SETDB2 SET domain bifurcated histone lysine methyltransferase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SETDB2provided by HGNC
Official Full Name: SET domain bifurcated histone lysine methyltransferase 2provided by HGNC
Primary source: HGNC:HGNC:20263
See related: Ensembl:ENSG00000136169 MIM:607865; AllianceGenome:HGNC:20263
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CLLD8; CLLL8; KMT1F; C13orf4
Summary: This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
Expression: Ubiquitous expression in testis (RPKM 6.5), lymph node (RPKM 5.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 13q14.2

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (49444274..49495003)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (48662906..48713649)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (50018410..50069139)

Chromosome 13 - NC_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46.
Title: Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46.
Histone lysine methyltransferase SETDB2 suppresses NRF2 to restrict tumor progression and modulates chemotherapy sensitivity in lung adenocarcinoma.
Title: Histone lysine methyltransferase SETDB2 suppresses NRF2 to restrict tumor progression and modulates chemotherapy sensitivity in lung adenocarcinoma.
Coronavirus induces diabetic macrophage-mediated inflammation via SETDB2.
Title: Coronavirus induces diabetic macrophage-mediated inflammation via SETDB2.
A number of converging phenotypes outline a stress-responsive mechanism for SETDB1 and SETDB2 activation and subsequent increased tumor survival, providing novel insights into epigenetic biology. [review]
Title: Emerging roles of H3K9me3, SETDB1 and SETDB2 in therapy-induced cellular reprogramming.
Setdb2 regulates macrophage plasticity during normal and pathologic wound repair
Title: The Histone Methyltransferase Setdb2 Modulates Macrophage Phenotype and Uric Acid Production in Diabetic Wound Repair.
an oncogenic role for the protein lysine methyltransferase SETDB2 in leukemia pathogenesis. It is overexpressed in pre-BCR(+) ALL and required for their maintenance in vitro and in vivo. SETDB2 expression is maintained as a direct target gene of the chimeric transcription factor E2A-PBX1 in a subset of ALL and suppresses expression of the cell-cycle inhibitor CDKN2C through histone H3K9 tri-methylation
Title: SETDB2 Links E2A-PBX1 to Cell-Cycle Dysregulation in Acute Leukemia through CDKN2C Repression.
SETDB2 transcripts were overexpressed in renal cell tumor subtypes and associated with prognosis.
Title: SETDB2 and RIOX2 are differentially expressed among renal cell tumor subtypes, associating with prognosis and metastization.
Findings implicate SET domain bifurcated 2 (SETDB2) locus in the longstanding links of handedness with asthma and other atopic diseases.
Title: The SETDB2 locus: evidence for a genetic link between handedness and atopic disease.
our data indicated that SETDB2 is often over-expressed in gastric cancer tissues and cell lines and SETDB2 overexpression significantly accelerated cell proliferation, migration and invasion of gastric cancer cells
Title: Oncogenic roles of the SETDB2 histone methyltransferase in gastric cancer.
the relation of genetic variation in SETDB2-and its paralogue SETDB1-with different handedness phenotypes in 950 healthy adult participants, was investigated.
Title: Left-Right Axis Differentiation and Functional Lateralization: a Haplotype in the Methyltransferase Encoding Gene SETDB2 Might Mediate Handedness in Healthy Adults.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat associates with SETDB2 in vitro	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH93583 (e-PCR)
- UniSTS:92435

RH48846 (e-PCR)
- UniSTS:23121

SHGC-67307 (e-PCR)
- UniSTS:89991

RH69241 (e-PCR)
- UniSTS:40916

STS-AA039375 (e-PCR)
- UniSTS:46833

Readthrough SETDB2-PHF11

Readthrough gene: SETDB2-PHF11, Included gene: PHF11

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables histone H3 methyltransferase activity	TAS Traceable Author Statement more info
enables histone H3K9 methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables histone H3K9 methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K9 monomethyltransferase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart looping	ISS Inferred from Sequence or Structural Similarity more info
involved_in heterochromatin organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in left/right axis specification	ISS Inferred from Sequence or Structural Similarity more info
involved_in methylation	IEA Inferred from Electronic Annotation more info
involved_in mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of DNA methylation-dependent heterochromatin formation	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: histone-lysine N-methyltransferase SETDB2

Names: SET domain bifurcated 2; chronic lymphocytic leukemia deletion region gene 8 protein; lysine N-methyltransferase 1F

NP_001153780.1

EC 2.1.1.366

NP_001307628.1

EC 2.1.1.366

NP_001380904.1

EC 2.1.1.366

NP_001380905.1

EC 2.1.1.366

NP_001380906.1

EC 2.1.1.366

NP_001380907.1

EC 2.1.1.366

NP_001380908.1

EC 2.1.1.366

NP_001380909.1

EC 2.1.1.366

NP_114121.2

EC 2.1.1.366

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001160308.3 → NP_001153780.1 histone-lysine N-methyltransferase SETDB2 isoform b

See identical proteins and their annotated locations for NP_001153780.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The encoded isoform (b) is shorter than isoform a.

