Q92499 (DDX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-dependent RNA helicase DDX1
EC=3.6.4.13

Alternative name(s):
DEAD box protein 1
DEAD box protein retinoblastoma
Short name=DBP-RB

Gene names

Name:

DDX1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	740 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Required for HIV-1 Rev function as well as for HIV-1 replication. Binds to the RRE sequence of HIV-1 mRNAs. Ref.4 Ref.5 Ref.8 Ref.9 Ref.12
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Interacts with PHF5A (via C-terminus) By similarity. Interacts with MBNL1. Interacts with CSTF2. Interacts with HNRNPK. Interacts with ATM. Interacts with RELA (via C-terminus). Interacts (via C-terminus) with the replicase polyprotein 1ab Nsp14 of the avian infectious bronchitis virus (IBV). Interacts with Rev of HIV-1. Interacts with severe acute respiratory syndrome coronavirus (SARS-CoV) (via N-terminus). Component of the tRNA-splicing ligase complex. Ref.3 Ref.4 Ref.5 Ref.8 Ref.9 Ref.10 Ref.12
Subcellular location	Nucleus. Cytoplasm. Cytoplasmic granule. 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. Relocalized to the cytoplasm with a perinuclear staining pattern in avian infectious bronchitis virus (IBV)-infected cells. Required for proper localization of HIV-1 Rev. Ref.3 Ref.5 Ref.8 Ref.9 Ref.10 Ref.12
Tissue specificity	Highest levels of transcription in 2 retinoblastoma cell lines and in tissues of neuroectodermal origin including the retina, brain, and spinal cord. Ref.1
Domain	The helicase domain is involved in the stimulation of RELA transcriptional activity.
Post-translational modification	Phosphorylated. Phosphorylated by ATM kinase; phosphorylation is increased in response to ionizing radiation (IR). Ref.6 Ref.7 Ref.9
Sequence similarities	Belongs to the DEAD box helicase family. DDX1 subfamily. Contains 1 B30.2/SPRY domain. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.
Caution	According to some authors the unwinding activity is ADP-dependent and not ATP-dependent (Ref.9).

