UniProt functional annotation for Q92499



	UniProt functional annotation for Q92499

UniProt code: Q92499.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Acts as an ATP-dependent RNA helicase, able to unwind both RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang nuclease activity. Possesses ATPase activity on various RNA, but not DNA polynucleotides. May play a role in RNA clearance at DNA double- strand breaks (DSBs), thereby facilitating the template-guided repair of transcriptionally active regions of the genome. Together with RELA, acts as a coactivator to enhance NF-kappa-B-mediated transcriptional activation. Acts as a positive transcriptional regulator of cyclin CCND2 expression. Binds to the cyclin CCND2 promoter region. Associates with chromatin at the NF-kappa-B promoter region via association with RELA. Binds to poly(A) RNA. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB: together with archease (ZBTB8OS), acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (PubMed:24870230). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of proinflammatory cytokines via the adapter molecule TICAM1. Specifically binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (By similarity). {ECO:0000250|UniProtKB:Q91VR5, ECO:0000269|PubMed:12183465, ECO:0000269|PubMed:15567440, ECO:0000269|PubMed:18335541, ECO:0000269|PubMed:18710941, ECO:0000269|PubMed:20573827, ECO:0000269|PubMed:24870230}.

Function: (Microbial infection) Required for HIV-1 Rev function as well as for HIV-1 and coronavirus IBV replication. Binds to the RRE sequence of HIV-1 mRNAs. {ECO:0000269|PubMed:15567440}.

Function: (Microbial infection) Required for Coronavirus IBV replication. {ECO:0000269|PubMed:20573827}.

Catalytic activity: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000269|PubMed:21589879};

Biophysicochemical properties: Kinetic parameters: KM=0.120 mM for ATP (in the absence of nucleic acid) {ECO:0000269|PubMed:21589879}; KM=0.090 mM for ATP (in the presence of RNA oligo(rU)20) {ECO:0000269|PubMed:21589879}; KM=0.095 mM for ATP (in the presence of DNA oligo(dT)20) {ECO:0000269|PubMed:21589879}; Note=kcat is 1.9 min(-1) for ATP hydrolysis in the absence of nucleic acid (PubMed:21589879). kcat is 3.8 min(-1) for ATP hydrolysis in the presence of RNA oligo(rU)20 (PubMed:21589879). kcat is 2.1 min(-1) for ATP hydrolysis in the presence of DNA oligo(dT)20 (PubMed:21589879). {ECO:0000269|PubMed:21589879};

Subunit: (Microbial infection) Interacts with Venezuelan equine encephalitis virus non-structural protein 3. {ECO:0000269|PubMed:27105836}.

Subunit: Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without poly(I:C) RNA ligand stimulation. Interacts with DHX36. Interacts (via B30.2/SPRY domain) with DDX21 (via N-terminus); this interaction serves as bridges to TICAM1 (By similarity). Interacts with FAM98A (via N- and C-terminus) (PubMed:28040436). Interacts with MBNL1 (PubMed:18335541). Interacts with CSTF2 (PubMed:11598190). Interacts with HNRNPK (PubMed:12183465). Interacts with ATM (PubMed:18710941). Interacts with RELA (via C-terminus) (PubMed:19058135). Component of the tRNA-splicing ligase complex (PubMed:21311021, PubMed:24870230). Interacts with PQBP1 (PubMed:21933836). Interacts with PHF5A (via C- terminus) (By similarity). Interacts with ERCC6 (PubMed:26030138). {ECO:0000250|UniProtKB:Q91VR5, ECO:0000269|PubMed:11598190, ECO:0000269|PubMed:12183465, ECO:0000269|PubMed:18335541, ECO:0000269|PubMed:18710941, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:21311021, ECO:0000269|PubMed:21933836, ECO:0000269|PubMed:24870230, ECO:0000269|PubMed:26030138, ECO:0000269|PubMed:28040436}.

Subunit: (Microbial infection) Interacts with Rev of HIV-1. {ECO:0000269|PubMed:15567440}.

Subunit: (Microbial infection) Interacts with Severe acute respiratory syndrome coronavirus (SARS-CoV) (via N-terminus) (PubMed:20573827). Interacts (via C-terminus) with the replicase polyprotein 1ab Nsp14 of the Avian infectious bronchitis virus (IBV). {ECO:0000269|PubMed:20573827}.

