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Protein

ATP-dependent DNA/RNA helicase DHX36

Gene

Dhx36

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

Functioni

Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:25611385). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:21703541, PubMed:21590736). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-ADN and G4-RNA) (By similarity). Plays a role in genomic integrity (By similarity). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (By similarity). Plays a role in transcriptional regulation. Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:25611385) (By similarity). Plays a role in post-transcriptional regulation (By similarity). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (By similarity). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (By similarity). Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression (By similarity). Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively (By similarity). Binds also to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (By similarity). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (By similarity). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of proinflammatory cytokines via the adapter molecule TICAM1 (PubMed:21703541). Required for the early embryonic development and hematopoiesis (PubMed:22422825). Involved in the regulation of cardioblast differentiation and proliferation during heart development (PubMed:26489465). Involved in spermatogonia differentiation (PubMed:25611385). May play a role in ossification (PubMed:21590736).By similarity5 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.By similarity

Cofactori

Mg2+By similarity

Activity regulationi

ATPase activity is enhanced in the presence of homopolymeric poly(U) RNAs, but not by double-stranded DNA (dsDNA), double-stranded RNA (dsRNA) and tRNA.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi328MagnesiumBy similarity1
Metal bindingi330MagnesiumBy similarity1
Binding sitei550ATP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi226 – 231ATPBy similarity6
Nucleotide bindingi595 – 598ATPBy similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding, Helicase, Hydrolase, Repressor, RNA-binding
Biological processAntiviral defense, Differentiation, Immunity, Innate immunity, Transcription, Transcription regulation, Translation regulation, Transport
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-MMU-933541 TRAF6 mediated IRF7 activation
R-MMU-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-dependent DNA/RNA helicase DHX36Curated (EC:3.6.4.13By similarity)
Alternative name(s):
DEAD/H box polypeptide 361 Publication
DEAH box protein 36Curated
MLE-like protein 1By similarity
RNA helicase associated with AU-rich element AREBy similarity
Gene namesi
Name:Dhx36Imported
Synonyms:Ddx36By similarity, Kiaa1488, Mlel1By similarity
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1919412 Dhx36

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

Cell projection, Chromosome, Cytoplasm, Mitochondrion, Nucleus, Telomere

Pathology & Biotechi

Disruption phenotypei

Mice die at around embryonic 7 days post-coitum (dpc). Conditional knockout mice in the hematopoeitic system leads to hemolytic anemia, a reduction in blood platelet and erythroblast development (PubMed:22422825). Cardiac progenitor-cell-specific knockout mice die around 12.5 dpc and lead to abnormal cardiovascular development with a reduction in cardiomyocyte proliferation. Mice display increased NKX2-5 mRNA but decreased NKX2-5 protein levels, respectively, in the heart at 12.5 dpc compared to wild-type mice (PubMed:26489465). Male germ-cell-specific knockout mice lead to testicular hypoplasia development, due to spermatogonia differentiation block, meiosis initiation arrest as early as meiosis I stage and an absence of mature sperm in the epididymis (PubMed:25611385). Mice show several alteration in meiosis-related gene expression such as the differentiating spermatogonia markers KIT/c-kit (PubMed:25611385).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002475311 – 1001ATP-dependent DNA/RNA helicase DHX36Add BLAST1001

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei154PhosphoserineBy similarity1
Modified residuei940N6-acetyllysineBy similarity1
Modified residuei956PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8VHK9
MaxQBiQ8VHK9
PaxDbiQ8VHK9
PeptideAtlasiQ8VHK9
PRIDEiQ8VHK9

PTM databases

iPTMnetiQ8VHK9
PhosphoSitePlusiQ8VHK9

Expressioni

Tissue specificityi

Expressed in spermatogonia stem cells and primary spermatocytes (at protein level) (PubMed:25611385). Expressed strongly in testis. Weakly expressed in heart, lung, liver, kidney, small intestine, spleen, lymphe node and thymus (PubMed:25611385).1 Publication

Developmental stagei

Expressed in the embryonic heart at 10.5 and increases from 14.5 to 16.5 dpc, and then gradually decreases until postnal day 7 (PubMed:26489465). Expressed during the testicular development from embryonic day 18.5 to postnatal day 35 (PubMed:25611385).2 Publications

