UniProt Accession

 DDX5_HUMAN; P17844; B5BU21; D3DU32; O75681; Q53Y61 

Genbank Protein ID

 X52104; AF015812; BT006943; AB451257; CH471109; CH471109; BC016027; X15729; AJ010931 

Genbank Nucleotide ID

 CAA36324.1; AAB84094.1; AAP35589.1; BAG70071.1; EAW94202.1; EAW94203.1; AAH16027.1; CAA33751.1; CAA09408.1 

Protein Name

 Probable ATP-dependent RNA helicase DDX5 

Protein Synonyms/Alias

 DEAD box protein 5; RNA helicase p68 

Gene Name

 DDX5 

Gene Synonyms/Alias

 G17P1; HELR; HLR1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
32	RAGPLSGKKFGNPGE	acetylation	[1, 2]
33	AGPLSGKKFGNPGEK	acetylation	[1, 2]
40	KFGNPGEKLVKKKWN	acetylation	[1, 2]
40	KFGNPGEKLVKKKWN	ubiquitination	[3, 4]
43	NPGEKLVKKKWNLDE	acetylation	[2]
44	PGEKLVKKKWNLDEL	acetylation	[2]
45	GEKLVKKKWNLDELP	acetylation	[2]
45	GEKLVKKKWNLDELP	ubiquitination	[5]
53	WNLDELPKFEKNFYQ	sumoylation	[6, 7]
53	WNLDELPKFEKNFYQ	ubiquitination	[4, 8]
56	DELPKFEKNFYQEHP	acetylation	[2]
56	DELPKFEKNFYQEHP	ubiquitination	[4, 5, 8, 9, 10]
80	VETYRRSKEITVRGH	acetylation	[2]
80	VETYRRSKEITVRGH	ubiquitination	[4, 8]
91	VRGHNCPKPVLNFYE	ubiquitination	[4]
197	YCRACRLKSTCIYGG	ubiquitination	[3, 4, 11]
207	CIYGGAPKGPQIRDL	ubiquitination	[3, 4, 5, 8]
236	IDFLECGKTNLRRTT	ubiquitination	[3, 4, 8, 12]
264	GFEPQIRKIVDQIRP	ubiquitination	[4]
284	MWSATWPKEVRQLAE	ubiquitination	[3, 4, 5, 8, 9, 10, 13]
340	MEEIMSEKENKTIVF	ubiquitination	[3, 4, 8, 13]
343	IMSEKENKTIVFVET	ubiquitination	[4]
351	TIVFVETKRRCDELT	ubiquitination	[3, 4, 8, 13]
375	AMGIHGDKSQQERDW	ubiquitination	[4, 8]
388	DWVLNEFKHGKAPIL	ubiquitination	[3, 4, 8, 9, 10, 13]
391	LNEFKHGKAPILIAT	ubiquitination	[3, 4, 8, 12, 13]
411	GLDVEDVKFVINYDY	ubiquitination	[4, 8, 13]
437	GRTARSTKTGTAYTF	ubiquitination	[3, 4, 5, 8, 9, 10, 12, 13]
451	FFTPNNIKQVSDLIS	ubiquitination	[4, 8, 12, 13]
470	ANQAINPKLLQLVED	ubiquitination	[3, 4, 5, 8, 9, 10, 11, 12, 13, 14]
523	RGYSSLLKRDFGAKT	ubiquitination	[3, 4, 8, 9, 10, 13]

Reference

 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Pleiotropic effects of p300-mediated acetylation on p68 and p72 RNA helicase.
 Mooney SM, Goel A, D'Assoro AB, Salisbury JL, Janknecht R.
 J Biol Chem. 2010 Oct 1;285(40):30443-52. [PMID: 20663877]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] SUMO modification of the DEAD box protein p68 modulates its transcriptional activity and promotes its interaction with HDAC1.
 Jacobs AM, Nicol SM, Hislop RG, Jaffray EG, Hay RT, Fuller-Pace FV.
 Oncogene. 2007 Aug 30;26(40):5866-76. [PMID: 17369852]
 [7] Sumoylation of p68 and p72 RNA helicases affects protein stability and transactivation potential.
 Mooney SM, Grande JP, Salisbury JL, Janknecht R.
 Biochemistry. 2010 Jan 12;49(1):1-10. [PMID: 19995069]
 [8] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [9] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [10] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [11] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [12] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [13] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [14] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865] 

Functional Description

 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. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for estrogen receptor ESR1 and androgen receptor AR. Increases ESR1 AF-1 domain-mediated transactivation and ESR1 AF-1 and AF-2 domains transcriptional synergistic activity. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as transcriptional repressor in a promoter-specicic manner; the function probbaly involves association with histone deacetylases, such as HDAC1. 

Sequence Annotation

 DOMAIN 125 300 Helicase ATP-binding.
 DOMAIN 328 475 Helicase C-terminal.
 NP_BIND 114 116 ATP.
 NP_BIND 138 145 ATP.
 REGION 477 614 Transactivation domain.
 MOTIF 94 122 Q motif.
 MOTIF 248 251 DEAD box.
 BINDING 121 121 ATP.
 MOD_RES 32 32 N6-acetyllysine.
 MOD_RES 33 33 N6-acetyllysine.
 MOD_RES 40 40 N6-acetyllysine.
 MOD_RES 297 297 Phosphotyrosine.
 MOD_RES 480 480 Phosphoserine.
 CROSSLNK 53 53 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; ATP-binding; Complete proteome; Helicase; Hydrolase; Isopeptide bond; mRNA processing; mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; RNA-binding; Spliceosome; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 614 AA 

Protein Sequence

Gene Ontology

 GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0050681; F:androgen receptor binding; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004004; F:ATP-dependent RNA helicase activity; IEA:Compara.
 GO:0030331; F:estrogen receptor binding; IDA:UniProtKB.
 GO:0036002; F:pre-mRNA binding; IDA:UniProtKB.
 GO:0003724; F:RNA helicase activity; IMP:UniProtKB.
 GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
 GO:0016049; P:cell growth; NAS:UniProtKB.
 GO:0007623; P:circadian rhythm; IEA:Compara.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB.
 GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
 GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
 GO:0060765; P:regulation of androgen receptor signaling pathway; IMP:UniProtKB.
 GO:0045667; P:regulation of osteoblast differentiation; ISS:UniProtKB.
 GO:2001014; P:regulation of skeletal muscle cell differentiation; ISS:UniProtKB.
 GO:0045069; P:regulation of viral genome replication; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
 IPR014001; Helicase_ATP-bd.
 IPR001650; Helicase_C.
 IPR027417; P-loop_NTPase.
 IPR012587; P68HR.
 IPR000629; RNA-helicase_DEAD-box_CS.
 IPR014014; RNA_helicase_DEAD_Q_motif. 

Pfam

 PF00270; DEAD
 PF00271; Helicase_C
 PF08061; P68HR 

SMART

 SM00487; DEXDc
 SM00490; HELICc 

PROSITE

 PS00039; DEAD_ATP_HELICASE
 PS51192; HELICASE_ATP_BIND_1
 PS51194; HELICASE_CTER
 PS51195; Q_MOTIF 

PRINTS