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DDX25 (DEAD (Asp-Glu-Ala-Asp) box helicase 25)

Written2012-02Chon-Hwa Tsai-Morris, Maria L Dufau
Section on Molecular Endocrinology, Program in Developmental Endocrinology, Genetics, NICHD, National Institutes of Health, Bethesda, MD 20892-4510, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesDEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 25
DEAD (Asp-Glu-Ala-Asp) box polypeptide 25
DEAD (Asp-Glu-Ala-Asp) box helicase 25
Alias_symbol (synonym)GRTH
Other alias
HGNC (Hugo) DDX25
LocusID (NCBI) 29118
Atlas_Id 46826
Location 11q24.2  [Link to chromosome band 11q24]
Location_base_pair Starts at 125774261 and ends at 125793006 bp from pter ( according to hg19-Feb_2009)  [Mapping DDX25.png]
Fusion genes
(updated 2016)
PAPPA (9q33.1) / DDX25 (11q24.2)PPM1G (2p23.3) / DDX25 (11q24.2)
Note Gonadotropin Regulated Testicular RNA Helicase (GRTH), a member of the Glu-Asp-Ala-Glu (DEAD)-box protein family, is a testis-specific gonadotropin/androgen-regulated RNA Helicase.

DNA/RNA

 
  Genomic organization of the Human GRTH gene. Exons presented by boxes. The positions of the translation initiation ATG and termination TGA codon are indicated. Conserved domains of DEAD-box family of the RNA helicase are presented above its respective exon.
Description Human GRTH gene contains 12 exons and all but one of its conserved helicase motifs are contained within single exon (Tsai-Morris et al., 2004). Motif ARG-D resides in exon 10/11.
Transcription The GRTH gene belongs to the TATA-less/non-initiator class (Tsai-Morris et al., 2004). A single transcript of 1,6 Kb is expressed in the testis (Tang et al., 1999). Gonadotropin-induced androgen increases cause autocrine stimulation of GRTH gene transcription in Leydig cells through a non-classical half-site element residing at -827/-822 5' from the initiation codon (Tang et al., 1999; Tsai-Morris et al., 2010; Villar et al., 2012). The induction of the GRTH gene expression in germ cells (meiotic spermatocytes, round and elongated spermatids) presumbably results from paracrine actions of androgen through cognate receptors in Sertoli cells (adjacent to germinal cells).
Pseudogene One related pseudo DDX25 (LOC100421309) was found in chromosome 5.

Protein

Description GRTH contains three ATG in frame codons with the potential for generation of multiple protein species (61/56, 48/43 and 33 kDa) (Sheng et al., 2003). The 61/56 kDa proteins are the major species observed in the human testis (Tang et al., 1999; Tsai-Morris et al., 2007). GRTH 56- and 61-kDa species are present in nucleus and cytoplasm (Sheng et al., 2006), respectively. Based on the mouse model, the 56 kDa nuclear species interacts with CRM1 and participates in mRNA transport in the human testis and the phosphorylated 61 kDa species associates with mRNAs at polysomal sites and also within the Chromatoid Body of round spermatids.
Expression GRTH (484 aa) is highly expressed in the testis: somatic (Leydig cells) and germinal (meiotic spermatocytes, round spermatids and elongated spermatids) cells (Sheng et al., 2003; Tsai-Morris, et al., 2004). GRTH is genetically close to DBP5/DDX19b (63% overall aa homology) involved in mRNA export (Schmitt et al., 1999).
Localisation GRTH is localized in the nucleus and at cytoplasmic sites in polyribosomes and the Chromatoid Body (CB) of round spermatids (Tsai-Morris et al., 2004; Sheng et al., 2006; Sato et al., 2010; Tsai-Morris et al., 2012).
Function GRTH is a multifunctional protein essential for completion of spermatogenesis as a post-transcriptional regulator of relevant genes during germ cells development (Tsai-Morris et al., 2004; Sheng et al., 2006; Dufau and Tsai-Morris, 2007; Tsai-Morris et al., 2010). It contains ATPase activity (ATP/Mg dependent), and is a bi-directional RNA helicase. As a translational regulator it participates in the in vitro and in vivo translation of RNA templates. GRTH is a shuttling protein that exports germ cell specific RNA as mRNP particles from nucleus to cytoplasm via the CRM1-dependent pathway. A specific set of testicular gene transcripts, including those of chromatin-remodeling proteins (Tp1 and Tp2, Prm1 and PRM2), cytoskeletal structural proteins (Fsc1/Odf1) and tACE are associated with GRTH protein. GRTH also selectively binds mRNAs of pro-apoptotic and anti-apoptotic genes, the death receptor and proteins involved in the NF-kB pathways to mediate anti-apoptotic regulation (Gutti et al., 2008). GRTH is required to maintain the structural integrity of the chromatoid body (storage/processing organelle of mRNAs that contains members of the small miRNA RISC-complex) during spermatogenesis (Sato et al., 2010). GRTH also participates in the regulation of microRNA biogenesis in germ cells (Dai et al., 2011) and associates with polyribosome for translational initiation of target genes. In Leydig cells, GRTH prevents overstimulation of gonadotropin-induced androgen pathway by promoting degradation of StAR protein (Fukushima et al., 2011).
 
