DDX21_RAT
ID DDX21_RAT Reviewed; 782 AA.
AC Q3B8Q1;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Nucleolar RNA helicase 2 {ECO:0000305};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q9NR30};
DE AltName: Full=DEAD box protein 21;
DE AltName: Full=Gu-alpha;
DE AltName: Full=Nucleolar RNA helicase Gu;
DE AltName: Full=Nucleolar RNA helicase II;
DE AltName: Full=RH II/Gu;
GN Name=Ddx21; Synonyms=Ddx21a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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).
CC -!- FUNCTION: RNA helicase that acts as a sensor of the transcriptional
CC status of both RNA polymerase (Pol) I and II: promotes ribosomal RNA
CC (rRNA) processing and transcription from polymerase II (Pol II). Binds
CC various RNAs, such as rRNAs, snoRNAs, 7SK and, at lower extent, mRNAs.
CC In the nucleolus, localizes to rDNA locus, where it directly binds
CC rRNAs and snoRNAs, and promotes rRNA transcription, processing and
CC modification. Required for rRNA 2'-O-methylation, possibly by promoting
CC the recruitment of late-acting snoRNAs SNORD56 and SNORD58 with pre-
CC ribosomal complexes. In the nucleoplasm, binds 7SK RNA and is recruited
CC to the promoters of Pol II-transcribed genes: acts by facilitating the
CC release of P-TEFb from inhibitory 7SK snRNP in a manner that is
CC dependent on its helicase activity, thereby promoting transcription of
CC its target genes. Functions as cofactor for JUN-activated
CC transcription: required for phosphorylation of JUN at 'Ser-77'. Can
CC unwind double-stranded RNA (helicase) and can fold or introduce a
CC secondary structure to a single-stranded RNA (foldase). Together with
CC SIRT7, required to prevent R-loop-associated DNA damage and
CC transcription-associated genomic instability: deacetylation by SIRT7
CC activates the helicase activity, thereby overcoming R-loop-mediated
CC stalling of RNA polymerases. Involved in rRNA processing. May bind to
CC specific miRNA hairpins (By similarity). Component of a multi-helicase-
CC TICAM1 complex that acts as a cytoplasmic sensor of viral double-
CC stranded RNA (dsRNA) and plays a role in the activation of a cascade of
CC antiviral responses including the induction of pro-inflammatory
CC cytokines via the adapter molecule TICAM1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9JIK5, ECO:0000250|UniProtKB:Q9NR30}.
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:0000250|UniProtKB:Q9NR30};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:Q9NR30};
CC -!- ACTIVITY REGULATION: Acetylation inhibits the helicase activity.
CC {ECO:0000250|UniProtKB:Q9NR30}.
CC -!- SUBUNIT: Homodimer; homodimerizes via its N-terminus. Found in a multi-
CC helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and
CC TICAM1; this complex exists in resting cells with or without poly(I:C)
CC RNA ligand stimulation. Interacts (via C-terminus) with TICAM1 (via TIR
CC domain). Interacts with DHX36 (via C-terminus); this interaction serves
CC as bridges to TICAM1. Interacts (via C-terminus) with DDX1 (via
CC B30.2/SPRY domain); this interaction serves as bridges to TICAM1 (By
CC similarity). Component of the B-WICH complex, at least composed of
CC SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21.
CC Interacts with C1QBP. Interacts with JUN. Interacts with WDR46.
CC Interacts with MCM3AP (By similarity). Interacts with WDR43 (By
CC similarity). {ECO:0000250|UniProtKB:Q9JIK5,
CC ECO:0000250|UniProtKB:Q9NR30}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q9NR30}. Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q9NR30}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9JIK5}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9JIK5}. Note=Present both in nucleolus and
CC nucleoplasm. Interaction with JUN promotes translocation from the
CC nucleolus to the nucleoplasm. Interaction with WDR46 is required for
CC localization to the nucleolus. Colocalizes in the cytosol with DDX1,
CC DHX36 and TICAM1. The multi-helicase-TICAM1 complex may translocate to
CC the mitochondria upon poly(I:C) RNA ligand stimulation (By similarity).
CC {ECO:0000250|UniProtKB:Q9JIK5, ECO:0000250|UniProtKB:Q9NR30}.
CC -!- DOMAIN: The helicase and foldase activities reside in two separate
CC domains, the helicase in the N-terminus and the foldase in the C-
CC terminus. {ECO:0000250|UniProtKB:Q9NR30}.
CC -!- DOMAIN: The 3 X 5 AA repeats seem to be critical for the RNA folding
CC activity. {ECO:0000250}.
CC -!- PTM: Acetylation by CREBBP/CBP inhibits the helicase activity.
CC Deacetylation by SIRT7 promotes the helicase activity and overcomes R-
CC loop-mediated stalling of RNA polymerases.
CC {ECO:0000250|UniProtKB:Q9NR30}.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DDX21/DDX50
CC subfamily. {ECO:0000305}.
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DR EMBL; BC105878; AAI05879.1; -; mRNA.
DR RefSeq; NP_001032278.1; NM_001037201.1.
DR AlphaFoldDB; Q3B8Q1; -.
