DDX6_HUMAN
ID DDX6_HUMAN Reviewed; 483 AA.
AC P26196; Q5D048;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Probable ATP-dependent RNA helicase DDX6 {ECO:0000305};
DE EC=3.6.4.13 {ECO:0000305|PubMed:27342281};
DE AltName: Full=ATP-dependent RNA helicase p54;
DE AltName: Full=DEAD box protein 6;
DE AltName: Full=Oncogene RCK;
GN Name=DDX6; Synonyms=HLR2, RCK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1579499; DOI=10.1093/nar/20.8.1967;
RA Lu D., Yunis J.J.;
RT "Cloning, expression and localization of an RNA helicase gene from a human
RT lymphoid cell line with chromosomal breakpoint 11q23.3.";
RL Nucleic Acids Res. 20:1967-1972(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-483.
RC TISSUE=Lung;
RX PubMed=1394235;
RA Akao Y., Seto M., Yamamoto K., Iida S., Nakazawa S., Inazawa J., Abe T.,
RA Takahashi T., Ueda R.;
RT "The RCK gene associated with t(11;14) translocation is distinct from the
RT MLL/ALL-1 gene with t(4;11) and t(11;19) translocations.";
RL Cancer Res. 52:6083-6087(1992).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH DCP1A; DCP2; EDC3 AND
RP EDC4, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=16364915; DOI=10.1016/j.molcel.2005.10.031;
RA Fenger-Groen M., Fillman C., Norrild B., Lykke-Andersen J.;
RT "Multiple processing body factors and the ARE binding protein TTP activate
RT mRNA decapping.";
RL Mol. Cell 20:905-915(2005).
RN [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH APOBEC3G.
RX PubMed=16699599; DOI=10.1371/journal.ppat.0020041;
RA Wichroski M.J., Robb G.B., Rana T.M.;
RT "Human retroviral host restriction factors APOBEC3G and APOBEC3F localize
RT to mRNA processing bodies.";
RL PLoS Pathog. 2:E41-E41(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-36, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LIMD1; WTIP AND AJUBA.
RX PubMed=20616046; DOI=10.1073/pnas.0914987107;
RA James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M.,
RA Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J.,
RA Longmore G.D., Bushell M., Sharp T.V.;
RT "LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-
RT mediated gene silencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=22915799; DOI=10.1128/jvi.00595-12;
RA Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.;
RT "HIV-1 replication and APOBEC3 antiviral activity are not regulated by P
RT bodies.";
RL J. Virol. 86:11712-11724(2012).
RN [10]
RP INTERACTION WITH ATXN2L.
RX PubMed=23209657; DOI=10.1371/journal.pone.0050134;
RA Kaehler C., Isensee J., Nonhoff U., Terrey M., Hucho T., Lehrach H.,
RA Krobitsch S.;
RT "Ataxin-2-like is a regulator of stress granules and processing bodies.";
RL PLoS ONE 7:E50134-E50134(2012).
RN [11]
RP INTERACTION WITH TRIM71.
RX PubMed=23125361; DOI=10.1093/nar/gks1032;
RA Loedige I., Gaidatzis D., Sack R., Meister G., Filipowicz W.;
RT "The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA
RT function.";
RL Nucleic Acids Res. 41:518-532(2013).
RN [12]
RP INTERACTION WITH MCRIP1; MCRIP2 AND NUFIP2, SUBCELLULAR LOCATION, AND
RP SUMOYLATION.
RX PubMed=26184334; DOI=10.3390/biom5031441;
RA Bish R., Cuevas-Polo N., Cheng Z., Hambardzumyan D., Munschauer M.,
RA Landthaler M., Vogel C.;
RT "Comprehensive protein interactome analysis of a key RNA helicase:
RT detection of novel stress granule proteins.";
RL Biomolecules 5:1441-1466(2015).
RN [13]
RP INTERACTION WITH EIF4ENIF1.
RX PubMed=26027925; DOI=10.1016/j.celrep.2015.04.065;
RA Nishimura T., Padamsi Z., Fakim H., Milette S., Dunham W.H., Gingras A.C.,
RA Fabian M.R.;
RT "The eIF4E-Binding protein 4E-T is a component of the mRNA decay machinery
RT that bridges the 5' and 3' termini of target mRNAs.";
RL Cell Rep. 11:1425-1436(2015).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25995375; DOI=10.1091/mbc.e15-03-0136;
RA Ayache J., Benard M., Ernoult-Lange M., Minshall N., Standart N., Kress M.,
RA Weil D.;
RT "P-body assembly requires DDX6 repression complexes rather than decay or
RT Ataxin2/2L complexes.";
RL Mol. Biol. Cell 26:2579-2595(2015).
