Target Information

Target General Information

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Target ID

T86808 (Former ID: TTDI01793)

Target Name

Heme oxygenase 2 (HMOX2)

Synonyms

HO2; HO-2

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Gene Name

HMOX2

Target Type

Literature-reported target

[1]

Function

Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. Heme oxygenase 2 could be implicated in the production of carbon monoxide in brain where it could act as a neurotransmitter. Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin.

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BioChemical Class

Paired donor oxygen oxidoreductase

UniProt ID

HMOX2_HUMAN

EC Number

EC 1.14.14.18

Sequence

MSAEVETSEGVDESEKKNSGALEKENQMRMADLSELLKEGTKEAHDRAENTQFVKDFLKG
NIKKELFKLATTALYFTYSALEEEMERNKDHPAFAPLYFPMELHRKEALTKDMEYFFGEN
WEEQVQCPKAAQKYVERIHYIGQNEPELLVAHAYTRYMGDLSGGQVLKKVAQRALKLPST
GEGTQFYLFENVDNAQQFKQLYRARMNALDLNMKTKERIVEEANKAFEYNMQIFNELDQA
GSTLARETLEDGFPVHDGKGDMRKCPFYAAEQDKGALEGSSCPFRTAMAVLRKPSLQFIL
AAGVALAAGLLAWYYM

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3D Structure

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PDB

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: Myristic acid

Ligand Info

Structure Description

Crystal structure of human Heme Oxygenase-2 in complex with Myristate

PDB:5UC9

Method

X-ray diffraction

Resolution

1.90 Å

Mutation

[2]

PDB Sequence

ADLSELLKEG

⁴⁰

TKEAHDRAEN

⁵⁰

TQFVKDFLKG

⁶⁰

NIKKELFKLA

⁷⁰

TTALYFTYSA

⁸⁰

LEEEMERNKD

⁹⁰

HPAFAPLYFP

¹⁰⁰

MELHRKEALT

¹¹⁰

KDMEYFFGEN

¹²⁰

WEEQVQCPKA

¹³⁰

AQKYVERIHY

¹⁴⁰

IGQNEPELLV

¹⁵⁰

AHAYTRYMGD

¹⁶⁰

LSGGQVLKKV

¹⁷⁰

AQRALKLPST

¹⁸⁰

GEGTQFYLFE

¹⁹⁰

NVDNAQQFKQ

²⁰⁰

LYRARMNALD

²¹⁰

LNMKTKERIV

²²⁰

EEANKAFEYN

²³⁰

MQIFNELDQ

Residue

Distance (Å)

PHE53

3.625

VAL54

4.608

PHE57

4.418

ALA70

3.746

LEU74

3.706

THR77

4.571

TYR134

2.865

ARG156

2.896

LEU167

3.682

Residue

Distance (Å)

TYR187

4.230

ALA226

3.488

PHE227

4.784

TYR229

4.671

ASN230

2.998

ILE233

3.850

PHE234

3.543

LEU237

4.366

Ligand Name: Oxtoxynol-10

Ligand Info

Structure Description

Crystal structure of human heme oxygenase-2 C127A (HO-2)

PDB:2Q32

Method

X-ray diffraction

Resolution

2.40 Å

Mutation

Yes

[3]

PDB Sequence

RMADLSELLK

³⁸

EGTKEAHDRA

⁴⁸

ENTQFVKDFL

⁵⁸

KGNIKKELFK

⁶⁸

LATTALYFTY

⁷⁸

SALEEEMERN

⁸⁸

KDHPAFAPLY

⁹⁸

FPMELHRKEA

¹⁰⁸

LTKDMEYFFG

¹¹⁸

ENWEEQVQAP

¹²⁸

KAAQKYVERI

¹³⁸

HYIGQNEPEL

¹⁴⁸

LVAHAYTRYM

¹⁵⁸

GDLSGGQVLK

¹⁶⁸

KVAQRALKLP

¹⁷⁸

STGEGTQFYL

¹⁸⁸

FENVDNAQQF

¹⁹⁸

KQLYRARMNA

²⁰⁸

LDLNMKTKER

²¹⁸

IVEEANKAFE

²²⁸

YNMQIFNELD

²³⁸

QAG

Residue

Distance (Å)

HIS45

4.841

ALA48

3.704

GLU49

3.656

PHE53

4.587

VAL54

3.125

PHE57

3.580

ALA70

4.353

LEU74

3.495

THR77

3.939

TYR78

3.863

TYR134

3.597

Residue

Distance (Å)

HIS152

3.922

THR155

3.191

ARG156

2.703

ASP160

3.904

LEU167

3.320

PHE186

4.088

TYR187

3.354

ALA226

3.643

PHE227

3.508

ASN230

2.912

PHE234

3.326

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
Porphyrin metabolism	hsa00860	Affiliated Target
Class: Metabolism => Metabolism of cofactors and vitamins	Pathway Hierarchy
Mineral absorption	hsa04978	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy

Degree	3	Degree centrality	3.22E-04	Betweenness centrality	3.08E-06
Closeness centrality	1.55E-01	Radiality	1.22E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	5.67E+00	Topological coefficient	4.44E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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References

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REF 1

Heme oxygenase-2 suppresses acute inflammation and improves the survival of skin allografts. Int Immunopharmacol. 2018 Oct;63:191-197.

REF 2

Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling. Cell Host Microbe. 2017 Feb 8;21(2):220-230.

REF 3

Comparison of apo- and heme-bound crystal structures of a truncated human heme oxygenase-2. J Biol Chem. 2007 Dec 28;282(52):37624-31.

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