Ontologies

Keywords
Biological process	Transcription Transcription regulation mRNA processing
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding DNA-binding Nucleotide-binding RNA-binding
Molecular function	Activator Exonuclease Helicase Hydrolase Nuclease
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA duplex unwinding Inferred from direct assay Ref.9. Source: UniProtKB double-strand break repair Inferred from direct assay Ref.9. Source: UniProtKB multicellular organismal development Inferred from expression pattern Ref.1. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW regulation of translational initiation Non-traceable author statement Ref.1. Source: UniProtKB spliceosome assembly Non-traceable author statement Ref.1. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cleavage body Inferred from direct assay Ref.3. Source: UniProtKB cytoplasmic stress granule Inferred from direct assay Ref.8. Source: UniProtKB tRNA-splicing ligase complex Inferred from direct assay Ref.14. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from direct assay Ref.4. Source: UniProtKB DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA/RNA helicase activity Inferred from direct assay Ref.9. Source: UniProtKB RNA helicase activity Traceable author statement. Source: ProtInc chromatin binding Inferred from direct assay Ref.10. Source: UniProtKB exonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW poly(A) RNA binding Inferred from direct assay Ref.4. Source: UniProtKB protein binding Inferred from physical interaction Ref.3Ref.4Ref.8Ref.9Ref.10. Source: UniProtKB transcription cofactor activity Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 740	740	ATP-dependent RNA helicase DDX1		PRO_0000054986
Regions
	Domain	2 – 428	427	Helicase ATP-binding
	Domain	70 – 247	178	B30.2/SPRY
	Domain	493 – 681	189	Helicase C-terminal
	Nucleotide binding	46 – 53	8	ATP By similarity
	Region	1 – 525	525	Necessary for interaction with RELA
	Region	1 – 295	295	Necessary for interaction with HNRNPK
	Region	525 – 740	216	Necessary for interaction with HNRNPK
	Region	536 – 631	96	Necessary for interaction with replicase polyprotein 1ab nsp14 of IBV
	Motif	370 – 373	4	DEAD box
Amino acid modifications
	Modified residue	80	1	Phosphothreonine Ref.7
	Modified residue	83	1	Phosphothreonine Ref.7
	Modified residue	239	1	N6-acetyllysine Ref.11
	Modified residue	268	1	N6-acetyllysine Ref.11
	Modified residue	281	1	N6-acetyllysine Ref.11
	Modified residue	628	1	Phosphotyrosine Ref.6
Experimental info
	Mutagenesis	371	1	E → G: Inhibits the transcriptional activity of RELA and attenuates NF-kappa-B-mediated gene expression. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Q92499 [UniParc]. Last modified August 1, 1998. Version 2. Checksum: C6D0179F83BD8C73	FASTA	740	82,432
	10 20 30 40 50 60 MAAFSEMGVM PEIAQAVEEM DWLLPTDIQA ESIPLILGGG DVLMAAETGS GKTGAFSIPV 70 80 90 100 110 120 IQIVYETLKD QQEGKKGKTT IKTGASVLNK WQMNPYDRGS AFAIGSDGLC CQSREVKEWH 130 140 150 160 170 180 GCRATKGLMK GKHYYEVSCH DQGLCRVGWS TMQASLDLGT DKFGFGFGGT GKKSHNKQFD 190 200 210 220 230 240 NYGEEFTMHD TIGCYLDIDK GHVKFSKNGK DLGLAFEIPP HMKNQALFPA CVLKNAELKF 250 260 270 280 290 300 NFGEEEFKFP PKDGFVALSK APDGYIVKSQ HSGNAQVTQT KFLPNAPKAL IVEPSRELAE 310 320 330 340 350 360 QTLNNIKQFK KYIDNPKLRE LLIIGGVAAR DQLSVLENGV DIVVGTPGRL DDLVSTGKLN 370 380 390 400 410 420 LSQVRFLVLD EADGLLSQGY SDFINRMHNQ IPQVTSDGKR LQVIVCSATL HSFDVKKLSE 430 440 450 460 470 480 KIMHFPTWVD LKGEDSVPDT VHHVVVPVNP KTDRLWERLG KSHIRTDDVH AKDNTRPGAN 490 500 510 520 530 540 SPEMWSEAIK ILKGEYAVRA IKEHKMDQAI IFCRTKIDCD NLEQYFIQQG GGPDKKGHQF 550 560 570 580 590 600 SCVCLHGDRK PHERKQNLER FKKGDVRFLI CTDVAARGID IHGVPYVINV TLPDEKQNYV 610 620 630 640 650 660 HRIGRVGRAE RMGLAISLVA TEKEKVWYHV CSSRGKGCYN TRLKEDGGCT IWYNEMQLLS 670 680 690 700 710 720 EIEEHLNCTI SQVEPDIKVP VDEFDGKVTY GQKRAAGGGS YKGHVDILAP TVQELAALEK 730 740 EAQTSFLHLG YLPNQLFRTF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Amplification of a DEAD box protein gene in retinoblastoma cell lines." Godbout R., Squire J. Proc. Natl. Acad. Sci. U.S.A. 90:7578-7582(1993) [PubMed: 7689221] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Retinoblastoma.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Uterus.
[3]	"Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA." Bleoo S., Sun X., Hendzel M.J., Rowe J.M., Packer M., Godbout R. Mol. Biol. Cell 12:3046-3059(2001) [PubMed: 11598190] [Abstract] Cited for: INTERACTION WITH CSTF2, SUBCELLULAR LOCATION.
[4]	"An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K." Chen H.C., Lin W.C., Tsay Y.G., Lee S.C., Chang C.J. J. Biol. Chem. 277:40403-40409(2002) [PubMed: 12183465] [Abstract] Cited for: FUNCTION, INTERACTION WITH HNRNPK, RNA-BINDING.