RN [15]
RP FUNCTION.
RX PubMed=26098573; DOI=10.1038/ncb3189;
RA Hu G., McQuiston T., Bernard A., Park Y.D., Qiu J., Vural A., Zhang N.,
RA Waterman S.R., Blewett N.H., Myers T.G., Maraia R.J., Kehrl J.H., Uzel G.,
RA Klionsky D.J., Williamson P.R.;
RT "A conserved mechanism of TOR-dependent RCK-mediated mRNA degradation
RT regulates autophagy.";
RL Nat. Cell Biol. 17:930-942(2015).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH EIF4ENIF1, AND MUTAGENESIS
RP OF GLU-247 AND ARG-386.
RX PubMed=27342281; DOI=10.1093/nar/gkw565;
RA Kamenska A., Simpson C., Vindry C., Broomhead H., Benard M.,
RA Ernoult-Lange M., Lee B.P., Harries L.W., Weil D., Standart N.;
RT "The DDX6-4E-T interaction mediates translational repression and P-body
RT assembly.";
RL Nucleic Acids Res. 44:6318-6334(2016).
RN [18]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4ENIF1.
RX PubMed=28216671; DOI=10.1038/srep42853;
RA Huang J.H., Ku W.C., Chen Y.C., Chang Y.L., Chu C.Y.;
RT "Dual mechanisms regulate the nucleocytoplasmic localization of human
RT DDX6.";
RL Sci. Rep. 7:42853-42853(2017).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LSM14A; LSM14B; EIF4ENIF1;
RP PATL1; EDC3 AND EDC4, INVOLVEMENT IN IDDILF, VARIANTS IDDILF ARG-372;
RP GLN-373; ARG-390; ILE-391 AND PRO-391, AND CHARACTERIZATION OF VARIANTS
RP IDDILF GLN-373; ARG-390; ILE-391 AND PRO-391.
RX PubMed=31422817; DOI=10.1016/j.ajhg.2019.07.010;
RA Balak C., Benard M., Schaefer E., Iqbal S., Ramsey K., Ernoult-Lange M.,
RA Mattioli F., Llaci L., Geoffroy V., Courel M., Naymik M., Bachman K.K.,
RA Pfundt R., Rump P., Ter Beest J., Wentzensen I.M., Monaghan K.G.,
RA McWalter K., Richholt R., Le Bechec A., Jepsen W., De Both M., Belnap N.,
RA Boland A., Piras I.S., Deleuze J.F., Szelinger S., Dollfus H., Chelly J.,
RA Muller J., Campbell A., Lal D., Rangasamy S., Mandel J.L., Narayanan V.,
RA Huentelman M., Weil D., Piton A.;
RT "Rare de novo missense variants in RNA helicase DDX6 cause intellectual
RT disability and dysmorphic features and lead to P-body defects and RNA
RT dysregulation.";
RL Am. J. Hum. Genet. 105:509-525(2019).
RN [20]
RP INTERACTION WITH GIGYF1; GIGYF2; LSM14A; 4E-T; PATL1; EIF4ENIF1 AND EDC3,
RP AND MUTAGENESIS OF CYS-324; LEU-328; LEU-349 AND LYS-353.
RX PubMed=31439631; DOI=10.1101/gad.329219.119;
RA Peter D., Ruscica V., Bawankar P., Weber R., Helms S., Valkov E.,
RA Igreja C., Izaurralde E.;
RT "Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated
RT translational repression.";
RL Genes Dev. 33:1355-1360(2019).
RN [21]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4ENIF1.
RX PubMed=32354837; DOI=10.1101/gad.336073.119;
RA Raesch F., Weber R., Izaurralde E., Igreja C.;
RT "4E-T-bound mRNAs are stored in a silenced and deadenylated form.";
RL Genes Dev. 34:847-860(2020).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 94-299.
RX PubMed=14684915; DOI=10.1107/s0907444903024223;
RA Matsui T., Hogetsu K., Akao Y., Tanaka M., Sato T., Kumasaka T., Tanaka N.;
RT "Crystallization and X-ray analysis of the N-terminal core domain of a
RT tumour-associated human DEAD-box RNA helicase, rck/p54.";
RL Acta Crystallogr. D 60:156-159(2004).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 296-483 IN COMPLEX WITH EDC3,
RP MUTAGENESIS OF GLN-320; HIS-323; THR-327 AND ARG-331, AND INTERACTION WITH
RP EDC3.
