Target Information
| Target General Information | Top | |||||
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| Target ID |
T21507
(Former ID: TTDR00309)
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| Target Name |
Fatty acid-binding protein 5 (FABP5)
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| Synonyms |
Psoriasis-associated fatty acid-binding protein homolog; PA-FABP; Fatty acid-binding protein, epidermal; Fatty Acid BindingProtein mal1; Epidermal-type fatty acid-binding protein; E-FABP
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| Gene Name |
FABP5
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
Intracellular carrier for long-chain fatty acids and related active lipids, such as the endocannabinoid, that regulates the metabolism and actions of the ligands they bind. In addition to the cytosolic transport, selectively delivers specific fatty acids from the cytosol to the nucleus, wherein they activate nuclear receptors. Delivers retinoic acid to the nuclear receptor peroxisome proliferator-activated receptor delta; which promotes proliferation and survival. May also serve as a synaptic carrier of endocannabinoid at central synapses and thus controls retrograde endocannabinoid signaling. Modulates inflammation by regulating PTGES induction via NF-kappa-B activation, and prostaglandin E2 (PGE2) biosynthesis during inflammation. May be involved in keratinocyte differentiation.
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| BioChemical Class |
Fatty acid binding protein
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| UniProt ID | ||||||
| Sequence |
MATVQQLEGRWRLVDSKGFDEYMKELGVGIALRKMGAMAKPDCIITCDGKNLTIKTESTL
KTTQFSCTLGEKFEETTADGRKTQTVCNFTDGALVQHQEWDGKESTITRKLKDGKLVVEC VMNNVTCTRIYEKVE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T54WR0 | |||||
| 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: Myristic acid | Ligand Info | |||||
| Structure Description | Enantiomer-Specific Binding of the Potent Antinociceptive Agent SBFI-26 to Anandamide transporters FABP5 | PDB:5UR9 | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [4] |
| PDB Sequence |
ATVQQLEGRW
11 RLVDSKGFDE21 YMKELGVGIA31 LRKMGAMAKP41 DCIITCDGKN51 LTIKTESTLK 61 TTQFSCTLGE71 KFEETTADGR81 KTQTVCNFTD91 GALVQHQEWD101 GKESTITRKL 111 KDGKLVVECV121 MNNVTCTRIY131 EKVE
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| Ligand Name: Linoleic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of Human Epidermal Fatty Acid Binding Protein (FABP5) in Complex with Linoleic Acid | PDB:4LKT | ||||
| Method | X-ray diffraction | Resolution | 2.57 Å | Mutation | No | [5] |
| PDB Sequence |
NAMATVQQLE
8 GRWRLVDSKG18 FDEYMKELGV28 GIALRKMGAM38 AKPDCIITCD48 GKNLTIKTES 58 TLKTTQFSCT68 LGEKFEETTA78 DGRKTQTVCN88 FTDGALVQHQ98 EWDGKESTIT 108 RKLKDGKLVV118 ECVMNNVTCT128 RIYEKVE
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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).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Fatty acid-binding protein 1 (FABP1) | 28.395 (23/81) | 4.00E-03 |
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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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| PPAR signaling pathway | hsa03320 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | PPAR signaling pathway | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | IL1 Signaling Pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Hormone-sensitive lipase (HSL)-mediated triacylglycerol hydrolysis | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Fatty acid binding protein (FABP) inhibitors: a patent review (2012-2015).Expert Opin Ther Pat. 2016 Jul;26(7):767-76. | |||||
| REF 2 | NMR structure of a potent small molecule inhibitor bound to human keratinocyte fatty acid-binding protein. J Med Chem. 2006 Aug 10;49(16):5013-7. | |||||
| REF 3 | Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4445-8. | |||||
| REF 4 | The Antinociceptive Agent SBFI-26 Binds to Anandamide Transporters FABP5 and FABP7 at Two Different Sites. Biochemistry. 2017 Jul 11;56(27):3454-3462. | |||||
| REF 5 | Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor beta/Delta (FABP5-PPARbeta/Delta) signaling pathway. J Biol Chem. 2014 May 23;289(21):14941-54. | |||||
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