Tclin MME Neprilysin

Protein Summary

Description

Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of atrial natriuretic factor (ANF) (PubMed:2531377, PubMed:2972276). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573). The protein encoded by this gene is a type II transmembrane glycoprotein and a common acute lymphocytic leukemia antigen that is an important cell surface marker in the diagnosis of human acute lymphocytic leukemia (ALL). The encoded protein is present on leukemic cells of pre-B phenotype, which represent 85% of cases of ALL. This protein is not restricted to leukemic cells, however, and is found on a variety of normal tissues. The protein is a neutral endopeptidase that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. [provided by RefSeq, Aug 2017]

Uniprot Accession IDs

• P08473
• A8K6U6
• D3DNJ9
• Q3MIX4

Gene Name

• MME

Ensembl ID

• ENST00000360490
• ENSP00000353679
• ENSG00000196549
• ENST00000460393
• ENSP00000418525
• ENST00000462745
• ENSP00000419653
• ENST00000492661
• ENSP00000420389
• ENST00000493237
• ENSP00000417079
• ENST00000615825
• ENSP00000478173

Symbol

• EPN
• NEP
• SFE
• CD10
• CALLA
• CMT2T
• SCA43

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
PubMedID	0.95
cellular component	0.8
disease	0.78
protein domain	0.73
hub protein	0.71

Protein Classes

PANTHER Classes

Protein / ... / Metalloprotease / Neprilysin

DTO Classes

Protein / Enzyme / Protease / Metalloprotease / Neprilysin

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: 5347.71   (req: < 5)

Gene RIFs: 237   (req: <= 3)

Antibodies: 2082   (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: 5347.71   (req: >= 5)

Gene RIFs: 237   (req: > 3)

Antibodies: 2082   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

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

Active Ligands: 391

Tclin

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

Active Drugs: 3

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

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 (3)

Explore Approved Drugs

1 – 3 of 3

omapatrilat

MMETclin Enzyme

pKi : 8.05

racecadotril

MMETclin Enzyme

INHIBITOR pIC50 : 9

sacubitril

MMETclin Enzyme

INHIBITOR :

Active Ligands (391)

Explore Active Ligands

1 – 10 of 391

CHEMBL570718

MMETclin Enzyme

pKi : 6.62

CHEMBL570732

MMETclin Enzyme

pKi : 6.56

CHEMBL577753

MMETclin Enzyme

pKi : 7.58

CHEMBL253224

MMETclin Enzyme

pKi : 8.89

CHEMBL400526

MMETclin Enzyme

pKi : 8.82

compound 1a [PMID: 25692029]

MMETclin Enzyme

pKi : 8.85

CHEMBL163454

MMETclin Enzyme

pKi : 6.51

CHEMBL305388

MMETclin Enzyme

pKi : 6.75

CHEMBL43370

MMETclin Enzyme

pIC50 : 8.6

CHEMBL271225

MMETclin Enzyme

pKi : 8.85

Protein-Protein Interactions (261)

Explore Interacting Targets

1 – 10 of 261

• See Interactions on String-DB

P10314

Tbio

Novelty:  0.00270731

p_int:  0.999379371

p_ni:  0.000620629

Score:  0.364

Data Source:  BioPlex,STRINGDB

GLT8D2

Tbio

Family:  Enzyme

Novelty:  0.79488367

p_int:  0.995822912

p_ni:  0.000605202

p_wrong:  0.003571886

Score:  0.175

Data Source:  BioPlex,STRINGDB

LEMD3

Tbio

Novelty:  0.00579701

p_int:  0.994968151

p_ni:  0.005031849

Data Source:  BioPlex

PXMP2

Tbio

Novelty:  0.24472872

p_int:  0.990695666

p_ni:  0.009304332

p_wrong:  2e-9

Data Source:  BioPlex

POMGNT1

Tbio

Family:  Enzyme

Novelty:  0.00755927

p_int:  0.981334051

p_ni:  0.018665949

Score:  0.185

Data Source:  BioPlex,STRINGDB

SLC10A7

Tbio

Family:  Transporter

Novelty:  0.15556211

p_int:  0.979076437

p_ni:  0.020015103

p_wrong:  0.00090846

Data Source:  BioPlex

STARD3

Tbio

Novelty:  0.01540936

p_int:  0.976399229

p_ni:  0.023600544

p_wrong:  2.27e-7

Score:  0.152

Data Source:  BioPlex,STRINGDB

MANEAL

Tdark

Family:  Enzyme

Novelty:  0.71535497

p_int:  0.96881441

p_ni:  0.03118559

Data Source:  BioPlex

TENM3

Tbio

Novelty:  0.0251948

p_int:  0.968742657

p_ni:  0.030880987

p_wrong:  0.000376356

Score:  0.182

Data Source:  BioPlex,STRINGDB

TMEM223

Tdark

Novelty:  0.89146194

p_int:  0.949647882

p_ni:  0.050341454

p_wrong:  0.000010663

Data Source:  BioPlex

Nearest Tclin Targets

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

Pathways (12)

Reactome (6)

KEGG (4)

WikiPathways (2)

Immune System (R-HSA-168256)

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5

1 – 5 of 6

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Innate Immune System	1188 targets	R-HSA-168249
Reactome	Metabolism of Angiotensinogen to Angiotensins	18 targets	R-HSA-2022377
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499
Reactome	Neutrophil degranulation	543 targets	R-HSA-6798695

Name	Explore in Pharos	Explore in Source
Immune System	2246 targets	R-HSA-168256
Innate Immune System	1188 targets	R-HSA-168249
Metabolism of Angiotensinogen to Angiotensins	18 targets	R-HSA-2022377
Metabolism of proteins	2050 targets	R-HSA-392499
Neutrophil degranulation	543 targets	R-HSA-6798695

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (32)

Functions (6)

Components (13)

Processes (13)

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Items per page:

10

1 – 6 of 6

GO Term	Evidence	Assigned by
metallopeptidase activity	Inferred from Experiment (EXP)	Reactome
endopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
exopeptidase activity	Inferred from Direct Assay (IDA)	BHF-UCL
metalloendopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
peptide binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (3)

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5

1 – 3 of 3

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	2	1	2		50.6
diastolic blood pressure	EFO_0006336	1	1	1		12.8
hemoglobin measurement	EFO_0004509	1	1	1		5.8

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 3 of 3

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	2		50.6
diastolic blood pressure	EFO_0006336	1		12.8
hemoglobin measurement	EFO_0004509	1		5.8

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Cell membrane
Charcot-Marie-Tooth disease
Complete proteome
Disease mutation
Disulfide bond
Glycoprotein
Hydrolase
Lipoprotein
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
diastolic blood pressure
hemoglobin measurement
testosterone measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	membrane metalloendopeptidase	VGNC:14231	460792
Macaque	membrane metalloendopeptidase		707667
Mouse	membrane metallo endopeptidase	MGI:97004	17380
Rat	membrane metallo-endopeptidase	RGD:3098	24590
Dog	membrane metalloendopeptidase	VGNC:43271	477120

Species	Name	OMA	EggNOG	Inparanoid
Chimp	membrane metalloendopeptidase
Macaque	membrane metalloendopeptidase
Mouse	membrane metallo endopeptidase
Rat	membrane metallo-endopeptidase
Dog	membrane metalloendopeptidase

Publication Statistics

PubMed Score 5347.71

PubMed score by year

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PubTator Score 2796.30

PubTator score by year

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Related Publications

Text Mined References (283)

GeneRif Annotations (237)

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10

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PMID	Year	Title