RX PubMed=19285948; DOI=10.1016/j.molcel.2009.02.014;
RA Tritschler F., Braun J.E., Eulalio A., Truffault V., Izaurralde E.,
RA Weichenrieder O.;
RT "Structural basis for the mutually exclusive anchoring of P body components
RT EDC3 and Tral to the DEAD box protein DDX6/Me31B.";
RL Mol. Cell 33:661-668(2009).
RN [24] {ECO:0007744|PDB:5ANR}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 95-469 IN COMPLEX WITH EIF4ENIF1
RP AND CNOT1, AND INTERACTION WITH EIF4ENIF1.
RX PubMed=26489469; DOI=10.1016/j.celrep.2015.09.033;
RA Ozgur S., Basquin J., Kamenska A., Filipowicz W., Standart N., Conti E.;
RT "Structure of a human 4E-T/DDX6/CNOT1 complex reveals the different
RT interplay of DDX6-binding proteins with the CCR4-NOT complex.";
RL Cell Rep. 13:703-711(2015).
RN [25] {ECO:0007744|PDB:6F9S}
RP X-RAY CRYSTALLOGRAPHY (3.03 ANGSTROMS) OF 301-469, AND INTERACTION WITH
RP LSM14A.
RX PubMed=29510985; DOI=10.15252/embj.201797869;
RA Brandmann T., Fakim H., Padamsi Z., Youn J.Y., Gingras A.C., Fabian M.R.,
RA Jinek M.;
RT "Molecular architecture of LSM14 interactions involved in the assembly of
RT mRNA silencing complexes.";
RL EMBO J. 37:0-0(2018).
CC -!- FUNCTION: Essential for the formation of P-bodies, cytosolic membrane-
CC less ribonucleoprotein granules involved in RNA metabolism through the
CC coordinated storage of mRNAs encoding regulatory functions
CC (PubMed:25995375, PubMed:27342281, PubMed:31422817). Plays a role in P-
CC bodies to coordinate the storage of translationally inactive mRNAs in
CC the cytoplasm and prevent their degradation (PubMed:27342281). In the
CC process of mRNA degradation, plays a role in mRNA decapping
CC (PubMed:16364915). Blocks autophagy in nutrient-rich conditions by
CC repressing the expression of ATG-related genes through degradation of
CC their transcripts (PubMed:26098573). {ECO:0000269|PubMed:16364915,
CC ECO:0000269|PubMed:25995375, ECO:0000269|PubMed:26098573,
CC ECO:0000269|PubMed:27342281, ECO:0000269|PubMed:31422817}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000305|PubMed:27342281};
CC -!- SUBUNIT: Interacts with LSM14A, LSM14B, EIF4ENIF1/4E-T, PATL1, EDC3 and
CC EDC4 (PubMed:26027925, PubMed:31422817, PubMed:27342281,
CC PubMed:28216671, PubMed:32354837, PubMed:26489469, PubMed:29510985,
CC PubMed:31439631). Forms a complex with DCP1A, DCP2, EDC3 and EDC4/HEDLS
CC (PubMed:16364915, PubMed:19285948). Interacts with LIMD1, WTIP and
CC AJUBA (PubMed:20616046). Interacts with APOBEC3G in an RNA-dependent
CC manner (PubMed:16699599). Interacts with RC3H1 (By similarity).
CC Interacts with ATXN2L (PubMed:23209657). Interacts with MCRIP1
CC (PubMed:26184334). Interacts with MCRIP2 (PubMed:26184334). Interacts
CC with NUFIP2 (PubMed:26184334). Interacts with TRIM71 (via NHL repeats)
CC in an RNA-dependent manner (PubMed:23125361). Interacts with GIGYF1 and
CC GIGYF2 (PubMed:31439631). {ECO:0000250|UniProtKB:P54823,
CC ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:16699599,
CC ECO:0000269|PubMed:19285948, ECO:0000269|PubMed:20616046,
CC ECO:0000269|PubMed:23125361, ECO:0000269|PubMed:23209657,
CC ECO:0000269|PubMed:26027925, ECO:0000269|PubMed:26184334,
CC ECO:0000269|PubMed:26489469, ECO:0000269|PubMed:27342281,
CC ECO:0000269|PubMed:28216671, ECO:0000269|PubMed:29510985,
CC ECO:0000269|PubMed:31422817, ECO:0000269|PubMed:31439631,
CC ECO:0000269|PubMed:32354837}.