[5]	"A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev." Fang J., Kubota S., Yang B., Zhou N., Zhang H., Godbout R., Pomerantz R.J. Virology 330:471-480(2004) [PubMed: 15567440] [Abstract] Cited for: FUNCTION, INTERACTION WITH REV OF HIV-1, RNA-BINDING, SUBCELLULAR LOCATION.
[6]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-628, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[7]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-80 AND THR-83, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"MBNL1 associates with YB-1 in cytoplasmic stress granules." Onishi H., Kino Y., Morita T., Futai E., Sasagawa N., Ishiura S. J. Neurosci. Res. 86:1994-2002(2008) [PubMed: 18335541] [Abstract] Cited for: FUNCTION, INTERACTION WITH MBNL1, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[9]	"A role for DEAD box 1 at DNA double-strand breaks." Li L., Monckton E.A., Godbout R. Mol. Cell. Biol. 28:6413-6425(2008) [PubMed: 18710941] [Abstract] Cited for: FUNCTION, INTERACTION WITH ATM, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[10]	"The DEAD-box RNA helicase DDX1 interacts with RelA and enhances nuclear factor kappaB-mediated transcription." Ishaq M., Ma L., Wu X., Mu Y., Pan J., Hu J., Hu T., Fu Q., Guo D. J. Cell. Biochem. 106:296-305(2009) [PubMed: 19058135] [Abstract] Cited for: INTERACTION WITH RELA, MUTAGENESIS OF GLU-371, SUBCELLULAR LOCATION.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-239; LYS-268 AND LYS-281, MASS SPECTROMETRY.
[12]	"The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication." Xu L., Khadijah S., Fang S., Wang L., Tay F.P., Liu D.X. J. Virol. 84:8571-8583(2010) [PubMed: 20573827] [Abstract] Cited for: FUNCTION, INTERACTION WITH REPLICASE POLYPROTEIN 1AB NSP14 OF IBV AND SARS-COV, SUBCELLULAR LOCATION.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"HSPC117 is the essential subunit of a human tRNA splicing ligase complex." Popow J., Englert M., Weitzer S., Schleiffer A., Mierzwa B., Mechtler K., Trowitzsch S., Will C.L., Luhrmann R., Soll D., Martinez J. Science 331:760-764(2011) [PubMed: 21311021] [Abstract] Cited for: IDENTIFICATION IN THE TRNA SPLICING LIGASE COMPLEX.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X70649 mRNA. Translation: CAA49992.1. BC012132 mRNA. Translation: AAH12132.1. BC053673 mRNA. Translation: AAH53673.1.
IPI	IPI00293655.
RefSeq	NP_004930.1. NM_004939.1.
UniGene	Hs.440599.
3D structure databases
ProteinModelPortal	Q92499.
SMR	Q92499. Positions 102-245, 286-625.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92499. 11 interactions.
MINT	MINT-5005493.
STRING	Q92499.
PTM databases
PhosphoSite	Q92499.
Polymorphism databases
DMDM	6919862.
2D gel databases
REPRODUCTION-2DPAGE	IPI00293655.
Proteomic databases
PeptideAtlas	Q92499.
PRIDE	Q92499.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000233084; ENSP00000233084; ENSG00000079785. ENST00000381341; ENSP00000370745; ENSG00000079785.
GeneID	1653.
KEGG	hsa:1653.
UCSC	uc002rce.1. human.
Organism-specific databases
CTD	1653.
GeneCards	GC02P015731.
H-InvDB	HIX0001841.
HGNC	HGNC:2734. DDX1.
HPA	CAB012280. HPA034502. HPA034503.
MIM	601257. gene.
neXtProt	NX_Q92499.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000062880.
HOGENOM	HBG357250.
HOVERGEN	HBG005462.
InParanoid	Q92499.
OMA	SQHTGNA.
OrthoDB	EOG46HG95.
PhylomeDB	Q92499.
Gene expression databases
ArrayExpress	Q92499.
Bgee	Q92499.
CleanEx	HS_DDX1.
Genevestigator	Q92499.
GermOnline	ENSG00000079785. Homo sapiens.
Family and domain databases
InterPro	IPR001870. B30.2/SPRY. IPR008985. ConA-like_lec_gl. IPR014001. DEAD-like_helicase. IPR011545. DNA/RNA_helicase_DEAD/DEAH_N. IPR001650. Helicase_C. IPR014014. RNA_helicase_DEAD_Q_motif. IPR018355. SPla/RYanodine_receptor_subgr. IPR003877. SPRY_rcpt. [Graphical view]
KO	K13177.
Pfam	PF00270. DEAD. 1 hit. PF00271. Helicase_C. 1 hit. PF00622. SPRY. 1 hit. [Graphical view]
SMART	SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. SM00449. SPRY. 1 hit. [Graphical view]
SUPFAM	SSF49899. ConA_like_lec_gl. 1 hit.
PROSITE	PS50188. B302_SPRY. 1 hit. PS00039. DEAD_ATP_HELICASE. False negative. PS51192. HELICASE_ATP_BIND_1. 2 hits. PS51194. HELICASE_CTER. 1 hit. PS51195. Q_MOTIF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	6806.
SOURCE	Search...

Entry information

Entry name

DDX1_HUMAN

Accession

Primary (citable) accession number: Q92499

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	August 1, 1998
Last modified:	January 25, 2012
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.