Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T00933
(Former ID: TTDI03456)
|
|||||
| Target Name |
Histone lysine demethylase PHF8 (PHF8)
|
|||||
| Synonyms |
ZNF422; PHD finger protein 8; KIAA1111
Click to Show/Hide
|
|||||
| Gene Name |
PHF8
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| Function |
Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development.
Click to Show/Hide
|
|||||
| BioChemical Class |
Paired donor oxygen oxidoreductase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 1.14.11.27
|
|||||
| Sequence |
MNRSRAIVQRGRVLPPPAPLDTTNLAGRRTLQGRAKMASVPVYCLCRLPYDVTRFMIECD
MCQDWFHGSCVGVEEEKAADIDLYHCPNCEVLHGPSIMKKRRGSSKGHDTHKGKPVKTGS PTFVRELRSRTFDSSDEVILKPTGNQLTVEFLEENSFSVPILVLKKDGLGMTLPSPSFTV RDVEHYVGSDKEIDVIDVTRQADCKMKLGDFVKYYYSGKREKVLNVISLEFSDTRLSNLV ETPKIVRKLSWVENLWPEECVFERPNVQKYCLMSVRDSYTDFHIDFGGTSVWYHVLKGEK IFYLIRPTNANLTLFECWSSSSNQNEMFFGDQVDKCYKCSVKQGQTLFIPTGWIHAVLTP VDCLAFGGNFLHSLNIEMQLKAYEIEKRLSTADLFRFPNFETICWYVGKHILDIFRGLRE NRRHPASYLVHGGKALNLAFRAWTRKEALPDHEDEIPETVRTVQLIKDLAREIRLVEDIF QQNVGKTSNIFGLQRIFPAGSIPLTRPAHSTSVSMSRLSLPSKNGSKKKGLKPKELFKKA ERKGKESSALGPAGQLSYNLMDTYSHQALKTGSFQKAKFNITGACLNDSDDDSPDLDLDG NESPLALLMSNGSTKRVKSLSKSRRTKIAKKVDKARLMAEQVMEDEFDLDSDDELQIDER LGKEKATLIIRPKFPRKLPRAKPCSDPNRVREPGEVEFDIEEDYTTDEDMVEGVEGKLGN GSGAGGILDLLKASRQVGGPDYAALTEAPASPSTQEAIQGMLCMANLQSSSSSPATSSLQ AWWTGGQDRSSGSSSSGLGTVSNSPASQRTPGKRPIKRPAYWRTESEEEEENASLDEQDS LGACFKDAEYIYPSLESDDDDPALKSRPKKKKNSDDAPWSPKARVTPTLPKQDRPVREGT RVASIETGLAAAAAKLAQQELQKAQKKKYIKKKPLLKEVEQPRPQDSNLSLTVPAPTVAA TPQLVTSSSPLPPPEPKQEALSGSLADHEYTARPNAFGMAQANRSTTPMAPGVFLTQRRP SVGSQSNQAGQGKRPKKGLATAKQRLGRILKIHRNGKLLL Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 2-(carboxymethylamino)-2-oxoacetic acid | Ligand Info | |||||
| Structure Description | Structure of PHF8 in complex with histone H3 | PDB:3KV4 | ||||
| Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | No | [2] |
| PDB Sequence |
SVPVYCLCRL
12 PYDVTRFMIE22 CDMCQDWFHG32 SCVGVEEEKA42 ADIDLYHCPN52 CEVLHGPSIM 62 KKKPVKTGSP85 TFVRELRSRT95 FDSSDEVILK105 PTGNQLTVEF115 LEENSFSVPI 125 LVLKKDGLGM135 TLPSPSFTVR145 DVEHYVGSDK155 EIDVIDVTRQ165 ADCKMKLGDF 175 VKYYYSGKRE185 KVLNVISLEF195 SDTRLSNLVE205 TPKIVRKLSW215 VENLWPEECV 225 FERPNVQKYC235 LMSVRDSYTD245 FHIDFGGTSV255 WYHVLKGEKI265 FYLIRPTNAN 275 LTLFECWSSS285 SNQNEMFFGD295 QVDKCYKCSV305 KQGQTLFIPT315 GWIHAVLTPV 325 DCLAFGGNFL335 HSLNIEMQLK345 AYEIEKRLST355 ADLFRFPNFE365 TICWYVGKHI 375 LDIFRGLREN385 RRHPASYLVH395 GGKALNLAFR405 AWTRKEALPD415 HEDEIPETVR 425 TVQLIKDLAR435 EIRLVEDIFQ445 QN
|
|||||
|
|
||||||
| Ligand Name: N-Trimethyllysine | Ligand Info | |||||
| Structure Description | Structure of PHF8 in complex with histone H3 | PDB:3KV4 | ||||
| Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | No | [2] |
| PDB Sequence |
SVPVYCLCRL
12 PYDVTRFMIE22 CDMCQDWFHG32 SCVGVEEEKA42 ADIDLYHCPN52 CEVLHGPSIM 62 KKKPVKTGSP85 TFVRELRSRT95 FDSSDEVILK105 PTGNQLTVEF115 LEENSFSVPI 125 LVLKKDGLGM135 TLPSPSFTVR145 DVEHYVGSDK155 EIDVIDVTRQ165 ADCKMKLGDF 175 VKYYYSGKRE185 KVLNVISLEF195 SDTRLSNLVE205 TPKIVRKLSW215 VENLWPEECV 225 FERPNVQKYC235 LMSVRDSYTD245 FHIDFGGTSV255 WYHVLKGEKI265 FYLIRPTNAN 275 LTLFECWSSS285 SNQNEMFFGD295 QVDKCYKCSV305 KQGQTLFIPT315 GWIHAVLTPV 325 DCLAFGGNFL335 HSLNIEMQLK345 AYEIEKRLST355 ADLFRFPNFE365 TICWYVGKHI 375 LDIFRGLREN385 RRHPASYLVH395 GGKALNLAFR405 AWTRKEALPD415 HEDEIPETVR 425 TVQLIKDLAR435 EIRLVEDIFQ445 QN
|
|||||
|
|
||||||
| 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
|
|
|
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 | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 1.86E-01 | Radiality | 1.31E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 9.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases. J Med Chem. 2012 Jul 26;55(14):6639-43. | |||||
| REF 2 | Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases. Nat Struct Mol Biol. 2010 Jan;17(1):38-43. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.