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 27-MAR-2024, entry version 231. 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 INTERACTION WITH ROTAVIRUS A NON-STRUCTURAL PROTEIN 2 (MICROBIAL RP INFECTION), AND INTERACTION WITH ROTAVIRUS A NON-STRUCTURAL PROTEIN 5 RP (MICROBIAL INFECTION). RX PubMed=30258011; DOI=10.1128/jvi.01363-18; RA Dhillon P., Rao C.D.; RT "Rotavirus Induces Formation of Remodeled Stress Granules and P Bodies and RT Their Sequestration in Viroplasms To Promote Progeny Virus Production."; RL J. Virol. 92:0-0(2018). RN [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] {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 [26] {ECO:0007744|PDB:6F9S} RP X-RAY CRYSTALLOGRAPHY (3.03 ANGSTROMS) OF 301-469 IN COMPLEX WITH C.ELEGANS RP CAR-1, AND INTERACTION WITH 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: (Microbial infection) Interacts with rotavirus A non- CC structural protein 2; this interaction probably plays a role in the CC sequestration of DDX6 in viral factories (PubMed:30258011). Interacts CC with rotavirus A non-structural protein 5; this interaction probably CC plays a role in its sequestration in viral factories (PubMed:30258011). CC {ECO:0000269|PubMed:30258011}. 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=11; 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; 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=4; 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=19; IntAct=EBI-351257, EBI-997311; CC P26196; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-351257, EBI-2349927; CC P26196; Q9NRA8: EIF4ENIF1; NbExp=15; 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; Q6PI77: GPRASP3; NbExp=3; IntAct=EBI-351257, EBI-11519926; 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=10; 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=15; 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 P26196; P0DTC9: N; Xeno; NbExp=5; IntAct=EBI-351257, EBI-25475856; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 477. DR ComplexPortal; CPX-2338; 4EHP-GIGYF2 co-translational mRNA decay complex, DDX6 variant. DR ComplexPortal; CPX-2342; 4EHP-GIGYF1 co-translational mRNA decay complex, DDX6 variant. DR ComplexPortal; CPX-2870; RNA decapping and exonuclease complex, DCP1A variant. DR ComplexPortal; CPX-7341; RNA decapping and exonuclease complex, DCP1B variant. DR CORUM; P26196; -. DR DIP; DIP-29195N; -. DR IntAct; P26196; 213. DR MINT; P26196; -. DR STRING; 9606.ENSP00000478754; -. DR ChEMBL; CHEMBL4105783; -. DR DrugBank; DB01694; D-tartaric acid. DR GlyCosmos; P26196; 1 site, 1 glycan. DR GlyGen; P26196; 4 sites, 1 O-linked glycan (3 sites). 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; 9606-ENSP00000478754; -. DR PeptideAtlas; P26196; -. DR ProteomicsDB; 54313; -. DR Pumba; P26196; -. DR Antibodypedia; 3315; 510 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 AGR; HGNC:2747; -. 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; ECPLFVM; -. DR OrthoDB; 1087080at2759; -. 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; 625 hits in 1146 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 190 other cell types or tissues. DR ExpressionAtlas; P26196; baseline and differential. 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 CDD; cd17940; DEADc_DDX6; 1. DR CDD; cd18787; SF2_C_DEAD; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR IDEAL; IID00712; -. 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 PANTHER; PTHR47960:SF17; ATP-DEPENDENT RNA HELICASE DDX6-RELATED; 1. DR PANTHER; PTHR47960; DEAD-BOX ATP-DEPENDENT RNA HELICASE 50; 1. DR Pfam; PF00270; DEAD; 1. DR Pfam; PF00271; Helicase_C; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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. DR Genevisible; P26196; HS. 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 //