  Model of GRTH action in male germ cells during development (derived from mouse studies). 56 kDa GRTH species enters the nucleus (1), where it binds messages and associates with CRM1 (2) as mRNP complex to export messages through nuclear pores via the CRM1 pathway to the cytoplasm (3a) and to the chromatoid body (CB), either directly (via nuclear pores adjacent to or associated with the CB) (3b) or indirectly via the cytoplasmic route (4b). It is phosphorylated at cytoplasmic sites, and participates in translation at polyribosomes (4a). In the CB, messages are potentially regulated via si/mi/pi RNA pathway (5a and b). Stored messages are subsequently translated in polyribosomes (4a and 6) at specific times during spermatogenesis.
 

Implicated in

Note
  
Entity Azoospermia
Note A missense mutation (R242H) in exon 8 identified in 5% of an infertile Japanese patient population with non-obstructive azoospermia (NOA) abrogated the generation of the 61 kDa phosphorylated-GRTH species (Tsai-Morris et al., 2007; Tsai-Morris et al., 2008). A silent mutation located in exon 10 (C1194T, nt) identified in Chinese patients with idiopathic azoospermia was proposed to increase the risk of impaired spermatogenesis (Zhoucun et al., 2006). This could result from its location in the binding motif of splicing factor 2 through affecting pre-RNA splicing of the GRTH gene and ultimately its expression. However, such mutation was not observed in the infertile Japanese patients with non-obstructive azoospermia (Tsai-Morris et al., 2008), which indicated segregration of the mutation to the Chinese population.
  

Bibliography

Single nucleotide polymorphisms of the gonadotrophin-regulated testicular helicase (GRTH) gene may be associated with the human spermatogenesis impairment.
A Z, Zhang S, Yang Y, Ma Y, Lin L, Zhang W.
Hum Reprod. 2006 Mar;21(3):755-9. Epub 2005 Nov 17.
PMID 16293649
 
Testis-specific miRNA-469 up-regulated in gonadotropin-regulated testicular RNA helicase (GRTH/DDX25)-null mice silences transition protein 2 and protamine 2 messages at sites within coding region: implications of its role in germ cell development.
Dai L, Tsai-Morris CH, Sato H, Villar J, Kang JH, Zhang J, Dufau ML.
J Biol Chem. 2011 Dec 30;286(52):44306-18. Epub 2011 Nov 15.
PMID 22086916
 
Gonadotropin-regulated testicular helicase (GRTH/DDX25): a master post-transcriptional regulator of spermatogenesis.
Dufau ML, Sato H, Gutti R, Tsai-Morris CH.
Adv Exp Med Biol. 2011;707:23-9.
PMID 21691948
 
Gonadotropin-regulated testicular helicase (GRTH/DDX25): an essential regulator of spermatogenesis.
Dufau ML, Tsai-Morris CH.
Trends Endocrinol Metab. 2007 Oct;18(8):314-20. Epub 2007 Sep 21. (REVIEW)
PMID 17889551
 
Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), a negative regulator of luteinizing/chorionic gonadotropin hormone-induced steroidogenesis in Leydig cells: central role of steroidogenic acute regulatory protein (StAR).
Fukushima M, Villar J, Tsai-Morris CH, Dufau ML.
J Biol Chem. 2011 Aug 26;286(34):29932-40. Epub 2011 Jun 30.
PMID 21719703
 
Gonadotropin-regulated testicular helicase (DDX25), an essential regulator of spermatogenesis, prevents testicular germ cell apoptosis.
Gutti RK, Tsai-Morris CH, Dufau ML.
J Biol Chem. 2008 Jun 20;283(25):17055-64. Epub 2008 Apr 22.
PMID 18430733
 