CC -!- INTERACTION:
CC P26196; Q9UKV8: AGO2; NbExp=14; IntAct=EBI-351257, EBI-528269;
CC P26196; Q99700: ATXN2; NbExp=8; IntAct=EBI-351257, EBI-697691;
CC P26196; Q9BUH8: BEGAIN; NbExp=3; IntAct=EBI-351257, EBI-742722;
CC P26196; Q8N7W2-2: BEND7; NbExp=3; IntAct=EBI-351257, EBI-10181188;
CC P26196; Q6PI77: BHLHB9; NbExp=3; IntAct=EBI-351257, EBI-11519926;
CC P26196; Q96CA5: BIRC7; NbExp=7; IntAct=EBI-351257, EBI-517623;
CC P26196; Q13137: CALCOCO2; NbExp=6; IntAct=EBI-351257, EBI-739580;
CC P26196; Q49A88-3: CCDC14; NbExp=3; IntAct=EBI-351257, EBI-12105646;
CC P26196; Q8NHQ1: CEP70; NbExp=6; IntAct=EBI-351257, EBI-739624;
CC P26196; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-351257, EBI-742887;
CC P26196; Q6P9H4: CNKSR3; NbExp=3; IntAct=EBI-351257, EBI-10253274;
CC P26196; Q9NPI6: DCP1A; NbExp=9; IntAct=EBI-351257, EBI-374238;
CC P26196; Q92841: DDX17; NbExp=3; IntAct=EBI-351257, EBI-746012;
CC P26196; P17661: DES; NbExp=3; IntAct=EBI-351257, EBI-1055572;
CC P26196; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-351257, EBI-11988027;
CC P26196; Q86X45: DNAAF11; NbExp=3; IntAct=EBI-351257, EBI-9379658;
CC P26196; Q96F86: EDC3; NbExp=15; IntAct=EBI-351257, EBI-997311;
CC P26196; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-351257, EBI-2349927;
CC P26196; Q9NRA8: EIF4ENIF1; NbExp=6; IntAct=EBI-351257, EBI-301024;
CC P26196; Q96C92-2: ENTR1; NbExp=3; IntAct=EBI-351257, EBI-10178036;
CC P26196; A0A0C3SFZ9: FCHO1; NbExp=3; IntAct=EBI-351257, EBI-11977403;
CC P26196; P51114-2: FXR1; NbExp=3; IntAct=EBI-351257, EBI-11022345;
CC P26196; O75420: GIGYF1; NbExp=3; IntAct=EBI-351257, EBI-947774;
CC P26196; Q08379: GOLGA2; NbExp=6; IntAct=EBI-351257, EBI-618309;
CC P26196; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-351257, EBI-10961706;
CC P26196; Q13123: IK; NbExp=3; IntAct=EBI-351257, EBI-713456;
CC P26196; Q13422: IKZF1; NbExp=3; IntAct=EBI-351257, EBI-745305;
CC P26196; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-351257, EBI-11522367;
CC P26196; Q96EL1: INKA1; NbExp=3; IntAct=EBI-351257, EBI-10285157;
CC P26196; Q96N16: JAKMIP1; NbExp=3; IntAct=EBI-351257, EBI-2680803;
CC P26196; P14923: JUP; NbExp=3; IntAct=EBI-351257, EBI-702484;
CC P26196; O76011: KRT34; NbExp=5; IntAct=EBI-351257, EBI-1047093;
CC P26196; Q6A162: KRT40; NbExp=3; IntAct=EBI-351257, EBI-10171697;
CC P26196; P60410: KRTAP10-8; NbExp=6; IntAct=EBI-351257, EBI-10171774;
CC P26196; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-351257, EBI-1216080;
CC P26196; Q9Y5V3: MAGED1; NbExp=3; IntAct=EBI-351257, EBI-716006;
CC P26196; P10636-8: MAPT; NbExp=7; IntAct=EBI-351257, EBI-366233;
CC P26196; Q14696: MESD; NbExp=3; IntAct=EBI-351257, EBI-6165891;
CC P26196; Q5JR59-3: MTUS2; NbExp=4; IntAct=EBI-351257, EBI-11522433;
CC P26196; Q15742: NAB2; NbExp=3; IntAct=EBI-351257, EBI-8641936;
CC P26196; Q15233-2: NONO; NbExp=3; IntAct=EBI-351257, EBI-10203843;
CC P26196; Q9P286: PAK5; NbExp=3; IntAct=EBI-351257, EBI-741896;
CC P26196; Q86TB9: PATL1; NbExp=12; IntAct=EBI-351257, EBI-2562092;
CC P26196; Q9NR12: PDLIM7; NbExp=3; IntAct=EBI-351257, EBI-350517;
