P17844 (DDX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable ATP-dependent RNA helicase DDX5
EC=3.6.4.13

Alternative name(s):
DEAD box protein 5
RNA helicase p68

Gene names

Name:	DDX5
Synonyms:	G17P1, HELR, HLR1

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	614 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Ref.22
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Identified in the spliceosome C complex. Interacts with RBM4; the interaction occurs in a RNA-independent manner. Interacts with EIF2C1 and EIF2C2. Ref.14 Ref.22
Subcellular location	Nucleus › nucleolus Ref.2.
Post-translational modification	Arg-502 is dimethylated, probably to asymmetric dimethylarginine. Ref.11
Sequence similarities	Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Nucleus Spliceosome
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Helicase Hydrolase
PTM	Acetylation Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell growth Non-traceable author statement Ref.8. Source: UniProtKB nuclear mRNA splicing, via spliceosome Inferred by curator Ref.10. Source: UniProtKB regulation of alternative nuclear mRNA splicing, via spliceosome Inferred from direct assay Ref.22. Source: UniProtKB
Cellular component	catalytic step 2 spliceosome Inferred from direct assay Ref.10. Source: UniProtKB nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro RNA helicase activity Inferred from mutant phenotype Ref.22. Source: UniProtKB pre-mRNA binding Inferred from direct assay Ref.22. Source: UniProtKB protein binding Inferred from physical interaction Ref.14Ref.22. Source: UniProtKB transcription cofactor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CHD3	Q12873	4	EBI-351962,EBI-523590
MBD3	O95983	4	EBI-351962,EBI-1783068
TP53	P04637-1	2	EBI-351962,EBI-3895849
TP53	P04637-7	2	EBI-351962,EBI-3895873

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 614

614

Probable ATP-dependent RNA helicase DDX5

PRO_0000054991

Regions

Domain

125 – 300

176

Helicase ATP-binding

Domain

328 – 475

148

Helicase C-terminal

Nucleotide binding

114 – 116

3

ATP

Nucleotide binding

138 – 145

8

ATP

Motif

94 – 122

29

Q motif

Motif

248 – 251

4

DEAD box

Sites

Binding site

121

1

ATP

Amino acid modifications

Modified residue

6

1

Phosphoserine Ref.19

Modified residue

30

1

Phosphoserine Ref.15

Modified residue

32

1

N6-acetyllysine Ref.20

Modified residue

33

1

N6-acetyllysine Ref.20

Modified residue

40

1

N6-acetyllysine Ref.20

Modified residue

202

1

Phosphotyrosine Ref.13

Modified residue

297

1

Phosphotyrosine Ref.12

Modified residue

480

1

Phosphoserine Ref.17 Ref.18

Modified residue

502

1

Omega-N-methylated arginine Ref.11

Modified residue

507

1

Phosphothreonine Ref.16

Modified residue

520

1

Phosphoserine Ref.16

Natural variations

Natural variant

480

1

S → A.
Corresponds to variant rs1140409 [ dbSNP | Ensembl ].

VAR_029241

Experimental info

Mutagenesis

403

1

R → L: Binds to the tau stem-loop-containing RNA. Inhibits tau exon 10 inclusion and RNA cleavage. Does not inhibit interaction with RBM4. Ref.22

Secondary structure

1

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614

Helix Strand Turn

Details...