Gene expression databases

BgeeiENSMUSG00000027770 Expressed in 283 organ(s), highest expression level in ventromedial nucleus of hypothalamus
CleanExiMM_DHX36
GenevisibleiQ8VHK9 MM

Interactioni

Subunit structurei

Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without dsRNA poly(I:C) ligand stimulation (PubMed:21703541). Interacts (via C-terminus) with TICAM1 (via TIR domain) (PubMed:21703541). Interacts (via C-terminus) with DDX21; this interaction serves as bridges to TICAM1 (PubMed:21703541). Interacts with TERT; this interaction is dependent on the ability of DHX36 to bind to the G-quadruplex RNA (G4-RNA) structure present in the telomerase RNA template component (TERC). Interacts with DKC1; this interaction is dependent on the ability of DHX36 to bind to the G4-RNA structure present in TERC. Interacts with PARN; this interaction stimulates PARN to enhance uPA mRNA decay. Interacts with EXOSC3; this interaction occurs in a RNase-insensitive manner. Interacts with EXOSC10; this interaction occurs in a RNase-insensitive manner. Interacts with ILF3; this interaction occurs in a RNA-dependent manner. Interacts with ELAVL1; this interaction occurs in an RNA-dependent manner. Interacts with DDX5; this interaction occurs in a RNA-dependent manner. Interacts with DDX17; this interaction occurs in a RNA-dependent manner. Interacts with HDAC1; this interaction occurs in a RNA-dependent manner (By similarity) (PubMed:21590736). Interacts with HDAC3; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with HDAC4 (PubMed:21590736). Interacts with AGO1. Interacts with AGO2 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi215193, 3 interactors
DIPiDIP-48576N
IntActiQ8VHK9, 3 interactors
STRINGi10090.ENSMUSP00000029336

Structurei

3D structure databases

ProteinModelPortaliQ8VHK9
SMRiQ8VHK9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini210 – 380Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST171
Domaini470 – 640Helicase C-terminalPROSITE-ProRule annotationAdd BLAST171

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 193Necessary for nuclear and nucleolar caps localizationsBy similarityAdd BLAST193
Regioni1 – 97Required for the pre-miR-134 transportBy similarityAdd BLAST97
Regioni1 – 44Required for recruitment to cytoplasmic stress granulesBy similarityAdd BLAST44
Regioni46 – 98Required for G4-DNA- and G4-RNA-bindingBy similarityAdd BLAST53
Regioni46 – 68DSM (DHX36-specific motif)By similarityAdd BLAST23
Regioni99 – 379RecA-like domain 1By similarityAdd BLAST281
Regioni258 – 310Necessary for interaction with single-stranded DNA at the 3'-end of the G4-DNA structureBy similarityAdd BLAST53
Regioni380 – 621RecA-like domain 2By similarityAdd BLAST242
Regioni491 – 550Necessary for interaction with single-stranded DNA at the 3'-end of the G4-DNA structureBy similarityAdd BLAST60
Regioni622 – 691WH domainBy similarityAdd BLAST70
Regioni631 – 690Necessary for interaction with single-stranded DNA at the 3'-end of the G4-DNA structureBy similarityAdd BLAST60
Regioni834 – 898OB-fold-like subdomainsBy similarityAdd BLAST65
Regioni842 – 853Necessary for interaction with single-stranded DNA at the 3'-end of the G4-DNA structureBy similarityAdd BLAST12
Regioni863 – 893Necessary for interaction with single-stranded DNA at the 3'-end of the G4-DNA structureBy similarityAdd BLAST31

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili120 – 147Sequence analysisAdd BLAST28

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi327 – 330DEAH boxPROSITE-ProRule annotation4
Motifi510 – 521Nuclear localization signalBy similarityAdd BLAST12

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi13 – 44Gly-richAdd BLAST32

Domaini

The DHX36-specific motif (DSM) form folds into a DNA-binding-induced alpha-helix that together with the oligonucleotide and oligosaccharide-binding-fold-like (OB-fold-like) subdomain bind to Myc-promoter G4-DNA-containing stucture in an ATP-dependent manner. Upon G4-DNA-binding, DHX36 pulls on DSM in the 3'-direction, inducing rearrangement of the RecA-like 1 and 2 and the degenerate-winged-helix (WH) regions; these rearrangements are propbably responsible for the ATP-independent repetitive G4-DNA unfolding activity, one residue at a time. Upon resolving of G4-DNA into separate nucleotide strands, and ATP hydrolysis, the apoprotein of DHX36 seems incompatible with G4-DNA-binding (By similarity). The N-terminus is necessary for its recruitment to cytoplasmic stress granules (SGs) upon arsenite-induced treatment (By similarity).By similarity

