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Protein

Probable ATP-dependent RNA helicase DDX17

Gene

Ddx17

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

As an RNA helicase, unwinds RNA and alters RNA structures through ATP binding and hydrolysis. Involved in multiple cellular processes, including pre-mRNA splicing, alternative splicing, ribosomal RNA processing and miRNA processing, as well as transcription regulation. Regulates the alternative splicing of exons exhibiting specific features. This function requires the RNA helicase activity. Affects NFAT5 and histone macro-H2A.1/H2AFY alternative splicing in a CDK9-dependent manner. Affects splicing of mediators of steroid hormone signaling pathway, including kinases that phosphorylates ESR1 and transcriptional regulators. By acting splicing of regulatory factors, participates in ESR1 and AR stabilization. Promotes the inclusion of specific AC-rich alternative exons in CD44 transcripts. In myoblasts and epithelial cells, cooperates with HNRNPH1 to control the splicing of specific subsets of exons. In addition to binding mature mRNAs, also interacts with certain pri-microRNAs, including MIR132/miR-132, and stabilizes the primary transcript. Also participates in the MIR132 processing, resulting in significantly higher levels of mature MIR132 than MIR212 despite the fact that both are cotranscribed and co-regulated (PubMed:26947125). Binding of pri-microRNAs may occur on the 3' segment flanking the stem loop via the 5'-[ACG]CAUC[ACU]-3' consensus sequence (By similarity). Participates in MYC down-regulation at high cell density through the production of MYC-targeting microRNAs. Along with DDX5, may be involved in the processing of the 32S intermediate into the mature 28S rRNA. Promoter-specific transcription regulator, functioning as a coactivator or corepressor depending on the context of the promoter and the transcriptional complex in which it exists. Enhances NFAT5 transcriptional activity. Synergizes with TP53 in the activation of the MDM2 promoter; this activity requires acetylation on lysine residues. May also coactivate MDM2 transcription through a TP53-independent pathway. Coactivates MMP7 transcription. Along with CTNNB1, coactivates MYC, JUN, FOSL1 and cyclin D1/CCND1 transcription. Alone or in combination with DDX5 and/or SRA1 non-coding RNA, plays a critical role in promoting the assembly of proteins required for the formation of the transcription initiation complex and chromatin remodeling leading to coactivation of MYOD1-dependent transcription. This helicase-independent activity is required for skeletal muscle cells to properly differentiate into myotubes (PubMed:17011493). During epithelial-to-mesenchymal transition, coregulates SMAD-dependent transcriptional activity, directly controlling key effectors of differentiation, including miRNAs which in turn directly repress its expression. Plays a role in estrogen and testosterone signaling pathway at several levels. Mediates the use of alternative promoters in estrogen-responsive genes and regulates transcription and splicing of a large number of steroid hormone target genes. Contrary to the splicing regulation activity, transcriptional coregulation of the estrogen receptor ESR1 is helicase activity-independent. Plays a role in innate immunity. Specifically restricts bunyavirus infection, including Rift Valley fever virus (RVFV) or La Crosse virus (LACV), but not vesicular stomatitis virus (VSV), in an interferon- and DROSHA-independent manner. Binds to RVFV RNA, likely via structured viral RNA elements (By similarity). Promotes mRNA degradation mediated by the antiviral zinc-finger protein ZC3HAV1, in an ATPase-dependent manner (By similarity).By similarity2 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi136 – 143ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHelicase, Hydrolase, RNA-binding
Biological processAntiviral defense, Immunity, mRNA processing, mRNA splicing, RNA-mediated gene silencing, rRNA processing, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.6.4.13. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Probable ATP-dependent RNA helicase DDX17 (EC:3.6.4.13)
Alternative name(s):
DEAD box protein 17
Gene namesi
Name:Ddx17
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1914290. Ddx17.

