Target Information

Target General Information

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Target ID

T77174 (Former ID: TTDI02623)

Target Name

mRNA cap guanine-N7 methyltransferase (RNMT)

Synonyms

hcm1p; hMet; hCMT1; RG7MT1; KIAA0398

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Gene Name

RNMT

Target Type

Literature-reported target

[1]

Function

Binds RNA containing 5'-terminal GpppC. Catalytic subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs.

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BioChemical Class

Methyltransferase

UniProt ID

MCES_HUMAN

EC Number

EC 2.1.1.56

Sequence

MANSAKAEEYEKMSLEQAKASVNSETESSFNINENTTASGTGLSEKTSVCRQVDIARKRK
EFEDDLVKESSSCGKDTPSKKRKLDPEIVPEEKDCGDAEGNSKKRKRETEDVPKDKSSTG
DGTQNKRKIALEDVPEKQKNLEEGHSSTVAAHYNELQEVGLEKRSQSRIFYLRNFNNWMK
SVLIGEFLEKVRQKKKRDITVLDLGCGKGGDLLKWKKGRINKLVCTDIADVSVKQCQQRY
EDMKNRRDSEYIFSAEFITADSSKELLIDKFRDPQMCFDICSCQFVCHYSFESYEQADMM
LRNACERLSPGGYFIGTTPNSFELIRRLEASETESFGNEIYTVKFQKKGDYPLFGCKYDF
NLEGVVDVPEFLVYFPLLNEMAKKYNMKLVYKKTFLEFYEEKIKNNENKMLLKRMQALEP
YPANESSKLVSEKVDDYEHAAKYMKNSQVRLPLGTLSKSEWEATSIYLVFAFEKQQ

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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: Sinefungin

Ligand Info

Structure Description

Crystal structure of mRNA cap guanine-N7 methyltransferase (RNMT) in complex with sinefungin

PDB:3EPP

Method

X-ray diffraction

Resolution

2.41 Å

Mutation

[2]

PDB Sequence

IFYLRNFNNW

¹⁵

MKSVLIGEFL

²⁵

EKVRQKKDIT

³⁷

VLDLGCGKGG

⁴⁷

DLLKWKKGRI

⁵⁷

NKLVCTDIAD

⁶⁷

VSVKQCQQRY

⁷⁷

EDMKNRSEYI

⁸⁹

FSAEFITADS

⁹⁹

SKELLIDKFR

¹⁰⁹

DPQMCFDICS

¹¹⁹

CQFVCHYSFE

¹²⁹

SYEQADMMLR

¹³⁹

NACERLSPGG

¹⁴⁹

YFIGTTPNSF

¹⁵⁹

ELIRRLEASE

¹⁶⁹

TESFGNEIYT

¹⁷⁹

VKFQKKGDYP

¹⁸⁹

LFGCKYDFND

²⁰⁴

VPEFLVYFPL

²¹⁴

LNEMAKKYNM

²²⁴

KLVYKKTFLE

²³⁴

FYEEKIKNNE

²⁴⁴

NKMLLKRMQL

²⁸⁸

PLGTLSKSEW

²⁹⁸

EATSIYLVFA

³⁰⁸

FEKQQ

Residue

Distance (Å)

LYS17

2.784

ASP40

4.868

GLY42

2.776

CYS43

3.961

GLY44

3.588

GLY47

4.679

ASP48

4.370

THR63

4.992

ASP64

2.761

ILE65

3.306

Residue

Distance (Å)

ALA66

4.259

ALA97

3.954

ASP98

2.812

SER99

3.264

SER100

3.552

GLN121

3.023

PHE122

2.788

VAL123

3.395

TYR126

3.563

MET137

3.650

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	Pathway Map
mRNA surveillance pathway	hsa03015	Affiliated Target
Class: Genetic Information Processing => Translation	Pathway Hierarchy

Degree	5	Degree centrality	5.37E-04	Betweenness centrality	4.16E-04
Closeness centrality	1.78E-01	Radiality	1.29E+01	Clustering coefficient	1.00E-01
Neighborhood connectivity	1.18E+01	Topological coefficient	2.95E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

Oncogenic PIK3CA mutations increase dependency on the mRNA cap methyltransferase, RNMT, in breast cancer cells. Open Biol. 2019 Apr 26;9(4):190052.

REF 2

Crystal structure of mRNA cap guanine-N7 methyltransferase (RNMT) in complex with sinefungin.

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