SETD2
entrez
29072
canonical
uniprot
Q9BYW2
canonical
ensembl
ENSG00000181555
resolver
ensp
ENSP00000386759
resolver
ensp
ENSP00000491413
resolver
ensp
ENSP00000509568
resolver
enst
ENST00000638947
resolver
genesymbol
SETD2
resolver
genesymbol_syn
HIF1
resolver
genesymbol_syn
HYPB
resolver
genesymbol_syn
KIAA1732
resolver
genesymbol_syn
KMT3A
resolver
genesymbol_syn
SET2
resolver
hgnc
HGNC:18420
resolver
uniprot
A0A1W2PPX9
resolver
uniprot
O75397
resolver
uniprot
O75405
resolver
uniprot
Q17RW8
resolver
uniprot
Q5BKS9
resolver
uniprot
Q5QGN2
resolver
uniprot
Q69YI5
resolver
uniprot
Q6IN64
resolver
uniprot
Q6ZN53
resolver
uniprot
Q6ZS25
resolver
uniprot
Q8N3R0
resolver
uniprot
Q8TCN0
resolver
uniprot
Q9C0D1
resolver
uniprot
Q9H696
resolver
uniprot
Q9NZW9
resolver
uniprot_entry
A0A1W2PPX9_HUMAN
resolver
uniprot_entry
SETD2_HUMAN
resolver
uniprot_sec
O75397
resolver
uniprot_sec
O75405
resolver
uniprot_sec
Q17RW8
resolver
uniprot_sec
Q5BKS9
resolver
uniprot_sec
Q5QGN2
resolver
uniprot_sec
Q69YI5
resolver
uniprot_sec
Q6IN64
resolver
uniprot_sec
Q6ZN53
resolver
uniprot_sec
Q6ZS25
resolver
uniprot_sec
Q8N3R0
resolver
uniprot_sec
Q8TCN0
resolver
uniprot_sec
Q9C0D1
resolver
uniprot_sec
Q9H696
resolver
uniprot_sec
Q9NZW9
resolver
activity_regulation
ACTIVITY REGULATION: Specifically inhibited by sinefungin derivatives. N-propyl sinefungin (Pr-SNF) interacts preferentially with SETD2. {ECO:0000269|PubMed:23043551}.
uniprot
proteins
amino_acid_sequence
MKQLQPQPPPKMGDFYDPEHPTPEEEENEAKIENVQKTGFIKGPMFKGVASSRFLPKGTKTKVNLEEQGRQKVSFSFSLTKKTLQNRFLTALGNEKQSDTPNPPAVPLQVDSTPKMKMEIGDTLSTAEESSPPKSRVELGKIHFKKHLLHVTSRPLLATTTAVASPPTHAAPLPAVIAESTTVDSPPSSPPPPPPPAQATTLSSPAPVTEPVALPHTPITVLMAAPVPLPVDVAVRSLKEPPIIIVPESLEADTKQDTISNSLEEHVTQILNEQADISSKKEDSHIGKDEEIPDSSKISLSCKKTGSKKKSSQSEGIFLGSESDEDSVRTSSSQRSHDLKFSASIEKERDFKKSSAPLKSEDLGKPSRSKTDRDDKYFSYSKLERDTRYVSSRCRSERERRRSRSHSRSERGSRTNLSYSRSERSHYYDSDRRYHRSSPYRERTRYSRPYTDNRARESSDSEEEYKKTYSRRTSSHSSSYRDLRTSSYSKSDRDCKTETSYLEMERRGKYSSKLERESKRTSENEAIKRCCSPPNELGFRRGSSYSKHDSSASRYKSTLSKPIPKSDKFKNSFCCTELNEEIKQSHSFSLQTPCSKGSELRMINKNPEREKAGSPAPSNRLNDSPTLKKLDELPIFKSEFITHDSHDSIKELDSLSKVKNDQLRSFCPIELNINGSPGAESDLATFCTSKTDAVLMTSDDSVTGSELSPLVKACMLSSNGFQNISRCKEKDLDDTCMLHKKSESPFRETEPLVSPHQDKLMSMPVMTVDYSKTVVKEPVDTRVSCCKTKDSDIYCTLNDSNPSLCNSEAENIEPSVMKISSNSFMNVHLESKPVICDSRNLTDHSKFACEEYKQSIGSTSSASVNHFDDLYQPIGSSGIASSLQSLPPGIKVDSLTLLKCGENTSPVLDAVLKSKKSSEFLKHAGKETIVEVGSDLPDSGKGFASRENRRNNGLSGKCLQEAQEEGNSILPERRGRPEISLDERGEGGHVHTSDDSEVVFSSCDLNLTMEDSDGVTYALKCDSSGHAPEIVSTVHEDYSGSSESSNDESDSEDTDSDDSSIPRNRLQSVVVVPKNSTLPMEETSPCSSRSSQSYRHYSDHWEDERLESRRHLYEEKFESIASKACPQTDKFFLHKGTEKNPEISFTQSSRKQIDNRLPELSHPQSDGVDSTSHTDVKSDPLGHPNSEETVKAKIPSRQQEELPIYSSDFEDVPNKSWQQTTFQNRPDSRLGKTELSFSSSCEIPHVDGLHSSEELRNLGWDFSQEKPSTTYQQPDSSYGACGGHKYQQNAEQYGGTRDYWQGNGYWDPRSGRPPGTGVVYDRTQGQVPDSLTDDREEEENWDQQDGSHFSDQSDKFLLSLQKDKGSVQAPEISSNSIKDTLAVNEKKDFSKNLEKNDIKDRGPLKKRRQEIESDSESDGELQDRKKVRVEVEQGETSVPPGSALVGPSCVMDDFRDPQRWKECAKQGKMPCYFDLIEENVYLTERKKNKSHRDIKRMQCECTPLSKDERAQGEIACGEDCLNRLLMIECSSRCPNGDYCSNRRFQRKQHADVEVILTEKKGWGLRAAKDLPSNTFVLEYCGEVLDHKEFKARVKEYARNKNIHYYFMALKNDEIIDATQKGNCSRFMNHSCEPNCETQKWTVNGQLRVGFFTTKLVPSGSELTFDYQFQRYGKEAQKCFCGSANCRGYLGGENRVSIRAAGGKMKKERSRKKDSVDGELEALMENGEGLSDKNQVLSLSRLMVRIETLEQKLTCLELIQNTHSQSCLKSFLERHGLSLLWIWMAELGDGRESNQKLQEEIIKTLEHLPIPTKNMLEESKVLPIIQRWSQTKTAVPPLSEGDGYSSENTSRAHTPLNTPDPSTKLSTEADTDTPKKLMFRRLKIISENSMDSAISDATSELEGKDGKEDLDQLENVPVEEEEELQSQQLLPQQLPECKVDSETNIEASKLPTSEPEADAEIEPKESNGTKLEEPINEETPSQDEEEGVSDVESERSQEQPDKTVDISDLATKLLDSWKDLKEVYRIPKKSQTEKENTTTERGRDAVGFRDQTPAPKTPNRSRERDPDKQTQNKEKRKRRSSLSPPSSAYERGTKRPDDRYDTPTSKKKVRIKDRNKLSTEERRKLFEQEVAQREAQKQQQQMQNLGMTSPLPYDSLGYNAPHHPFAGYPPGYPMQAYVDPSNPNAGKVLLPTPSMDPVCSPAPYDHAQPLVGHSTEPLSAPPPVPVVPHVAAPVEVSSSQYVAQSDGVVHQDSSVAVLPVPAPGPVQGQNYSVWDSNQQSVSVQQQYSPAQSQATIYYQGQTCPTVYGVTSPYSQTTPPIVQSYAQPSLQYIQGQQIFTAHPQGVVVQPAAAVTTIVAPGQPQPLQPSEMVVTNNLLDLPPPSPPKPKTIVLPPNWKTARDPEGKIYYYHVITRQTQWDPPTWESPGDDASLEHEAEMDLGTPTYDENPMKASKKPKTAEADTSSELAKKSKEVFRKEMSQFIVQCLNPYRKPDCKVGRITTTEDFKHLARKLTHGVMNKELKYCKNPEDLECNENVKHKTKEYIKKYMQKFGAVYKPKEDTELE
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:20054297, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}. Note=The disease may be caused by variants affecting the gene represented in this entry. Defects of SETD2 are associated with loss of DNA methylation at non-promoter regions (PubMed:23792563). SETD2 defects lead to aberrant and reduced nucleosome compaction and chromatin association of key replication proteins, such as MCM7 and DNA polymerase delta, leading to hinder replication fork progression and prevent loading of RAD51 homologous recombination repair factor at DNA breaks (PubMed:25728682). {ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}.; DISEASE: Luscan-Lumish syndrome (LLS) [MIM:616831]: 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. {ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:24852293, ECO:0000269|PubMed:26084711, ECO:0000269|PubMed:27317772}. Note=The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Leukemia, acute lymphoblastic (ALL) [MIM:613065]: 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. {ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24662245}. Note=The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: 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. {ECO:0000269|PubMed:16314571, ECO:0000269|PubMed:24509477}. Note=The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Intellectual developmental disorder, autosomal dominant 70 (MRD70) [MIM:620157]: An autosomal dominant disorder characterized by mild global developmental delay, moderately impaired intellectual disability with speech difficulties, and behavioral abnormalities. {ECO:0000269|PubMed:32710489}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Rabin-Pappas syndrome (RAPAS) [MIM:620155]: An autosomal dominant neurodevelopmental disorder characterized by severely impaired global development, intellectual disability, microcephaly, facial dysmorphism, and variable congenital anomalies affecting the skeletal, genitourinary, cardiac, and other organ systems. {ECO:0000269|PubMed:32710489}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.1.1.-
uniprot
proteins
ec_number
2.1.1.359
uniprot
proteins
function
FUNCTION: 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). {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}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}.
