Probable ATP-dependent RNA helicase DDX17 (DDX17)

The protein contains 729 amino acids for an estimated molecular weight of 80272 Da.

 

As an RNA helicase, unwinds RNA and alters RNA structures through ATP binding and hydrolysis. Involved in multiple cellular processes, including pre-mRNA splicing, alternative splicing, ribosomal RNA processing and miRNA processing, as well as transcription regulation. Regulates the alternative splicing of exons exhibiting specific features (PubMed:12138182, PubMed:23022728, PubMed:24910439, PubMed:22266867). For instance, promotes the inclusion of AC-rich alternative exons in CD44 transcripts (PubMed:12138182). This function requires the RNA helicase activity (PubMed:12138182, PubMed:23022728, PubMed:24910439, PubMed:22266867). Affects NFAT5 and histone macro-H2A.1/MACROH2A1 alternative splicing in a CDK9-dependent manner (PubMed:26209609, PubMed:22266867). In NFAT5, promotes the introduction of alternative exon 4, which contains 2 stop codons and may target NFAT5 exon 4-containing transcripts to nonsense-mediated mRNA decay, leading to the down-regulation of NFAT5 protein (PubMed:22266867). Affects splicing of mediators of steroid hormone signaling pathway, including kinases that phosphorylates ESR1, such as CDK2, MAPK1 and GSK3B, and transcriptional regulators, such as CREBBP, MED1, NCOR1 and NCOR2. By affecting GSK3B splicing, participates in ESR1 and AR stabilization (PubMed:24275493). In myoblasts and epithelial cells, cooperates with HNRNPH1 to control the splicing of specific subsets of exons (PubMed:24910439). In addition to binding mature mRNAs, also interacts with (updated: Feb. 26, 2020)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 64%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 608469

Dead/h box 17; ddx17
Rna helicase, 70-kd; rh70
P72

DESCRIPTION

Members of the DEAD box (asp-glu-ala-asp/his) protein family of RNA helicases are involved in diverse cellular functions including mRNA splicing, ribosome assembly, translation initiation, mRNA stability, and cell growth and division (Lamm et al., 1996).

CLONING

Lamm et al. (1996) cloned DDX17, which they designated p72, from a HeLa cell cDNA library. The deduced 650-amino acid protein has a calculated molecular mass of 71.9 kD. DDX17 contains 4 N-terminal RGG box repeats followed by a central conserved DEAD box domain, a run of 7 glycines, and a serine/glycine-rich C-terminal domain ending in 9 consecutive prolines. RGG box repeats mediate RNA binding, and both the serine/glycine-rich region and the proline-rich motif mediate protein-protein interactions. DDX17 shares 69.7% identity with p68 (DDX5; 180630), with highest similarity in the DEAD box region. Northern blot analysis detected ubiquitous expression of 5.3- and 9.3-kb transcripts. Both transcripts were abundantly expressed in kidney and pancreas, and the 5.3-kb transcript was also abundantly expressed in skeletal muscle. Endogenous p72 isolated from HeLa cell nuclear extracts and recombinant p72 expressed through in vitro translation yielded an apparent 79-kD protein by SDS/PAGE and Western blot analysis. From HeLa cell cDNA, Uhlmann-Schiffler et al. (2002) cloned a variant of DDX17, which they designated p82. The deduced protein, translated from a non-AUG start codon, contains an N-terminal extension of 80 to 90 amino acids. Northern blot analysis detected this variant at about 9.3 kb in HeLa cell RNA. Both HeLa cells and COS cells endogenously expressed both DDX17 variants, which migrated at apparent molecular masses of 82 and 72 kD.

GENE FUNCTION

Lamm et al. (1996) confirmed that, like other DEAD box proteins, DDX17 hydrolyzed ATP in the presence of RNA. Several RNA species, including total RNA, tRNA, E. coli rRNA, and both adenovirus and beta-globin pre-mRNA, stimulated the ATPase activity. Single-stranded phage DNA also stimulated a low level of ATP hydrolysis. No activity was observed in the presence of total HeLa cell DNA or poly(U) RNA. These results led Lamm et al. (1996) to hypothesize that the ATPase activity of DDX17 is dependent on the secondary structure of RNA. Uhlmann-Schiffler et al. (2002) determined that p82 DDX17 showed RNA-dependent ATPase activity resembling that measured in p72 DDX17. The p82 form also showed helicase activity against partial dsRNA substrates in the presence of ATP. A 3-prime single-strand overhang was required, and no helicase activity was observed with substrates containing a 5-prime single-strand overhang. Using minigenes that undergo different types of alternative splicing, Honig et al. (2002) demonstrated that p72 DDX17 affects the splicing of alternative exons containing AC-rich exon enhancer elements. Mutation of the ATP-binding sites or deletion of the C-terminal region reduced the ability of DDX17 to effect variable exon splicing. Use of in vitro extracts overexpressing p72 DDX17 showed that p72 becomes associated with complexes containing precursor RNA. Honig et al. (2002) also found evidence that DDX17 may alter protein-RNA interactions. They concluded that DDX17 may be an alternative splicing regulatory factor. Lee (2002) found that DDX17 catalyzed the unwinding of duplex RNA containing single-stranded regions at either the 5-prime or 3-prime end. DDX17 also copurified with U1snRNP ... More on the omim web site

Subscribe to this protein entry history

March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608469 was added.