P26196 (DDX6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable ATP-dependent RNA helicase DDX6
EC=3.6.4.13

Alternative name(s):
ATP-dependent RNA helicase p54
DEAD box protein 6
Oncogene RCK

Gene names

Name:	DDX6
Synonyms:	HLR2, RCK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	483 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In the process of mRNA degradation, may play a role in mRNA decapping.
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Forms a complex with DCP1A, DCP2, EDC3 and EDC4/HEDLS. Interacts with LIMD1, WTIP and AJUBA. Interacts with APOBEC3G in an RNA-dependent manner. Ref.4 Ref.5 Ref.7 Ref.11
Subcellular location	Cytoplasm › P-body Ref.4 Ref.5 Ref.7 Ref.9.
Tissue specificity	Abundantly expressed in most tissues.
Involvement in disease	A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).
Sequence similarities	Belongs to the DEAD box helicase family. DDX6/DHH1 subfamily. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Chromosomal rearrangement
Disease	Proto-oncogene
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Helicase Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cytoplasmic mRNA processing body assembly Inferred from direct assay PubMed 20826699. Source: MGI exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay Traceable author statement. Source: Reactome gene expression Traceable author statement. Source: Reactome
Cellular_component	RNA-induced silencing complex Inferred from direct assay Ref.7. Source: MGI cytoplasmic mRNA processing body Inferred from direct assay Ref.5Ref.9. Source: UniProtKB cytoplasmic stress granule Inferred from direct assay PubMed 17392519. Source: UniProtKB cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA helicase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DCP1A	Q9NPI6	4	EBI-351257,EBI-374238
EDC3	Q96F86	2	EBI-351257,EBI-997311

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 483

483

Probable ATP-dependent RNA helicase DDX6

PRO_0000054983

Regions

Domain

127 – 298

172

Helicase ATP-binding

Domain

308 – 468

161

Helicase C-terminal

Nucleotide binding

140 – 147

8

ATP By similarity

Motif

96 – 124

29

Q motif

Motif

246 – 249

4

DEAD box

Amino acid modifications

Modified residue

36

1

Phosphothreonine Ref.6

Experimental info

Mutagenesis

320

1

Q → A: Abolishes interaction with EDC3; when associated with A-323; A-327 and A-331. Ref.11

Mutagenesis

323

1

H → A: Abolishes interaction with EDC3; when associated with A-320; A-327 and A-331. Ref.11

Mutagenesis

327

1

T → A: Abolishes interaction with EDC3; when associated with A-320; A-323 and A-331. Ref.11

Mutagenesis

331

1

R → A: Abolishes interaction with EDC3; when associated with A-320; A-323 and A-327. Ref.11

Sequence conflict

293

1

Q → E in Z11685. Ref.1

Secondary structure

1

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483

Helix Strand Turn

Details...

