Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T35265
(Former ID: TTDI02166)
|
|||||
Target Name |
S100 calcium-binding protein A4 (S100A4)
|
|||||
Synonyms |
Protein S100-A4; Protein Mts1; Placental calcium-binding protein; Metastasin; MTS1; Calvasculin; CAPL
Click to Show/Hide
|
|||||
Gene Name |
S100A4
|
|||||
Target Type |
Literature-reported target
|
[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
Function |
collagen-containing extracellular matrix, extracellular exosome, extracellular region, extracellular space, nucleus, perinuclear region of cytoplasm, calcium ion binding, identical protein binding, RAGE receptor binding, RNA binding
Click to Show/Hide
|
|||||
BioChemical Class |
S100 calcium-binding protein
|
|||||
UniProt ID | ||||||
Sequence |
MACPLEKALDVMVSTFHKYSGKEGDKFKLNKSELKELLTRELPSFLGKRTDEAAFQKLMS
NLDSNRDNEVDFQEYCVFLSCIAMMCNEFFEGFPDKQPRKK Click to Show/Hide
|
|||||
3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T68W7Y |
Drugs and Modes of Action | Top | |||||
---|---|---|---|---|---|---|
Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
1 | SP-MET-1 | Drug Info | Preclinical | Breast cancer | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Antagonist | [+] 1 Antagonist drugs | + | ||||
1 | SP-MET-1 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
---|---|---|---|---|---|---|
Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
---|---|---|---|---|---|---|
Ligand Name: Trifluoperazine | Ligand Info | |||||
Structure Description | Structure of the tfp-ca2+-bound activated form of the s100a4 Metastasis factor | PDB:3KO0 | ||||
Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
PDB Sequence |
ACPLEKALDV
11 MVSTFHKYSG21 KEGDKFKLNK31 SELKELLTRE41 LPSFLGKRTD51 EAAFQKLMSN 61 LDSNRDNEVD71 FQEYCVFLSC81 IAMMCNEFFE91 GFP
|
|||||
|
||||||
Ligand Name: Prochlorperazine | Ligand Info | |||||
Structure Description | Structure of S100A4 with PCP | PDB:3M0W | ||||
Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [4] |
PDB Sequence |
ACPLEKALDV
11 MVSTFHKYSG21 KEGDKFKLNK31 SELKELLTRE41 LPSFLGKRTD51 EAAFQKLMSN 61 LDSNRDNEVD71 FQEYCVFLSC81 IAMMCNEFFE91
|
|||||
|
||||||
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).
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
Biological Network Descriptors
|
Protein Name | Pfam ID | Percentage of Identity (%) | E value |
---|---|---|---|
Sentan (SNTN) | 27.711 (23/83) | 1.72E-05 |
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.
|
Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 5.00E-04 |
---|---|---|---|---|---|
Closeness centrality | 2.34E-01 | Radiality | 1.41E+01 | Clustering coefficient | 4.76E-02 |
Neighborhood connectivity | 4.46E+01 | Topological coefficient | 1.48E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
---|---|---|---|---|---|---|
Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
---|---|---|---|---|---|---|
NetPath Pathway | [+] 5 NetPath Pathways | + | ||||
1 | FSH Signaling Pathway | |||||
2 | IL2 Signaling Pathway | |||||
3 | TGF_beta_Receptor Signaling Pathway | |||||
4 | TSH Signaling Pathway | |||||
5 | TCR Signaling Pathway | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Vitamin D Receptor Pathway | |||||
2 | Hair Follicle Development: Cytodifferentiation (Part 3 of 3) |
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | Lost in migration. Nat Biotechnol. 2010 Mar;28(3):214-29. | |||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022727) | |||||
REF 3 | Phenothiazines inhibit S100A4 function by inducing protein oligomerization. Proc Natl Acad Sci U S A. 2010 May 11;107(19):8605-10. | |||||
REF 4 | Structure of S100A4 with PCP |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.