CC P26196; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-351257, EBI-79165;
CC P26196; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-351257, EBI-10171633;
CC P26196; P78424: POU6F2; NbExp=3; IntAct=EBI-351257, EBI-12029004;
CC P26196; P41219: PRPH; NbExp=3; IntAct=EBI-351257, EBI-752074;
CC P26196; P57052: RBM11; NbExp=3; IntAct=EBI-351257, EBI-741332;
CC P26196; Q04864-2: REL; NbExp=3; IntAct=EBI-351257, EBI-10829018;
CC P26196; Q59EK9: RUNDC3A; NbExp=3; IntAct=EBI-351257, EBI-747225;
CC P26196; Q96KG9-4: SCYL1; NbExp=5; IntAct=EBI-351257, EBI-12023020;
CC P26196; P34896: SHMT1; NbExp=3; IntAct=EBI-351257, EBI-715117;
CC P26196; Q9P2F8-2: SIPA1L2; NbExp=5; IntAct=EBI-351257, EBI-10326741;
CC P26196; Q8ND83: SLAIN1; NbExp=3; IntAct=EBI-351257, EBI-10269374;
CC P26196; O60504: SORBS3; NbExp=3; IntAct=EBI-351257, EBI-741237;
CC P26196; Q9NWH7-2: SPATA6; NbExp=3; IntAct=EBI-351257, EBI-17860101;
CC P26196; Q99081-3: TCF12; NbExp=3; IntAct=EBI-351257, EBI-11952764;
CC P26196; P15884: TCF4; NbExp=3; IntAct=EBI-351257, EBI-533224;
CC P26196; P15884-3: TCF4; NbExp=3; IntAct=EBI-351257, EBI-13636688;
CC P26196; Q08117: TLE5; NbExp=3; IntAct=EBI-351257, EBI-717810;
CC P26196; Q08117-2: TLE5; NbExp=3; IntAct=EBI-351257, EBI-11741437;
CC P26196; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-351257, EBI-11952721;
CC P26196; Q12933: TRAF2; NbExp=3; IntAct=EBI-351257, EBI-355744;
CC P26196; P14373: TRIM27; NbExp=6; IntAct=EBI-351257, EBI-719493;
CC P26196; O94972: TRIM37; NbExp=3; IntAct=EBI-351257, EBI-741602;
CC P26196; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-351257, EBI-2130429;
CC P26196; Q495M9: USH1G; NbExp=3; IntAct=EBI-351257, EBI-8601749;
CC P26196; Q8N1B4: VPS52; NbExp=6; IntAct=EBI-351257, EBI-2799833;
CC P26196; Q96DT7-3: ZBTB10; NbExp=3; IntAct=EBI-351257, EBI-12017160;
CC P26196; O43829: ZBTB14; NbExp=3; IntAct=EBI-351257, EBI-10176632;
CC P26196; O43298: ZBTB43; NbExp=3; IntAct=EBI-351257, EBI-740718;
CC P26196; Q96BR9: ZBTB8A; NbExp=6; IntAct=EBI-351257, EBI-742740;
CC P26196; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-351257, EBI-14104088;
CC P26196; P17028: ZNF24; NbExp=3; IntAct=EBI-351257, EBI-707773;
CC P26196; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-351257, EBI-527853;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:16364915,
CC ECO:0000269|PubMed:16699599, ECO:0000269|PubMed:20616046,
CC ECO:0000269|PubMed:22915799, ECO:0000269|PubMed:25995375,
CC ECO:0000269|PubMed:26184334, ECO:0000269|PubMed:31422817,
CC ECO:0000269|PubMed:32354837}. Cytoplasm {ECO:0000269|PubMed:26184334,
CC ECO:0000269|PubMed:28216671}. Nucleus {ECO:0000269|PubMed:26184334,
CC ECO:0000269|PubMed:28216671}. Note=Imported in the nucleus via
CC interaction with EIF4ENIF1/4E-T via a piggy-back mechanism
CC (PubMed:28216671). Upon cellular stress, relocalizes to stress granules
CC (PubMed:26184334). {ECO:0000269|PubMed:26184334,
CC ECO:0000269|PubMed:28216671}.
CC -!- TISSUE SPECIFICITY: Abundantly expressed in most tissues.
CC -!- PTM: Sumoylated (PubMed:26184334). {ECO:0000269|PubMed:26184334}.
