ID DDX1_HUMAN Reviewed; 740 AA.
AC Q92499; B4DME8; B4DPN6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 2.
DT 27-MAR-2024, entry version 213.
DE RecName: Full=ATP-dependent RNA helicase DDX1;
DE EC=3.6.4.13 {ECO:0000269|PubMed:21589879};
DE AltName: Full=DEAD box protein 1;
DE AltName: Full=DEAD box protein retinoblastoma;
DE Short=DBP-RB;
GN Name=DDX1;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Retinoblastoma;
RX PubMed=7689221; DOI=10.1073/pnas.90.16.7578;
RA Godbout R., Squire J.;
RT "Amplification of a DEAD box protein gene in retinoblastoma cell lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:7578-7582(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, and Uterus;
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 [4]
RP INTERACTION WITH CSTF2, AND SUBCELLULAR LOCATION.
RX PubMed=11598190; DOI=10.1091/mbc.12.10.3046;
RA Bleoo S., Sun X., Hendzel M.J., Rowe J.M., Packer M., Godbout R.;
RT "Association of human DEAD box protein DDX1 with a cleavage stimulation
RT factor involved in 3'-end processing of pre-MRNA.";
RL Mol. Biol. Cell 12:3046-3059(2001).
RN [5]
RP FUNCTION, INTERACTION WITH HNRNPK, AND RNA-BINDING.
RX PubMed=12183465; DOI=10.1074/jbc.m206981200;
RA Chen H.C., Lin W.C., Tsay Y.G., Lee S.C., Chang C.J.;
RT "An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous
RT nuclear ribonucleoprotein K.";
RL J. Biol. Chem. 277:40403-40409(2002).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [7]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH REV OF HIV-1 (MICROBIAL
RP INFECTION), RNA-BINDING (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION
RP (MICROBIAL INFECTION).
RX PubMed=15567440; DOI=10.1016/j.virol.2004.09.039;
RA Fang J., Kubota S., Yang B., Zhou N., Zhang H., Godbout R., Pomerantz R.J.;
RT "A DEAD box protein facilitates HIV-1 replication as a cellular co-factor
RT of Rev.";
RL Virology 330:471-480(2004).
RN [8]
RP FUNCTION, INTERACTION WITH MBNL1, SUBCELLULAR LOCATION, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RX PubMed=18335541; DOI=10.1002/jnr.21655;
RA Onishi H., Kino Y., Morita T., Futai E., Sasagawa N., Ishiura S.;
RT "MBNL1 associates with YB-1 in cytoplasmic stress granules.";
RL J. Neurosci. Res. 86:1994-2002(2008).
RN [9]
RP FUNCTION, INTERACTION WITH ATM, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=18710941; DOI=10.1128/mcb.01053-08;
RA Li L., Monckton E.A., Godbout R.;
RT "A role for DEAD box 1 at DNA double-strand breaks.";
RL Mol. Cell. Biol. 28:6413-6425(2008).
RN [10]
RP INTERACTION WITH RELA, MUTAGENESIS OF GLU-371, SUBCELLULAR LOCATION, AND
RP DOMAIN HELICASE ATP-BINDING.
RX PubMed=19058135; DOI=10.1002/jcb.22004;
RA Ishaq M., Ma L., Wu X., Mu Y., Pan J., Hu J., Hu T., Fu Q., Guo D.;
RT "The DEAD-box RNA helicase DDX1 interacts with RelA and enhances nuclear
RT factor kappaB-mediated transcription.";
RL J. Cell. Biochem. 106:296-305(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-239; LYS-268 AND LYS-281, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH REPLICASE POLYPROTEIN 1AB
RP NSP14 OF IBV AND SARS-COV (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION
RP (MICROBIAL INFECTION).
RX PubMed=20573827; DOI=10.1128/jvi.00392-10;
RA Xu L., Khadijah S., Fang S., Wang L., Tay F.P., Liu D.X.;
RT "The cellular RNA helicase DDX1 interacts with coronavirus nonstructural
RT protein 14 and enhances viral replication.";
RL J. Virol. 84:8571-8583(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
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 [15]
RP INTERACTION WITH PQBP1.
