Details of the Target

General Information of Target

Target ID LDTP13703
Target Name Histone lysine demethylase PHF8 (PHF8)
Gene Name PHF8
Gene ID 23133
Synonyms
KIAA1111; ZNF422; Histone lysine demethylase PHF8; EC 1.14.11.27; EC 1.14.11.65; PHD finger protein 8; [histone H3]-dimethyl-L-lysine(36) demethylase PHF8; [histone H3]-dimethyl-L-lysine(9) demethylase PHF8
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAENKGGGEAESGGGGSGSAPVTAGAAGPAAQEAEPPLTAVLVEEEEEEGGRAGAEGGAA
GPDDGGVAAASSGSAQAASSPAASVGTGVAGGAVSTPAPAPASAPAPGPSAGPPPGPPAS
LLDTCAVCQQSLQSRREAEPKLLPCLHSFCLRCLPEPERQLSVPIPGGSNGDIQQVGVIR
CPVCRQECRQIDLVDNYFVKDTSEAPSSSDEKSEQVCTSCEDNASAVGFCVECGEWLCKT
CIEAHQRVKFTKDHLIRKKEDVSESVGASGQRPVFCPVHKQEQLKLFCETCDRLTCRDCQ
LLEHKEHRYQFLEEAFQNQKGAIENLLAKLLEKKNYVHFAATQVQNRIKEVNETNKRVEQ
EIKVAIFTLINEINKKGKSLLQQLENVTKERQMKLLQQQNDITGLSRQVKHVMNFTNWAI
ASGSSTALLYSKRLITFQLRHILKARCDPVPAANGAIRFHCDPTFWAKNVVNLGNLVIES
KPAPGYTPNVVVGQVPPGTNHISKTPGQINLAQLRLQHMQQQVYAQKHQQLQQMRMQQPP
APVPTTTTTTQQHPRQAAPQMLQQQPPRLISVQTMQRGNMNCGAFQAHQMRLAQNAARIP
GIPRHSGPQYSMMQPHLQRQHSNPGHAGPFPVVSVHNTTINPTSPTTATMANANRGPTSP
SVTAIELIPSVTNPENLPSLPDIPPIQLEDAGSSSLDNLLSRYISGSHLPPQPTSTMNPS
PGPSALSPGSSGLSNSHTPVRPPSTSSTGSRGSCGSSGRTAEKTSLSFKSDQVKVKQEPG
TEDEICSFSGGVKQEKTEDGRRSACMLSSPESSLTPPLSTNLHLESELDALASLENHVKI
EPADMNESCKQSGLSSLVNGKSPIRSLMHRSARIGGDGNNKDDDPNEDWCAVCQNGGDLL
CCEKCPKVFHLTCHVPTLLSFPSGDWICTFCRDIGKPEVEYDCDNLQHSKKGKTAQGLSP
VDQRKCERLLLYLYCHELSIEFQEPVPASIPNYYKIIKKPMDLSTVKKKLQKKHSQHYQI
PDDFVADVRLIFKNCERFNEMMKVVQVYADTQEINLKADSEVAQAGKAVALYFEDKLTEI
YSDRTFAPLPEFEQEEDDGEVTEDSDEDFIQPRRKRLKSDERPVHIK
Target Type
Literature-reported
Target Bioclass
Enzyme
Family
JHDM1 histone demethylase family, JHDM1D subfamily
Subcellular location
Nucleus
Function
Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. 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. Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements.
