Target Information
| Target General Information | Top | |||||
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| Target ID |
T56057
(Former ID: TTDI03364)
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| Target Name |
Lysine-specific demethylase 6B (KDM6B)
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| Synonyms |
Lysine demethylase 6B; KIAA0346; Jumonji domain-containing protein 3; JmjC domain-containing protein 3; JMJD3
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| Gene Name |
KDM6B
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation. Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (By similarity).
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| UniProt ID | ||||||
| EC Number |
EC 1.14.11.-
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| Sequence |
MHRAVDPPGARAAREAFALGGLSCAGAWSSCPPHPPPRSAWLPGGRCSASIGQPPLPAPL
PPSHGSSSGHPSKPYYAPGAPTPRPLHGKLESLHGCVQALLREPAQPGLWEQLGQLYESE HDSEEATRCYHSALRYGGSFAELGPRIGRLQQAQLWNFHTGSCQHRAKVLPPLEQVWNLL HLEHKRNYGAKRGGPPVKRAAEPPVVQPVPPAALSGPSGEEGLSPGGKRRRGCNSEQTGL PPGLPLPPPPLPPPPPPPPPPPPPLPGLATSPPFQLTKPGLWSTLHGDAWGPERKGSAPP ERQEQRHSLPHPYPYPAPAYTAHPPGHRLVPAAPPGPGPRPPGAESHGCLPATRPPGSDL RESRVQRSRMDSSVSPAATTACVPYAPSRPPGLPGTTTSSSSSSSSNTGLRGVEPNPGIP GADHYQTPALEVSHHGRLGPSAHSSRKPFLGAPAATPHLSLPPGPSSPPPPPCPRLLRPP PPPAWLKGPACRAAREDGEILEELFFGTEGPPRPAPPPLPHREGFLGPPASRFSVGTQDS HTPPTPPTPTTSSSNSNSGSHSSSPAGPVSFPPPPYLARSIDPLPRPPSPAQNPQDPPLV PLTLALPPAPPSSCHQNTSGSFRRPESPRPRVSFPKTPEVGPGPPPGPLSKAPQPVPPGV GELPARGPRLFDFPPTPLEDQFEEPAEFKILPDGLANIMKMLDESIRKEEEQQQHEAGVA PQPPLKEPFASLQSPFPTDTAPTTTAPAVAVTTTTTTTTTTTATQEEEKKPPPALPPPPP LAKFPPPSQPQPPPPPPPSPASLLKSLASVLEGQKYCYRGTGAAVSTRPGPLPTTQYSPG PPSGATALPPTSAAPSAQGSPQPSASSSSQFSTSGGPWARERRAGEEPVPGPMTPTQPPP PLSLPPARSESEVLEEISRACETLVERVGRSATDPADPVDTAEPADSGTERLLPPAQAKE EAGGVAAVSGSCKRRQKEHQKEHRRHRRACKDSVGRRPREGRAKAKAKVPKEKSRRVLGN LDLQSEEIQGREKSRPDLGGASKAKPPTAPAPPSAPAPSAQPTPPSASVPGKKAREEAPG PPGVSRADMLKLRSLSEGPPKELKIRLIKVESGDKETFIASEVEERRLRMADLTISHCAA DVVRASRNAKVKGKFRESYLSPAQSVKPKINTEEKLPREKLNPPTPSIYLESKRDAFSPV LLQFCTDPRNPITVIRGLAGSLRLNLGLFSTKTLVEASGEHTVEVRTQVQQPSDENWDLT GTRQIWPCESSRSHTTIAKYAQYQASSFQESLQEEKESEDEESEEPDSTTGTPPSSAPDP KNHHIIKFGTNIDLSDAKRWKPQLQELLKLPAFMRVTSTGNMLSHVGHTILGMNTVQLYM KVPGSRTPGHQENNNFCSVNINIGPGDCEWFAVHEHYWETISAFCDRHGVDYLTGSWWPI LDDLYASNIPVYRFVQRPGDLVWINAGTVHWVQATGWCNNIAWNVGPLTAYQYQLALERY EWNEVKNVKSIVPMIHVSWNVARTVKISDPDLFKMIKFCLLQSMKHCQVQRESLVRAGKK IAYQGRVKDEPAYYCNECDVEVFNILFVTSENGSRNTYLVHCEGCARRRSAGLQGVVVLE QYRTEELAQAYDAFTLAPASTSR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T88UDX | |||||
| 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: 2-Methyl-2-Propanol | Ligand Info | |||||
| Structure Description | The catalytic domain of KDM6B in complex with H3(17-33)K18IA21M peptide | PDB:6F6D | ||||
| Method | X-ray diffraction | Resolution | 1.82 Å | Mutation | No | [3] |