RX PubMed=21933836; DOI=10.1093/hmg/ddr430;
RA Kunde S.A., Musante L., Grimme A., Fischer U., Mueller E., Wanker E.E.,
RA Kalscheuer V.M.;
RT "The X-chromosome-linked intellectual disability protein PQBP1 is a
RT component of neuronal RNA granules and regulates the appearance of stress
RT granules.";
RL Hum. Mol. Genet. 20:4916-4931(2011).
RN [16]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21589879; DOI=10.1371/journal.pone.0019810;
RA Garbelli A., Beermann S., Di Cicco G., Dietrich U., Maga G.;
RT "A motif unique to the human DEAD-box protein DDX3 is important for nucleic
RT acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication.";
RL PLoS ONE 6:E19810-E19810(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP IDENTIFICATION IN THE TRNA SPLICING LIGASE COMPLEX.
RX PubMed=21311021; DOI=10.1126/science.1197847;
RA Popow J., Englert M., Weitzer S., Schleiffer A., Mierzwa B., Mechtler K.,
RA Trowitzsch S., Will C.L., Luhrmann R., Soll D., Martinez J.;
RT "HSPC117 is the essential subunit of a human tRNA splicing ligase
RT complex.";
RL Science 331:760-764(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP FUNCTION, IDENTIFICATION IN THE TRNA SPLICING LIGASE COMPLEX, AND
RP MUTAGENESIS OF LYS-52 AND GLU-371.
RX PubMed=24870230; DOI=10.1038/nature13284;
RA Popow J., Jurkin J., Schleiffer A., Martinez J.;
RT "Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing
RT factors.";
RL Nature 511:104-107(2014).
RN [22]
RP SUBCELLULAR LOCATION.
RX PubMed=24608264; DOI=10.1371/journal.pone.0090957;
RA Perez-Gonzalez A., Pazo A., Navajas R., Ciordia S., Rodriguez-Frandsen A.,
RA Nieto A.;
RT "hCLE/C14orf166 associates with DDX1-HSPC117-FAM98B in a novel
RT transcription-dependent shuttling RNA-transporting complex.";
RL PLoS ONE 9:E90957-E90957(2014).
RN [23]
RP INTERACTION WITH ERCC6.
RX PubMed=26030138; DOI=10.1371/journal.pone.0128558;
RA Nicolai S., Filippi S., Caputo M., Cipak L., Gregan J., Ammerer G.,
RA Frontini M., Willems D., Prantera G., Balajee A.S., Proietti-De-Santis L.;
RT "Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group
RT B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin
RT Dynamics.";
RL PLoS ONE 10:E0128558-E0128558(2015).
RN [24]
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 [25]
RP INTERACTION WITH VENEZUELAN EQUINE ENCEPHALITIS VIRUS NON-STRUCTURAL
RP PROTEIN 3 (MICROBIAL INFECTION).
RX PubMed=27105836; DOI=10.1016/j.antiviral.2016.04.008;
RA Amaya M., Brooks-Faulconer T., Lark T., Keck F., Bailey C., Raman V.,
RA Narayanan A.;
RT "Venezuelan equine encephalitis virus non-structural protein 3 (nsP3)
RT interacts with RNA helicases DDX1 and DDX3 in infected cells.";
RL Antiviral Res. 131:49-60(2016).
RN [26]
RP INTERACTION WITH FAM98A, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=28040436; DOI=10.1016/j.biocel.2016.12.013;
RA Akter K.A., Mansour M.A., Hyodo T., Senga T.;
RT "FAM98A associates with DDX1-C14orf166-FAM98B in a novel complex involved
RT in colorectal cancer progression.";
RL Int. J. Biochem. Cell Biol. 84:1-13(2017).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-281, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 72-283.
RX PubMed=26323305; DOI=10.1107/s2053230x15013709;
RA Kellner J.N., Meinhart A.;
RT "Structure of the SPRY domain of the human RNA helicase DDX1, a putative
RT interaction platform within a DEAD-box protein.";
RL Acta Crystallogr. F 71:1176-1188(2015).