TTD ID
T00933
Uniprot ID
Q9UPP1
DrugMap ID
TT81PFE
Ensemble ID
ENST00000322659.12
HGNC ID
HGNC:20672
ChEMBL ID
CHEMBL1938212

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 15 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		12.82  LDD0402  [1]
Alkylaryl probe 2
 Probe Info  		20.00  LDD0389  [2]
STPyne
 Probe Info  		K467(1.19)  LDD0277  [3]
DBIA
 Probe Info  		C271(2.98)  LDD3310  [4]
BTD
 Probe Info  		C684(0.77)  LDD2096  [5]
AHL-Pu-1
 Probe Info  		C684(2.09)  LDD0169  [6]
HHS-475
 Probe Info  		Y383(1.22)  LDD0264  [7]
Acrolein
 Probe Info  		N.A.  LDD0221  [8]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [9]
IA-alkyne
 Probe Info  		C684(0.00); C404(0.00)  LDD0036  [9]
Lodoacetamide azide
 Probe Info  		C684(0.00); C260(0.00)  LDD0037  [9]
ENE
 Probe Info  		N.A.  LDD0006  [10]
IPM
 Probe Info  		N.A.  LDD0147  [11]
Phosphinate-6
 Probe Info  		N.A.  LDD0018  [12]
AOyne
 Probe Info  		11.70  LDD0443  [13]
PAL-AfBPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C170
 Probe Info  		10.48  LDD1850  [14]
C361
 Probe Info  		20.97  LDD2022  [14]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0026  4SU-RNA+native RNA HEK-293T C684(2.09)  LDD0169  [6]
 LDCM0214  AC1 PaTu 8988t C404(0.51)  LDD1093  [15]
 LDCM0215  AC10 PaTu 8988t C404(0.86)  LDD1094  [15]
 LDCM0226  AC11 PaTu 8988t C404(0.70)  LDD1105  [15]
 LDCM0237  AC12 PaTu 8988t C404(0.89)  LDD1116  [15]
 LDCM0259  AC14 PaTu 8988t C404(1.21)  LDD1138  [15]
 LDCM0270  AC15 PaTu 8988t C404(0.79)  LDD1149  [15]
 LDCM0276  AC17 PaTu 8988t C260(0.99); C404(0.78)  LDD1155  [15]
 LDCM0277  AC18 PaTu 8988t C260(1.01); C404(0.67)  LDD1156  [15]
 LDCM0278  AC19 PaTu 8988t C260(0.92); C404(0.68)  LDD1157  [15]
 LDCM0279  AC2 PaTu 8988t C404(0.54)  LDD1158  [15]
 LDCM0280  AC20 PaTu 8988t C260(0.92); C404(0.57)  LDD1159  [15]
 LDCM0281  AC21 PaTu 8988t C260(1.06); C404(0.61)  LDD1160  [15]
 LDCM0282  AC22 PaTu 8988t C260(1.06); C404(0.70)  LDD1161  [15]
 LDCM0283  AC23 PaTu 8988t C260(0.90); C404(0.70)  LDD1162  [15]
 LDCM0284  AC24 PaTu 8988t C260(1.08); C404(0.82)  LDD1163  [15]
 LDCM0290  AC3 PaTu 8988t C404(0.60)  LDD1169  [15]
 LDCM0296  AC35 PaTu 8988t C260(1.05)  LDD1175  [15]
 LDCM0297  AC36 PaTu 8988t C260(1.02)  LDD1176  [15]
 LDCM0298  AC37 PaTu 8988t C260(1.03)  LDD1177  [15]
 LDCM0299  AC38 PaTu 8988t C260(1.07)  LDD1178  [15]
 LDCM0300  AC39 PaTu 8988t C260(0.98)  LDD1179  [15]
 LDCM0301  AC4 PaTu 8988t C404(0.65)  LDD1180  [15]
 LDCM0302  AC40 PaTu 8988t C260(0.90)  LDD1181  [15]
 LDCM0303  AC41 PaTu 8988t C260(1.07)  LDD1182  [15]
 LDCM0304  AC42 PaTu 8988t C260(1.06)  LDD1183  [15]
 LDCM0305  AC43 PaTu 8988t C260(0.87)  LDD1184  [15]
 LDCM0306  AC44 PaTu 8988t C260(1.05)  LDD1185  [15]
 LDCM0307  AC45 PaTu 8988t C260(1.02)  LDD1186  [15]
 LDCM0308  AC46 PaTu 8988t C260(0.90); C404(0.79)  LDD1187  [15]
 LDCM0309  AC47 PaTu 8988t C260(0.80); C404(0.73)  LDD1188  [15]
 LDCM0310  AC48 PaTu 8988t C260(0.85); C404(0.59)  LDD1189  [15]
 LDCM0311  AC49 PaTu 8988t C260(0.84); C404(0.61)  LDD1190  [15]
 LDCM0312  AC5 PaTu 8988t C404(0.53)  LDD1191  [15]
 LDCM0313  AC50 PaTu 8988t C260(0.96); C404(0.59)  LDD1192  [15]
 LDCM0314  AC51 PaTu 8988t C260(0.31); C404(1.08)  LDD1193  [15]
 LDCM0315  AC52 PaTu 8988t C260(0.82); C404(0.64)  LDD1194  [15]
