AJ010931 Genomic DNA Translation: CAA09408.1
CCDSiCCDS11659.1 [P17844-1]
PIRiJC1087
RefSeqiNP_001307524.1, NM_001320595.1 [P17844-1]
NP_001307525.1, NM_001320596.1 [P17844-1]
NP_004387.1, NM_004396.4 [P17844-1]
UniGeneiHs.279806

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FE2X-ray2.60A/B68-307[»]
4A4DX-ray2.70A52-304[»]
ProteinModelPortaliP17844
SMRiP17844
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108021, 237 interactors
CORUMiP17844
DIPiDIP-29844N
IntActiP17844, 128 interactors
MINTiP17844
STRINGi9606.ENSP00000225792

PTM databases

iPTMnetiP17844
PhosphoSitePlusiP17844
SwissPalmiP17844

Polymorphism and mutation databases

BioMutaiDDX5
DMDMi129383

2D gel databases

SWISS-2DPAGEiP17844

Proteomic databases

EPDiP17844
MaxQBiP17844
PaxDbiP17844
PeptideAtlasiP17844
PRIDEiP17844
ProteomicsDBi53519

Protocols and materials databases

DNASUi1655
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000225792; ENSP00000225792; ENSG00000108654 [P17844-1]
ENST00000450599; ENSP00000403085; ENSG00000108654 [P17844-2]
GeneIDi1655
KEGGihsa:1655
UCSCiuc002jek.3 human [P17844-1]

Organism-specific databases

CTDi1655
DisGeNETi1655
EuPathDBiHostDB:ENSG00000108654.11
GeneCardsiDDX5
HGNCiHGNC:2746 DDX5
HPAiCAB005868
HPA020043
MIMi180630 gene
neXtProtiNX_P17844
OpenTargetsiENSG00000108654
PharmGKBiPA27228
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0331 Eukaryota
COG0513 LUCA
GeneTreeiENSGT00930000150858
HOGENOMiHOG000268804
HOVERGENiHBG015893
InParanoidiP17844
KOiK12823
PhylomeDBiP17844
TreeFamiTF300332

Enzyme and pathway databases

BRENDAi3.6.4.13 2681
ReactomeiR-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-9018519 Estrogen-dependent gene expression
SIGNORiP17844

Miscellaneous databases

ChiTaRSiDDX5 human
EvolutionaryTraceiP17844
GeneWikiiDDX5
GenomeRNAii1655
PROiPR:P17844
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108654 Expressed in 200 organ(s), highest expression level in testis
CleanExiHS_DDX5
ExpressionAtlasiP17844 baseline and differential
GenevisibleiP17844 HS

Family and domain databases

CDDicd00079 HELICc, 1 hit
InterProiView protein in InterPro
IPR033488 DDX5
IPR011545 DEAD/DEAH_box_helicase_dom
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
IPR012587 P68_rpt
IPR000629 RNA-helicase_DEAD-box_CS
IPR014014 RNA_helicase_DEAD_Q_motif
PANTHERiPTHR24031:SF404 PTHR24031:SF404, 1 hit
PfamiView protein in Pfam
PF00270 DEAD, 1 hit
PF00271 Helicase_C, 1 hit
PF08061 P68HR, 2 hits
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00490 HELICc, 1 hit
SM01414 P68HR, 2 hits
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00039 DEAD_ATP_HELICASE, 1 hit
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit
PS51195 Q_MOTIF, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDDX5_HUMAN
AccessioniPrimary (citable) accession number: P17844
Secondary accession number(s): B4DLW8
, B5BU21, D3DU32, E7ETL9, O75681, Q53Y61
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 7, 2018
This is version 211 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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