CC -!- FUNCTION: Acts as an ATP-dependent RNA helicase, able to unwind both
CC RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang
CC nuclease activity. Possesses ATPase activity on various RNA, but not
CC DNA polynucleotides. May play a role in RNA clearance at DNA double-
CC strand breaks (DSBs), thereby facilitating the template-guided repair
CC of transcriptionally active regions of the genome. Together with RELA,
CC acts as a coactivator to enhance NF-kappa-B-mediated transcriptional
CC activation. Acts as a positive transcriptional regulator of cyclin
CC CCND2 expression. Binds to the cyclin CCND2 promoter region. Associates
CC with chromatin at the NF-kappa-B promoter region via association with
CC RELA. Binds to poly(A) RNA. May be involved in 3'-end cleavage and
CC polyadenylation of pre-mRNAs. Component of the tRNA-splicing ligase
CC complex required to facilitate the enzymatic turnover of catalytic
CC subunit RTCB: together with archease (ZBTB8OS), acts by facilitating
CC the guanylylation of RTCB, a key intermediate step in tRNA ligation
CC (PubMed:24870230). Component of a multi-helicase-TICAM1 complex that
CC acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and
CC plays a role in the activation of a cascade of antiviral responses
CC including the induction of pro-inflammatory cytokines via the adapter
CC molecule TICAM1. Specifically binds (via helicase ATP-binding domain)
CC on both short and long poly(I:C) dsRNA (By similarity).
CC {ECO:0000250|UniProtKB:Q91VR5, ECO:0000269|PubMed:12183465,
CC ECO:0000269|PubMed:15567440, ECO:0000269|PubMed:18335541,
CC ECO:0000269|PubMed:18710941, ECO:0000269|PubMed:20573827,
CC ECO:0000269|PubMed:24870230}.
CC -!- FUNCTION: (Microbial infection) Required for HIV-1 Rev function as well
CC as for HIV-1 and coronavirus IBV replication. Binds to the RRE sequence
CC of HIV-1 mRNAs. {ECO:0000269|PubMed:15567440}.
CC -!- FUNCTION: (Microbial infection) Required for Coronavirus IBV
CC replication. {ECO:0000269|PubMed:20573827}.
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:0000269|PubMed:21589879};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.120 mM for ATP (in the absence of nucleic acid)
CC {ECO:0000269|PubMed:21589879};
CC KM=0.090 mM for ATP (in the presence of RNA oligo(rU)20)
CC {ECO:0000269|PubMed:21589879};
CC KM=0.095 mM for ATP (in the presence of DNA oligo(dT)20)
CC {ECO:0000269|PubMed:21589879};
CC Note=kcat is 1.9 min(-1) for ATP hydrolysis in the absence of nucleic
CC acid (PubMed:21589879). kcat is 3.8 min(-1) for ATP hydrolysis in the
CC presence of RNA oligo(rU)20 (PubMed:21589879). kcat is 2.1 min(-1)
CC for ATP hydrolysis in the presence of DNA oligo(dT)20
CC (PubMed:21589879). {ECO:0000269|PubMed:21589879};
CC -!- SUBUNIT: (Microbial infection) Interacts with Venezuelan equine
CC encephalitis virus non-structural protein 3.
CC {ECO:0000269|PubMed:27105836}.
CC -!- SUBUNIT: Found in a multi-helicase-TICAM1 complex at least composed of
CC DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells
CC with or without poly(I:C) RNA ligand stimulation. Interacts with DHX36.
CC Interacts (via B30.2/SPRY domain) with DDX21 (via N-terminus); this
CC interaction serves as bridges to TICAM1 (By similarity). Interacts with
CC FAM98A (via N- and C-terminus) (PubMed:28040436). Interacts with MBNL1
CC (PubMed:18335541). Interacts with CSTF2 (PubMed:11598190). Interacts
CC with HNRNPK (PubMed:12183465). Interacts with ATM (PubMed:18710941).
CC Interacts with RELA (via C-terminus) (PubMed:19058135). Component of
CC the tRNA-splicing ligase complex (PubMed:21311021, PubMed:24870230).
CC Interacts with PQBP1 (PubMed:21933836). Interacts with PHF5A (via C-
CC terminus) (By similarity). Interacts with ERCC6 (PubMed:26030138).