Relevance of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) in the structural integrity of the chromatoid body during spermatogenesis.
Sato H, Tsai-Morris CH, Dufau ML.
Biochim Biophys Acta. 2010 May;1803(5):534-43. Epub 2010 Feb 20.
PMID 20176059
 
Dbp5, a DEAD-box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p.
Schmitt C, von Kobbe C, Bachi A, Pante N, Rodrigues JP, Boscheron C, Rigaut G, Wilm M, Seraphin B, Carmo-Fonseca M, Izaurralde E.
EMBO J. 1999 Aug 2;18(15):4332-47.
PMID 10428971
 
Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is a transport protein involved in gene-specific mRNA export and protein translation during spermatogenesis.
Sheng Y, Tsai-Morris CH, Gutti R, Maeda Y, Dufau ML.
J Biol Chem. 2006 Nov 17;281(46):35048-56. Epub 2006 Sep 12.
PMID 16968703
 
A novel gonadotropin-regulated testicular RNA helicase. A new member of the dead-box family.
Tang PZ, Tsai-Morris CH, Dufau ML.
J Biol Chem. 1999 Dec 31;274(53):37932-40.
PMID 10608860
 
Role of Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) on Polysomal Associated mRNAs in Mouse Testis.
Tsai-Morris CH, Sato H, Gutti R, Dufau ML.
PLoS One. 2012;7(3):e32470. Epub 2012 Mar 30.
PMID 22479328
 
Androgen-Induced Activation of Gonadotropin-Regulated Testicular RNA Helicase (GRTH/Ddx25) Transcription: Essential Role of a Nonclassical Androgen Response Element Half-Site.
Villar J, Tsai-Morris CH, Dai L, Dufau ML.
Mol Cell Biol. 2012 Apr;32(8):1566-80. Epub 2012 Feb 13.
PMID 22331472
 

Citation

This paper should be referenced as such :
Tsai-Morris, CH ; Dufau, ML
DDX25 (DEAD (Asp-Glu-Ala-Asp) box helicase 25)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(7):459-462.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DDX25ID46826ch11q24.html


