InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SETD2

Summary

InnateDB Protein

IDBP-293915.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SETD2

Protein Name

SET domain containing 2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000386759

InnateDB Gene

IDBG-31184 (SETD2)

Protein Structure

UniProt Annotation

Function

Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation. Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A. Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction. H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A. H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase. Required during angiogenesis. Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269PubMed:16118227, ECO:0000269PubMed:19141475, ECO:0000269PubMed:21526191, ECO:0000269PubMed:21792193, ECO:0000269PubMed:23043551, ECO:0000269PubMed:23325844, ECO:0000269PubMed:23622243}.

Subcellular Localization

Nucleus {ECO:0000305}. Chromosome {ECO:0000305}.

Disease Associations

Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. {ECO:0000269PubMed:20054297, ECO:0000269PubMed:23622243, ECO:0000269PubMed:23792563}. Note=The disease may be caused by mutations affecting the gene represented in this entry. Defects of SETD2 are associated with loss of DNA methylation at non-promoter regions (PubMed:23792563). {ECO:0000269PubMed:23792563}.

Tissue Specificity

Ubiquitously expressed. {ECO:0000269PubMed:11461154}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 18 experimentally validated interaction(s) in this database.

Experimentally validated
Total	18 [view]
Protein-Protein	18 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0018024	histone-lysine N-methyltransferase activity

Biological Process

GO:0001525	angiogenesis
GO:0001570	vasculogenesis
GO:0001763	morphogenesis of a branching structure
GO:0001843	neural tube closure
GO:0006298	mismatch repair
GO:0006355	regulation of transcription, DNA-templated
GO:0006368	transcription elongation from RNA polymerase II promoter
GO:0010452	histone H3-K36 methylation
GO:0010468	regulation of gene expression
GO:0010793	regulation of mRNA export from nucleus
GO:0018023	peptidyl-lysine trimethylation
GO:0030900	forebrain development
GO:0034728	nucleosome organization
GO:0034968	histone lysine methylation
GO:0035441	cell migration involved in vasculogenesis
GO:0048332	mesoderm morphogenesis
GO:0048568	embryonic organ development
GO:0048701	embryonic cranial skeleton morphogenesis
GO:0048864	stem cell development
GO:0060039	pericardium development
GO:0060669	embryonic placenta morphogenesis
GO:0060977	coronary vasculature morphogenesis
GO:0097198	histone H3-K36 trimethylation

Cellular Component

GO:0005634	nucleus
GO:0005694	chromosome

Protein Structure and Domains

PDB ID

InterPro

IPR001202 WW domain
IPR001214 SET domain
IPR003616 Post-SET domain
IPR006560 AWS domain
IPR009078 Ferritin-like superfamily
IPR013257 SRI, Set2 Rpb1 interacting

PFAM

PF00397
PF00856
PF08236

PRINTS

PIRSF

SMART

SM00456
SM00317
SM00508
SM00570

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9BYW2