CC {ECO:0000250|UniProtKB:Q91VR5, ECO:0000269|PubMed:11598190,
CC ECO:0000269|PubMed:12183465, ECO:0000269|PubMed:18335541,
CC ECO:0000269|PubMed:18710941, ECO:0000269|PubMed:19058135,
CC ECO:0000269|PubMed:21311021, ECO:0000269|PubMed:21933836,
CC ECO:0000269|PubMed:24870230, ECO:0000269|PubMed:26030138,
CC ECO:0000269|PubMed:28040436}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Rev of HIV-1.
CC {ECO:0000269|PubMed:15567440}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Severe acute respiratory
CC syndrome coronavirus (SARS-CoV) (via N-terminus) (PubMed:20573827).
CC Interacts (via C-terminus) with the replicase polyprotein 1ab Nsp14 of
CC the Avian infectious bronchitis virus (IBV).
CC {ECO:0000269|PubMed:20573827}.
CC -!- INTERACTION:
CC Q92499; Q8NCA5: FAM98A; NbExp=4; IntAct=EBI-358474, EBI-1210765;
CC Q92499; Q9Y224: RTRAF; NbExp=3; IntAct=EBI-358474, EBI-1104547;
CC Q92499; P0DTC9: N; Xeno; NbExp=3; IntAct=EBI-358474, EBI-25475856;
CC Q92499; PRO_0000037415 [P0C6Y1]: rep; Xeno; NbExp=5; IntAct=EBI-358474, EBI-25826989;
CC Q92499-1; P04618: rev; Xeno; NbExp=6; IntAct=EBI-15532186, EBI-6164309;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasmic granule.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q91VR5}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q91VR5}. Note=Localized with MBNL1, TIAL1 and
CC YBX1 in stress granules upon stress. Localized with CSTF2 in cleavage
CC bodies. Forms large aggregates called DDX1 bodies. Relocalized into
CC multiple foci (IR-induced foci or IRIF) after IR treatment, a process
CC that depends on the presence of chromosomal DNA and/or RNA-DNA
CC duplexes. Relocalized at sites of DNA double-strand breaks (DSBs) in an
CC ATM-dependent manner after IR treatment. Colocalized with RELA in the
CC nucleus upon TNF-alpha induction. Enters into the nucleus in case of
CC active transcription while it accumulates in cytosol when transcription
CC level is low (PubMed:24608264). Colocalizes in the cytosol with DDX21,
CC DHX36 and TICAM1. Colocalizes in the mitochondria with TICAM1 and
CC poly(I:C) RNA ligand. The multi-helicase-TICAM1 complex may translocate
CC to the mitochondria upon poly(I:C) stimulation (By similarity).
CC {ECO:0000250|UniProtKB:Q91VR5, ECO:0000269|PubMed:24608264}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20573827}.
CC Note=(Microbial infection) Relocalized to the cytoplasm with a
CC perinuclear staining pattern in avian infectious bronchitis virus
CC (IBV)-infected cells (PubMed:20573827). Required for proper
CC localization of HIV-1 Rev (PubMed:15567440).
CC {ECO:0000269|PubMed:15567440, ECO:0000269|PubMed:20573827}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q92499-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92499-2; Sequence=VSP_055454, VSP_055455;
CC Name=3;
CC IsoId=Q92499-3; Sequence=VSP_055453;
CC -!- TISSUE SPECIFICITY: Highest levels of transcription in 2 retinoblastoma
CC cell lines and in tissues of neuroectodermal origin including the
CC retina, brain, and spinal cord. {ECO:0000269|PubMed:7689221}.
CC -!- DOMAIN: The helicase domain is involved in the stimulation of RELA
CC transcriptional activity. {ECO:0000269|PubMed:19058135}.
CC -!- PTM: Phosphorylated by ATM kinase; phosphorylation is increased in
CC response to ionizing radiation (IR). {ECO:0000269|PubMed:18710941}.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DDX1 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: According to some authors the unwinding activity is ADP-
CC dependent and not ATP-dependent. {ECO:0000305|PubMed:18710941}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/40283/DDX1";
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DR EMBL; X70649; CAA49992.1; -; mRNA.
