Target Information
| Target General Information | Top | |||||
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| Target ID |
T45074
(Former ID: TTDI01936)
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| Target Name |
Carnitine acyltransferase (CRAT)
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| Synonyms |
Carnitine acetylase; Carnitine O-acetyltransferase; CRAT
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| Gene Name |
CRAT
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| Target Type |
Discontinued target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Acute diabete complication [ICD-11: 5A2Y] | |||||
| 2 | Ischemia [ICD-11: 8B10-8B11] | |||||
| Function |
Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion. Plays an important role in triglyceride metabolism.
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| BioChemical Class |
Acyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.3.1.7
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| Sequence |
MLAFAARTVVKPLGFLKPFSLMKASSRFKAHQDALPRLPVPPLQQSLDHYLKALQPIVSE
EEWAHTKQLVDEFQASGGVGERLQKGLERRARKTENWLSEWWLKTAYLQYRQPVVIYSSP GVMLPKQDFVDLQGQLRFAAKLIEGVLDFKVMIDNETLPVEYLGGKPLCMNQYYQILSSC RVPGPKQDTVSNFSKTKKPPTHITVVHNYQFFELDVYHSDGTPLTADQIFVQLEKIWNSS LQTNKEPVGILTSNHRNSWAKAYNTLIKDKVNRDSVRSIQKSIFTVCLDATMPRVSEDVY RSHVAGQMLHGGGSRLNSGNRWFDKTLQFIVAEDGSCGLVYEHAAAEGPPIVTLLDYVIE YTKKPELVRSPLVPLPMPKKLRFNITPEIKSDIEKAKQNLSIMIQDLDITVMVFHHFGKD FPKSEKLSPDAFIQMALQLAYYRIYGQACATYESASLRMFHLGRTDTIRSASMDSLTFVK AMDDSSVTEHQKVELLRKAVQAHRGYTDRAIRGEAFDRHLLGLKLQAIEDLVSMPDIFMD TSYAIAMHFHLSTSQVPAKTDCVMFFGPVVPDGYGVCYNPMEAHINFSLSAYNSCAETNA ARLAHYLEKALLDMRALLQSHPRAKL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A02140 | |||||
| Drugs and Modes of Action | Top | |||||
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| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | Teglicar | Drug Info | Discontinued in Phase 2 | Diabetic complication | [2] | |
| 2 | LXR-015-2 | Drug Info | Terminated | Ischemia | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | Teglicar | Drug Info | [1] | |||
| 2 | LXR-015-2 | Drug Info | [4] | |||
| 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: CS-4771 | Ligand Info | |||||
| Structure Description | Structural and Mutational Characterization of L-carnitine Binding to Human carnitine Acetyltransferase | PDB:1S5O | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [5] |
| PDB Sequence |
HHTDPLPRLP
18 VPPLQQSLDH28 YLKALQPIVS38 EEEWAHTKQL48 VDEFQASGGV58 GERLQKGLER 68 RARKTENWLS78 EWWLKTAYLQ88 YRQPVVIYSS98 PGVMLPKQDF108 VDLQGQLRFA 118 AKLIEGVLDF128 KVMIDNETLP138 VEYLGGKPLC148 MNQYYQILSS158 CRVPGPKQDT 168 VSNFSKTKKP178 PTHITVVHNY188 QFFELDVYHS198 DGTPLTADQI208 FVQLEKIWNS 218 SLQTNKEPVG228 ILTSNHRNSW238 AKAYNTLIKD248 KVNRDSVRSI258 QKSIFTVCLD 268 ATMPRVSEDV278 YRSHVAGQML288 HGGGSRLNSG298 NRWFDKTLQF308 IVAEDGSCGL 318 VYEHAAAEGP328 PIVTLLDYVI338 EYTKKPELVR348 SPMVPLPMPK358 KLRFNITPEI 368 KSDIEKAKQN378 LSIMIQDLDI388 TVMVFHHFGK398 DFPKSEKLSP408 DAFIQMALQL 418 AYYRIYGQAC428 ATYESASLRM438 FHLGRTDTIR448 SASMDSLTFV458 KAMDDSSVTE 468 HQKVELLRKA478 VQAHRGYTDR488 AIRGEAFDRH498 LLGLKLQAIE508 DLVSTPDIFM 518 DTSYAIAMHF528 HLSTSQVPAK538 TDCVMFFGPV548 VPDGYGVCYN558 PMEAHINFSL 568 SAYNSCAETN578 AARLAHYLEK588 ALLDMRALLQ598 S
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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).
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
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There is no similarity protein (E value < 0.005) for this target
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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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| Degree | 9 | Degree centrality | 9.67E-04 | Betweenness centrality | 1.62E-05 |
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| Closeness centrality | 1.77E-01 | Radiality | 1.29E+01 | Clustering coefficient | 6.94E-01 |
| Neighborhood connectivity | 2.14E+01 | Topological coefficient | 3.44E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Selective Reversible Inhibition of Liver Carnitine Palmitoyl-Transferase 1 by Teglicar Reduces Gluconeogenesis and Improves Glucose Homeostasis. Diabetes. 2011 February; 60(2): 644-651. | |||||
| 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 800017026) | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011210) | |||||
| REF 4 | EDG receptors as a potential therapeutic target in retinal ischemia-reperfusion injury. Brain Res. 2006 Nov 6;1118(1):168-75. | |||||
| REF 5 | Structural and mutational characterization of L-carnitine binding to human carnitine acetyltransferase. J Struct Biol. 2004 Jun;146(3):416-24. | |||||
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