Subcellular location: Nucleus. Cytoplasm. Cytoplasmic granule. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q91VR5}. Mitochondrion {ECO:0000250|UniProtKB:Q91VR5}. Note=Localized with MBNL1, TIAL1 and YBX1 in stress granules upon stress. Localized with CSTF2 in cleavage bodies. Forms large aggregates called DDX1 bodies. Relocalized into multiple foci (IR-induced foci or IRIF) after IR treatment, a process that depends on the presence of chromosomal DNA and/or RNA-DNA duplexes. Relocalized at sites of DNA double-strand breaks (DSBs) in an ATM-dependent manner after IR treatment. Colocalized with RELA in the nucleus upon TNF-alpha induction. Enters into the nucleus in case of active transcription while it accumulates in cytosol when transcription level is low (PubMed:24608264). Colocalizes in the cytosol with DDX21, DHX36 and TICAM1. Colocalizes in the mitochondria with TICAM1 and poly(I:C) RNA ligand. The multi-helicase-TICAM1 complex may translocate to the mitochondria upon poly(I:C) stimulation (By similarity). {ECO:0000250|UniProtKB:Q91VR5, ECO:0000269|PubMed:24608264}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:20573827}. Note=(Microbial infection) Relocalized to the cytoplasm with a perinuclear staining pattern in avian infectious bronchitis virus (IBV)-infected cells (PubMed:20573827). Required for proper localization of HIV-1 Rev (PubMed:15567440). {ECO:0000269|PubMed:15567440, ECO:0000269|PubMed:20573827}.

Tissue specificity: Highest levels of transcription in 2 retinoblastoma cell lines and in tissues of neuroectodermal origin including the retina, brain, and spinal cord. {ECO:0000269|PubMed:7689221}.

Domain: The helicase domain is involved in the stimulation of RELA transcriptional activity. {ECO:0000269|PubMed:19058135}.

Ptm: Phosphorylated by ATM kinase; phosphorylation is increased in response to ionizing radiation (IR). {ECO:0000269|PubMed:18710941}.

Similarity: Belongs to the DEAD box helicase family. DDX1 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Acts as an ATP-dependent RNA helicase, able to unwind both RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang nuclease activity. Possesses ATPase activity on various RNA, but not DNA polynucleotides. May play a role in RNA clearance at DNA double- strand breaks (DSBs), thereby facilitating the template-guided repair of transcriptionally active regions of the genome. Together with RELA, acts as a coactivator to enhance NF-kappa-B-mediated transcriptional activation. Acts as a positive transcriptional regulator of cyclin CCND2 expression. Binds to the cyclin CCND2 promoter region. Associates with chromatin at the NF-kappa-B promoter region via association with RELA. Binds to poly(A) RNA. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB: together with archease (ZBTB8OS), acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (PubMed:24870230). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of proinflammatory cytokines via the adapter molecule TICAM1. Specifically binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (By similarity). {ECO:0000250\|UniProtKB:Q91VR5, ECO:0000269\|PubMed:12183465, ECO:0000269\|PubMed:15567440, ECO:0000269\|PubMed:18335541, ECO:0000269\|PubMed:18710941, ECO:0000269\|PubMed:20573827, ECO:0000269\|PubMed:24870230}.



Function:		(Microbial infection) Required for HIV-1 Rev function as well as for HIV-1 and coronavirus IBV replication. Binds to the RRE sequence of HIV-1 mRNAs. {ECO:0000269\|PubMed:15567440}.



Function:		(Microbial infection) Required for Coronavirus IBV replication. {ECO:0000269\|PubMed:20573827}.


