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   17-JUN-2020, entry version 194.
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 proinflammatory 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       Q92499-1; 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="http://atlasgeneticsoncology.org/Genes/DDX1ID40283ch2p24.html";
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   PDBsum; 4XW3; -.
DR   SMR; Q92499; -.
DR   BioGRID; 108019; 271.
DR   CORUM; Q92499; -.
DR   DIP; DIP-38163N; -.
DR   IntAct; Q92499; 68.
DR   MINT; Q92499; -.
DR   STRING; 9606.ENSP00000370745; -.
DR   BindingDB; Q92499; -.
DR   ChEMBL; CHEMBL2010634; -.
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; Q92499; -.
DR   PeptideAtlas; Q92499; -.
DR   PRIDE; Q92499; -.
DR   ProteomicsDB; 4603; -.
DR   ProteomicsDB; 4798; -.
DR   ProteomicsDB; 75269; -. [Q92499-1]
DR   Antibodypedia; 3224; 236 antibodies.
DR   Ensembl; ENST00000233084; ENSP00000233084; ENSG00000079785. [Q92499-1]
DR   Ensembl; ENST00000381341; ENSP00000370745; ENSG00000079785. [Q92499-1]
DR   GeneID; 1653; -.
DR   KEGG; hsa:1653; -.
DR   UCSC; uc002rce.5; human. [Q92499-1]
DR   CTD; 1653; -.
DR   DisGeNET; 1653; -.
DR   EuPathDB; HostDB:ENSG00000079785.14; -.
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   eggNOG; KOG0349; Eukaryota.
DR   eggNOG; COG0513; LUCA.
DR   GeneTree; ENSGT00940000155678; -.
DR   HOGENOM; CLU_016321_0_0_1; -.
DR   InParanoid; Q92499; -.
DR   KO; K13177; -.
DR   OMA; DGVHDRD; -.
DR   PhylomeDB; Q92499; -.
DR   TreeFam; TF106114; -.
DR   BioCyc; MetaCyc:ENSG00000079785-MONOMER; -.
DR   Reactome; R-HSA-6784531; tRNA processing in the nucleus.
DR   BioGRID-ORCS; 1653; 302 hits in 797 CRISPR screens.
DR   ChiTaRS; DDX1; human.
DR   GeneWiki; DDX1; -.
DR   GenomeRNAi; 1653; -.
DR   Pharos; Q92499; Tbio.
DR   PRO; PR:Q92499; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q92499; protein.
DR   Bgee; ENSG00000079785; Expressed in tendon and 234 other 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: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:0004386; F:helicase activity; IDA:UniProtKB.
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; IBA: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:0007275; P:multicellular organism development; IEP:UniProtKB.
DR   GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IDA:UniProtKB.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; 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   GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.120.920; -; 1.
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   Pfam; PF00270; DEAD; 1.
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; SSF49899; 1.
DR   SUPFAM; SSF52540; SSF52540; 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   NP_BIND         46..53
FT                   /note="ATP"
FT                   /evidence="ECO:0000305"
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   MOD_RES         239
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000244|PubMed:19608861"
FT   MOD_RES         268
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000244|PubMed:19608861"
FT   MOD_RES         281
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000244|PubMed:19608861"
FT   MOD_RES         481
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:20068231,
FT                   ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163"
FT   CROSSLNK        281
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0000244|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   STRAND          90..98
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          102..104
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          110..113
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          120..139
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          141..150
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          164..168
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   TURN            169..171
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          172..175
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          178..181
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          191..197
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   TURN            198..201
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          202..207
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          210..217
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   HELIX           220..222
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          227..245
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   HELIX           258..260
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   HELIX           263..265
FT                   /evidence="ECO:0000244|PDB:4XW3"
FT   STRAND          266..268
FT                   /evidence="ECO:0000244|PDB:4XW3"
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
//