 LDCM0316  AC53 PaTu 8988t C260(0.90); C404(0.60)  LDD1195  [15]
 LDCM0317  AC54 PaTu 8988t C260(0.98); C404(0.62)  LDD1196  [15]
 LDCM0318  AC55 PaTu 8988t C260(0.96); C404(0.77)  LDD1197  [15]
 LDCM0319  AC56 PaTu 8988t C260(0.85); C404(1.12)  LDD1198  [15]
 LDCM0323  AC6 PaTu 8988t C404(1.26)  LDD1202  [15]
 LDCM0332  AC68 PaTu 8988t C404(0.76)  LDD1211  [15]
 LDCM0333  AC69 PaTu 8988t C404(0.83)  LDD1212  [15]
 LDCM0334  AC7 PaTu 8988t C404(1.07)  LDD1213  [15]
 LDCM0335  AC70 PaTu 8988t C404(0.68)  LDD1214  [15]
 LDCM0336  AC71 PaTu 8988t C404(0.91)  LDD1215  [15]
 LDCM0337  AC72 PaTu 8988t C404(1.07)  LDD1216  [15]
 LDCM0338  AC73 PaTu 8988t C404(0.90)  LDD1217  [15]
 LDCM0339  AC74 PaTu 8988t C404(0.84)  LDD1218  [15]
 LDCM0340  AC75 PaTu 8988t C404(0.56)  LDD1219  [15]
 LDCM0341  AC76 PaTu 8988t C404(0.88)  LDD1220  [15]
 LDCM0342  AC77 PaTu 8988t C404(0.99)  LDD1221  [15]
 LDCM0343  AC78 PaTu 8988t C404(0.67)  LDD1222  [15]
 LDCM0344  AC79 PaTu 8988t C404(0.67)  LDD1223  [15]
 LDCM0345  AC8 PaTu 8988t C404(1.00)  LDD1224  [15]
 LDCM0346  AC80 PaTu 8988t C404(0.83)  LDD1225  [15]
 LDCM0347  AC81 PaTu 8988t C404(0.69)  LDD1226  [15]
 LDCM0348  AC82 PaTu 8988t C404(0.71)  LDD1227  [15]
 LDCM0248  AKOS034007472 PaTu 8988t C404(1.16)  LDD1127  [15]
 LDCM0356  AKOS034007680 PaTu 8988t C404(0.84)  LDD1235  [15]
 LDCM0275  AKOS034007705 PaTu 8988t C404(0.74)  LDD1154  [15]
 LDCM0369  CL100 PaTu 8988t C404(0.59)  LDD1248  [15]
 LDCM0370  CL101 PaTu 8988t C404(0.91)  LDD1249  [15]
 LDCM0371  CL102 PaTu 8988t C404(0.82)  LDD1250  [15]
 LDCM0372  CL103 PaTu 8988t C404(0.86)  LDD1251  [15]
 LDCM0373  CL104 PaTu 8988t C404(1.06)  LDD1252  [15]
 LDCM0374  CL105 PaTu 8988t C260(0.91); C404(0.77)  LDD1253  [15]
 LDCM0375  CL106 PaTu 8988t C260(0.85); C404(1.37)  LDD1254  [15]
 LDCM0376  CL107 PaTu 8988t C260(0.91); C404(0.90)  LDD1255  [15]
 LDCM0377  CL108 PaTu 8988t C260(0.91); C404(0.76)  LDD1256  [15]
 LDCM0378  CL109 PaTu 8988t C260(0.90); C404(0.67)  LDD1257  [15]
 LDCM0380  CL110 PaTu 8988t C260(1.02); C404(0.62)  LDD1259  [15]
 LDCM0381  CL111 PaTu 8988t C260(1.17); C404(0.64)  LDD1260  [15]
 LDCM0387  CL117 PaTu 8988t C260(1.00)  LDD1266  [15]
 LDCM0388  CL118 PaTu 8988t C260(1.08)  LDD1267  [15]
 LDCM0389  CL119 PaTu 8988t C260(1.04)  LDD1268  [15]
 LDCM0391  CL120 PaTu 8988t C260(1.08)  LDD1270  [15]
 LDCM0392  CL121 PaTu 8988t C260(0.78); C404(0.77)  LDD1271  [15]
 LDCM0393  CL122 PaTu 8988t C260(0.78); C404(2.33)  LDD1272  [15]
 LDCM0394  CL123 PaTu 8988t C260(0.82); C404(0.57)  LDD1273  [15]
 LDCM0395  CL124 PaTu 8988t C260(0.88); C404(0.55)  LDD1274  [15]
 LDCM0453  CL61 PaTu 8988t C260(0.97)  LDD1332  [15]
 LDCM0454  CL62 PaTu 8988t C260(1.09)  LDD1333  [15]
 LDCM0455  CL63 PaTu 8988t C260(1.03)  LDD1334  [15]
 LDCM0456  CL64 PaTu 8988t C260(1.12)  LDD1335  [15]
 LDCM0457  CL65 PaTu 8988t C260(0.92)  LDD1336  [15]
 LDCM0458  CL66 PaTu 8988t C260(0.83)  LDD1337  [15]
 LDCM0459  CL67 PaTu 8988t C260(1.06)  LDD1338  [15]
 LDCM0460  CL68 PaTu 8988t C260(1.13)  LDD1339  [15]
 LDCM0461  CL69 PaTu 8988t C260(1.01)  LDD1340  [15]
 LDCM0463  CL70 PaTu 8988t C260(0.93)  LDD1342  [15]
 LDCM0464  CL71 PaTu 8988t C260(0.98)  LDD1343  [15]
 LDCM0465  CL72 PaTu 8988t C260(1.39)  LDD1344  [15]
 LDCM0466  CL73 PaTu 8988t C260(0.99)  LDD1345  [15]
 LDCM0467  CL74 PaTu 8988t C260(1.04)  LDD1346  [15]
