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Entry: SETD2_MOUSE
LinkDB: SETD2_MOUSE
Original site: SETD2_MOUSE 
ID   SETD2_MOUSE             Reviewed;        2537 AA.
AC   E9Q5F9; Q69ZC0; Q6PCY9; Q8K0F3;
DT   18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 1.
DT   24-JAN-2024, entry version 92.
DE   RecName: Full=Histone-lysine N-methyltransferase SETD2 {ECO:0000305};
DE            EC=2.1.1.359 {ECO:0000269|PubMed:18157086};
DE   AltName: Full=Lysine N-methyltransferase 3A {ECO:0000250|UniProtKB:Q9BYW2};
DE   AltName: Full=Protein-lysine N-methyltransferase SETD2 {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000269|PubMed:27518565};
DE   AltName: Full=SET domain-containing protein 2 {ECO:0000303|PubMed:18157086};
GN   Name=Setd2 {ECO:0000303|PubMed:18157086, ECO:0000312|MGI:MGI:1918177};
GN   Synonyms=Kiaa1732 {ECO:0000303|PubMed:15368895},
GN   Kmt3a {ECO:0000250|UniProtKB:Q9BYW2};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2121-2537 AND 1800-2537 (ISOFORM
RP   2).
RC   TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1834-2537 (ISOFORM 1).
RC   TISSUE=Thymus;
RX   PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA   Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA   Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT   The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT   identified by screening of terminal sequences of cDNA clones randomly
RT   sampled from size-fractionated libraries.";
RL   DNA Res. 11:205-218(2004).
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX   PubMed=18157086; DOI=10.1038/sj.emboj.7601967;
RA   Edmunds J.W., Mahadevan L.C., Clayton A.L.;
RT   "Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates
RT   all H3K36 trimethylation.";
RL   EMBO J. 27:406-420(2008).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1387; SER-1389 AND SER-1391,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA   Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA   Thibault P.;
RT   "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL   Immunity 30:143-154(2009).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-242; SER-322;
RP   SER-324; SER-624; SER-633; SER-697; SER-1818; SER-1819; THR-1827; SER-1954;
RP   SER-1962 AND SER-1969, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC   Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20133625; DOI=10.1073/pnas.0915033107;
RA   Hu M., Sun X.J., Zhang Y.L., Kuang Y., Hu C.Q., Wu W.L., Shen S.H.,
RA   Du T.T., Li H., He F., Xiao H.S., Wang Z.G., Liu T.X., Lu H., Huang Q.H.,
RA   Chen S.J., Chen Z.;
RT   "Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for
RT   embryonic vascular remodeling.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:2956-2961(2010).
RN   [8]
RP   FUNCTION.
RX   PubMed=25242323; DOI=10.1016/j.celrep.2014.08.031;
RA   Zhang Y., Xie S., Zhou Y., Xie Y., Liu P., Sun M., Xiao H., Jin Y., Sun X.,
RA   Chen Z., Huang Q., Chen S.;
RT   "H3K36 histone methyltransferase Setd2 is required for murine embryonic
RT   stem cell differentiation toward endoderm.";
RL   Cell Rep. 8:1989-2002(2014).
RN   [9]
RP   FUNCTION AS ALPHA-TUBULIN METHYLTRANSFERASE.
RX   PubMed=27518565; DOI=10.1016/j.cell.2016.07.005;
RA   Park I.Y., Powell R.T., Tripathi D.N., Dere R., Ho T.H., Blasius T.L.,
RA   Chiang Y.C., Davis I.J., Fahey C.C., Hacker K.E., Verhey K.J.,
RA   Bedford M.T., Jonasch E., Rathmell W.K., Walker C.L.;
RT   "Dual chromatin and cytoskeletal remodeling by SETD2.";
RL   Cell 166:950-962(2016).
