Target Information

Target General Information

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Target ID

T83284 (Former ID: TTDI02224)

Target Name

Quinone oxidoreductase (CRYZ)

Synonyms

Zeta-crystallin; NADPH:quinone reductase; CRYZ

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Gene Name

CRYZ

Target Type

Literature-reported target

[1]

Function

Does not have alcohol dehydrogenase activity. Binds NADP and acts through a one-electron transfer process. Orthoquinones, such as 1,2-naphthoquinone or 9,10-phenanthrenequinone, are the best substrates (in vitro). May act in the detoxification of xenobiotics. Interacts with (AU)-rich elements (ARE) in the 3'-UTR of target mRNA species. Enhances the stability of mRNA coding for BCL2. NADPH binding interferes with mRNA binding.

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UniProt ID

QOR_HUMAN

EC Number

EC 1.6.5.5

Sequence

MATGQKLMRAVRVFEFGGPEVLKLRSDIAVPIPKDHQVLIKVHACGVNPVETYIRSGTYS
RKPLLPYTPGSDVAGVIEAVGDNASAFKKGDRVFTSSTISGGYAEYALAADHTVYKLPEK
LDFKQGAAIGIPYFTAYRALIHSACVKAGESVLVHGASGGVGLAACQIARAYGLKILGTA
GTEEGQKIVLQNGAHEVFNHREVNYIDKIKKYVGEKGIDIIIEMLANVNLSKDLSLLSHG
GRVIVVGSRGTIEINPRDTMAKESSIIGVTLFSSTKEEFQQYAAALQAGMEIGWLKPVIG
SQYPLEKVAEAHENIIHGSGATGKMILLL

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3D Structure

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PDB

HIT2.0 ID

T22MME

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: NADP+

Ligand Info

Structure Description

Crystal structure of human Zeta-Crystallin with bound NADP

PDB:1YB5

Method

X-ray diffraction

Resolution

1.85 Å

Mutation

[2]

PDB Sequence

KLMRAVRVFE

¹⁵

FGGPEVLKLR

²⁵

SDIAVPIPKD

³⁵

HQVLIKVHAC

⁴⁵

GVNPVETYIR

⁵⁵

SGTYSRKPLL

⁶⁵

PYTPGSDVAG

⁷⁵

VIEAVGDNAS

⁸⁵

AFKKGDRVFT

⁹⁵

SSTISGGYAE

¹⁰⁵

YALAADHTVY

¹¹⁵

KLPEKLDFKQ

¹²⁵

GAAIGIPYFT

¹³⁵

AYRALIHSAC

¹⁴⁵

VKAGESVLVH

¹⁵⁵

GASGGVGLAA

¹⁶⁵

CQIARAYGLK

¹⁷⁵

ILGTAGTEEG

¹⁸⁵

QKIVLQNGAH

¹⁹⁵

EVFNHREVNY

²⁰⁵

IDKIKKYVGE

²¹⁵

KGIDIIIEML

²²⁵

ANVNLSKDLS

²³⁵

LLSHGGRVIV

²⁴⁵

VGSRGTIEIN

²⁵⁵

PRDTMAKESS

²⁶⁵

IIGVTLFSST

²⁷⁵

KEEFQQYAAA

²⁸⁵

LQAGMEIGWL

²⁹⁵

KPVIGSQYPL

³⁰⁵

EKVAEAHENI

³¹⁵

IHGSGATGKM

³²⁵

ILLL

Residue

Distance (Å)

ASN48

4.602

PRO49

3.298

VAL50

4.284

TYR53

2.708

ILE131

3.325

THR135

3.182

HIS155

3.683

GLY156

3.179

ALA157

3.817

SER158

2.744

GLY159

2.994

GLY160

2.966

VAL161

2.941

GLY162

4.021

THR179

4.328

ALA180

3.521

GLY181

2.786

THR182

4.361

HIS200

2.820

ARG201

3.861

Residue

Distance (Å)

TYR205

4.582

GLU223

4.298

MET224

3.829

LEU225

3.615

VAL228

4.283

ASN229

2.874

VAL245

4.627

VAL246

2.911

GLY247

3.719

SER248

4.510

ARG249

3.396

VAL269

2.842

THR270

3.295

LEU271

2.820

PHE272

4.896

ILE315

3.409

GLY320

3.340

ALA321

2.738

GLY323

4.663

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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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Quinone oxidoreductase-like protein 1 (CRYZL1)		23.404 (77/329)	2.26E-12


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	1	Degree centrality	1.07E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.80E-01	Radiality	1.30E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.10E+01	Topological coefficient	1.00E+00	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Target Affiliated Biological Pathways

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Panther Pathway

[+] 1 Panther Pathways

Huntington disease

References

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REF 1

NADPH/quinone oxidoreductase is a priority target of glioblastoma chemotherapy. Int J Oncol. 2000 Feb;16(2):295-303.

REF 2

Crystal Structure of human Zeta-Crystallin at 1.85A

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