Catalytic activity:		Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000269\|PubMed:21589879};
Biophysicochemical properties:		Kinetic parameters: KM=0.120 mM for ATP (in the absence of nucleic acid) {ECO:0000269\|PubMed:21589879}; KM=0.090 mM for ATP (in the presence of RNA oligo(rU)20) {ECO:0000269\|PubMed:21589879}; KM=0.095 mM for ATP (in the presence of DNA oligo(dT)20) {ECO:0000269\|PubMed:21589879}; Note=kcat is 1.9 min(-1) for ATP hydrolysis in the absence of nucleic acid (PubMed:21589879). kcat is 3.8 min(-1) for ATP hydrolysis in the presence of RNA oligo(rU)20 (PubMed:21589879). kcat is 2.1 min(-1) for ATP hydrolysis in the presence of DNA oligo(dT)20 (PubMed:21589879). {ECO:0000269\|PubMed:21589879};
Subunit:		(Microbial infection) Interacts with Venezuelan equine encephalitis virus non-structural protein 3. {ECO:0000269\|PubMed:27105836}.
Subunit:		Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without poly(I:C) RNA ligand stimulation. Interacts with DHX36. Interacts (via B30.2/SPRY domain) with DDX21 (via N-terminus); this interaction serves as bridges to TICAM1 (By similarity). Interacts with FAM98A (via N- and C-terminus) (PubMed:28040436). Interacts with MBNL1 (PubMed:18335541). Interacts with CSTF2 (PubMed:11598190). Interacts with HNRNPK (PubMed:12183465). Interacts with ATM (PubMed:18710941). Interacts with RELA (via C-terminus) (PubMed:19058135). Component of the tRNA-splicing ligase complex (PubMed:21311021, PubMed:24870230). Interacts with PQBP1 (PubMed:21933836). Interacts with PHF5A (via C- terminus) (By similarity). Interacts with ERCC6 (PubMed:26030138). {ECO:0000250\|UniProtKB:Q91VR5, ECO:0000269\|PubMed:11598190, ECO:0000269\|PubMed:12183465, ECO:0000269\|PubMed:18335541, ECO:0000269\|PubMed:18710941, ECO:0000269\|PubMed:19058135, ECO:0000269\|PubMed:21311021, ECO:0000269\|PubMed:21933836, ECO:0000269\|PubMed:24870230, ECO:0000269\|PubMed:26030138, ECO:0000269\|PubMed:28040436}.
Subunit:		(Microbial infection) Interacts with Rev of HIV-1. {ECO:0000269\|PubMed:15567440}.
Subunit:		(Microbial infection) Interacts with Severe acute respiratory syndrome coronavirus (SARS-CoV) (via N-terminus) (PubMed:20573827). Interacts (via C-terminus) with the replicase polyprotein 1ab Nsp14 of the Avian infectious bronchitis virus (IBV). {ECO:0000269\|PubMed:20573827}.
Subcellular location:		Nucleus. Cytoplasm. Cytoplasmic granule. Cytoplasm, cytosol {ECO:0000250\|UniProtKB:Q91VR5}. Mitochondrion {ECO:0000250\|UniProtKB:Q91VR5}. Note=Localized with MBNL1, TIAL1 and YBX1 in stress granules upon stress. Localized with CSTF2 in cleavage bodies. Forms large aggregates called DDX1 bodies. Relocalized into multiple foci (IR-induced foci or IRIF) after IR treatment, a process that depends on the presence of chromosomal DNA and/or RNA-DNA duplexes. Relocalized at sites of DNA double-strand breaks (DSBs) in an ATM-dependent manner after IR treatment. Colocalized with RELA in the nucleus upon TNF-alpha induction. Enters into the nucleus in case of active transcription while it accumulates in cytosol when transcription level is low (PubMed:24608264). Colocalizes in the cytosol with DDX21, DHX36 and TICAM1. Colocalizes in the mitochondria with TICAM1 and poly(I:C) RNA ligand. The multi-helicase-TICAM1 complex may translocate to the mitochondria upon poly(I:C) stimulation (By similarity). {ECO:0000250\|UniProtKB:Q91VR5, ECO:0000269\|PubMed:24608264}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:20573827}. Note=(Microbial infection) Relocalized to the cytoplasm with a perinuclear staining pattern in avian infectious bronchitis virus (IBV)-infected cells (PubMed:20573827). Required for proper localization of HIV-1 Rev (PubMed:15567440). {ECO:0000269\|PubMed:15567440, ECO:0000269\|PubMed:20573827}.
Tissue specificity:		Highest levels of transcription in 2 retinoblastoma cell lines and in tissues of neuroectodermal origin including the retina, brain, and spinal cord. {ECO:0000269\|PubMed:7689221}.
Domain:		The helicase domain is involved in the stimulation of RELA transcriptional activity. {ECO:0000269\|PubMed:19058135}.
Ptm:		Phosphorylated by ATM kinase; phosphorylation is increased in response to ionizing radiation (IR). {ECO:0000269\|PubMed:18710941}.
Similarity:		Belongs to the DEAD box helicase family. DDX1 subfamily. {ECO:0000305}.