Subcellular locationi

  • Nucleus By similarity
  • Nucleusnucleolus By similarity
  • Cytoplasmcytosol By similarity

  • Note: In the course of bunyavirus infection, relocalizes from the nucleus to the cytosol where it binds viral RNA to antagonize replication.By similarity

GO - Cellular componenti

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000549941 – 650Probable ATP-dependent RNA helicase DDX17Add BLAST650

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei29N6-acetyllysineBy similarity1
Modified residuei30N6-acetyllysineBy similarity1
Modified residuei42N6-acetyllysineBy similarity1
Cross-linki50Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki50Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki50Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei444PhosphothreonineBy similarity1
Cross-linki449Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei605Omega-N-methylarginineCombined sources1

Post-translational modificationi

Sumoylation significantly increases stability. It also promotes interaction specifically with HDAC1 (but not HDAC2, nor HDAC3) and strongly stimulates ESR1 and TP53 coactivation.By similarity
Acetylation at lysine residues stabilizes the protein, stimulates interaction with HDAC1 and HDAC3, but not HDAC2, and represses ESR1 and TP53 coactivation activity.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ501J6.
PaxDbiQ501J6.
PeptideAtlasiQ501J6.
PRIDEiQ501J6.

2D gel databases

REPRODUCTION-2DPAGEiIPI00405364.

PTM databases

iPTMnetiQ501J6.
PhosphoSitePlusiQ501J6.

Expressioni

Gene expression databases

CleanExiMM_DDX17.

Interactioni

Subunit structurei

Interacts with DDX5 in an RNA-independent manner (By similarity). Interacts with CDK9 transcription elongation complex under basal conditions. Following cell stimulation with poly(I:C), a synthetic double-stranded RNA mimicking viral infection, the interaction with CDK9 is decreased (By similarity). Interacts with ESR1 in an estrogen-independent manner (By similarity). Interacts with HNRNPH1; this interaction is important for the regulation of alternative splicing on G-quadruplex structures (By similarity). At high, but not low, cell density, interacts with DROSHA and DGCR8, the core components of the microprocessor complex involved in the maturation of primary microRNAs (pri-miRNAs) into pre-miRNAs. The interaction with DGCR8 is reduced during mitosis. At low, but not high, cell density, interacts with YAP1 and with its paralog, WWTR1/TAZ. Interactions with DROSHA and YAP1 are mutually exclusive. In vitro, the pre-miRNA processing activity of the DDX17-containing microprocessor complex is weaker than that of the DROSHA/DGCR8 microprocessor complex (By similarity). Interacts with UPF3B (By similarity). Interacts with NFAT5; this interaction leads to DDX17 recruitment to LNC2 and S100A4 promoters and NFAT5-mediated DDX17-enhanced transactivation (By similarity). Interacts with HDAC1, HDAC2 and HDAC3; this interaction with HDAC1 and HDAC3, but not HDAC2, depends upon DDX17 acetylation (By similarity). Interacts with ZC3HAV1 (via N-terminal domain) in an RNA-independent manner. Interacts with EXOSC3/RRP40 and EXOSC5/RRP46; this interaction may be indirect and mediated by ZC3HAV1-binding (By similarity). Interacts with EP300; this interaction leads to acetylation at lysine residues (By similarity). Interacts with CREBBP/CBP and KAT2B/P/CAF (By similarity). Directly interacts with CTNNB1 (By similarity). Interacts with MYOD1 (PubMed:17011493). Interacts with TP53 (By similarity). Interacts with DCP1A in an RNA-independent manner. Interacts with DCP2 in an RNA-dependent manner (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Yap1P469383EBI-911206,EBI-1211949

GO - Molecular functioni

Protein-protein interaction databases

BioGridi211894. 5 interactors.
IntActiQ501J6. 9 interactors.
MINTiMINT-1867698.
STRINGi10090.ENSMUSP00000055535.

