SET2 histone methyltransferase SET2 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: SET2
Official Full Name: histone methyltransferase SET2
Primary source: SGD:S000003704
Locus tag: YJL168C
See related: AllianceGenome:SGD:S000003704; FungiDB:YJL168C; VEuPathDB:YJL168C
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Also known as: EZL1; KMT3
Summary: Enables RNA binding activity and histone H3K36 methyltransferase activity. Involved in DNA-templated transcription; ascospore formation; and regulation of nucleobase-containing compound metabolic process. Acts upstream of or within transcription-coupled nucleotide-excision repair. Located in cytosol and nucleus. Human ortholog(s) of this gene implicated in autosomal dominant intellectual developmental disorder 70; clear cell renal cell carcinoma; gastrointestinal system cancer (multiple); lung disease (multiple); and malignant mesothelioma (multiple). Orthologous to human SETD2 (SET domain containing 2, histone lysine methyltransferase). [provided by Alliance of Genome Resources, Jul 2025]
Orthologs: all
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Genomic context

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See SET2 in Genome Data Viewer

Location:: chromosome: X

Exon count:: 1

Sequence:: Chromosome: X; NC_001142.9 (102227..104428, complement)

Chromosome X - NC_001142.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001142.9

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Site-specific Phosphorylation of Histone H3K36 Methyltransferase Set2p and Demethylase Jhd1p is Required for Stress Responses in Saccharomyces cerevisiae.
Title: Site-specific Phosphorylation of Histone H3K36 Methyltransferase Set2p and Demethylase Jhd1p is Required for Stress Responses in Saccharomyces cerevisiae.
An optogenetic switch for the Set2 methyltransferase provides evidence for transcription-dependent and -independent dynamics of H3K36 methylation.
Title: An optogenetic switch for the Set2 methyltransferase provides evidence for transcription-dependent and -independent dynamics of H3K36 methylation.
Core promoter activity contributes to chromatin-based regulation of internal cryptic promoters.
Title: Core promoter activity contributes to chromatin-based regulation of internal cryptic promoters.
Methylation of histone H3 at lysine 37 by Set1 and Set2 prevents spurious DNA replication.
Title: Methylation of histone H3 at lysine 37 by Set1 and Set2 prevents spurious DNA replication.
Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence.
Title: Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence.
The conserved elongation factor Spn1 is required for normal transcription, histone modifications, and splicing in Saccharomyces cerevisiae.
Title: The conserved elongation factor Spn1 is required for normal transcription, histone modifications, and splicing in Saccharomyces cerevisiae.
the histone H3K4 methyltransferase Set1, and the histone H3K36 methyltransferase Set2, control choice ofpolyadenylation site in Saccharomyces cerevisiae
Title: Regulation of alternative polyadenylation in the yeast Saccharomyces cerevisiae by histone H3K4 and H3K36 methyltransferases.
A conserved genetic interaction between Spt6 and Set2 regulates H3K36 methylation.
Title: A conserved genetic interaction between Spt6 and Set2 regulates H3K36 methylation.
Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity.
Title: Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity.
report that both methyltransferases can be UV cross-linked to RNA in vivo High-throughput sequencing of the bound RNAs revealed strong Set1 enrichment near the transcription start site, whereas Set2 was distributed along pre-mRNAs
Title: RNA Binding by Histone Methyltransferases Set1 and Set2.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K36 methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables histone H3K36 methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K36 methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone H3K36 methyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3K36 trimethyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	RCA inferred from Reviewed Computational Analysis more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA-templated transcription elongation	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA-templated transcription termination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ascospore formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in methylation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of antisense RNA transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of reciprocal meiotic recombination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated DNA replication initiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sno(s)RNA transcription	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within transcription-coupled nucleotide-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed

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

General protein information

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Preferred Names: histone methyltransferase SET2

NP_012367.2

EC 2.1.1.359

Histone methyltransferase with a role in transcriptional elongation; methylates H3 lysine 36 (H3K36), which suppresses incorporation of acetylated histones and signals for their deacetylation within transcribed genes; involved in transcription coupled-nucleotide excision repair; associates with C-terminal domain (CTD) of Rpo21p; H3K36me3 (trimethylation) requires Spt6p, proline 38 on H3, CTD of Rpo21p, Ctk1p, and C-terminal SRI domain of Ste2p; relocalizes to cytosol in response to hypoxia

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_001142.9 Reference assembly

Range

102227..104428 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001181601.2 → NP_012367.2 TPA: histone methyltransferase SET2

See identical proteins and their annotated locations for NP_012367.2

Status: REVIEWED

UniProtKB/Swiss-Prot

D6VW19, P46995

UniProtKB/TrEMBL

A6ZQG4, B3LPV5, B5VL18, C7GRZ6, G2WGK5

Conserved Domains (3) summary

smart00570
Location:64 → 119

AWS; associated with SET domains

COG2940
Location:215 → 695

SET; SET domain-containing protein (function unknown) [General function prediction only]

cd19172
Location:119 → 260

SET_SETD2; SET domain (including post-SET domain) found in SET domain-containing protein 2 (SETD2) and similar proteins