CC   -!- FUNCTION: Histone methyltransferase that specifically trimethylates
CC       'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36'
CC       (H3K36me2) as substrate (PubMed:18157086, PubMed:20133625). It is
CC       capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (By
CC       similarity). Represents the main enzyme generating H3K36me3, a specific
CC       tag for epigenetic transcriptional activation (PubMed:18157086,
CC       PubMed:20133625). Plays a role in chromatin structure modulation during
CC       elongation by coordinating recruitment of the FACT complex and by
CC       interacting with hyperphosphorylated POLR2A (By similarity). Acts as a
CC       key regulator of DNA mismatch repair in G1 and early S phase by
CC       generating H3K36me3, a mark required to recruit MSH6 subunit of the
CC       MutS alpha complex: early recruitment of the MutS alpha complex to
CC       chromatin to be replicated allows a quick identification of mismatch
CC       DNA to initiate the mismatch repair reaction (By similarity). Required
CC       for DNA double-strand break repair in response to DNA damage: acts by
CC       mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA
CC       repair via homologous recombination (HR) (By similarity). Acts as a
CC       tumor suppressor (By similarity). H3K36me3 also plays an essential role
CC       in the maintenance of a heterochromatic state, by recruiting DNA
CC       methyltransferase DNMT3A (By similarity). H3K36me3 is also enhanced in
CC       intron-containing genes, suggesting that SETD2 recruitment is enhanced
CC       by splicing and that splicing is coupled to recruitment of elongating
CC       RNA polymerase (By similarity). Required during angiogenesis
CC       (PubMed:20133625). Required for endoderm development by promoting
CC       embryonic stem cell differentiation toward endoderm: acts by mediating
CC       formation of H3K36me3 in distal promoter regions of FGFR3, leading to
CC       regulate transcription initiation of FGFR3 (PubMed:25242323). In
CC       addition to histones, also mediates methylation of other proteins, such
CC       as tubulins and STAT1 (PubMed:27518565). Trimethylates 'Lys-40' of
CC       alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is
CC       required for normal mitosis and cytokinesis and may be a specific tag
CC       in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-
CC       alpha-induced antiviral defense by mediating both monomethylation of
CC       STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some
CC       interferon-stimulated genes (ISGs) to activate gene transcription (By
CC       similarity). {ECO:0000250|UniProtKB:Q9BYW2,
CC       ECO:0000269|PubMed:18157086, ECO:0000269|PubMed:20133625,
CC       ECO:0000269|PubMed:25242323, ECO:0000269|PubMed:27518565}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC         + N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-
CC         homocysteine; Xref=Rhea:RHEA:60324, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC         COMP:15536, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.359;
CC         Evidence={ECO:0000269|PubMed:18157086};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)-
CC         methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC         Evidence={ECO:0000250|UniProtKB:Q9BYW2};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[protein] + 3 S-adenosyl-L-methionine = 3 H(+) +
CC         N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-
CC         homocysteine; Xref=Rhea:RHEA:54192, Rhea:RHEA-COMP:9752, Rhea:RHEA-
CC         COMP:13826, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61961;
CC         Evidence={ECO:0000269|PubMed:27518565};
CC   -!- ACTIVITY REGULATION: Specifically inhibited by sinefungin derivatives.
CC       {ECO:0000250|UniProtKB:Q9BYW2}.
CC   -!- SUBUNIT: Specifically interacts with hyperphosphorylated C-terminal
CC       domain (CTD) of RNA polymerase II large subunit (POLR2A): binds to CTD
CC       heptad repeats doubly phosphorylated on 'Ser-2' and 'Ser-5' of each
CC       heptad. Interacts with HTT. Interacts with IWS1. Interacts with
CC       p53/TP53; leading to regulate p53/TP53 target genes. Component of a
CC       complex with HNRNPL. Interacts with TUBA1A; the interaction is
CC       independent on alpha-tubulin acetylation on 'Lys-40'.
CC       {ECO:0000250|UniProtKB:Q9BYW2}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18157086}. Chromosome
CC       {ECO:0000269|PubMed:18157086}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=E9Q5F9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=E9Q5F9-2; Sequence=VSP_047946;
CC   -!- DOMAIN: The low charge region mediates the transcriptional activation
CC       activity. {ECO:0000250|UniProtKB:Q9BYW2}.
CC   -!- PTM: May be automethylated. {ECO:0000250|UniProtKB:Q9BYW2}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality at 10.5-11.5 dpc. Embryos
CC       show severe vascular defects in embryo, yolk sac and placenta.
CC       Capillaries are abnormally dilated in embryos and yolk sacs and cannot
CC       be remodeled into large blood vessels or intricate networks. The
CC       embryonic vessels fail to invade the labyrinthine layer of placenta,
CC       which impair the embryonic-maternal vascular connection. Defects are
CC       not caused by the extraembryonic tissues. Impaired H3K36me3, but not
CC       H3K36me2 or H3K36me1. {ECO:0000269|PubMed:20133625}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC       superfamily. Histone-lysine methyltransferase family. SET2 subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR   EMBL; AC132103; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC031601; AAH31601.1; -; mRNA.