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG0920 Eukaryota
COG1643 LUCA
GeneTreeiENSGT00760000119189
HOGENOMiHOG000247063
HOVERGENiHBG081438
InParanoidiQ8VHK9
KOiK14442
OMAiTMVFPMA
OrthoDBiEOG091G01I0
TreeFamiTF324744

Family and domain databases

CDDicd00079 HELICc, 1 hit
InterProiView protein in InterPro
IPR011545 DEAD/DEAH_box_helicase_dom
IPR002464 DNA/RNA_helicase_DEAH_CS
IPR011709 DUF1605
IPR007502 Helicase-assoc_dom
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00270 DEAD, 1 hit
PF04408 HA2, 1 hit
PF00271 Helicase_C, 1 hit
PF07717 OB_NTP_bind, 1 hit
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00847 HA2, 1 hit
SM00490 HELICc, 1 hit
SUPFAMiSSF52540 SSF52540, 2 hits
PROSITEiView protein in PROSITE
PS00690 DEAH_ATP_HELICASE, 1 hit
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit

Sequencei

Sequence statusi: Complete.

Q8VHK9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSYDYHQSWS RDGGPRGSGQ GSSGGGGGGS RGSGGGGGGR GGRGRHPAHL
60 70 80 90 100
KGREIGLWYA KKQTQKNKEA ERQERAVVHM DERREEQIVQ LLNSVQAKTD
110 120 130 140 150
KDSEAQISWF APEDHGYGTE VSSEKKINSE KKLDNQEKKL LNQEKKTFRI
160 170 180 190 200
TDKSYIDRDS EYLLQENEPN LSLDQHLLED LQRKKTDPRY IEMQRFRKKL
210 220 230 240 250
PSYGMQKELV NLINNHQVTV ISGETGCGKT TQVTQFILDN YIERGKGSAC
260 270 280 290 300
RIVCTQPRRI SAISVAERVA TERAESCGNG NSTGYQIRLQ SRLPRKQGSI
310 320 330 340 350
LYCTTGIILQ WLQSDSRLSS VSHIVLDEIH ERNLQSDVLM TVIKDLLHFR
360 370 380 390 400
SDLKVILMSA TLNAEKFSEY FGNCPMIHIP GFTFPVVEYL LEDIIEKIRY
410 420 430 440 450
VPDQKEHRSQ FKRGFMQGHV NRQEKEEKEA IYKERWPAYI KELRTRYSAS
460 470 480 490 500
TVDVLQMMDD DKVDLNLIAA LIRYIVLEEE DGAILVFLPG WDNISTLHDL
510 520 530 540 550
LMSQVMFKSD KFLIIPLHSL MPTVNQTQVF KKTPPGVRKI VIATNIAETS
560 570 580 590 600
ITIDDVVYVI DGGKIKETHF DTQNNISTMS AEWVSKANAK QRKGRAGRVQ
610 620 630 640 650
PGHCYHLYNG LRASLLDDYQ LPEILRTPLE ELCLQIKILR LGGIAYFLSR
660 670 680 690 700
LMDPPSNEAV VLSIKHLMEL SALDKQEELT PLGVHLARLP VEPHIGKMIL
710 720 730 740 750
FGALFCCLDP VLTIAASLSF KDPFVIPLGK EKIADARRKE LAKETRSDHL
760 770 780 790 800
TVVNAFEGWE EAKRRGFRYE KDYCWEYFLS SNTLQMLHNM KGQFAEHLLG
810 820 830 840 850
AGFVSSRSPK DPKANINSDN EKIIKAVICA GLYPKVAKIR LNLGKKRKMV
860 870 880 890 900
KVHTKSDGLV SIHPKSVNVE QTDFHYNWLI YHLKMRTSSI YLYDCTEVSP
910 920 930 940 950
YCLLFFGGDI SIQKDKDQEI IAVDEWIVFQ SPERIAHLVK GLRKELDSLL
960 970 980 990 1000
QEKIESPHPV DWDDTKSRDC AVLSAILDLI KTQEKATPRN LPPRSQDGYY