 LDCM0486  CL91 PaTu 8988t C404(0.76)  LDD1365  [15]
 LDCM0487  CL92 PaTu 8988t C404(0.55)  LDD1366  [15]
 LDCM0488  CL93 PaTu 8988t C404(0.56)  LDD1367  [15]
 LDCM0489  CL94 PaTu 8988t C404(0.84)  LDD1368  [15]
 LDCM0490  CL95 PaTu 8988t C404(0.61)  LDD1369  [15]
 LDCM0491  CL96 PaTu 8988t C404(0.56)  LDD1370  [15]
 LDCM0492  CL97 PaTu 8988t C404(0.63)  LDD1371  [15]
 LDCM0493  CL98 PaTu 8988t C404(0.65)  LDD1372  [15]
 LDCM0494  CL99 PaTu 8988t C404(0.66)  LDD1373  [15]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C684(1.44)  LDD1702  [5]
 LDCM0468  Fragment33 PaTu 8988t C260(0.93)  LDD1347  [15]
 LDCM0116  HHS-0101 DM93 Y383(1.22)  LDD0264  [7]
 LDCM0117  HHS-0201 DM93 Y383(6.43)  LDD0265  [7]
 LDCM0118  HHS-0301 DM93 Y383(2.91)  LDD0266  [7]
 LDCM0119  HHS-0401 DM93 Y383(3.14)  LDD0267  [7]
 LDCM0120  HHS-0701 DM93 Y383(3.06)  LDD0268  [7]
 LDCM0107  IAA HeLa N.A.  LDD0221  [8]
 LDCM0022  KB02 HEK-293T C684(1.03); C86(1.00); C260(0.94); C86(1.05)  LDD1492  [16]
 LDCM0023  KB03 HEK-293T C684(0.97); C86(0.98); C260(0.92); C86(0.97)  LDD1497  [16]
 LDCM0024  KB05 COLO792 C271(2.98)  LDD3310  [4]
 LDCM0503  Nucleophilic fragment 14b MDA-MB-231 C684(0.77)  LDD2096  [5]
 LDCM0518  Nucleophilic fragment 22a MDA-MB-231 C684(1.03)  LDD2111  [5]
 LDCM0527  Nucleophilic fragment 26b MDA-MB-231 C684(0.95)  LDD2120  [5]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C684(0.72)  LDD2125  [5]
 LDCM0535  Nucleophilic fragment 30b MDA-MB-231 C684(0.94)  LDD2128  [5]
 LDCM0536  Nucleophilic fragment 31 MDA-MB-231 C684(0.94)  LDD2129  [5]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C684(0.96)  LDD2136  [5]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C684(0.56)  LDD2140  [5]
 LDCM0549  Nucleophilic fragment 43 MDA-MB-231 C684(1.35)  LDD2143  [5]
 LDCM0556  Nucleophilic fragment 8a MDA-MB-231 C684(0.18)  LDD2150  [5]
 LDCM0099  Phenelzine HEK-293T 15.00  LDD0390  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transcription factor
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger protein 711 (ZNF711) Krueppel C2H2-type zinc-finger protein family Q9Y462
Retinoic acid receptor alpha (RARA) Nuclear hormone receptor family P10276
Homeobox protein ARX (ARX) Paired homeobox family Q96QS3
Recombining binding protein suppressor of hairless (RBPJ) Su(H) family Q06330

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Daminozide Small molecular drug D0B2WZ

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes. bioRxiv, 2020-06.
3 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
4 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
5 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
6 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
7 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
8 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
9 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
10 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
11 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
12 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
13 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
14 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
15 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
16 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402