Target Information

Target General Information

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Target ID

T27918

Target Name

ATP-dependent RNA helicase DDX5 (DDX5)

Synonyms

RNA helicase p68; Probable ATP-dependent RNA helicase DDX5; HLR1; HELR; G17P1; DEAD box protein 5

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Gene Name

DDX5

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Breast cancer [ICD-11: 2C60-2C6Y]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Function

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 androgen receptor AR but probably not ESR1. 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-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. 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.

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UniProt ID

DDX5_HUMAN

EC Number

EC 3.6.4.13

Sequence

MSGYSSDRDRGRDRGFGAPRFGGSRAGPLSGKKFGNPGEKLVKKKWNLDELPKFEKNFYQ
EHPDLARRTAQEVETYRRSKEITVRGHNCPKPVLNFYEANFPANVMDVIARQNFTEPTAI
QAQGWPVALSGLDMVGVAQTGSGKTLSYLLPAIVHINHQPFLERGDGPICLVLAPTRELA
QQVQQVAAEYCRACRLKSTCIYGGAPKGPQIRDLERGVEICIATPGRLIDFLECGKTNLR
RTTYLVLDEADRMLDMGFEPQIRKIVDQIRPDRQTLMWSATWPKEVRQLAEDFLKDYIHI
NIGALELSANHNILQIVDVCHDVEKDEKLIRLMEEIMSEKENKTIVFVETKRRCDELTRK
MRRDGWPAMGIHGDKSQQERDWVLNEFKHGKAPILIATDVASRGLDVEDVKFVINYDYPN
SSEDYIHRIGRTARSTKTGTAYTFFTPNNIKQVSDLISVLREANQAINPKLLQLVEDRGS
GRSRGRGGMKDDRRDRYSAGKRGGFNTFRDRENYDRGYSSLLKRDFGAKTQNGVYSAANY
TNGSFGSNFVSAGIQTSFRTGNPTGTYQNGYDSTQQYGSNVPNMHNGMNQQAYAYPATAA
APMIGYPMPTGYSQ

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3D Structure

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AlphaFold

HIT2.0 ID

T27IR2

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

RX-5902

Drug Info

Phase 2

Triple negative breast cancer

[2]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 1 Modulator drugs

RX-5902

Drug Info

[1]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: adenosine diphosphate

Ligand Info

Structure Description

Human DEAD-BOX RNA helicase DDX5 (P68), conserved domain I in complex with ADP

PDB:3FE2

Method

X-ray diffraction

Resolution

2.60 Å

Mutation

[3]

PDB Sequence

QEVETYRRSK

⁸⁰

EITVRGHNCP

⁹⁰

KPVLNFYEAN

¹⁰⁰

FPANVMDVIA

¹¹⁰

RQNFTEPTAI

¹²⁰

QAQGWPVALS

¹³⁰

GLDMVGVAQT

¹⁴⁰

GSGKTLSYLL

¹⁵⁰

PAIVHINHQP

¹⁶⁰

FLERGDGPIC

¹⁷⁰

LVLAPTRELA

¹⁸⁰

QQVQQVAAEY

¹⁹⁰

CRACRLKSTC

²⁰⁰

IYGGAPKGPQ

²¹⁰

IRDLERGVEI

²²⁰

CIATPGRLID

²³⁰

FLECGKTNLR

²⁴⁰

RTTYLVLDEA

²⁵⁰

DRMLDMGFEP

²⁶⁰

QIRKIVDQIR

²⁷⁰

PDRQTLMWSA

²⁸⁰

TWPKEVRQLA

²⁹⁰

EDFLKDYIHI

³⁰⁰

NIGA

Residue

Distance (Å)

PHE96

3.645

PHE114

3.306

THR115

4.972

GLU116

2.712

PRO117

3.824

THR118

3.474

GLN121

2.818

GLN139

3.667

Residue

Distance (Å)

THR140

3.394

GLY141

2.484

SER142

3.145

GLY143

2.992

LYS144

2.746

THR145

2.350

LEU146

3.788

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Spliceosome	hsa03040	Affiliated Target
Class: Genetic Information Processing => Transcription	Pathway Hierarchy

Degree	17	Degree centrality	1.83E-03	Betweenness centrality	1.77E-03
Closeness centrality	2.53E-01	Radiality	1.44E+01	Clustering coefficient	2.65E-01
Neighborhood connectivity	6.71E+01	Topological coefficient	8.84E-02	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target