CC -!- DISEASE: Intellectual developmental disorder with impaired language and
CC dysmorphic facies (IDDILF) [MIM:618653]: An autosomal dominant disorder
CC characterized by intellectual disability, developmental delay, impaired
CC language development, and dysmorphic features including telecanthus,
CC epicanthus, arched eyebrows and low-set ears. Additional features
CC include feeding difficulties, mild cardiac or genitourinary defects,
CC and distal skeletal anomalies. {ECO:0000269|PubMed:31422817}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=A chromosomal aberration involving DDX6 may be a cause of
CC hematopoietic tumors such as B-cell lymphomas. Translocation
CC t(11;14)(q23;q32).
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DDX6/DHH1
CC subfamily. {ECO:0000305}.
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DR EMBL; Z11685; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC065007; AAH65007.1; -; mRNA.
DR EMBL; D17532; BAA04482.1; -; mRNA.
DR CCDS; CCDS44751.1; -.
DR PIR; S22651; S22651.
DR RefSeq; NP_001244120.1; NM_001257191.2.
DR RefSeq; NP_004388.2; NM_004397.5.
DR RefSeq; XP_005271474.1; XM_005271417.3.
DR PDB; 1VEC; X-ray; 2.01 A; A/B=94-299.
DR PDB; 2WAX; X-ray; 2.30 A; A/C=296-483.
DR PDB; 2WAY; X-ray; 2.30 A; A/C=296-483.
DR PDB; 4CRW; X-ray; 1.75 A; B=307-483.
DR PDB; 4CT4; X-ray; 2.30 A; B/D=95-469.
DR PDB; 4CT5; X-ray; 3.00 A; A/B=95-469.
DR PDB; 5ANR; X-ray; 2.10 A; B=95-469.
DR PDB; 6F9S; X-ray; 3.03 A; A=301-469.
DR PDB; 6S8S; X-ray; 2.21 A; A/C=295-483.
DR PDBsum; 1VEC; -.
DR PDBsum; 2WAX; -.
DR PDBsum; 2WAY; -.
DR PDBsum; 4CRW; -.
DR PDBsum; 4CT4; -.
DR PDBsum; 4CT5; -.
DR PDBsum; 5ANR; -.
DR PDBsum; 6F9S; -.
DR PDBsum; 6S8S; -.
DR AlphaFoldDB; P26196; -.
DR SMR; P26196; -.
DR BioGRID; 108022; 288.
DR CORUM; P26196; -.
DR DIP; DIP-29195N; -.
DR IntAct; P26196; 149.
DR MINT; P26196; -.
DR STRING; 9606.ENSP00000478754; -.
DR ChEMBL; CHEMBL4105783; -.
DR DrugBank; DB01694; D-tartaric acid.
DR GlyGen; P26196; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P26196; -.
DR MetOSite; P26196; -.
DR PhosphoSitePlus; P26196; -.
DR SwissPalm; P26196; -.
DR BioMuta; DDX6; -.
DR DMDM; 116241327; -.
DR DOSAC-COBS-2DPAGE; P26196; -.
DR EPD; P26196; -.
DR jPOST; P26196; -.
DR MassIVE; P26196; -.
DR MaxQB; P26196; -.
DR PaxDb; P26196; -.
DR PeptideAtlas; P26196; -.
DR PRIDE; P26196; -.
DR ProteomicsDB; 54313; -.
DR Antibodypedia; 3315; 451 antibodies from 38 providers.
DR DNASU; 1656; -.
DR Ensembl; ENST00000526070.2; ENSP00000433704.1; ENSG00000110367.14.
DR Ensembl; ENST00000534980.7; ENSP00000442266.1; ENSG00000110367.14.
DR Ensembl; ENST00000620157.4; ENSP00000478754.1; ENSG00000110367.14.
DR GeneID; 1656; -.
DR KEGG; hsa:1656; -.
DR MANE-Select; ENST00000534980.7; ENSP00000442266.1; NM_004397.6; NP_004388.2.
DR UCSC; uc031ygs.2; human.
DR CTD; 1656; -.
DR DisGeNET; 1656; -.
DR GeneCards; DDX6; -.
DR HGNC; HGNC:2747; DDX6.
DR HPA; ENSG00000110367; Low tissue specificity.
DR MalaCards; DDX6; -.
DR MIM; 600326; gene.
DR MIM; 618653; phenotype.
DR neXtProt; NX_P26196; -.
DR OpenTargets; ENSG00000110367; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA27229; -.
DR VEuPathDB; HostDB:ENSG00000110367; -.
DR eggNOG; KOG0326; Eukaryota.