DR EMBL; AK297432; BAG59860.1; -; mRNA.
DR EMBL; AK298426; BAG60648.1; -; mRNA.
DR EMBL; BC012132; AAH12132.1; -; mRNA.
DR EMBL; BC053673; AAH53673.1; -; mRNA.
DR CCDS; CCDS1686.1; -. [Q92499-1]
DR RefSeq; NP_004930.1; NM_004939.2. [Q92499-1]
DR PDB; 4XW3; X-ray; 2.00 A; A/B=72-283.
DR PDB; 8TBX; X-ray; 2.71 A; A=1-74, A=286-674.
DR PDBsum; 4XW3; -.
DR PDBsum; 8TBX; -.
DR AlphaFoldDB; Q92499; -.
DR SMR; Q92499; -.
DR BioGRID; 108019; 444.
DR ComplexPortal; CPX-6411; tRNA-splicing ligase complex.
DR CORUM; Q92499; -.
DR DIP; DIP-38163N; -.
DR IntAct; Q92499; 106.
DR MINT; Q92499; -.
DR STRING; 9606.ENSP00000370745; -.
DR BindingDB; Q92499; -.
DR ChEMBL; CHEMBL2010634; -.
DR GlyGen; Q92499; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92499; -.
DR PhosphoSitePlus; Q92499; -.
DR SwissPalm; Q92499; -.
DR BioMuta; DDX1; -.
DR DMDM; 6919862; -.
DR REPRODUCTION-2DPAGE; IPI00293655; -.
DR CPTAC; CPTAC-190; -.
DR CPTAC; CPTAC-191; -.
DR EPD; Q92499; -.
DR jPOST; Q92499; -.
DR MassIVE; Q92499; -.
DR MaxQB; Q92499; -.
DR PaxDb; 9606-ENSP00000370745; -.
DR PeptideAtlas; Q92499; -.
DR ProteomicsDB; 4603; -.
DR ProteomicsDB; 4798; -.
DR ProteomicsDB; 75269; -. [Q92499-1]
DR Pumba; Q92499; -.
DR Antibodypedia; 3224; 292 antibodies from 32 providers.
DR DNASU; 1653; -.
DR Ensembl; ENST00000233084.8; ENSP00000233084.3; ENSG00000079785.16. [Q92499-1]
DR Ensembl; ENST00000381341.7; ENSP00000370745.1; ENSG00000079785.16. [Q92499-1]
DR Ensembl; ENST00000434671.2; ENSP00000413767.2; ENSG00000079785.16. [Q92499-1]
DR Ensembl; ENST00000677302.1; ENSP00000504080.1; ENSG00000079785.16. [Q92499-1]
DR GeneID; 1653; -.
DR KEGG; hsa:1653; -.
DR MANE-Select; ENST00000233084.8; ENSP00000233084.3; NM_004939.3; NP_004930.1.
DR UCSC; uc002rce.5; human. [Q92499-1]
DR AGR; HGNC:2734; -.
DR CTD; 1653; -.
DR DisGeNET; 1653; -.
DR GeneCards; DDX1; -.
DR HGNC; HGNC:2734; DDX1.
DR HPA; ENSG00000079785; Low tissue specificity.
DR MIM; 601257; gene.
DR neXtProt; NX_Q92499; -.
DR OpenTargets; ENSG00000079785; -.
DR PharmGKB; PA27199; -.
DR VEuPathDB; HostDB:ENSG00000079785; -.
DR eggNOG; KOG0349; Eukaryota.
DR GeneTree; ENSGT00940000155678; -.
DR HOGENOM; CLU_016321_0_0_1; -.
DR InParanoid; Q92499; -.
DR OMA; EYCIRAI; -.
DR OrthoDB; 102545at2759; -.
DR PhylomeDB; Q92499; -.
DR TreeFam; TF106114; -.
DR BioCyc; MetaCyc:ENSG00000079785-MONOMER; -.
DR PathwayCommons; Q92499; -.
DR Reactome; R-HSA-6784531; tRNA processing in the nucleus.
DR SignaLink; Q92499; -.
DR SIGNOR; Q92499; -.
