Tchem SUV39H1 Histone-lysine N-methyltransferase SUV39H1

Protein Summary

Description

Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. Also weakly methylates histone H1 (in vitro). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation. This gene encodes an evolutionarily-conserved protein containing an N-terminal chromodomain and a C-terminal SET domain. The encoded protein is a histone methyltransferase that trimethylates lysine 9 of histone H3, which results in transcriptional gene silencing. Loss of function of this gene disrupts heterochromatin formation and may cause chromosome instability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Uniprot Accession IDs

• O43463
• B2R6E8
• B4DST0
• Q53G60
• Q6FHK6

Gene Name

• SUV39H1

Ensembl ID

• ENST00000337852
• ENSP00000337976
• ENSG00000101945
• ENST00000376687
• ENSP00000365877

Symbol

• KMT1A
• SUV39H
• MG44
• KMT1A
• SUV39H
• H3-K9-HMTase 1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.99
molecular function	0.95
histone modification site profile	0.89
biological process	0.87
cellular component	0.73

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 208.82   (req: < 5)

Gene RIFs: 49   (req: <= 3)

Antibodies: 377   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 208.82   (req: >= 5)

Gene RIFs: 49   (req: > 3)

Antibodies: 377   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 22

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (4)

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1 – 4 of 4

CHEMBL2172426

SUV39H1Tchem Epigenetic

IC50 : 6.28

CHEMBL331627

SUV39H1Tchem Epigenetic

IC50 : 6.58

CHEMBL499593

SUV39H1Tchem Epigenetic

IC50 : 7.18

CHEMBL1089316

SUV39H1Tchem Epigenetic

IC50 : 6.1

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	suppressor of variegation 3-9 homolog 1		107971148
Macaque	suppressor of variegation 3-9 homolog 1		711040
Mouse	suppressor of variegation 3-9 1	MGI:1099440	20937
Rat	suppressor of variegation 3-9 homolog 1 (Drosophila)-like 1	RGD:1565028	302553
Dog	suppressor of variegation 3-9 homolog 1	VGNC:47001	491868

Species	Name	OMA	EggNOG	Inparanoid
Chimp	suppressor of variegation 3-9 homolog 1
Macaque	suppressor of variegation 3-9 homolog 1
Mouse	suppressor of variegation 3-9 1
Rat	suppressor of variegation 3-9 homolog 1 (Drosophila)-like 1
Dog	suppressor of variegation 3-9 homolog 1

Protein Structure (1 Structure, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-O43463-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 1 of 1

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (14)

Reactome (7)

KEGG (1)

PathwayCommons (1)

WikiPathways (5)

Chromatin modifying enzymes (R-HSA-3247509)

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5

1 – 5 of 7

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Chromatin modifying enzymes	238 targets	R-HSA-3247509
Reactome	Chromatin organization	238 targets	R-HSA-4839726
Reactome	Epigenetic regulation of gene expression	118 targets	R-HSA-212165
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Negative epigenetic regulation of rRNA expression	79 targets	R-HSA-5250941

Name	Explore in Pharos	Explore in Source
Chromatin modifying enzymes	238 targets	R-HSA-3247509
Chromatin organization	238 targets	R-HSA-4839726
Epigenetic regulation of gene expression	118 targets	R-HSA-212165
Gene expression (Transcription)	1452 targets	R-HSA-74160
Negative epigenetic regulation of rRNA expression	79 targets	R-HSA-5250941

Gene Ontology Terms (30)

Functions (8)

Components (8)

Processes (14)

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Items per page:

10

1 – 8 of 8

GO Term	Evidence	Assigned by
histone methyltransferase activity	Inferred from Direct Assay (IDA)	UniProtKB
histone methyltransferase activity (H3-K9 specific)	Inferred from Direct Assay (IDA)	UniProtKB
histone-lysine N-methyltransferase activity	Inferred from Direct Assay (IDA)	UniProtKB
S-adenosylmethionine-dependent methyltransferase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein N-terminus binding	Inferred from Physical Interaction (IPI)	UniProtKB
transcription regulatory region sequence-specific DNA binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
chromatin binding	Traceable Author Statement (TAS)	ProtInc
zinc ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Protein-Protein Interactions (253)

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1 – 10 of 253

• See Interactions on String-DB

MAGEC1

Tbio

Novelty: 0.01123023

p_int: 0.999996121

p_wrong: 0.000003879

Score: 0.416

Data Source: BioPlex,STRINGDB

USP34

Tbio

Family: Enzyme

Novelty: 0.16444192

p_int: 0.999882384

p_ni: 0.000117616

Score: 0.188

Data Source: BioPlex,STRINGDB

ATF7IP

Tbio

Novelty: 0.04269323

p_int: 0.999566597

p_ni: 0.000433402

p_wrong: 1e-9

Score: 0.752

Data Source: BioPlex,STRINGDB

MCMBP

Tbio

Novelty: 0.13330215

p_int: 0.999544235

p_ni: 0.000455765

Score: 0.16

Data Source: BioPlex,STRINGDB

ENKD1

Tdark

Novelty: 21.40077406

p_int: 0.999287533

p_ni: 0.000001292

p_wrong: 0.000711176

Score: 0.427

Data Source: BioPlex,STRINGDB

CBX5

Tbio

Family: Epigenetic

Novelty: 0.00653413

p_int: 0.998288402

p_ni: 0.001711598

Score: 0.921

Data Source: BioPlex,STRINGDB

ZNF644

Tbio

Family: TF

Novelty: 0.12816167

p_int: 0.997215112

p_ni: 0.002784888

Score: 0.234

Data Source: BioPlex,STRINGDB

USP24

Tbio

Family: Enzyme

Novelty: 0.07281326

p_int: 0.996884894

p_ni: 0.003115104

p_wrong: 2e-9

Score: 0.32

Data Source: BioPlex,STRINGDB

SETDB1

Tbio

Family: TF; Epigenetic

Novelty: 0.00609294

p_int: 0.996111025

p_ni: 0.003888964

p_wrong: 1.1e-8

Score: 0.589

Data Source: BioPlex,STRINGDB

MID1IP1

Tbio

Novelty: 0.11443752

p_int: 0.994031838

p_ni: 0.005352799

p_wrong: 0.000615362

Score: 0.187

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  208.82

PubMed score by year

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PubTator Score  139.75

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Amino Acid Sequence

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Protein Sequence

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3D-structure
Acetylation
Alternative splicing
Biological rhythms
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hematopoietic system phenotype
immune system phenotype
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