DR GeneTree; ENSGT00900000141067; -.
DR HOGENOM; CLU_003041_30_0_1; -.
DR InParanoid; P26196; -.
DR OMA; VCADEAP; -.
DR OrthoDB; 583315at2759; -.
DR PhylomeDB; P26196; -.
DR TreeFam; TF300440; -.
DR BRENDA; 3.6.4.13; 2681.
DR PathwayCommons; P26196; -.
DR Reactome; R-HSA-430039; mRNA decay by 5' to 3' exoribonuclease.
DR SignaLink; P26196; -.
DR SIGNOR; P26196; -.
DR BioGRID-ORCS; 1656; 594 hits in 1064 CRISPR screens.
DR ChiTaRS; DDX6; human.
DR EvolutionaryTrace; P26196; -.
DR GeneWiki; DDX6; -.
DR GenomeRNAi; 1656; -.
DR Pharos; P26196; Tbio.
DR PRO; PR:P26196; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P26196; protein.
DR Bgee; ENSG00000110367; Expressed in ganglionic eminence and 188 other tissues.
DR ExpressionAtlas; P26196; baseline and differential.
DR Genevisible; P26196; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0016442; C:RISC complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0004386; F:helicase activity; TAS:ProtInc.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003724; F:RNA helicase activity; TAS:ProtInc.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; IDA:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0033962; P:P-body assembly; IDA:UniProtKB.
DR GO; GO:0019827; P:stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0034063; P:stress granule assembly; IBA:GO_Central.
DR GO; GO:0019074; P:viral RNA genome packaging; IMP:CACAO.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000629; RNA-helicase_DEAD-box_CS.
DR InterPro; IPR014014; RNA_helicase_DEAD_Q_motif.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00039; DEAD_ATP_HELICASE; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51195; Q_MOTIF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Chromosomal rearrangement; Cytoplasm;
KW Disease variant; Helicase; Hydrolase; Intellectual disability;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; RNA-binding; Ubl conjugation.
FT CHAIN 1..483
FT /note="Probable ATP-dependent RNA helicase DDX6"
FT /id="PRO_0000054983"
FT DOMAIN 127..298
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 308..468
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..316
FT /note="Gyf binding"
FT /evidence="ECO:0000269|PubMed:31439631"
FT REGION 307..483
FT /note="RecA-like domain 2"
FT /evidence="ECO:0000269|PubMed:31439631"
FT MOTIF 96..124
FT /note="Q motif"
FT MOTIF 246..249
FT /note="DEAD box"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 140..147
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOD_RES 36
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VARIANT 372
FT /note="H -> R (in IDDILF)"
FT /evidence="ECO:0000269|PubMed:31422817"
FT /id="VAR_083368"
FT VARIANT 373
FT /note="R -> Q (in IDDILF; decreased P-body assembly;
FT decreased interaction with LSM14A; decreased interaction
FT with LSM14B; decreased interaction with EIF4ENIF1/4E-T;
FT decreased interaction with PATL1)"
FT /evidence="ECO:0000269|PubMed:31422817"
FT /id="VAR_083369"
FT VARIANT 390
FT /note="C -> R (in IDDILF; decreased P-body assembly;
FT decreased interaction with LSM14A; decreased interaction
FT with LSM14B; decreased interaction with EIF4ENIF1/4E-T)"
FT /evidence="ECO:0000269|PubMed:31422817"
FT /id="VAR_083370"
FT VARIANT 391
FT /note="T -> I (in IDDILF; decreased P-body assembly)"
FT /evidence="ECO:0000269|PubMed:31422817"
FT /id="VAR_083371"
FT VARIANT 391
FT /note="T -> P (in IDDILF; decreased P-body assembly)"
FT /evidence="ECO:0000269|PubMed:31422817"
FT /id="VAR_083372"
FT MUTAGEN 247
FT /note="E->Q: Abolished helicase activity and ability to
FT regulate RNA metabolism."
FT /evidence="ECO:0000269|PubMed:27342281"
FT MUTAGEN 320
FT /note="Q->A: Abolishes interaction with EDC3; when
FT associated with A-323; A-327 and A-331."
FT /evidence="ECO:0000269|PubMed:19285948"
FT MUTAGEN 323
FT /note="H->A: Abolishes interaction with EDC3; when
FT associated with A-320; A-327 and A-331."
FT /evidence="ECO:0000269|PubMed:19285948"
FT MUTAGEN 324
FT /note="C->A: In CL-AA; abolishes interaction with PATL1 and
FT reduces interaction with GIGYF1 and GIGYF2, but has no
FT affect on interaction with EDC3, EIF4ENIF1 and LSM14A; when
FT associated with A-328. In 4xmut; abolishes interaction with
FT EDC3; when associated with A-328, A-349 and A-353."
