Target Information
| Target General Information | Top | |||||
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| Target ID |
T68777
(Former ID: TTDR00391)
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| Target Name |
Lysine N-methyltransferase 3B (NSD1)
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| Synonyms |
Nuclear receptor-binding SET domain-containing protein 1; NR-binding SET domain-containing protein; NR-binding SET domain containing protein; KMT3B; Hypothetical protein FLJ22263 similar to nuclear receptor-binding SET-domain protein 1; Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific; H4-K20-HMTase; H3-K36-HMTase; Androgen receptor-associated protein of 267 kDa; Androgen receptor-associated coregulator 267; Androgen receptor coactivator 267 kDa protein; Androgen receptor associated coregulator 267; ARA267
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| Gene Name |
NSD1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Preferentially methylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4 (in vitro). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. Histone methyltransferase.
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| BioChemical Class |
Methyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.1.1.43
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| Sequence |
MDQTCELPRRNCLLPFSNPVNLDAPEDKDSPFGNGQSNFSEPLNGCTMQLSTVSGTSQNA
YGQDSPSCYIPLRRLQDLASMINVEYLNGSADGSESFQDPEKSDSRAQTPIVCTSLSPGG PTALAMKQEPSCNNSPELQVKVTKTIKNGFLHFENFTCVDDADVDSEMDPEQPVTEDESI EEIFEETQTNATCNYETKSENGVKVAMGSEQDSTPESRHGAVKSPFLPLAPQTETQKNKQ RNEVDGSNEKAALLPAPFSLGDTNITIEEQLNSINLSFQDDPDSSTSTLGNMLELPGTSS SSTSQELPFCQPKKKSTPLKYEVGDLIWAKFKRRPWWPCRICSDPLINTHSKMKVSNRRP YRQYYVEAFGDPSERAWVAGKAIVMFEGRHQFEELPVLRRRGKQKEKGYRHKVPQKILSK WEASVGLAEQYDVPKGSKNRKCIPGSIKLDSEEDMPFEDCTNDPESEHDLLLNGCLKSLA FDSEHSADEKEKPCAKSRARKSSDNPKRTSVKKGHIQFEAHKDERRGKIPENLGLNFISG DISDTQASNELSRIANSLTGSNTAPGSFLFSSCGKNTAKKEFETSNGDSLLGLPEGALIS KCSREKNKPQRSLVCGSKVKLCYIGAGDEEKRSDSISICTTSDDGSSDLDPIEHSSESDN SVLEIPDAFDRTENMLSMQKNEKIKYSRFAATNTRVKAKQKPLISNSHTDHLMGCTKSAE PGTETSQVNLSDLKASTLVHKPQSDFTNDALSPKFNLSSSISSENSLIKGGAANQALLHS KSKQPKFRSIKCKHKENPVMAEPPVINEECSLKCCSSDTKGSPLASISKSGKVDGLKLLN NMHEKTRDSSDIETAVVKHVLSELKELSYRSLGEDVSDSGTSKPSKPLLFSSASSQNHIP IEPDYKFSTLLMMLKDMHDSKTKEQRLMTAQNLVSYRSPGRGDCSTNSPVGVSKVLVSGG STHNSEKKGDGTQNSANPSPSGGDSALSGELSASLPGLLSDKRDLPASGKSRSDCVTRRN CGRSKPSSKLRDAFSAQMVKNTVNRKALKTERKRKLNQLPSVTLDAVLQGDRERGGSLRG GAEDPSKEDPLQIMGHLTSEDGDHFSDVHFDSKVKQSDPGKISEKGLSFENGKGPELDSV MNSENDELNGVNQVVPKKRWQRLNQRRTKPRKRMNRFKEKENSECAFRVLLPSDPVQEGR DEFPEHRTPSASILEEPLTEQNHADCLDSAGPRLNVCDKSSASIGDMEKEPGIPSLTPQA ELPEPAVRSEKKRLRKPSKWLLEYTEEYDQIFAPKKKQKKVQEQVHKVSSRCEEESLLAR GRSSAQNKQVDENSLISTKEEPPVLEREAPFLEGPLAQSELGGGHAELPQLTLSVPVAPE VSPRPALESEELLVKTPGNYESKRQRKPTKKLLESNDLDPGFMPKKGDLGLSKKCYEAGH LENGITESCATSYSKDFGGGTTKIFDKPRKRKRQRHAAAKMQCKKVKNDDSSKEIPGSEG ELMPHRTATSPKETVEEGVEHDPGMPASKKMQGERGGGAALKENVCQNCEKLGELLLCEA QCCGAFHLECLGLTEMPRGKFICNECRTGIHTCFVCKQSGEDVKRCLLPLCGKFYHEECV QKYPPTVMQNKGFRCSLHICITCHAANPANVSASKGRLMRCVRCPVAYHANDFCLAAGSK ILASNSIICPNHFTPRRGCRNHEHVNVSWCFVCSEGGSLLCCDSCPAAFHRECLNIDIPE GNWYCNDCKAGKKPHYREIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFG SNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTYKKALQEAAARFEELKAQKELRQLQED RKNDKKPPPYKHIKVNRPIGRVQIFTADLSEIPRCNCKATDENPCGIDSECINRMLLYEC HPTVCPAGGRCQNQCFSKRQYPEVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEE CRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNHCCQPNCETQKWSVNGDTRV GLFALSDIKAGTELTFNYNLECLGNGKTVCKCGAPNCSGFLGVRPKNQPIATEEKSKKFK KKQQGKRRTQGEITKEREDECFSCGDAGQLVSCKKPGCPKVYHADCLNLTKRPAGKWECP WHQCDICGKEAASFCEMCPSSFCKQHREGMLFISKLDGRLSCTEHDPCGPNPLEPGEIRE YVPPPVPLPPGPSTHLAEQSTGMAAQAPKMSDKPPADTNQMLSLSKKALAGTCQRPLLPE RPLERTDSRPQPLDKVRDLAGSGTKSQSLVSSQRPLDRPPAVAGPRPQLSDKPSPVTSPS SSPSVRSQPLERPLGTADPRLDKSIGAASPRPQSLEKTSVPTGLRLPPPDRLLITSSPKP QTSDRPTDKPHASLSQRLPPPEKVLSAVVQTLVAKEKALRPVDQNTQSKNRAALVMDLID LTPRQKERAASPHQVTPQADEKMPVLESSSWPASKGLGHMPRAVEKGCVSDPLQTSGKAA APSEDPWQAVKSLTQARLLSQPPAKAFLYEPTTQASGRASAGAEQTPGPLSQSPGLVKQA KQMVGGQQLPALAAKSGQSFRSLGKAPASLPTEEKKLVTTEQSPWALGKASSRAGLWPIV AGQTLAQSCWSAGSTQTLAQTCWSLGRGQDPKPEQNTLPALNQAPSSHKCAESEQK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| 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 Human Histone-Lysine N-methyltransferase NSD1 SET domain in Complex with S-adenosyl-L-methionine | PDB:3OOI | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [2] |
| PDB Sequence |
SKELRQLQED
9 RKNDKKPPPY19 KHIKVNRPIG29 RVQIFTADLS39 EIPRCNCKAT49 DENPCGIDSE 59 CINRMLLYEC69 HPTVCPAGGR79 CQNQCFSKRQ89 YPEVEIFRTL99 QRGWGLRTKT 109 DIKKGEFVNE119 YVGELIDEEE129 CRARIRYAQE139 HDITNFYMLT149 LDKDRIIDAG 159 PKGNYARFMN169 HCCQPNCETQ179 KWSVNGDTRV189 GLFALSDIKA199 GTELTFNYNL 209 ECLGNGKTVC219 KCGAPNCSGF229 LG
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GLN100
4.737
ARG101
2.720
GLY102
3.716
TRP103
2.802
TYR120
4.174
THR143
2.923
ASN144
3.294
PHE145
3.020
TYR146
2.706
ARG166
3.252
PHE167
3.788
MET168
3.773
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 2-Azanyl-6-sulfanyl-1,3-benzothiazol-4-ol | Ligand Info | |||||
| Structure Description | NSD1 SET domain in complex with BT3 and SAM | PDB:6KQQ | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [3] |
| PDB Sequence |
NDKKPPPYKH
1872 IKVNRPIGRV1882 QIFTADLSEI1892 PRCNCKATDE1902 NPCGIDSECI1912 NRMLLYECHP 1922 TVCPAGGRCQ1932 NQCFSKRQYP1942 EVEIFRTLQR1952 GWGLRTKTDI1962 KKGEFVNEYV 1972 GELIDEEECR1982 ARIRYAQEHD1992 ITNFYMLTLD2002 KDRIIDAGPK2012 GNYARFMNHC 2022 CQPNCETQKW2032 SVNGDTRVGL2042 FALSDIKAGT2052 ELTFNYNLEC2062 LGNGKTVCKC 2072 GAPNCSGFLG2082 VRP
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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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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 | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Identification and characterization of androgen receptor associated coregulators in prostate cancer cells. J Biol Regul Homeost Agents. 2001 Apr-Jun;15(2):123-9. | |||||
| REF 2 | The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation. J Biol Chem. 2011 Mar 11;286(10):8361-8368. | |||||
| REF 3 | Covalent inhibition of NSD1 histone methyltransferase. Nat Chem Biol. 2020 Dec;16(12):1403-1410. | |||||
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