DR   EMBL; BC059049; AAH59049.1; -; mRNA.
DR   EMBL; AK173246; BAD32524.1; -; mRNA.
DR   CCDS; CCDS40781.2; -. [E9Q5F9-1]
DR   RefSeq; NP_001074809.2; NM_001081340.2. [E9Q5F9-1]
DR   AlphaFoldDB; E9Q5F9; -.
DR   BMRB; E9Q5F9; -.
DR   SMR; E9Q5F9; -.
DR   BioGRID; 231695; 15.
DR   IntAct; E9Q5F9; 8.
DR   STRING; 10090.ENSMUSP00000116313; -.
DR   GlyGen; E9Q5F9; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; E9Q5F9; -.
DR   PhosphoSitePlus; E9Q5F9; -.
DR   EPD; E9Q5F9; -.
DR   jPOST; E9Q5F9; -.
DR   MaxQB; E9Q5F9; -.
DR   PaxDb; 10090-ENSMUSP00000116313; -.
DR   PeptideAtlas; E9Q5F9; -.
DR   ProteomicsDB; 261169; -. [E9Q5F9-1]
DR   ProteomicsDB; 261170; -. [E9Q5F9-2]
DR   Pumba; E9Q5F9; -.
DR   Antibodypedia; 29842; 401 antibodies from 34 providers.
DR   Ensembl; ENSMUST00000153838.8; ENSMUSP00000116313.3; ENSMUSG00000044791.17. [E9Q5F9-1]
DR   GeneID; 235626; -.
DR   KEGG; mmu:235626; -.
DR   UCSC; uc009rug.2; mouse. [E9Q5F9-1]
DR   AGR; MGI:1918177; -.
DR   CTD; 29072; -.
DR   MGI; MGI:1918177; Setd2.
DR   VEuPathDB; HostDB:ENSMUSG00000044791; -.
DR   eggNOG; KOG4442; Eukaryota.
DR   GeneTree; ENSGT00940000160086; -.
DR   HOGENOM; CLU_000810_1_0_1; -.
DR   InParanoid; E9Q5F9; -.
DR   OMA; VAYDRIQ; -.
DR   OrthoDB; 950362at2759; -.
DR   PhylomeDB; E9Q5F9; -.
DR   TreeFam; TF106477; -.
DR   BRENDA; 2.1.1.359; 3474.
DR   Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR   BioGRID-ORCS; 235626; 24 hits in 122 CRISPR screens.
DR   ChiTaRS; Setd2; mouse.
DR   PRO; PR:E9Q5F9; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; E9Q5F9; Protein.
DR   Bgee; ENSMUSG00000044791; Expressed in manus and 228 other cell types or tissues.
DR   ExpressionAtlas; E9Q5F9; baseline and differential.
DR   Genevisible; E9Q5F9; MM.
DR   GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0043014; F:alpha-tubulin binding; ISO:MGI.
DR   GO; GO:0046975; F:histone H3K36 methyltransferase activity; IMP:UniProtKB.
DR   GO; GO:0140955; F:histone H3K36 trimethyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016279; F:protein-lysine N-methyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR   GO; GO:0035441; P:cell migration involved in vasculogenesis; IMP:MGI.
DR   GO; GO:0060977; P:coronary vasculature morphogenesis; IMP:MGI.
DR   GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR   GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:MGI.
DR   GO; GO:0048568; P:embryonic organ development; IMP:MGI.
DR   GO; GO:0060669; P:embryonic placenta morphogenesis; IMP:MGI.
DR   GO; GO:0035987; P:endodermal cell differentiation; IMP:UniProtKB.
DR   GO; GO:0030900; P:forebrain development; IMP:MGI.
DR   GO; GO:0048332; P:mesoderm morphogenesis; IMP:MGI.
DR   GO; GO:1902850; P:microtubule cytoskeleton organization involved in mitosis; ISS:UniProtKB.
DR   GO; GO:0006298; P:mismatch repair; ISS:UniProtKB.
DR   GO; GO:0001763; P:morphogenesis of a branching structure; IMP:MGI.
DR   GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR   GO; GO:0034728; P:nucleosome organization; ISS:UniProtKB.
