SETD2 [The Human Chemical-Genetic Interaction Map Project]

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======= SETD2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SETD2
  * **<color #00a2e8>Official Name</color>**: SET domain containing 2, histone lysine methyltransferase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=29072|29072]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9BYW2|Q9BYW2]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SETD2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SETD2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/612778|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). 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). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|WW|
|SET|
|SRI|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|histone H3-K36 trimethylation|
|cell migration involved in vasculogenesis|
|histone H3-K36 dimethylation|
|regulation of mRNA export from nucleus|
|regulation of protein localization to chromatin|
|regulation of ribonucleoprotein complex localization|
|histone methyltransferase activity (H3-K36 specific)|
|histone H3-K36 methylation|
|peptidyl-lysine monomethylation|
|regulation of RNA export from nucleus|
|peptidyl-lysine dimethylation|
|regulation of nucleobase-containing compound transport|
|coronary vasculature morphogenesis|
|histone-lysine N-methyltransferase activity|
|pericardium development|
|positive regulation of interferon-alpha production|
|protein-lysine N-methyltransferase activity|
|embryonic placenta morphogenesis|
|peptidyl-lysine trimethylation|
|regulation of interferon-alpha production|
|mismatch repair|
|regulation of protein export from nucleus|
|alpha-tubulin binding|
|endodermal cell differentiation|
|coronary vasculature development|
|embryonic cranial skeleton morphogenesis|
|regulation of double-strand break repair via homologous recombination|
|endoderm formation|
|cranial skeletal system development|
|vasculogenesis|
|mesoderm morphogenesis|
|response to type I interferon|
|histone lysine methylation|
|endoderm development|
|transcription elongation from RNA polymerase II promoter|
|positive regulation of type I interferon production|
|regulation of double-strand break repair|
|stem cell development|
|embryonic placenta development|
|peptidyl-lysine methylation|
|regulation of cytokinesis|
|DNA-templated transcription, elongation|
|neural tube closure|
|tube closure|
|histone methylation|
|embryonic skeletal system morphogenesis|
|primary neural tube formation|
|microtubule cytoskeleton organization involved in mitosis|
|regulation of DNA recombination|
|neural tube formation|
|regulation of nucleocytoplasmic transport|
|formation of primary germ layer|
|chromosome|
|embryonic epithelial tube formation|
|mesoderm development|
|regulation of DNA repair|
|embryonic skeletal system development|
|regulation of type I interferon production|
|epithelial tube formation|
|protein methylation|
|protein alkylation|
|morphogenesis of embryonic epithelium|
|tube formation|
|placenta development|
|nucleosome organization|
|stem cell differentiation|
|gastrulation|
|neural tube development|
|regulation of cell division|
|morphogenesis of a branching structure|
|defense response to virus|
|regulation of response to DNA damage stimulus|
|regulation of intracellular protein transport|
|skeletal system morphogenesis|
|protein-DNA complex subunit organization|
|macromolecule methylation|
|response to virus|
|embryonic organ morphogenesis|
|epithelial tube morphogenesis|
|methylation|
|peptidyl-lysine modification|
|angiogenesis|
|regulation of intracellular transport|
|regulation of DNA metabolic process|
|histone modification|
|covalent chromatin modification|
|in utero embryonic development|
|forebrain development|
|blood vessel morphogenesis|
|reproductive structure development|
|reproductive system development|
|morphogenesis of an epithelium|
|embryonic organ development|
|positive regulation of cytokine production|
|microtubule cytoskeleton organization|
|transcription by RNA polymerase II|
|blood vessel development|
|skeletal system development|
|DNA repair|
|vasculature development|
|cardiovascular system development|
|heart development|
|regulation of cellular protein localization|
|tissue morphogenesis|
|embryonic morphogenesis|
|mitotic cell cycle process|
|chordate embryonic development|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|embryo development ending in birth or egg hatching|
|RNA biosynthetic process|
|tube morphogenesis|
|developmental process involved in reproduction|
|microtubule-based process|
|mitotic cell cycle|
|regulation of cytokine production|
|chromatin organization|
|regulation of protein transport|
|regulation of cellular response to stress|
|regulation of peptide transport|
|brain development|
|DNA metabolic process|
|regulation of establishment of protein localization|
|regulation of cell cycle process|
|innate immune response|
|cellular response to DNA damage stimulus|
|head development|
|tube development|
|circulatory system development|
|peptidyl-amino acid modification|
|anatomical structure formation involved in morphogenesis|
|regulation of cellular localization|
|defense response to other organism|
|animal organ morphogenesis|
|cell migration|
|embryo development|
|central nervous system development|
|cell cycle process|
|regulation of protein localization|
|chromosome organization|
|cell motility|
|localization of cell|
|immune effector process|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|cytoskeleton organization|
|epithelium development|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|regulation of cell cycle|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|cell cycle|
|defense response|
|reproductive process|
|reproduction|
|regulation of response to stress|
|movement of cell or subcellular component|
|cellular nitrogen compound biosynthetic process|
|cell development|
|RNA metabolic process|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|positive regulation of multicellular organismal process|
|tissue development|
|macromolecule biosynthetic process|
|protein-containing complex subunit organization|
|regulation of transport|
|immune response|
|gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp291|LLY-284 2.6μM R06 exp291]]|-1.85|
|[[:results:exp36|TRAIL 50ng/ml R00 exp36]]|1.72|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|1.73|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|1.89|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|2.05|
|[[:results:exp423|Zebularine 20μM R07 exp423]]|2.11|
|[[:results:exp66|BI-D1870 3.15μM R02 exp66]]|2.21|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rrm1|RRM1]]|0.438|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 15/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|1/28|
|blood|0/28|
|bone|1/25|
|breast|1/33|
|central nervous system|1/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|1/21|
|liver|0/20|
|lung|1/75|
|lymphocyte|2/14|
|ovary|0/26|
|pancreas|1/24|
|peripheral nervous system|1/16|
|plasma cell|1/15|
|prostate|0/1|
|skin|1/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|1/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1381
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.82 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SETD2 Expression in NALM6 Cells: 7.82'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>