Tchem METAP2 Methionine aminopeptidase 2

Protein Summary

Description

Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo. Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis. The protein encoded by this gene is a member of the methionyl aminopeptidase family. The encoded protein functions both by protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation and by removing the amino-terminal methionine residue from nascent proteins. Increased expression of this gene is associated with various forms of cancer, and the anti-cancer drugs fumagillin and ovalicin inhibit the protein by irreversibly binding to its active site. Inhibitors of this gene have also been shown to be effective for the treatment of obesity. A pseudogene of this gene is located on chromosome 2. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

Uniprot Accession IDs

• P50579
• B2RDI8
• B4DUX5
• G3XA91
• Q8NB11
• MAP 2

Gene Name

• METAP2

Ensembl ID

• ENST00000261220
• ENSP00000261220
• ENSG00000111142
• ENST00000323666
• ENSP00000325312
• ENST00000546753
• ENSP00000448169

Symbol

• MNPEP
• P67EIF2
• MAP2
• MNPEP
• p67eIF2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.91
kinase perturbation	0.88
disease perturbation	0.87
virus perturbation	0.83
drug	0.79

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 195.81   (req: < 5)

Gene RIFs: 22   (req: <= 3)

Antibodies: 248   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 195.81   (req: >= 5)

Gene RIFs: 22   (req: > 3)

Antibodies: 248   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 659

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (2)

Explore Approved Drugs

1 – 2 of 2

nitroxoline

METAP2Tchem Enzyme

pKi : 6

fumagillin

METAP2Tchem Enzyme

pIC50 : 9.2

Active Ligands (659)

Explore Active Ligands

1 – 10 of 659

CHEMBL352943

METAP2Tchem Enzyme

pIC50 : 7.52

Bengamide A

METAP2Tchem Enzyme

pIC50 : 6.4

CHEMBL4078211

METAP2Tchem Enzyme

pIC50 : 6.4

CHEMBL3798844

METAP2Tchem Enzyme

pIC50 : 8.1

CHEMBL3797286

METAP2Tchem Enzyme

pIC50 : 8.3

CHEMBL3798249

METAP2Tchem Enzyme

pIC50 : 8.3

CHEMBL3797707

METAP2Tchem Enzyme

pIC50 : 8

CHEMBL3797386

METAP2Tchem Enzyme

pIC50 : 7.9

CHEMBL3800236

METAP2Tchem Enzyme

pIC50 : 8.1

CHEMBL3800546

METAP2Tchem Enzyme

pIC50 : 8.1

Protein-Protein Interactions (181)

Explore Interacting Targets

1 – 10 of 181

• See Interactions on String-DB

RARRES1

Tbio

Family:  Enzyme

Novelty:  0.04701793

p_int:  0.999906182

p_ni:  0.000093818

p_wrong:  1e-9

Data Source:  BioPlex

SUCLA2

Tchem

Family:  Enzyme

Novelty:  0.02029861

p_int:  0.999834674

p_ni:  0.000165326

Score:  0.19

Data Source:  BioPlex,STRINGDB

GPBP1L1

Tdark

Novelty:  0.69320833

p_int:  0.99982514

p_ni:  0.00017486

Data Source:  BioPlex

TMEM213

Tdark

Novelty:  0.87036241

p_int:  0.999525757

p_ni:  0.000474243

Score:  0.165

Data Source:  BioPlex,STRINGDB

ALDH5A1

Tclin

Family:  Enzyme

Novelty:  0.00461791

p_int:  0.999013531

p_ni:  0.000986469

Data Source:  BioPlex

DDX28

Tbio

Family:  Enzyme

Novelty:  0.16760542

p_int:  0.998678105

p_ni:  0.001321895

Score:  0.201

Data Source:  BioPlex,STRINGDB

HYOU1

Tbio

Novelty:  0.00833649

p_int:  0.998645293

p_ni:  0.001354707

Data Source:  BioPlex

CCT7

Tbio

Novelty:  0.02247038

p_int:  0.997222322

p_ni:  0.002777678

Score:  0.257

Data Source:  BioPlex,STRINGDB

CCT2

Tbio

Novelty:  0.01967139

p_int:  0.99718456

p_ni:  0.00281544

Score:  0.399

Data Source:  BioPlex,STRINGDB

SLC25A25

Tbio

Family:  Transporter

Novelty:  0.05562006

p_int:  0.990217798

p_ni:  0.009782202

Score:  0.198

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (7)

Reactome (7)

G alpha (i) signalling events (R-HSA-418594)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	G alpha (i) signalling events	408 targets	R-HSA-418594
Reactome	GPCR downstream signalling	1152 targets	R-HSA-388396
Reactome	Inactivation, recovery and regulation of the phototransduction cascade	33 targets	R-HSA-2514859
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by GPCR	1212 targets	R-HSA-372790

Name	Explore in Pharos	Explore in Source
G alpha (i) signalling events	408 targets	R-HSA-418594
GPCR downstream signalling	1152 targets	R-HSA-388396
Inactivation, recovery and regulation of the phototransduction cascade	33 targets	R-HSA-2514859
Signal Transduction	2704 targets	R-HSA-162582
Signaling by GPCR	1212 targets	R-HSA-372790

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (13)

Functions (5)

Components (3)

Processes (5)

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Items per page:

10

1 – 5 of 5

GO Term	Evidence	Assigned by
aminopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
metalloexopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
RNA binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-UniRule
metalloaminopeptidase activity	Inferred from Electronic Annotation (IEA)	UniProtKB-UniRule

Disease Associations (null)

No disease associations found

GWAS Traits (7)

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5

1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
C-reactive protein measurement	EFO_0004458	4	5	5		95.6
reticulocyte count	EFO_0007986	7	3	7		93.4
reticulocyte measurement	EFO_0010700	3	3	3		93.4
type II diabetes mellitus	EFO_0001360	3	2	2	1	57.1
sex hormone-binding globulin measurement	EFO_0004696	4	2	4		39.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 7

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
C-reactive protein measurement	EFO_0004458	5		95.6
reticulocyte count	EFO_0007986	7		93.4
reticulocyte measurement	EFO_0010700	3		93.4
type II diabetes mellitus	EFO_0001360	2	1	57.1
sex hormone-binding globulin measurement	EFO_0004696	4		39.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Aminopeptidase
Complete proteome
Cytoplasm
Direct protein sequencing
Glycoprotein
Hydrolase
Metal-binding

GWAS Trait Find Similar Targets

No Header	No Header
C-reactive protein measurement
red blood cell distribution width
reticulocyte count
reticulocyte measurement
serum gamma-glutamyl transferase measurement
sex hormone-binding globulin measurement
type II diabetes mellitus

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (18)

1 – 5 of 18

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	methionyl aminopeptidase 2	VGNC:13217	452141
Macaque	methionyl aminopeptidase 2		712400
Mouse	methionine aminopeptidase 2	MGI:1929701	56307
Rat	methionyl aminopeptidase 2	RGD:70995	64370
Dog	methionyl aminopeptidase 2	VGNC:43168	475429

Species	Name	OMA	EggNOG	Inparanoid
Chimp	methionyl aminopeptidase 2
Macaque	methionyl aminopeptidase 2
Mouse	methionine aminopeptidase 2
Rat	methionyl aminopeptidase 2
Dog	methionyl aminopeptidase 2

Publication Statistics

PubMed Score 195.81

PubMed score by year

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PubTator Score 97.45

PubTator score by year

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Related Publications

Text Mined References (47)

GeneRif Annotations (22)

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PMID	Year	Title