Target Information

Target General Information

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Target ID

T27457 (Former ID: TTDI01880)

Target Name

Gamma-actin (ACTG)

Synonyms

Actin, cytoplasmic 2; ACTG

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Gene Name

ACTG1

Target Type

Literature-reported target

[1]

Function

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

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UniProt ID

ACTG_HUMAN

Sequence

MEEEIAALVIDNGSGMCKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQS
KRGILTLKYPIEHGIVTNWDDMEKIWHHTFYNELRVAPEEHPVLLTEAPLNPKANREKMT
QIMFETFNTPAMYVAIQAVLSLYASGRTTGIVMDSGDGVTHTVPIYEGYALPHAILRLDL
AGRDLTDYLMKILTERGYSFTTTAEREIVRDIKEKLCYVALDFEQEMATAASSSSLEKSY
ELPDGQVITIGNERFRCPEALFQPSFLGMESCGIHETTFNSIMKCDVDIRKDLYANTVLS
GGTTMYPGIADRMQKEITALAPSTMKIKIIAPPERKYSVWIGGSILASLSTFQQMWISKQ
EYDESGPSIVHRKCF

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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: Ademetionine

Ligand Info

Structure Description

SETD3 mutant (N255V) in Complex with an Actin Peptide with His73 Replaced with Methionine

PDB:6WK2

Method

X-ray diffraction

Resolution

1.76 Å

Mutation

Yes

[2]

PDB Sequence

TLKYPIEMGI

⁷⁵

VTNWDDMEK

Residue

Distance (Å)

MET73

3.388

Residue

Distance (Å)

Ligand Name: adenosine diphosphate

Ligand Info

Structure Description

Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution

PDB:5JLH

Method

Electron microscopy

Resolution

3.90 Å

Mutation

[3]

PDB Sequence

EEEIAALVID

¹⁰

NGSGMCKAGF

²⁰

AGDDAPRAVF

³⁰

PSIVGRPRHQ

⁴⁰

GVMVGMGQKD

⁵⁰

SYVGDEAQSK

⁶⁰

RGILTLKYPI

⁷⁰

EHGIVTNWDD

⁸⁰

MEKIWHHTFY

⁹⁰

NELRVAPEEH

¹⁰⁰

PVLLTEAPLN

¹¹⁰

PKANREKMTQ

¹²⁰

IMFETFNTPA

¹³⁰

MYVAIQAVLS

¹⁴⁰

LYASGRTTGI

¹⁵⁰

VMDSGDGVTH

¹⁶⁰

TVPIYEGYAL

¹⁷⁰

PHAILRLDLA

¹⁸⁰

GRDLTDYLMK

¹⁹⁰

ILTERGYSFT

²⁰⁰

TTAEREIVRD

²¹⁰

IKEKLCYVAL

²²⁰

DFEQEMATAA

²³⁰

SSSSLEKSYE

²⁴⁰

LPDGQVITIG

²⁵⁰

NERFRCPEAL

²⁶⁰

FQPSFLGMES

²⁷⁰

CGIHETTFNS

²⁸⁰

IMKCDVDIRK

²⁹⁰

DLYANTVLSG

³⁰⁰

GTTMYPGIAD

³¹⁰

RMQKEITALA

³²⁰

PSTMKIKIIA

³³⁰

PPERKYSVWI

³⁴⁰

GGSILASLST

³⁵⁰

FQQMWISKQE

³⁶⁰

YDESGPSIVH

³⁷⁰

RKCF

Residue

Distance (Å)

ASP10

3.469

ASN11

4.797

GLY12

2.817

SER13

2.427

GLY14

4.433

MET15

3.496

LYS17

3.227

GLN136

4.335

GLY155

3.078

ASP156

2.560

GLY157

4.497

GLY181

3.417

Residue

Distance (Å)

ARG182

4.718

THR185

4.599

ARG209

3.653

LYS212

2.664

GLU213

2.945

LYS214

4.804

GLY300

3.778

GLY301

2.770

THR302

3.277

MET304

3.585

TYR305

3.052

LYS335

2.897

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
Rap1 signaling pathway	hsa04015	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Phagosome	hsa04145	Affiliated Target
Class: Cellular Processes => Transport and catabolism	Pathway Hierarchy
Apoptosis	hsa04210	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Hippo signaling pathway	hsa04390	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Focal adhesion	hsa04510	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Adherens junction	hsa04520	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Tight junction	hsa04530	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Platelet activation	hsa04611	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Neutrophil extracellular trap formation	hsa04613	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Leukocyte transendothelial migration	hsa04670	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Thermogenesis	hsa04714	Affiliated Target
Class: Organismal Systems => Environmental adaptation	Pathway Hierarchy
Regulation of actin cytoskeleton	hsa04810	Affiliated Target
Class: Cellular Processes => Cell motility	Pathway Hierarchy
Thyroid hormone signaling pathway	hsa04919	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Oxytocin signaling pathway	hsa04921	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Gastric acid secretion	hsa04971	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	9	Degree centrality	9.67E-04	Betweenness centrality	1.98E-04
Closeness centrality	2.12E-01	Radiality	1.37E+01	Clustering coefficient	1.94E-01
Neighborhood connectivity	1.97E+01	Topological coefficient	1.38E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

Cross-reacting material 197 (CRM197) affects actin cytoskeleton of endothelial cells. Gen Physiol Biophys. 2017 Oct;36(4):383-389.

REF 2

Characterization of SETD3 methyltransferase-mediated protein methionine methylation. J Biol Chem. 2020 Aug 7;295(32):10901-10910.

REF 3

Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution. Nature. 2016 Jun 30;534(7609):724-8.

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