FT /evidence="ECO:0000269|PubMed:31439631"
FT MUTAGEN 327
FT /note="T->A: Abolishes interaction with EDC3; when
FT associated with A-320; A-323 and A-331."
FT /evidence="ECO:0000269|PubMed:19285948"
FT MUTAGEN 328
FT /note="L->A: In CL-AA; abolishes interaction with PATL1 and
FT reduces interaction with GIGYF1 and GIGYF2, but has no
FT affect on interaction with EDC3, EIF4ENIF1 and LSM14A; when
FT associated with A-324. In 4xmut; abolishes interaction with
FT EDC3; when associated with A-324, A-349 and A-353."
FT /evidence="ECO:0000269|PubMed:31439631"
FT MUTAGEN 331
FT /note="R->A: Abolishes interaction with EDC3; when
FT associated with A-320; A-323 and A-327."
FT /evidence="ECO:0000269|PubMed:19285948"
FT MUTAGEN 349
FT /note="L->A: In LK-AA; abolishes interaction with PATL1 and
FT reduces interaction with GIGYF1, GIGYF2, EDC3, EIF4ENIF1
FT and LSM14A; when associated with A-353. In 4xmut; abolishes
FT interaction with EDC3; when associated with A-324, A-328
FT and A-353."
FT /evidence="ECO:0000269|PubMed:31439631"
FT MUTAGEN 353
FT /note="K->A: In LK-AA; abolishes interaction with PATL1 and
FT reduces interaction with GIGYF1, GIGYF2, EDC3, EIF4ENIF1
FT and LSM14A; when associated with A-349. In 4xmut; abolishes
FT interaction with EDC3; when associated with A-324; A-328
FT and A-349."
FT /evidence="ECO:0000269|PubMed:31439631"
FT MUTAGEN 386
FT /note="R->E: Abolished ability to regulate RNA metabolism."
FT /evidence="ECO:0000269|PubMed:27342281"
FT CONFLICT 293
FT /note="Q -> E (in Ref. 1; Z11685)"
FT /evidence="ECO:0000305"
FT HELIX 98..100
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 105..112
FT /evidence="ECO:0007829|PDB:1VEC"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 121..131
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 174..187
FT /evidence="ECO:0007829|PDB:1VEC"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 205..211
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 223..231
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 242..247
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:1VEC"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 257..266
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 272..278
FT /evidence="ECO:0007829|PDB:1VEC"
FT HELIX 282..291
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:1VEC"
FT STRAND 309..315
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 321..331
FT /evidence="ECO:0007829|PDB:4CRW"
FT STRAND 335..340
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 344..356
FT /evidence="ECO:0007829|PDB:4CRW"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:4CRW"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 370..381
FT /evidence="ECO:0007829|PDB:4CRW"
FT STRAND 384..390
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 397..399
FT /evidence="ECO:0007829|PDB:4CT4"
FT STRAND 403..410
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 415..422
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:4CRW"
FT STRAND 432..438
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 443..453
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 462..465
FT /evidence="ECO:0007829|PDB:4CT4"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:6S8S"
SQ SEQUENCE 483 AA; 54417 MW; F802C642861793FB CRC64;
MSTARTENPV IMGLSSQNGQ LRGPVKPTGG PGGGGTQTQQ QMNQLKNTNT INNGTQQQAQ
SMTTTIKPGD DWKKTLKLPP KDLRIKTSDV TSTKGNEFED YCLKRELLMG IFEMGWEKPS
PIQEESIPIA LSGRDILARA KNGTGKSGAY LIPLLERLDL KKDNIQAMVI VPTRELALQV
SQICIQVSKH MGGAKVMATT GGTNLRDDIM RLDDTVHVVI ATPGRILDLI KKGVAKVDHV
QMIVLDEADK LLSQDFVQIM EDIILTLPKN RQILLYSATF PLSVQKFMNS HLQKPYEINL
MEELTLKGVT QYYAYVTERQ KVHCLNTLFS RLQINQSIIF CNSSQRVELL AKKISQLGYS
CFYIHAKMRQ EHRNRVFHDF RNGLCRNLVC TDLFTRGIDI QAVNVVINFD FPKLAETYLH
RIGRSGRFGH LGLAINLITY DDRFNLKSIE EQLGTEIKPI PSNIDKSLYV AEYHSEPVED
EKP
