Target Information
| Target General Information | Top | |||||
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| Target ID |
T95238
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| Target Name |
Protein enabled homolog MENA (ENAH)
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| Synonyms |
MENA
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| Gene Name |
ENAH
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation.
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| UniProt ID | ||||||
| Sequence |
MSEQSICQARAAVMVYDDANKKWVPAGGSTGFSRVHIYHHTGNNTFRVVGRKIQDHQVVI
NCAIPKGLKYNQATQTFHQWRDARQVYGLNFGSKEDANVFASAMMHALEVLNSQETGPTL PRQNSQLPAQVQNGPSQEELEIQRRQLQEQQRQKELERERLERERMERERLERERLERER LERERLEQEQLERERQERERQERLERQERLERQERLERQERLDRERQERQERERLERLER ERQERERQEQLEREQLEWERERRISSAAAPASVETPLNSVLGDSSASEPGLQAASQPAET PSQQGIVLGPLAPPPPPPLPPGPAQASVALPPPPGPPPPPPLPSTGPPPPPPPPPLPNQV PPPPPPPPAPPLPASGFFLASMSEDNRPLTGLAAAIAGAKLRKVSRMEDTSFPSGGNAIG VNSASSKTDTGRGNGPLPLGGSGLMEEMSALLARRRRIAEKGSTIETEQKEDKGEDSEPV TSKASSTSTPEPTRKPWERTNTMNGSKSPVISRRDSPRKNQIVFDNRSYDSLHRPKSTPL SQPSANGVQTEGLDYDRLKQDILDEMRKELTKLKEELIDAIRQELSKSNTA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: (3S,7R,10R,13S)-4-[(3S,6R,8aS)-1'-[(2S)-2-acetamido-3-(2-chlorophenyl)propanoyl]-5-oxospiro[1,2,3,8a-tetrahydroindolizine-6,2'-pyrrolidine]-3-carbonyl]-2-oxo-1,4-diazatricyclo[8.3.0.03,7]tridec-8-ene-13-carboxylic acid | Ligand Info | |||||
| Structure Description | ENAH EVH1 in complex with Ac-[2-Cl-F]-[ProM-2]-[ProM-1]-TEDEL-NH2 | PDB:6RD2 | ||||
| Method | X-ray diffraction | Resolution | 1.00 Å | Mutation | No | [2] |
| PDB Sequence |
EQSICQARAA
12 VMVYDDANKK22 WVPAGGSTGF32 SRVHIYHHTG42 NNTFRVVGRK52 IQDHQVVINC 62 AIPKGLKYNQ72 ATQTFHQWRD82 ARQVYGLNFG92 SKEDANVFAS102 AMMHALEVL |
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| Ligand Name: (S)-2-Amino-4-methylpentanamide | Ligand Info | |||||
| Structure Description | ENAH EVH1 in complex with Ac-[2-Cl-F]-[ProM-2]-[ProM-1]-TEDEL-NH2 | PDB:6RD2 | ||||
| Method | X-ray diffraction | Resolution | 1.00 Å | Mutation | No | [2] |
| PDB Sequence |
EQSICQARAA
12 VMVYDDANKK22 WVPAGGSTGF32 SRVHIYHHTG42 NNTFRVVGRK52 IQDHQVVINC 62 AIPKGLKYNQ72 ATQTFHQWRD82 ARQVYGLNFG92 SKEDANVFAS102 AMMHALEVL |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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
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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.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Rap1 signaling pathway | hsa04015 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Axon guidance | hsa04360 | Affiliated Target |
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| Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
| Regulation of actin cytoskeleton | hsa04810 | Affiliated Target |
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| Class: Cellular Processes => Cell motility | Pathway Hierarchy | ||
| Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 2.83E-04 |
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| Closeness centrality | 2.19E-01 | Radiality | 1.39E+01 | Clustering coefficient | 1.90E-01 |
| Neighborhood connectivity | 3.27E+01 | Topological coefficient | 1.63E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Rap1 signaling pathway | |||||
| 2 | Axon guidance | |||||
| 3 | Regulation of actin cytoskeleton | |||||
| References | Top | |||||
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| REF 1 | Mammalian-enabled (MENA) protein enhances oncogenic potential and cancer stem cell-like phenotype in hepatocellular carcinoma cells. FEBS Open Bio. 2017 Jun 22;7(8):1144-1153. | |||||
| REF 2 | Designed nanomolar small-molecule inhibitors of Ena/VASP EVH1 interaction impair invasion and extravasation of breast cancer cells. Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29684-29690. | |||||
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