Helix

72 – 80

9

Beta strand

83 – 85

3

Beta strand

94 – 96

3

Turn

97 – 99

3

Helix

103 – 110

8

Turn

111 – 113

3

Helix

119 – 122

4

Helix

126 – 129

4

Helix

145 – 157

13

Beta strand

170 – 173

4

Helix

177 – 193

17

Beta strand

198 – 201

4

Helix

210 – 215

6

Beta strand

220 – 223

4

Helix

228 – 233

6

Beta strand

244 – 247

4

Helix

250 – 255

6

Helix

259 – 266

8

Beta strand

274 – 277

4

Helix

284 – 293

10

Beta strand

298 – 302

5

Sequences

	Sequence		Length	Mass (Da)
	P17844 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 84DF684FD6871594	FASTA	614	69,148
	10 20 30 40 50 60 MSGYSSDRDR GRDRGFGAPR FGGSRAGPLS GKKFGNPGEK LVKKKWNLDE LPKFEKNFYQ 70 80 90 100 110 120 EHPDLARRTA QEVETYRRSK EITVRGHNCP KPVLNFYEAN FPANVMDVIA RQNFTEPTAI 130 140 150 160 170 180 QAQGWPVALS GLDMVGVAQT GSGKTLSYLL PAIVHINHQP FLERGDGPIC LVLAPTRELA 190 200 210 220 230 240 QQVQQVAAEY CRACRLKSTC IYGGAPKGPQ IRDLERGVEI CIATPGRLID FLECGKTNLR 250 260 270 280 290 300 RTTYLVLDEA DRMLDMGFEP QIRKIVDQIR PDRQTLMWSA TWPKEVRQLA EDFLKDYIHI 310 320 330 340 350 360 NIGALELSAN HNILQIVDVC HDVEKDEKLI RLMEEIMSEK ENKTIVFVET KRRCDELTRK 370 380 390 400 410 420 MRRDGWPAMG IHGDKSQQER DWVLNEFKHG KAPILIATDV ASRGLDVEDV KFVINYDYPN 430 440 450 460 470 480 SSEDYIHRIG RTARSTKTGT AYTFFTPNNI KQVSDLISVL REANQAINPK LLQLVEDRGS 490 500 510 520 530 540 GRSRGRGGMK DDRRDRYSAG KRGGFNTFRD RENYDRGYSS LLKRDFGAKT QNGVYSAANY 550 560 570 580 590 600 TNGSFGSNFV SAGIQTSFRT GNPTGTYQNG YDSTQQYGSN VPNMHNGMNQ QAYAYPATAA 610 APMIGYPMPT GYSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete cDNA sequence of the human p68 protein." Hloch P., Stahl H. Nucleic Acids Res. 18:3045-3045(1990) [PubMed: 2349099] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"p68 RNA helicase: identification of a nucleolar form and cloning of related genes containing a conserved intron in yeasts." Iggo R.D., Jamieson D.J., McNeill S.A., Southgate J., McPheat J., Lane D.P. Mol. Cell. Biol. 11:1326-1333(1991) [PubMed: 1996094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION.
[3]	"Structure and expression of the human p68 RNA helicase gene." Roessler O.G., Hloch P., Schutz N., Weitzenegger T., Stahl H. Nucleic Acids Res. 28:932-939(2000) [PubMed: 10648785] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Muscle.
[8]	"Nuclear protein with sequence homology to translation initiation factor eIF-4A." Ford M.J., Anton I.A., Lane D.P. Nature 332:736-738(1988) [PubMed: 2451786] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-614.
[9]	"Molecular organization of the murine p68 RNA helicase gene promotor region." Petry P., Bammer S., Heinlein U.A.O. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 53-163.
[10]	"Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis." Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J. RNA 8:426-439(2002) [PubMed: 11991638] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SPLICEOSOMAL C COMPLEX.
[11]	"Identifying and quantifying in vivo methylation sites by heavy methyl SILAC." Ong S.E., Mittler G., Mann M. Nat. Methods 1:119-126(2004) [PubMed: 15782174] [Abstract] Cited for: METHYLATION [LARGE SCALE ANALYSIS] AT ARG-502, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-297, MASS SPECTROMETRY.
[13]	"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-202, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[14]	"Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells." Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M., Urlaub H., Meister G. EMBO Rep. 8:1052-1060(2007) [PubMed: 17932509] [Abstract] Cited for: INTERACTION WITH EIF2C1 AND EIF2C2.
[15]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"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-507 AND SER-520, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[17]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[20]	"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-32; LYS-33 AND LYS-40, MASS SPECTROMETRY.
[21]	"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].
[22]	"RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5' splice site." Kar A., Fushimi K., Zhou X., Ray P., Shi C., Chen X., Liu Z., Chen S., Wu J.Y. Mol. Cell. Biol. 31:1812-1821(2011) [PubMed: 21343338] [Abstract] Cited for: FUNCTION, INTERACTION WITH RBM4, MUTAGENESIS OF ARG-403, RNA-BINDING.
[23]	"Comparative structural analysis of human DEAD-box RNA helicases." Schutz P., Karlberg T., van den Berg S., Collins R., Lehtio L., Hogbom M., Holmberg-Schiavone L., Tempel W., Park H.W., Hammarstrom M., Moche M., Thorsell A.G., Schuler H. PLoS ONE 5:0-0(2010) [PubMed: 20941364] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 68-307 IN COMPLEX WITH ADP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X52104 mRNA. Translation: CAA36324.1.
AF015812 Genomic DNA. Translation: AAB84094.1.
BT006943 mRNA. Translation: AAP35589.1.
AB451257 mRNA. Translation: BAG70071.1.
CH471109 Genomic DNA. Translation: EAW94202.1.
CH471109 Genomic DNA. Translation: EAW94203.1.
BC016027 mRNA. Translation: AAH16027.1.
X15729 mRNA. Translation: CAA33751.1.
AJ010931 Genomic DNA. Translation: CAA09408.1.

IPI

IPI00017617.

PIR

JC1087.

RefSeq

NP_004387.1. NM_004396.3.

UniGene

Hs.279806.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3FE2	X-ray	2.60	A/B	68-307	[»]

ProteinModelPortal

P17844.

SMR

P17844. Positions 71-478.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29844N.

IntAct

P17844. 39 interactions.

MINT

MINT-5000516.

STRING

P17844.

PTM databases

PhosphoSite

P17844.

Polymorphism databases

DMDM

129383.

2D gel databases

SWISS-2DPAGE

P17844.

Aarhus/Ghent-2DPAGE

1605. NEPHGE.

Proteomic databases

PeptideAtlas

P17844.

PRIDE

P17844.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225792; ENSP00000225792; ENSG00000108654.

GeneID

1655.

KEGG

hsa:1655.

UCSC

uc002jek.1. human.

Organism-specific databases

CTD

1655.

GeneCards

GC17M062494.

HGNC

HGNC:2746. DDX5.

HPA

CAB005868.
HPA020043.

MIM

180630. gene.

neXtProt

NX_P17844.

PharmGKB

PA27228.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04242.

HOGENOM

HBG737336.

HOVERGEN

HBG015893.

InParanoid

P17844.

OMA

TIDAMSG.

OrthoDB

EOG4BVRTM.

PhylomeDB

P17844.

Gene expression databases

ArrayExpress

P17844.

Bgee

P17844.

CleanEx

HS_DDX5.

Genevestigator

P17844.

GermOnline

ENSG00000108654. Homo sapiens.

Family and domain databases

InterPro

IPR014001. DEAD-like_helicase.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR001650. Helicase_C.
IPR012587. P68HR.
IPR000629. RNA-helicase_DEAD-box_CS.
IPR014014. RNA_helicase_DEAD_Q_motif.
[Graphical view]

KO

K12823.

Pfam

PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
PF08061. P68HR. 2 hits.
[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

NextBio

6816.

SOURCE

Search...

Entry information

Entry name

DDX5_HUMAN

Accession

Primary (citable) accession number: P17844
Secondary accession number(s): B5BU21 , D3DU32, O75681, Q53Y61

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	January 25, 2012
This is version 139 of the entry and version 1 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.