Helix

98 – 100

3

Helix

105 – 112

8

Turn

113 – 115

3

Helix

121 – 131

11

Beta strand

136 – 139

4

Beta strand

142 – 144

3

Helix

147 – 157

11

Beta strand

167 – 170

4

Helix

174 – 187

14

Turn

188 – 190

3

Beta strand

191 – 193

3

Beta strand

196 – 199

4

Beta strand

201 – 203

3

Helix

205 – 211

7

Beta strand

217 – 221

5

Helix

223 – 231

9

Beta strand

242 – 247

6

Helix

248 – 251

4

Turn

254 – 256

3

Helix

257 – 266

10

Beta strand

272 – 278

7

Helix

282 – 291

10

Beta strand

296 – 298

3

Beta strand

309 – 315

7

Helix

318 – 320

3

Helix

321 – 331

11

Beta strand

335 – 340

6

Helix

344 – 357

14

Beta strand

361 – 364

4

Beta strand

366 – 368

3

Helix

370 – 381

12

Beta strand

386 – 392

7

Beta strand

403 – 410

8

Helix

415 – 422

8

Beta strand

432 – 438

7

Helix

440 – 442

3

Helix

443 – 453

11

Helix

466 – 468

3

Sequences

	Sequence		Length	Mass (Da)
	P26196 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: F802C642861793FB	FASTA	483	54,417
	10 20 30 40 50 60 MSTARTENPV IMGLSSQNGQ LRGPVKPTGG PGGGGTQTQQ QMNQLKNTNT INNGTQQQAQ 70 80 90 100 110 120 SMTTTIKPGD DWKKTLKLPP KDLRIKTSDV TSTKGNEFED YCLKRELLMG IFEMGWEKPS 130 140 150 160 170 180 PIQEESIPIA LSGRDILARA KNGTGKSGAY LIPLLERLDL KKDNIQAMVI VPTRELALQV 190 200 210 220 230 240 SQICIQVSKH MGGAKVMATT GGTNLRDDIM RLDDTVHVVI ATPGRILDLI KKGVAKVDHV 250 260 270 280 290 300 QMIVLDEADK LLSQDFVQIM EDIILTLPKN RQILLYSATF PLSVQKFMNS HLQKPYEINL 310 320 330 340 350 360 MEELTLKGVT QYYAYVTERQ KVHCLNTLFS RLQINQSIIF CNSSQRVELL AKKISQLGYS 370 380 390 400 410 420 CFYIHAKMRQ EHRNRVFHDF RNGLCRNLVC TDLFTRGIDI QAVNVVINFD FPKLAETYLH 430 440 450 460 470 480 RIGRSGRFGH LGLAINLITY DDRFNLKSIE EQLGTEIKPI PSNIDKSLYV AEYHSEPVED EKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression and localization of an RNA helicase gene from a human lymphoid cell line with chromosomal breakpoint 11q23.3." Lu D., Yunis J.J. Nucleic Acids Res. 20:1967-1972(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[3]	"The RCK gene associated with t(11;14) translocation is distinct from the MLL/ALL-1 gene with t(4;11) and t(11;19) translocations." Akao Y., Seto M., Yamamoto K., Iida S., Nakazawa S., Inazawa J., Abe T., Takahashi T., Ueda R. Cancer Res. 52:6083-6087(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-483. Tissue: Lung.
[4]	"Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping." Fenger-Groen M., Fillman C., Norrild B., Lykke-Andersen J. Mol. Cell 20:905-915(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH DCP1A; DCP2; EDC3 AND EDC4, SUBCELLULAR LOCATION.
[5]	"Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies." Wichroski M.J., Robb G.B., Rana T.M. PLoS Pathog. 2:E41-E41(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH APOBEC3G.
[6]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-36, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing." James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M., Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J., Longmore G.D., Bushell M., Sharp T.V. Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH LIMD1; WTIP AND AJUBA.
[8]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies." Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H. J. Virol. 86:11712-11724(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"Crystallization and X-ray analysis of the N-terminal core domain of a tumour-associated human DEAD-box RNA helicase, rck/p54." Matsui T., Hogetsu K., Akao Y., Tanaka M., Sato T., Kumasaka T., Tanaka N. Acta Crystallogr. D 60:156-159(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 94-299.
[11]	"Structural basis for the mutually exclusive anchoring of P body components EDC3 and Tral to the DEAD box protein DDX6/Me31B." Tritschler F., Braun J.E., Eulalio A., Truffault V., Izaurralde E., Weichenrieder O. Mol. Cell 33:661-668(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 296-483 IN COMPLEX WITH EDC3, MUTAGENESIS OF GLN-320; HIS-323; THR-327 AND ARG-331, INTERACTION WITH EDC3.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z11685 mRNA. No translation available.
BC065007 mRNA. Translation: AAH65007.1.
D17532 mRNA. Translation: BAA04482.1.

IPI

IPI00030320.

PIR

S22651.

RefSeq

NP_001244120.1. NM_001257191.1.
NP_004388.2. NM_004397.4.

UniGene

Hs.408461.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VEC	X-ray	2.01	A/B	94-299	[»]
2WAX	X-ray	2.30	A/C	296-483	[»]
2WAY	X-ray	2.30	A/C	296-483	[»]

ProteinModelPortal

P26196.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29195N.

IntAct

P26196. 19 interactions.

STRING

9606.ENSP00000264018.

PTM databases

PhosphoSite

P26196.

Polymorphism databases

DMDM

116241327.

2D gel databases

DOSAC-COBS-2DPAGE

P26196.

Proteomic databases

PaxDb

P26196.

PeptideAtlas

P26196.

PRIDE

P26196.

Protocols and materials databases

DNASU

1656.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264018; ENSP00000264018; ENSG00000110367.
ENST00000526070; ENSP00000433704; ENSG00000110367.
ENST00000534980; ENSP00000442266; ENSG00000110367.
ENST00000593895; ENSP00000472890; ENSG00000269612.
ENST00000596625; ENSP00000471023; ENSG00000269612.
ENST00000600727; ENSP00000469200; ENSG00000269612.

GeneID

1656.

KEGG

hsa:1656.

UCSC

uc001pub.2. human.

Organism-specific databases

CTD

1656.

GeneCards

GC11M118654.

HGNC

HGNC:2747. DDX6.

HPA

CAB004668.
HPA024201.
HPA026644.

MIM

600326. gene.

neXtProt

NX_P26196.

PharmGKB

PA27229.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0513.

HOGENOM

HOG000268797.

HOVERGEN

HBG106685.

InParanoid

P26196.

KO

K12614.

OMA

YSHARMK.

OrthoDB

EOG4J1182.

PhylomeDB

P26196.

Enzyme and pathway databases

Reactome

REACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P26196.

Bgee

P26196.

CleanEx

HS_DDX6.

Genevestigator

P26196.

GermOnline

ENSG00000110367. Homo sapiens.

Family and domain databases

InterPro

IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR000629. RNA-helicase_DEAD-box_CS.
IPR014014. RNA_helicase_DEAD_Q_motif.
[Graphical view]

Pfam

PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
[Graphical view]

SMART

SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]

PROSITE

PS00039. DEAD_ATP_HELICASE. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51195. Q_MOTIF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

DDX6. human.

EvolutionaryTrace

P26196.

GenomeRNAi

1656.

NextBio

6820.

SOURCE

Search...

Entry information

Entry name

DDX6_HUMAN

Accession

Primary (citable) accession number: P26196
Secondary accession number(s): Q5D048

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 140 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.