| PDB Sequence |
ESYLSPAQSV
1166 KPKINTEEKL1176 PREKLNPPTP1186 SIYLESKRDA1196 FSPVLLQFCT1206 DPRNPITVIR 1216 GLAGSLRLNL1226 GLFSTKTLVE1236 ASGEHTVEVR1246 TQVQQPSDEN1256 WDLTGTRQIW 1266 PCESSRSHTT1276 IAKYAQYQAS1286 SFQESHIIKF1328 GTNIDLSDAK1338 RWKPQLQELL 1348 KLPAFMRVTS1358 TGNMLSHVGH1368 TILGMNTVQL1378 YMKVPGSRTP1388 GHQENNNFCS 1398 VNINIGPGDC1408 EWFAVHEHYW1418 ETISAFCDRH1428 GVDYLTGSWW1438 PILDDLYASN 1448 IPVYRFVQRP1458 GDLVWINAGT1468 VHWVQATGWC1478 NNIAWNVGPL1488 TAYQYQLALE 1498 RYEWNEVKNV1508 KSIVPMIHVS1518 WNVARTVKIS1528 DPDLFKMIKF1538 CLLQSMKHCQ 1548 VQRESLVRAG1558 KKIAYQGRVK1568 DEPAYYCNEC1578 DVEVFNILFV1588 TSENGSRNTY 1598 LVHCEGCARR1608 RSAGLQGVVV1618 LEQYRTEELA1628 QAYDAFTLAP1638 |
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ILE1188
2.726
TYR1189
4.703
LEU1190
2.736
ASP1195
3.458
ALA1196
4.900
SER1198
3.432
VAL1200
2.537
LEU1201
2.395
PHE1204
2.897
THR1231
3.082
THR1242
2.614
VAL1243
2.458
GLU1244
2.536
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Alpha-ketoglutaric acid | Ligand Info | |||||
| Structure Description | The catalytic domain of KDM6B in complex with H3(17-33)K18IA21M peptide | PDB:6F6D | ||||
| Method | X-ray diffraction | Resolution | 1.82 Å | Mutation | No | [3] |
| PDB Sequence |
ESYLSPAQSV
1166 KPKINTEEKL1176 PREKLNPPTP1186 SIYLESKRDA1196 FSPVLLQFCT1206 DPRNPITVIR 1216 GLAGSLRLNL1226 GLFSTKTLVE1236 ASGEHTVEVR1246 TQVQQPSDEN1256 WDLTGTRQIW 1266 PCESSRSHTT1276 IAKYAQYQAS1286 SFQESHIIKF1328 GTNIDLSDAK1338 RWKPQLQELL 1348 KLPAFMRVTS1358 TGNMLSHVGH1368 TILGMNTVQL1378 YMKVPGSRTP1388 GHQENNNFCS 1398 VNINIGPGDC1408 EWFAVHEHYW1418 ETISAFCDRH1428 GVDYLTGSWW1438 PILDDLYASN 1448 IPVYRFVQRP1458 GDLVWINAGT1468 VHWVQATGWC1478 NNIAWNVGPL1488 TAYQYQLALE 1498 RYEWNEVKNV1508 KSIVPMIHVS1518 WNVARTVKIS1528 DPDLFKMIKF1538 CLLQSMKHCQ 1548 VQRESLVRAG1558 KKIAYQGRVK1568 DEPAYYCNEC1578 DVEVFNILFV1588 TSENGSRNTY 1598 LVHCEGCARR1608 RSAGLQGVVV1618 LEQYRTEELA1628 QAYDAFTLAP1638 |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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).
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
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 4.97E-05 |
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| Closeness centrality | 2.31E-01 | Radiality | 1.41E+01 | Clustering coefficient | 1.00E-01 |
| Neighborhood connectivity | 7.08E+01 | Topological coefficient | 2.20E-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 | A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1. ChemMedChem. 2014 Mar;9(3):566-71. | |||||
| REF 2 | A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8. | |||||
| REF 3 | Structural Basis of Histone Demethylase KDM6B Histone 3 Lysine 27 Specificity. Biochemistry. 2018 Feb 6;57(5):585-592. | |||||
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