SETDB1 (SET domain bifurcated histone lysine methyltransferase 1)

Gene

• Entrez ID: 9869
• Gene name: SET domain bifurcated histone lysine methyltransferase 1
• Gene symbol: SETDB1
• Synonyms: ESET, H3-K9-HMTase4, KG1T, KMT1E, TDRD21
• Chromosome: 1
• Chromosome location: 1q21.3
• Summary: This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription d

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT048947	hsa-miR-92a-3p	CLASH	23622248
MIRT045818	hsa-miR-152-3p	CLASH	23622248
MIRT043011	hsa-miR-324-3p	CLASH	23622248
MIRT038516	hsa-miR-296-3p	CLASH	23622248
MIRT052718	hsa-miR-1260b	CLASH	23622248
MIRT439145	hsa-let-7c-5p	3'LIFE	25074381
MIRT439145	hsa-let-7c-5p	3'LIFE	25074381
MIRT059476	hsa-miR-29a-3p	ChIP-seq, Immunohistochemistry, Luciferase reporter assay, Next Generation Sequencing (NGS), qRT-PCR, Western blot	26481868
MIRT059476	hsa-miR-29a-3p	ChIP-seq, Immunohistochemistry, Luciferase reporter assay, Next Generation Sequencing (NGS), qRT-PCR, Western blot	26481868
MIRT1340761	hsa-miR-1972	CLIP-seq
MIRT1340762	hsa-miR-29a	CLIP-seq
MIRT1340763	hsa-miR-29b	CLIP-seq
MIRT1340764	hsa-miR-29c	CLIP-seq
MIRT1340765	hsa-miR-3689a-3p	CLIP-seq
MIRT1340766	hsa-miR-3689c	CLIP-seq
MIRT1340767	hsa-miR-4650-5p	CLIP-seq
MIRT1340768	hsa-miR-4722-3p	CLIP-seq
MIRT1340769	hsa-miR-4728-5p	CLIP-seq
MIRT1340770	hsa-miR-4763-5p	CLIP-seq
MIRT1340771	hsa-miR-621	CLIP-seq
MIRT1340772	hsa-miR-1296	CLIP-seq
MIRT1340761	hsa-miR-1972	CLIP-seq
MIRT1340773	hsa-miR-198	CLIP-seq
MIRT1340762	hsa-miR-29a	CLIP-seq
MIRT1340763	hsa-miR-29b	CLIP-seq
MIRT1340764	hsa-miR-29c	CLIP-seq
MIRT1340774	hsa-miR-3154	CLIP-seq
MIRT1340775	hsa-miR-3202	CLIP-seq
MIRT1340776	hsa-miR-3663-5p	CLIP-seq
MIRT1340777	hsa-miR-4533	CLIP-seq
MIRT1340767	hsa-miR-4650-5p	CLIP-seq
MIRT1340778	hsa-miR-4713-3p	CLIP-seq
MIRT1340768	hsa-miR-4722-3p	CLIP-seq
MIRT1340770	hsa-miR-4763-5p	CLIP-seq
MIRT1340771	hsa-miR-621	CLIP-seq
MIRT2100812	hsa-miR-1200	CLIP-seq
MIRT2100813	hsa-miR-3065-5p	CLIP-seq
MIRT2100814	hsa-miR-3130-5p	CLIP-seq
MIRT2100815	hsa-miR-3667-5p	CLIP-seq
MIRT2100816	hsa-miR-421	CLIP-seq
MIRT2100817	hsa-miR-4324	CLIP-seq
MIRT2100818	hsa-miR-4482	CLIP-seq
MIRT2100819	hsa-miR-544b	CLIP-seq
MIRT2100820	hsa-miR-7	CLIP-seq
MIRT2100821	hsa-miR-873	CLIP-seq
MIRT2325356	hsa-miR-4723-5p	CLIP-seq
MIRT2100821	hsa-miR-873	CLIP-seq
MIRT1340772	hsa-miR-1296	CLIP-seq
MIRT2459173	hsa-miR-4695-3p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
DNMT3A	Unknown	16682412
MBD1	Repression	17066076
MBD1	Unknown	15327775

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003677	Function	DNA binding	IEA
GO:0003682	Function	Chromatin binding	IDA	27029610
GO:0005515	Function	Protein binding	IPI	16682412, 17577629, 20871592, 21170338, 26022416, 27029610, 27732843, 29774127
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IMP	27732843
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0005737	Component	Cytoplasm	IMP	27732843
GO:0007265	Process	Ras protein signal transduction	IMP	24623306
GO:0008270	Function	Zinc ion binding	IEA
GO:0010629	Process	Negative regulation of gene expression	IBA	21873635
GO:0018024	Function	Histone-lysine N-methyltransferase activity	IDA	14536086
GO:0033273	Process	Response to vitamin	IEA
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0045471	Process	Response to ethanol	IEA
GO:0045869	Process	Negative regulation of single stranded viral RNA replication via double stranded DNA intermediate	ISS
GO:0046974	Function	Histone methyltransferase activity (H3-K9 specific)	IBA	21873635
GO:0046974	Function	Histone methyltransferase activity (H3-K9 specific)	IDA	14536086
GO:0051567	Process	Histone H3-K9 methylation	IBA	21873635
GO:0070828	Process	Heterochromatin organization	IBA	21873635
GO:0090309	Process	Positive regulation of DNA methylation-dependent heterochromatin assembly	IBA	21873635
GO:0090309	Process	Positive regulation of DNA methylation-dependent heterochromatin assembly	IMP	24623306, 27732843
GO:0090309	Process	Positive regulation of DNA methylation-dependent heterochromatin assembly	ISS
GO:1990841	Function	Promoter-specific chromatin binding	IDA	24623306