uniprot
proteins
mass_dalton
287597
uniprot
proteins
mutagenesis
MUTAGEN 1589; /note="F->A: Strongly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:27474439"; MUTAGEN 1604; /note="Y->A: Increased methyltransferase activity."; /evidence="ECO:0000269|PubMed:27474439"; MUTAGEN 1625; /note="R->H,G: Loss of methyltransferase activity. Abolishes ability to monomethylate STAT1."; /evidence="ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:28753426"; MUTAGEN 1631; /note="C->A: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:28753426"; MUTAGEN 1636; /note="E->A: Increased methyltransferase activity."; /evidence="ECO:0000269|PubMed:27474439"; MUTAGEN 1637; /note="T->A: Increased methyltransferase activity."; /evidence="ECO:0000269|PubMed:27474439"; MUTAGEN 1668; /note="F->A: Strongly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:27474439"; MUTAGEN 1669; /note="Q->A: Loss of methyltransferase activity."; /evidence="ECO:0000269|PubMed:23043551"; MUTAGEN 1670; /note="R->A,V,L,I,F: Impaired methyltransferase activity."; /evidence="ECO:0000269|PubMed:23043551"; MUTAGEN 1670; /note="R->P,W,K,Q: Loss of methyltransferase activity."; /evidence="ECO:0000269|PubMed:23043551"; MUTAGEN 1671; /note="Y->A: Strongly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:27474439"; MUTAGEN 2475; /note="R->A: Does not affect interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2476; /note="K->A: Does not affect interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2480; /note="Q->A: Does not affect interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2481; /note="F->A: Does not affect interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2483; /note="V->A: Impairs interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2506; /note="K->A: Impairs interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2510; /note="R->A: Impairs interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2514; /note="H->A: Impairs interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2515; /note="G->A,T: Does not affect interaction with hyperphosphorylated POLR2A."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2528; /note="E->A: Increases interaction with hyperphosphorylated POLR2A; when associated with A-2531."; /evidence="ECO:0000269|PubMed:16314571"; MUTAGEN 2531; /note="E->A: Increases interaction with hyperphosphorylated POLR2A; when associated with A-2528."; /evidence="ECO:0000269|PubMed:16314571
uniprot
proteins
post_translational_modification
PTM: May be automethylated. {ECO:0000269|PubMed:16118227}.
uniprot
proteins
protein_family
Class V-like SAM-binding methyltransferase superfamily
uniprot
proteins
protein_family
Histone-lysine methyltransferase family
uniprot
proteins
protein_family
SET2 subfamily
uniprot
proteins
pubmed
10958656
uniprot
proteins
pubmed
11042152
uniprot
proteins
pubmed
11214970
uniprot
proteins
pubmed
11461154
uniprot
proteins
pubmed
12168954
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16118227
uniprot
proteins
pubmed
16314571
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18585004
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19141475
uniprot
proteins
pubmed
19332550
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20054297
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21526191
uniprot
proteins
pubmed
21792193
uniprot
proteins
pubmed
23043551
uniprot
proteins
pubmed
23160955
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23325844
uniprot
proteins
pubmed
23622243
uniprot
proteins
pubmed
23792563
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24509477
uniprot
proteins
pubmed
24662245
uniprot
proteins
pubmed
24843002
uniprot
proteins
pubmed
24852293
uniprot
proteins
pubmed
25728682
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
26084711
uniprot
proteins
pubmed
26637798
uniprot
proteins
pubmed
27317772
uniprot
proteins
pubmed
27474439
uniprot
proteins
pubmed
27518565
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28256625
uniprot
proteins
pubmed
28753426
uniprot
proteins
pubmed
32710489
uniprot
proteins
pubmed
36537238
uniprot
proteins
pubmed
9700202
uniprot
proteins
sequence_length
2564
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:E9Q5F9}. Chromosome {ECO:0000250|UniProtKB:E9Q5F9}.
uniprot
proteins