DR BioGRID-ORCS; 1653; 367 hits in 1177 CRISPR screens.
DR ChiTaRS; DDX1; human.
DR GeneWiki; DDX1; -.
DR GenomeRNAi; 1653; -.
DR Pharos; Q92499; Tchem.
DR PRO; PR:Q92499; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q92499; Protein.
DR Bgee; ENSG00000079785; Expressed in skeletal muscle tissue of biceps brachii and 216 other cell types or tissues.
DR ExpressionAtlas; Q92499; baseline and differential.
DR Genevisible; Q92499; HS.
DR GO; GO:0071920; C:cleavage body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
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:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:0072669; C:tRNA-splicing ligase complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0033677; F:DNA/RNA helicase activity; IDA:UniProtKB.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:Ensembl.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0004518; F:nuclease activity; IDA:UniProtKB.
DR GO; GO:0008143; F:poly(A) binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003724; F:RNA helicase activity; IDA:GO_Central.
DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0032508; P:DNA duplex unwinding; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0090304; P:nucleic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB.
DR GO; GO:0002735; P:positive regulation of myeloid dendritic cell cytokine production; IEA:Ensembl.
DR GO; GO:1903608; P:protein localization to cytoplasmic stress granule; IMP:AgBase.
DR GO; GO:0006446; P:regulation of translational initiation; NAS:UniProtKB.
DR GO; GO:0043330; P:response to exogenous dsRNA; IEA:Ensembl.
DR GO; GO:0000245; P:spliceosomal complex assembly; NAS:UniProtKB.
DR GO; GO:0006388; P:tRNA splicing, via endonucleolytic cleavage and ligation; IMP:UniProtKB.
DR CDD; cd17938; DEADc_DDX1; 1.
DR CDD; cd18787; SF2_C_DEAD; 1.
DR CDD; cd12873; SPRY_DDX1; 1.
DR Gene3D; 2.60.120.920; -; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 3.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
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; IPR014014; RNA_helicase_DEAD_Q_motif.
DR InterPro; IPR003877; SPRY_dom.
DR PANTHER; PTHR47958; ATP-DEPENDENT RNA HELICASE DBP3; 1.
DR PANTHER; PTHR47958:SF186; ATP-DEPENDENT RNA HELICASE DDX1; 1.
DR Pfam; PF00270; DEAD; 2.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF00622; SPRY; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 2.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51195; Q_MOTIF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW Antiviral defense; ATP-binding; Cytoplasm; DNA-binding; Exonuclease;
KW Helicase; Host-virus interaction; Hydrolase; Immunity; Innate immunity;
KW Isopeptide bond; Mitochondrion; mRNA processing; Nuclease;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; Transcription; Transcription regulation; tRNA processing;
KW Ubl conjugation.
FT CHAIN 1..740
FT /note="ATP-dependent RNA helicase DDX1"
FT /id="PRO_0000054986"
FT DOMAIN 2..428
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 70..247
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT DOMAIN 493..681
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 1..525
FT /note="Necessary for interaction with RELA"
FT /evidence="ECO:0000269|PubMed:19058135"
FT REGION 1..448
FT /note="Interaction with dsRNA"
FT /evidence="ECO:0000250|UniProtKB:Q91VR5"
FT REGION 1..295
FT /note="Necessary for interaction with HNRNPK"
FT /evidence="ECO:0000269|PubMed:12183465"
FT REGION 525..740
FT /note="Necessary for interaction with HNRNPK"
FT /evidence="ECO:0000269|PubMed:12183465"
FT REGION 536..631
FT /note="Necessary for interaction with replicase polyprotein
FT 1ab nsp14 of IBV"
FT /evidence="ECO:0000269|PubMed:20573827"
FT MOTIF 370..373
FT /note="DEAD box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 46..53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 239
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 268
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 281
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT CROSSLNK 281
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..128
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055453"
FT VAR_SEQ 98..113
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055454"
FT VAR_SEQ 630..740
FT /note="VCSSRGKGCYNTRLKEDGGCTIWYNEMQLLSEIEEHLNCTISQVEPDIKVPV
FT DEFDGKVTYGQKRAAGGGSYKGHVDILAPTVQELAALEKEAQTSFLHLGYLPNQLFRTF
FT -> MVQRDAVTI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055455"
FT MUTAGEN 52
FT /note="K->N: Abolishes ability to promote guanylylation of
FT RTCB."
