SETD2

Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein belonging to a class of huntingtin interacting proteins characterized by WW motifs. This protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II. [provided by RefSeq, Aug 2008]

SET Domain Containing 2

Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439).
It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550).
Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity).
Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844).
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 (PubMed:23622243).
Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002).
Acts as a tumor suppressor (PubMed:24509477).
H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772).
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 (PubMed:21792193).
Required during angiogenesis (By similarity).
Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity).
In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426).
Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565).
Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426).
(Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.

Biological Process angiogenesisIEA:Ensembl
Biological Process cell migration involved in vasculogenesisIEA:Ensembl
Biological Process coronary vasculature morphogenesisIEA:Ensembl
Biological Process defense response to virusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process embryonic cranial skeleton morphogenesisIEA:Ensembl
Biological Process embryonic placenta morphogenesisIEA:Ensembl
Biological Process endodermal cell differentiationISS:UniProtKB
Biological Process forebrain developmentIEA:Ensembl
Biological Process histone H3-K36 dimethylationManual Assertion Based On ExperimentIDA:HGNC
Biological Process histone H3-K36 trimethylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process mesoderm morphogenesisIEA:Ensembl
Biological Process microtubule cytoskeleton organization involved in mitosisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process mismatch repairManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process morphogenesis of a branching structureIEA:Ensembl
Biological Process neural tube closureIEA:Ensembl
Biological Process nucleosome organizationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process peptidyl-lysine monomethylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process peptidyl-lysine trimethylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process pericardium developmentIEA:Ensembl
Biological Process positive regulation of interferon-alpha productionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of cytokinesisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of DNA-templated transcriptionIEA:InterPro
Biological Process regulation of double-strand break repair via homologous recombinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of gene expressionManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of mRNA export from nucleusManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of protein localization to chromatinManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process response to type I interferonManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process stem cell developmentIEA:Ensembl
Biological Process stem cell differentiationISS:UniProtKB
Biological Process transcription elongation by RNA polymerase II promoterManual Assertion Based On ExperimentIMP:UniProtKB

Nucleus
Chromosome

Renal cell carcinoma (RCC):
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.
Luscan-Lumish syndrome (LLS):
An autosomal dominant syndrome with a variable phenotype. Clinical features include macrocephaly, distinctive facial appearance, postnatal overgrowth, various degrees of learning difficulties, autism spectrum disorder, and intellectual disability.
Leukemia, acute lymphoblastic (ALL):
A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes.
Leukemia, acute myelogenous (AML):
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.

May be automethylated.