Target Information

Target General Information

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Target ID

T88404 (Former ID: TTDI00160)

Target Name

Optic atrophy protein 1 (OPA1)

Synonyms

OPA1; Dynaminlike 120 kDa protein, mitochondrial; Dynaminlike 120 kDa protein, form S1

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Gene Name

OPA1

Target Type

Literature-reported target

[1]

Function

Dynamin-like 120 kDa protein, form S1: Inactive form produced by cleavage at S1 position by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, leading to negative regulation of mitochondrial fusion.

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BioChemical Class

Carbon-carbon hydrolase

UniProt ID

OPA1_HUMAN

EC Number

EC 3.6.5.5

Sequence

MWRLRRAAVACEVCQSLVKHSSGIKGSLPLQKLHLVSRSIYHSHHPTLKLQRPQLRTSFQ
QFSSLTNLPLRKLKFSPIKYGYQPRRNFWPARLATRLLKLRYLILGSAVGGGYTAKKTFD
QWKDMIPDLSEYKWIVPDIVWEIDEYIDFEKIRKALPSSEDLVKLAPDFDKIVESLSLLK
DFFTSGSPEETAFRATDRGSESDKHFRKVSDKEKIDQLQEELLHTQLKYQRILERLEKEN
KELRKLVLQKDDKGIHHRKLKKSLIDMYSEVLDVLSDYDASYNTQDHLPRVVVVGDQSAG
KTSVLEMIAQARIFPRGSGEMMTRSPVKVTLSEGPHHVALFKDSSREFDLTKEEDLAALR
HEIELRMRKNVKEGCTVSPETISLNVKGPGLQRMVLVDLPGVINTVTSGMAPDTKETIFS
ISKAYMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPHGRRTIFVLTKVDLAEKNVASPS
RIQQIIEGKLFPMKALGYFAVVTGKGNSSESIEAIREYEEEFFQNSKLLKTSMLKAHQVT
TRNLSLAVSDCFWKMVRESVEQQADSFKATRFNLETEWKNNYPRLRELDRNELFEKAKNE
ILDEVISLSQVTPKHWEEILQQSLWERVSTHVIENIYLPAAQTMNSGTFNTTVDIKLKQW
TDKQLPNKAVEVAWETLQEEFSRFMTEPKGKEHDDIFDKLKEAVKEESIKRHKWNDFAED
SLRVIQHNALEDRSISDKQQWDAAIYFMEEALQARLKDTENAIENMVGPDWKKRWLYWKN
RTQEQCVHNETKNELEKMLKCNEEHPAYLASDEITTVRKNLESRGVEVDPSLIKDTWHQV
YRRHFLKTALNHCNLCRRGFYYYQRHFVDSELECNDVVLFWRIQRMLAITANTLRQQLTN
TEVRRLEKNVKEVLEDFAEDGEKKIKLLTGKRVQLAEDLKKVREIQEKLDAFIEALHQEK

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3D Structure

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AlphaFold

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: Guanosine-5'-Diphosphate

Ligand Info

Structure Description

Structural insights into G domain dimerization and pathogenic mutations of OPA1

PDB:6JTG

Method

X-ray diffraction

Resolution

2.40 Å

Mutation

[2]

PDB Sequence

SLIDMYSEVL

¹⁰

DVLSDYDASY

²⁰

NTQDHLPRVV

³⁰

VVGDQSAGKT

⁴⁰

SVLEMIAQAR

⁵⁰

IFPRGSGEMM

⁶⁰

TRSPVKVTLS

⁷⁰

EGPHHVALFK

⁸⁰

DSSREFDLTK

⁹⁰

EEDLAALRHE

¹⁰⁰

IELRMRKNVK

¹¹⁰

EGCTVSPETI

¹²⁰

SLNVKGPGLQ

¹³⁰

RMVLVDLPGV

¹⁴⁰

INTVTSGMAP

¹⁵⁰

DTKETIFSIS

¹⁶⁰

KAYMQNPNAI

¹⁷⁰

ILCIQDGSVD

¹⁸⁰

AERSIVTDLV

¹⁹⁰

SQMDPHGRRT

²⁰⁰

IFVLTKVDLA

²¹⁰

EKNVASPSRI

²²⁰

QQIIEGKLFP

²³⁰

MKALGYFAVV

²⁴⁰

TGKGNSSESI

²⁵⁰

EAIREYEEEF

²⁶⁰

FQNSKLLKTS

²⁷⁰

MLKAHQVTTR

²⁸⁰

NLSLAVSDCF

²⁹⁰

WKMVRESVEQ

³⁰⁰

QADSFKATRF

³¹⁰

NLEVREIQEK

³³⁸

LDAFIEALHQ

³⁴⁸

Residue

Distance (Å)

ASP34

3.878

GLN35

4.215

SER36

3.056

ALA37

3.303

GLY38

2.759

LYS39

2.695

THR40

2.772

SER41

2.595

PRO53

4.654

ARG54

3.430

GLY55

2.912

SER56

3.047

MET60

4.525

THR61

4.416

Residue

Distance (Å)

ASP136

4.805

THR205

4.315

LYS206

3.102

VAL207

4.702

ASP208

2.876

LEU209

3.363

VAL239

3.973

VAL240

3.211

THR241

2.731

GLY242

2.869

LYS243

3.624

GLY244

3.568

TYR256

4.942

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). 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	2.02E-04
Closeness centrality	1.71E-01	Radiality	1.27E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	4.00E+00	Topological coefficient	5.00E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

Dominant optic atrophy: updates on the pathophysiology and clinical manifestations of the optic atrophy 1 mutation. Curr Opin Ophthalmol. 2016 Nov;27(6):475-480.

REF 2

Structural insights into G domain dimerization and pathogenic mutation of OPA1. J Cell Biol. 2020 Jul 6;219(7):e201907098.

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