DR SMR; Q3B8Q1; -.
DR BioGRID; 261547; 1.
DR IntAct; Q3B8Q1; 4.
DR STRING; 10116.ENSRNOP00000063494; -.
DR iPTMnet; Q3B8Q1; -.
DR PhosphoSitePlus; Q3B8Q1; -.
DR jPOST; Q3B8Q1; -.
DR PaxDb; Q3B8Q1; -.
DR PRIDE; Q3B8Q1; -.
DR Ensembl; ENSRNOT00000068184; ENSRNOP00000063494; ENSRNOG00000043099.
DR GeneID; 317399; -.
DR KEGG; rno:317399; -.
DR UCSC; RGD:1307306; rat.
DR CTD; 9188; -.
DR RGD; 1307306; Ddx21.
DR eggNOG; KOG0331; Eukaryota.
DR GeneTree; ENSGT00940000155043; -.
DR HOGENOM; CLU_003041_20_0_1; -.
DR InParanoid; Q3B8Q1; -.
DR OMA; KQVHTDF; -.
DR OrthoDB; 1139373at2759; -.
DR PhylomeDB; Q3B8Q1; -.
DR TreeFam; TF328622; -.
DR Reactome; R-RNO-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-RNO-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR PRO; PR:Q3B8Q1; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000043099; Expressed in spleen and 18 other tissues.
DR Genevisible; Q3B8Q1; RN.
DR GO; GO:0110016; C:B-WICH complex; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0097322; F:7SK snRNA binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0035198; F:miRNA binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0003724; F:RNA helicase activity; ISS:UniProtKB.
DR GO; GO:0019843; F:rRNA binding; ISS:UniProtKB.
DR GO; GO:0030515; F:snoRNA binding; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
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; ISO:RGD.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; ISO:RGD.
DR GO; GO:0062176; P:R-loop disassembly; ISS:UniProtKB.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISO:RGD.
DR GO; GO:0009615; P:response to virus; ISO:RGD.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR012562; GUCT.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR035979; RBD_domain_sf.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF08152; GUCT; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51195; Q_MOTIF; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Antiviral defense; ATP-binding; Cytoplasm; Helicase;
KW Hydrolase; Immunity; Innate immunity; Isopeptide bond; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW RNA-binding; rRNA processing; Transcription; Ubl conjugation.
FT CHAIN 1..782
FT /note="Nucleolar RNA helicase 2"
FT /id="PRO_0000282712"
FT DOMAIN 213..392
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 425..569
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REPEAT 720..724
FT /note="1"
FT REPEAT 731..735
FT /note="2"
FT REPEAT 741..747
FT /note="3"
FT REGION 1..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 704..782
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 720..747
FT /note="3 X 5 AA repeats"
FT MOTIF 182..210
FT /note="Q motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00552"
FT MOTIF 335..338
FT /note="DEAD box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT COMPBIAS 10..142
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 733..782
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 226..233
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT MOD_RES 39
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIK5"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT MOD_RES 135
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIK5"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIK5"
FT MOD_RES 292
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT MOD_RES 596
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT MOD_RES 778
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT CROSSLNK 114
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
FT CROSSLNK 114
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9NR30"
SQ SEQUENCE 782 AA; 85966 MW; FD8074E373921621 CRC64;
MPGKLRSASK SESEGTEESM ETLQKPSEKK TRKEKPKSKT DEATEGVEEA ASSKVKAVKK
KGPSEDDVGP PKSKKAKKQE EEPQDDPASK SKTSKKKKEP LEKKAPSAKT KEMKAEEPSE
EEADAPKPKK TKKGKEANGD VGEKSPGLKN GLSHPKPDSS STQAPGEESE TEKEIPVEQK
EGAFSNFPIS EETVKLLKAR GVNFLFPIQA KTFHHVYSGK DLIAQARTGT GKTFSFAIPL
IEKLQGGLQE RKRGRAPQVL VLAPTRELAN QVSKDFSDIT KKLSVACFYG GTPYGGQIER
MRSGIDILVG TPGRIKDHLQ NGKLDLTKLK HVVLDEVDQM LDMGFADQVE EILCVAYKKD
SEDNPQTLLF SATCPHWVFN VAKKYMKSTY EQVDLIGKKT QKAAITVEHL AIKCHWTERA
AVIGDVIRVY SGHQGRTIIF CETKKDAQEL SQNTCIKQDA QSLHGDIPQK QREITLKGFR
NGNFGVLVAT NVAARGLDIP EVDLVVQSCP PKDVESYIHR SGRTGRAGRT GVCICFYQHK
EEYQLAQVEQ KAGIKFKRIG VPSATEIIKA SSKDAIRLLD SVPPTAIGHF KQSAEKLIEE
KGAVEALAAA LAHISGATSV DQRSLINSQA GFVTMILRCS VEMPNISYAW KELKEQLGES
IDAKVKGMVF LKGKLGVCFD VRTEAVTEIK EKWHDSRRWQ LTVATEQPEL EGPPEGYRGG
RGQRDGSRGS FRGQRGGSRN FRGQGQRGGS RNFRGQRPGG GNKSNRSPNK GQKRSFSKAF
GQ