Source sequence(s)

AL136218, AL139321, AW297242, BC028202, BC047434, DB164537

Consensus CDS

CCDS53868.1

UniProtKB/TrEMBL

A0A087WYZ9

Related

ENSP00000482240.2, ENST00000611815.2

Conserved Domains (3) summary

smart00317
Location:618 → 684

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

cd01395
Location:152 → 212

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

pfam05033
Location:234 → 347

Pre-SET; Pre-SET motif
NM_001320699.2 → NP_001307628.1 histone-lysine N-methyltransferase SETDB2 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate exon in the 5' region and initiates translation at downstream start codon compared to variant 1. The encoded isoform (c) has a shorter N-terminus than isoform a.

Source sequence(s)

AL136218, AL139321

UniProtKB/TrEMBL

A0A087WYZ9

Conserved Domains (3) summary

smart00317
Location:618 → 684

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

cd01395
Location:152 → 212

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

pfam05033
Location:234 → 347

Pre-SET; Pre-SET motif
NM_001393975.1 → NP_001380904.1 histone-lysine N-methyltransferase SETDB2 isoform d

Status: REVIEWED

Source sequence(s)

AL136218, AL139321

UniProtKB/TrEMBL

A0A087WYZ9

Conserved Domains (2) summary

cd01395
Location:140 → 200

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

cd10523
Location:198 → 694

SET_SETDB2; SET domain (including pre-SET and post-SET domains) found in SET domain bifurcated 2 (SETDB2) and similar proteins
NM_001393976.1 → NP_001380905.1 histone-lysine N-methyltransferase SETDB2 isoform e

Status: REVIEWED

Source sequence(s)

AL136218, AL139321

Conserved Domains (2) summary

cd01395
Location:152 → 212

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

cd10523
Location:210 → 561

SET_SETDB2; SET domain (including pre-SET and post-SET domains) found in SET domain bifurcated 2 (SETDB2) and similar proteins
NM_001393977.1 → NP_001380906.1 histone-lysine N-methyltransferase SETDB2 isoform f

Status: REVIEWED

Source sequence(s)

AL136218

Conserved Domains (2) summary

cd01395
Location:164 → 224

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

cl40432
Location:222 → 433

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily
NM_001393978.1 → NP_001380907.1 histone-lysine N-methyltransferase SETDB2 isoform g

Status: REVIEWED

Source sequence(s)

AL136218, AL139321

Conserved Domains (2) summary

cd01395
Location:140 → 200

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

cd10523
Location:198 → 549

SET_SETDB2; SET domain (including pre-SET and post-SET domains) found in SET domain bifurcated 2 (SETDB2) and similar proteins
NM_001393979.1 → NP_001380908.1 histone-lysine N-methyltransferase SETDB2 isoform h

Status: REVIEWED

Source sequence(s)

AL136218

Conserved Domains (2) summary

cd01395
Location:152 → 212

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

cl40432
Location:210 → 421

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily
NM_001393980.1 → NP_001380909.1 histone-lysine N-methyltransferase SETDB2 isoform i

Status: REVIEWED

Source sequence(s)

AL136218

Conserved Domains (2) summary

cd01395
Location:140 → 200

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

cl40432
Location:198 → 409

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily
NM_031915.3 → NP_114121.2 histone-lysine N-methyltransferase SETDB2 isoform a

See identical proteins and their annotated locations for NP_114121.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AF334407, AL136218, AL139321, AW297242, BC028202, DB164537

Consensus CDS

CCDS9417.1

UniProtKB/Swiss-Prot

Q5TC65, Q5TC66, Q5W0A7, Q659A7, Q86UD6, Q96AI6, Q96T68

UniProtKB/TrEMBL

A0A087WYZ9

Related

ENSP00000346175.5, ENST00000354234.8

Conserved Domains (3) summary

smart00317
Location:630 → 696

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

cd01395
Location:164 → 224

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...

pfam05033
Location:246 → 359

Pre-SET; Pre-SET motif