Other IDs

• MIM: 604396
• HGNC: 10761
• e!Ensembl: ENSG00000143379

Protein

• UniProt ID: Q15047
• Protein name: Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (Histone H3-K9 methyltransferase 4) (H3-K9-HMTase 4) (Lysine N-methyltransferase 1E) (SET domain bifurcated 1)
• Protein function: Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated hist
• PDB: 3DLM, 4X3S, 5KCH, 5KCO, 5KE2, 5KE3, 5KH6, 5QT1, 5QT2, 6AU2, 6AU3, 6BHD, 6BHE, 6BHG, 6BHH, 6BHI, 6BPI, 7C9N, 7CAJ, 7CD9, 7CJT, 8G5E, 8IYA, 8UWP, 9CUW, 9CUX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF18300	DUF5604	193 → 250	Domain of unknown function (DUF5604)	Domain
  PF18359	TUDOR_5	258 → 309	Histone methyltransferase Tudor domain 1	Domain
  PF18358	Tudor_4	348 → 397	Histone methyltransferase Tudor domain	Domain
  PF01429	MBD	594 → 668	Methyl-CpG binding domain	Domain
  PF05033	Pre-SET	682 → 795	Pre-SET motif	Family
  PF00856	SET	814 → 1266	SET domain	Family

• Sequence:

  MSSLPGCIGLDAATATVESEEIAELQQAVVEELGISMEELRHFIDEELEKMDCVQQRKKQ
  LAELETWVIQKESEVAHVDQLFDDASRAVTNCESLVKDFYSKLGLQYRDSSSEDESSRPT
  EIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDL
  HKGTLSQMSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGPGKKYKVKFDNKGKS
  LLSGNHIAYDYHPPADKLYVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDG
  YASYVTQSELYPICRPLKKTWEDIEDISCRDFIEEYVTAYPNRPMVLLKSGQLIKTEWEG
  TWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASALEKKQGQLRTRP
  NMGAVRSKGPVVQYTQDLTGTGTQFKPVEPPQPTAPPAPPFPPAPPLSPQAGDSDLESQL
  AQSRKQVAKKSTSFRPGSVGSGHSSPTSPALSENVSGGKPGINQTYRSPLGSTASAPAPS
  ALPAPPAPPVFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRVRPMRNEQYRGKNPL
  LVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCL
  DPYVLVDRKFQPYKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFIN
  TGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQINPNSGYQYKRLEECLPTGVYE
  CNKRCKCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDD
  FADKEGLEMGDEYFANLDHIESVENFKEGYESDAPCSSDSSGVDLKDQEDGNSGTEDPEE
  SNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENGLSETTSKDSHPPDLGPPHIPVP
  PSIPVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSHSSFKTNEGGEGRAGGSRME
  AEKASTSGLGIKDEGDIKQAKKEDTDDRNKMSVVTESSRNYGYNPSPVKPEGLRRPPSKT
  SMHQSRRLMASAQSNPDDVLTLSSSTESEGESGTSRKPTAGQTSATAVDSDDIQTISSGS
  EGDDFEDKKNMTGPMKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQF
  YDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTE
  LTWDYNYEVGSVEGKELLCCCGAIECRGRLL

• Sequence length: 1291

Pathways

KEGG:

Lysine degradation
Metabolic pathways
Signaling pathways regulating pluripotency of stem cells

Reactome:

PKMTs methylate histone lysines

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Melanoma	melanoma	rs121913315, rs121913323, rs137853080, rs137853081, rs121909232, rs121913388, rs104894094, rs1563902635, rs104894095, rs104894097, rs104894098, rs104894099, rs104894109, rs137854599, rs11547328, rs104894340, rs398123152, rs587780668, rs587782083, rs587782206, rs587782792, rs180177042, rs121913381, rs730881675, rs730881674, rs730881677, rs730881673, rs1800586, rs768966657, rs587778189, rs786204195, rs121913321, rs45476696, rs864622636, rs864622263, rs869025340, rs876660436, rs876658534, rs876658556, rs878853647, rs878853644, rs878853650, rs886041162, rs121913389, rs1057519852, rs121913384, rs121913387, rs1060501266, rs1060501263, rs1060501262, rs749714198, rs1060501265, rs559848002, rs1064794292, rs1131691187, rs1131691186, rs199907548, rs1554654052, rs1554656411, rs1554656624, rs1554653915, rs1554653956, rs1554656253, rs1554654224, rs754806883, rs1057520039, rs1563889584, rs1563889685, rs1287464120, rs1563888944, rs1563892715, rs1563889847, rs141798398, rs1587332338, rs1587340291, rs11552823, rs561034503, rs138677674, rs1819962958, rs1820531050	21983785
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	29610475
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	23815974

Unknown
Disease name	Disease term	dbSNP ID	References
Anhedonia	Anhedonia		20505083
Malignant mesothelioma	Malignant mesothelioma		26928227
Prostatic neoplasms	Prostatic Neoplasms		29610475