Structurei

3D structure databases

ProteinModelPortaliQ501J6.
SMRiQ501J6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini123 – 298Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST176
Domaini326 – 473Helicase C-terminalPROSITE-ProRule annotationAdd BLAST148

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni468 – 650Transactivation domainBy similarityAdd BLAST183
Regioni639 – 647Interaction with YAP1By similarity9

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi92 – 120Q motifAdd BLAST29
Motifi246 – 249DEAD box4

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0331. Eukaryota.
COG0513. LUCA.
HOVERGENiHBG015893.
InParanoidiQ501J6.
KOiK13178.

Family and domain databases

InterProiView protein in 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.
PfamiView protein in Pfam
PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
SMARTiView protein in SMART
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
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

Isoform 1 (identifier: Q501J6-1) [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
MRGGGFGDRD RDRDRGGFGA RGGSGLPPKK FGNPGERLRK KKWDLSELPK
60 70 80 90 100
FEKNFYVEHP EVARLTPYEV DELRRKKEIT VRGGDVCPKP VFAFHHANFP
110 120 130 140 150
QYVMDVLMDQ HFTEPTPIQC QGFPLALSGR DMVGIAQTGS GKTLAYLLPA
160 170 180 190 200
IVHINHQPYL ERGDGPICLV LAPTRELAQQ VQQVADDYGK CSRLKSTCIY
210 220 230 240 250
GGAPKGPQIR DLERGVEICI ATPGRLIDFL ESGKTNLRRC TYLVLDEADR
260 270 280 290 300
MLDMGFEPQI RKIVDQIRPD RQTLMWSATW PKEVRQLAED FLRDYTQINV
310 320 330 340 350
GNLELSANHN ILQIVDVCME SEKDHKLIQL MEEIMAEKEN KTIIFVETKR
360 370 380 390 400
RCDDLTRRMR RDGWPAMCIH GDKSQPERDW VLNEFRSGKA PILIATDVAS
410 420 430 440 450
RGLDVEDVKF VINYDYPNSS EDYVHRIGRT ARSTNKGTAY TFFTPGNLKQ
460 470 480 490 500
ARELIKVLEE ANQAINPKLM QLVDHRGGGG GGGGRSRYRT TSSANNPNLM
510 520 530 540 550
YQDECDRRLR GVKDGGRRDS TSYRDRSETD RASYANGSGY GSPNSAFGAQ
560 570 580 590 600
AGQYTYAQGT YGAAAYGTSG YTAQEYAAGT YGASSTASAG RSSQSSSQQF
610 620 630 640 650
SGIGRSGQQP QPLMSQQFAQ PPGATNMIGY MGQTAYQYPP PPPPPPPSRK
Length:650
Mass (Da):72,399
Last modified:June 7, 2005 - v1
Checksum:iE2590F3E53883D3C
GO
Isoform 2 (identifier: Q501J6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     404-407: DVED → GLYR
     408-650: Missing.

Show »
Length:407
Mass (Da):46,364
Checksum:iB263C228210F5BAF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti320E → V in AAH62910 (PubMed:15489334).Curated1
Sequence conflicti362D → Y in AAH62910 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015780404 – 407DVED → GLYR in isoform 2. 2 Publications4
Alternative sequenceiVSP_015781408 – 650Missing in isoform 2. 2 PublicationsAdd BLAST243

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK039888 mRNA. Translation: BAC30474.1.
BC062910 mRNA. Translation: AAH62910.1.
BC096036 mRNA. Translation: AAH96036.1.
RefSeqiNP_001035277.1. NM_001040187.1. [Q501J6-1]
NP_951061.1. NM_199079.1. [Q501J6-2]
NP_951062.1. NM_199080.2.
UniGeneiMm.29644.

Genome annotation databases

GeneIDi67040.
KEGGimmu:67040.
UCSCiuc007wtq.1. mouse. [Q501J6-1]
uc007wtt.1. mouse. [Q501J6-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDDX17_MOUSE
AccessioniPrimary (citable) accession number: Q501J6
Secondary accession number(s): Q6P5G1, Q8BIN2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: June 7, 2005
Last modified: August 30, 2017
This is version 117 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families