Target Information
| Target General Information | Top | |||||
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| Target ID |
T05164
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| Target Name |
Histone-lysine N-methyltransferase KMT5B (KMT5B)
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| Synonyms |
Lysine N-methyltransferase 5B; Lysine-specific methyltransferase 5B; Suppressor of variegation 4-20 homolog 1; Su(var)4-20 homolog 1; Suv4-20h1; [histone H4]-N-methyl-L-lysine20 N-methyltransferase KMT5B; [histone H4]-lysine20 N-methyltransferase KMT5B
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| Gene Name |
KMT5B
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| Target Type |
Preclinical target
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[1] | ||||
| Function |
Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity. In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes. H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by regulating the expression of target genes, such as EID3. Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4. May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).
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| UniProt ID | ||||||
| EC Number |
EC 2.1.1.361
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| Sequence |
MKWLGESKNMVVNGRRNGGKLSNDHQQNQSKLQHTGKDTLKAGKNAVERRSNRCNGNSGF
EGQSRYVPSSGMSAKELCENDDLATSLVLDPYLGFQTHKMNTSAFPSRSSRHFSKSDSFS HNNPVRFRPIKGRQEELKEVIERFKKDEHLEKAFKCLTSGEWARHYFLNKNKMQEKLFKE HVFIYLRMFATDSGFEILPCNRYSSEQNGAKIVATKEWKRNDKIELLVGCIAELSEIEEN MLLRHGENDFSVMYSTRKNCAQLWLGPAAFINHDCRPNCKFVSTGRDTACVKALRDIEPG EEISCYYGDGFFGENNEFCECYTCERRGTGAFKSRVGLPAPAPVINSKYGLRETDKRLNR LKKLGDSSKNSDSQSVSSNTDADTTQEKNNATSNRKSSVGVKKNSKSRTLTRQSMSRIPA SSNSTSSKLTHINNSRVPKKLKKPAKPLLSKIKLRNHCKRLEQKNASRKLEMGNLVLKEP KVVLYKNLPIKKDKEPEGPAQAAVASGCLTRHAAREHRQNPVRGAHSQGESSPCTYITRR SVRTRTNLKEASDIKLEPNTLNGYKSSVTEPCPDSGEQLQPAPVLQEEELAHETAQKGEA KCHKSDTGMSKKKSRQGKLVKQFAKIEESTPVHDSPGKDDAVPDLMGPHSDQGEHSGTVG VPVSYTDCAPSPVGCSVVTSDSFKTKDSFRTAKSKKKRRITRYDAQLILENNSGIPKLTL RRRHDSSSKTNDQENDGMNSSKISIKLSKDHDNDNNLYVAKLNNGFNSGSGSSSTKLKIQ LKRDEENRGSYTEGLHENGVCCSDPLSLLESRMEVDDYSQYEEESTDDSSSSEGDEEEDD YDDDFEDDFIPLPPAKRLRLIVGKDSIDIDISSRRREDQSLRLNA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | A-196 | Drug Info | Preclinical | Discovery agent | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | A-196 | Drug Info | [1] | |||
| 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: Ademetionine | Ligand Info | |||||
| Structure Description | Crystal Structure of the SET Domain of Human Histone-Lysine N-Methyltransferase SUV420H1 In Complex With S-Adenosyl-L-Methionine | PDB:3S8P | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [3] |
| PDB Sequence |
SAKELCENDD
82 LATSLVLDPY92 LGFQTHKNTR133 QEELKEVIER143 FKKDEHLEKA153 FKCLTSGEWA 163 RHYFLNKNKQ174 EKLFKEHVFI184 YLRFATDSGF195 EILPCNRYSS205 EQNGAKIVAT 215 KEWKRNDKIE225 LLVGCIAELS235 EIEENLLRHG246 ENDFSVYSTR257 KNCAQLWLGP 267 AAFINHDCRP277 NCKFVSTGRD287 TACVKALRDI297 EPGEEISCYY307 GDGFFGENNE 317 FCECYTCERR327 GTGAFKS
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HIS98
2.766
TYR203
3.374
SER205
2.723
GLU206
2.780
ASN208
4.454
GLY209
3.467
ALA210
2.719
PHE250
3.040
SER251
3.747
ALA269
3.186
PHE270
3.677
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: A-196 | Ligand Info | |||||
| Structure Description | The novel SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity | PDB:5CPR | ||||
| Method | X-ray diffraction | Resolution | 2.22 Å | Mutation | No | [1] |
| PDB Sequence |
MSAKELCEND
81 DLATSLVLDP91 YLGFQTHKMN101 RQEELKEVIE142 RFKKDEHLEK152 AFKCLTSGEW 162 ARHYFLNKNK172 MQEKLFKEHV182 FIYLRMFATD192 SGFEILPCNR202 YSSEQNGAKI 212 VATKEWKRND222 KIELLVGCIA232 ELSEIEENML242 LRHGENDFSV252 MYSTRKNCAQ 262 LWLGPAAFIN272 HDCRPNCKFV282 STGRDTACVK292 ALRDIEPGEE302 ISCYYGDGFF 312 GENNEFCECY322 TCERRGTGAF332 KS
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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).
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).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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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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| Lysine degradation | hsa00310 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| References | Top | |||||
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| REF 1 | The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity. Nat Chem Biol. 2017 Mar;13(3):317-324. | |||||
| REF 2 | Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286. | |||||
| REF 3 | Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2. FEBS Lett. 2013 Nov 29;587(23):3859-68. | |||||
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