FT /evidence="ECO:0000269|PubMed:24870230"
FT MUTAGEN 371
FT /note="E->G: Inhibits the transcriptional activity of RELA
FT and attenuates NF-kappa-B-mediated gene expression."
FT /evidence="ECO:0000269|PubMed:19058135,
FT ECO:0000269|PubMed:24870230"
FT MUTAGEN 371
FT /note="E->Q: Abolishes ability to promote guanylylation of
FT RTCB."
FT /evidence="ECO:0000269|PubMed:19058135,
FT ECO:0000269|PubMed:24870230"
FT HELIX 2..5
FT /evidence="ECO:0007829|PDB:8TBX"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 11..18
FT /evidence="ECO:0007829|PDB:8TBX"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 27..37
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 52..68
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 90..98
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 120..139
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 141..150
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:4XW3"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:4XW3"
FT TURN 198..201
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 210..217
FT /evidence="ECO:0007829|PDB:4XW3"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 227..245
FT /evidence="ECO:0007829|PDB:4XW3"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:4XW3"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:4XW3"
FT STRAND 288..292
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 296..309
FT /evidence="ECO:0007829|PDB:8TBX"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 320..323
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 329..338
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 347..354
FT /evidence="ECO:0007829|PDB:8TBX"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 366..369
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 372..377
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 381..390
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 402..411
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 413..422
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 427..429
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 439..448
FT /evidence="ECO:0007829|PDB:8TBX"
FT TURN 450..452
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 455..458
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 460..463
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 482..504
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 509..512
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 516..528
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 541..546
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 551..562
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 565..571
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 573..578
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 584..591
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 597..603
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 613..622
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 624..627
FT /evidence="ECO:0007829|PDB:8TBX"
FT TURN 632..637
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 644..646
FT /evidence="ECO:0007829|PDB:8TBX"
FT STRAND 649..653
FT /evidence="ECO:0007829|PDB:8TBX"
FT HELIX 655..665
FT /evidence="ECO:0007829|PDB:8TBX"
SQ SEQUENCE 740 AA; 82432 MW; C6D0179F83BD8C73 CRC64;
MAAFSEMGVM PEIAQAVEEM DWLLPTDIQA ESIPLILGGG DVLMAAETGS GKTGAFSIPV
IQIVYETLKD QQEGKKGKTT IKTGASVLNK WQMNPYDRGS AFAIGSDGLC CQSREVKEWH
GCRATKGLMK GKHYYEVSCH DQGLCRVGWS TMQASLDLGT DKFGFGFGGT GKKSHNKQFD
NYGEEFTMHD TIGCYLDIDK GHVKFSKNGK DLGLAFEIPP HMKNQALFPA CVLKNAELKF
NFGEEEFKFP PKDGFVALSK APDGYIVKSQ HSGNAQVTQT KFLPNAPKAL IVEPSRELAE
QTLNNIKQFK KYIDNPKLRE LLIIGGVAAR DQLSVLENGV DIVVGTPGRL DDLVSTGKLN
LSQVRFLVLD EADGLLSQGY SDFINRMHNQ IPQVTSDGKR LQVIVCSATL HSFDVKKLSE
KIMHFPTWVD LKGEDSVPDT VHHVVVPVNP KTDRLWERLG KSHIRTDDVH AKDNTRPGAN
SPEMWSEAIK ILKGEYAVRA IKEHKMDQAI IFCRTKIDCD NLEQYFIQQG GGPDKKGHQF
SCVCLHGDRK PHERKQNLER FKKGDVRFLI CTDVAARGID IHGVPYVINV TLPDEKQNYV
HRIGRVGRAE RMGLAISLVA TEKEKVWYHV CSSRGKGCYN TRLKEDGGCT IWYNEMQLLS
EIEEHLNCTI SQVEPDIKVP VDEFDGKVTY GQKRAAGGGS YKGHVDILAP TVQELAALEK
EAQTSFLHLG YLPNQLFRTF
//