Target Information
Target General Information | Top | |||||
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Target ID |
T81916
(Former ID: TTDI02109)
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Target Name |
Kruppel like factor 4 (KLF4)
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Synonyms |
Krueppellike factor 4; Krueppel-like factor 4; Gutenriched krueppellike factor; Gut-enriched krueppel-like factor; GKLF; Epithelial zinc finger protein EZF; EZF
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Gene Name |
KLF4
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription. Transcription factor; can act both as activator and as repressor.
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UniProt ID | ||||||
Sequence |
MRQPPGESDMAVSDALLPSFSTFASGPAGREKTLRQAGAPNNRWREELSHMKRLPPVLPG
RPYDLAAATVATDLESGGAGAACGGSNLAPLPRRETEEFNDLLDLDFILSNSLTHPPESV AATVSSSASASSSSSPSSSGPASAPSTCSFTYPIRAGNDPGVAPGGTGGGLLYGRESAPP PTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQPQPPGGGLMGKFVLKASLSAPGS EYGSPSVISVSKGSPDGSHPVVVAPYNGGPPRTCPKIKQEAVSSCTHLGAGPPLSNGHRP AAHDFPLGRQLPSRTTPTLGLEEVLSSRDCHPALPLPPGFHPHPGPNYPSFLPDQMQPQV PPLHYQGQSRGFVARAGEPCVCWPHFGTHGMMLTPPSSPLELMPPGSCMPEEPKPKRGRR SWPRKRTATHTCDYAGCGKTYTKSSHLKAHLRTHTGEKPYHCDWDGCGWKFARSDELTRH YRKHTGHRPFQCQKCDRAFSRSDHLALHMKRHF Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T96L4T |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | APTO-253 | Drug Info | Phase 1 | Solid tumour/cancer | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | APTO-253 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
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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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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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Signaling pathways regulating pluripotency of stem cells | hsa04550 | Affiliated Target |
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Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy |
Degree | 9 | Degree centrality | 9.67E-04 | Betweenness centrality | 1.96E-04 |
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Closeness centrality | 2.41E-01 | Radiality | 1.42E+01 | Clustering coefficient | 4.72E-01 |
Neighborhood connectivity | 7.30E+01 | Topological coefficient | 1.61E-01 | Eccentricity | 11 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Signaling pathways regulating pluripotency of stem cells | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | Regulation of nuclear beta catenin signaling and target gene transcription | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | Transcriptional regulation of white adipocyte differentiation | |||||
2 | Transcriptional regulation of pluripotent stem cells | |||||
WikiPathways | [+] 7 WikiPathways | + | ||||
1 | Vitamin D Receptor Pathway | |||||
2 | Mesodermal Commitment Pathway | |||||
3 | Transcriptional regulation of pluripotent stem cells | |||||
4 | Transcriptional Regulation of White Adipocyte Differentiation | |||||
5 | Cell Differentiation - meta | |||||
6 | SRF and miRs in Smooth Muscle Differentiation and Proliferation | |||||
7 | Synthesis, Secretion, and Deacylation of Ghrelin |
References | Top | |||||
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REF 1 | Phase 1 study of APTO-253 HCl, an inducer of KLF4, in patients with advanced or metastatic solid tumors. Invest New Drugs. 2015 Oct;33(5):1086-92. | |||||
REF 2 | ClinicalTrials.gov (NCT02267863) A Study of APTO-253 HCl in Patients With Relapsed or Refractory Hematologic Malignancies. U.S. National Institutes of Health. |
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