Target Information

Target General Information

Target ID

T76888 (Former ID: TTDI02430)

Target Name

Peroxiredoxin-4 (PRDX4)

Synonyms

Thioredoxindependent peroxide reductase A0372; Thioredoxin peroxidase AO372; PrxIV; Peroxiredoxin4; Peroxiredoxin IV; PRDX4; Antioxidant enzyme AOE372; AOE372

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Gene Name

PRDX4

Target Type

Literature-reported target

[1]

Function

Probably involved in redox regulation of the cell. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.

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BioChemical Class

Peroxidases

UniProt ID

PRDX4_HUMAN

EC Number

EC 1.11.1.15

Sequence

MEALPLLAATTPDHGRHRRLLLLPLLLFLLPAGAVQGWETEERPRTREEECHFYAGGQVY
PGEASRVSVADHSLHLSKAKISKPAPYWEGTAVIDGEFKELKLTDYRGKYLVFFFYPLDF
TFVCPTEIIAFGDRLEEFRSINTEVVACSVDSQFTHLAWINTPRRQGGLGPIRIPLLSDL
THQISKDYGVYLEDSGHTLRGLFIIDDKGILRQITLNDLPVGRSVDETLRLVQAFQYTDK
HGEVCPAGWKPGSETIIPDPAGKLKYFDKLN

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3D Structure

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PDB

ADReCS ID

BADD_A01285

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: 2-Mercaptoethanesulfonic acid

Ligand Info

Structure Description

Crystal structure of human peroxiredoxin 4(THIOREDOXIN PEROXIDASE) with MESNA

PDB:4RQX

Method

X-ray diffraction

Resolution

2.26 Å

Mutation

[2]

PDB Sequence

GTAKISKPAP

⁸⁶

YWEGTAVIDG

⁹⁶

EFKELKLTDY

¹⁰⁶

RGKYLVFFFY

¹¹⁶

PLDFTFVCPT

¹²⁶

EIIAFGDRLE

¹³⁶

EFRSINTEVV

¹⁴⁶

ACSVDSQFTH

¹⁵⁶

LAWINTPRRQ

¹⁶⁶

GGLGPIRIPL

¹⁷⁶

LSDLTHQISK

¹⁸⁶

DYGVYLEDSG

¹⁹⁶

HTLRGLFIID

²⁰⁶

DKGILRQITL

²¹⁶

NDLPVGRSVD

²²⁶

ETLRLVQAFQ

²³⁶

YTDKHG

Residue

Distance (Å)

CYS124

2.049

PRO125

3.857

Residue

Distance (Å)

ILE129

4.827

ARG164

3.434

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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). 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 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).

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

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.

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	2.53E-06
Closeness centrality	1.74E-01	Radiality	1.28E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	3.00E+00	Topological coefficient	5.00E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

The role of peroxiredoxin 4 in inflammatory response and aging. Biochim Biophys Acta. 2016 Feb;1862(2):265-73.

REF 2

Cysteine specific targeting of the functionally distinct peroxiredoxin and glutaredoxin proteins by the investigational disulfide BNP7787. Molecules. 2015 Mar 18;20(3):4928-50.

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