External links

Nomenclature
HGNC (Hugo)DDX25   18698
Cards
AtlasDDX25ID46826ch11q24
Entrez_Gene (NCBI)DDX25  29118  DEAD-box helicase 25
AliasesGRTH
GeneCards (Weizmann)DDX25
Ensembl hg19 (Hinxton)ENSG00000109832 [Gene_View]  chr11:125774261-125793006 [Contig_View]  DDX25 [Vega]
Ensembl hg38 (Hinxton)ENSG00000109832 [Gene_View]  chr11:125774261-125793006 [Contig_View]  DDX25 [Vega]
ICGC DataPortalENSG00000109832
TCGA cBioPortalDDX25
AceView (NCBI)DDX25
Genatlas (Paris)DDX25
WikiGenes29118
SOURCE (Princeton)DDX25
Genetics Home Reference (NIH)DDX25
Genomic and cartography
GoldenPath hg19 (UCSC)DDX25  -     chr11:125774261-125793006 +  11q24   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)DDX25  -     11q24   [Description]    (hg38-Dec_2013)
EnsemblDDX25 - 11q24 [CytoView hg19]  DDX25 - 11q24 [CytoView hg38]
Mapping of homologs : NCBIDDX25 [Mapview hg19]  DDX25 [Mapview hg38]
OMIM607663   
Gene and transcription
Genbank (Entrez)AF155140 AK295121 AK312772 BC031098 BC035388
RefSeq transcript (Entrez)NM_013264
RefSeq genomic (Entrez)NC_000011 NC_018922 NT_033899 NW_004929381
Consensus coding sequences : CCDS (NCBI)DDX25
Cluster EST : UnigeneHs.420263 [ NCBI ]
CGAP (NCI)Hs.420263
Alternative Splicing GalleryENSG00000109832
Gene ExpressionDDX25 [ NCBI-GEO ]   DDX25 [ EBI - ARRAY_EXPRESS ]   DDX25 [ SEEK ]   DDX25 [ MEM ]
Gene Expression Viewer (FireBrowse)DDX25 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)29118
GTEX Portal (Tissue expression)DDX25
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UHL0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UHL0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UHL0
Splice isoforms : SwissVarQ9UHL0
Catalytic activity : Enzyme3.6.4.13 [ Enzyme-Expasy ]   3.6.4.133.6.4.13 [ IntEnz-EBI ]   3.6.4.13 [ BRENDA ]   3.6.4.13 [ KEGG ]   
PhosPhoSitePlusQ9UHL0
Domaine pattern : Prosite (Expaxy)HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)    Q_MOTIF (PS51195)   
Domains : Interpro (EBI)DEAD/DEAH_box_helicase_dom    Helicase_ATP-bd    Helicase_C    P-loop_NTPase    RNA_helicase_DEAD_Q_motif   
Domain families : Pfam (Sanger)DEAD (PF00270)    Helicase_C (PF00271)   
Domain families : Pfam (NCBI)pfam00270    pfam00271   
Domain families : Smart (EMBL)DEXDc (SM00487)  HELICc (SM00490)  
Conserved Domain (NCBI)DDX25
DMDM Disease mutations29118
Blocks (Seattle)DDX25
PDB (SRS)2RB4   
PDB (PDBSum)2RB4   
PDB (IMB)2RB4   
PDB (RSDB)2RB4   
Structural Biology KnowledgeBase2RB4   
SCOP (Structural Classification of Proteins)2RB4   
CATH (Classification of proteins structures)2RB4   
SuperfamilyQ9UHL0
Human Protein AtlasENSG00000109832
Peptide AtlasQ9UHL0
HPRD06367
IPIIPI00296139   IPI00759454   IPI00984919   IPI00984425   
Protein Interaction databases
DIP (DOE-UCLA)Q9UHL0
IntAct (EBI)Q9UHL0
FunCoupENSG00000109832
BioGRIDDDX25
STRING (EMBL)DDX25
ZODIACDDX25
Ontologies - Pathways
QuickGOQ9UHL0
Ontology : AmiGORNA binding  ATP-dependent RNA helicase activity  ATP-dependent RNA helicase activity  ATP binding  nucleus  cytoplasm  mRNA export from nucleus  mRNA export from nucleus  regulation of translation  multicellular organism development  spermatid development  RNA secondary structure unwinding  chromatoid body  
Ontology : EGO-EBIRNA binding  ATP-dependent RNA helicase activity  ATP-dependent RNA helicase activity  ATP binding  nucleus  cytoplasm  mRNA export from nucleus  mRNA export from nucleus  regulation of translation  multicellular organism development  spermatid development  RNA secondary structure unwinding  chromatoid body  
NDEx NetworkDDX25
Atlas of Cancer Signalling NetworkDDX25
Wikipedia pathwaysDDX25
Orthology - Evolution
OrthoDB29118
GeneTree (enSembl)ENSG00000109832
Phylogenetic Trees/Animal Genes : TreeFamDDX25
HOVERGENQ9UHL0
HOGENOMQ9UHL0
Homologs : HomoloGeneDDX25
Homology/Alignments : Family Browser (UCSC)DDX25
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDDX25 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DDX25
dbVarDDX25
ClinVarDDX25
1000_GenomesDDX25 
Exome Variant ServerDDX25
ExAC (Exome Aggregation Consortium)DDX25 (select the gene name)
Genetic variants : HAPMAP29118
Genomic Variants (DGV)DDX25 [DGVbeta]
DECIPHER (Syndromes)11:125774261-125793006  ENSG00000109832
CONAN: Copy Number AnalysisDDX25 
Mutations
ICGC Data PortalDDX25 
TCGA Data PortalDDX25 
Broad Tumor PortalDDX25
OASIS PortalDDX25 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDDX25  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDDDX25
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch DDX25
DgiDB (Drug Gene Interaction Database)DDX25
DoCM (Curated mutations)DDX25 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)DDX25 (select a term)
intoGenDDX25
NCG5 (London)DDX25
Cancer3DDDX25(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM607663   
Orphanet
MedgenDDX25
Genetic Testing Registry DDX25
NextProtQ9UHL0 [Medical]
TSGene29118
GENETestsDDX25
Huge Navigator DDX25 [HugePedia]
snp3D : Map Gene to Disease29118
BioCentury BCIQDDX25
ClinGenDDX25
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD29118
Chemical/Pharm GKB GenePA38644
Clinical trialDDX25
Miscellaneous
canSAR (ICR)DDX25 (select the gene name)
Probes
Litterature
PubMed13 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineDDX25
EVEXDDX25
GoPubMedDDX25
iHOPDDX25
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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