S
Length:1,001
Mass (Da):113,883
Last modified:October 3, 2012 - v2
Checksum:i4DD9292011B8155A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti29Missing in BAC98183 (PubMed:14621295).Curated1
Sequence conflicti160S → T in BAC98183 (PubMed:14621295).Curated1
Sequence conflicti984E → K in AAL47006 (PubMed:12198572).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF448804 mRNA Translation: AAL47006.1
AC114424 Genomic DNA No translation available.
CH466530 Genomic DNA Translation: EDL35384.1
AK129373 mRNA Translation: BAC98183.1
AK013031 mRNA Translation: BAB28610.1
CCDSiCCDS17379.1
RefSeqiNP_082412.2, NM_028136.2
XP_011238540.1, XM_011240238.1
UniGeneiMm.224233

Genome annotation databases

EnsembliENSMUST00000029336; ENSMUSP00000029336; ENSMUSG00000027770
GeneIDi72162
KEGGimmu:72162
UCSCiuc008pjn.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF448804 mRNA Translation: AAL47006.1
AC114424 Genomic DNA No translation available.
CH466530 Genomic DNA Translation: EDL35384.1
AK129373 mRNA Translation: BAC98183.1
AK013031 mRNA Translation: BAB28610.1
CCDSiCCDS17379.1
RefSeqiNP_082412.2, NM_028136.2
XP_011238540.1, XM_011240238.1
UniGeneiMm.224233

3D structure databases

ProteinModelPortaliQ8VHK9
SMRiQ8VHK9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi215193, 3 interactors
DIPiDIP-48576N
IntActiQ8VHK9, 3 interactors
STRINGi10090.ENSMUSP00000029336

PTM databases

iPTMnetiQ8VHK9
PhosphoSitePlusiQ8VHK9

Proteomic databases

EPDiQ8VHK9
MaxQBiQ8VHK9
PaxDbiQ8VHK9
PeptideAtlasiQ8VHK9
PRIDEiQ8VHK9

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029336; ENSMUSP00000029336; ENSMUSG00000027770
GeneIDi72162
KEGGimmu:72162
UCSCiuc008pjn.2 mouse

Organism-specific databases

CTDi170506
MGIiMGI:1919412 Dhx36
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0920 Eukaryota
COG1643 LUCA
GeneTreeiENSGT00760000119189
HOGENOMiHOG000247063
HOVERGENiHBG081438
InParanoidiQ8VHK9
KOiK14442
OMAiTMVFPMA
OrthoDBiEOG091G01I0
TreeFamiTF324744

Enzyme and pathway databases

ReactomeiR-MMU-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-MMU-933541 TRAF6 mediated IRF7 activation
R-MMU-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling

Miscellaneous databases

ChiTaRSiDhx36 mouse
PROiPR:Q8VHK9
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027770 Expressed in 283 organ(s), highest expression level in ventromedial nucleus of hypothalamus
CleanExiMM_DHX36
GenevisibleiQ8VHK9 MM

Family and domain databases

CDDicd00079 HELICc, 1 hit
InterProiView protein in InterPro
IPR011545 DEAD/DEAH_box_helicase_dom
IPR002464 DNA/RNA_helicase_DEAH_CS
IPR011709 DUF1605
IPR007502 Helicase-assoc_dom
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00270 DEAD, 1 hit
PF04408 HA2, 1 hit
PF00271 Helicase_C, 1 hit
PF07717 OB_NTP_bind, 1 hit
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00847 HA2, 1 hit
SM00490 HELICc, 1 hit
SUPFAMiSSF52540 SSF52540, 2 hits
PROSITEiView protein in PROSITE
PS00690 DEAH_ATP_HELICASE, 1 hit
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDHX36_MOUSE
AccessioniPrimary (citable) accession number: Q8VHK9
Secondary accession number(s): G3X8Y4, Q6ZPP7, Q9CSE8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: October 3, 2012
Last modified: October 10, 2018
This is version 139 of the entry and version 2 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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