DR   GO; GO:0018023; P:peptidyl-lysine trimethylation; ISS:UniProtKB.
DR   GO; GO:0060039; P:pericardium development; IMP:MGI.
DR   GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI.
DR   GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR   GO; GO:0045778; P:positive regulation of ossification; ISO:MGI.
DR   GO; GO:0032465; P:regulation of cytokinesis; ISS:UniProtKB.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR   GO; GO:0010793; P:regulation of mRNA export from nucleus; ISO:MGI.
DR   GO; GO:1905634; P:regulation of protein localization to chromatin; ISS:UniProtKB.
DR   GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
DR   GO; GO:0010038; P:response to metal ion; IEA:Ensembl.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR   GO; GO:0034340; P:response to type I interferon; ISS:UniProtKB.
DR   GO; GO:0048864; P:stem cell development; IMP:MGI.
DR   GO; GO:0048863; P:stem cell differentiation; IMP:UniProtKB.
DR   GO; GO:0006368; P:transcription elongation by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR   CDD; cd19172; SET_SETD2; 1.
DR   CDD; cd00201; WW; 1.
DR   Gene3D; 2.20.70.10; -; 1.
DR   Gene3D; 1.20.930.10; Conserved domain common to transcription factors TFIIS, elongin A, CRSP70; 1.
DR   Gene3D; 2.170.270.10; SET domain; 1.
DR   Gene3D; 1.10.1740.100; Set2, Rpb1 interacting domain; 1.
DR   InterPro; IPR006560; AWS_dom.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR046341; SET_dom_sf.
DR   InterPro; IPR044437; SETD2/Set2_SET.
DR   InterPro; IPR042294; SETD2_animal.
DR   InterPro; IPR013257; SRI.
DR   InterPro; IPR038190; SRI_sf.
DR   InterPro; IPR035441; TFIIS/LEDGF_dom_sf.
DR   InterPro; IPR001202; WW_dom.
DR   InterPro; IPR036020; WW_dom_sf.
DR   PANTHER; PTHR46711; HISTONE-LYSINE N-METHYLTRANSFERASE SETD2; 1.
DR   PANTHER; PTHR46711:SF1; HISTONE-LYSINE N-METHYLTRANSFERASE SETD2; 1.
DR   Pfam; PF17907; AWS; 1.
DR   Pfam; PF00856; SET; 1.
DR   Pfam; PF08236; SRI; 1.
DR   Pfam; PF00397; WW; 1.
DR   SMART; SM00570; AWS; 1.
DR   SMART; SM00508; PostSET; 1.
DR   SMART; SM00317; SET; 1.
DR   SMART; SM00456; WW; 1.
DR   SUPFAM; SSF82199; SET domain; 1.
DR   SUPFAM; SSF51045; WW domain; 1.
DR   PROSITE; PS51215; AWS; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50280; SET; 1.
DR   PROSITE; PS01159; WW_DOMAIN_1; 1.
DR   PROSITE; PS50020; WW_DOMAIN_2; 1.
PE   1: Evidence at protein level;
KW   Activator; Alternative splicing; Antiviral defense; Chromatin regulator;
KW   Chromosome; Coiled coil; Developmental protein; Differentiation;
KW   DNA damage; DNA repair; Immunity; Innate immunity; Isopeptide bond;
KW   Metal-binding; Methyltransferase; Nucleus; Phosphoprotein;
KW   Reference proteome; S-adenosyl-L-methionine; Transcription;
KW   Transcription regulation; Transferase; Ubl conjugation; Zinc.
FT   CHAIN           1..2537
FT                   /note="Histone-lysine N-methyltransferase SETD2"
FT                   /id="PRO_0000423553"
FT   DOMAIN          1468..1522
FT                   /note="AWS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00562"
FT   DOMAIN          1524..1641
FT                   /note="SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   DOMAIN          1648..1664
FT                   /note="Post-SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT   DOMAIN          2362..2395
FT                   /note="WW"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          91..142
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          156..483
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          510..554
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          607..629
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          729..749
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          829..894
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          941..974
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1015..1078
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1135..1185
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1232..1254
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1280..1346
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1366..1396
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1392..1688
FT                   /note="Interaction with TUBA1A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   REGION          1806..1848
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1914..1981
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1993..2110
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2110..2339
FT                   /note="Low charge region"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   REGION          2412..2438
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2430..2537
FT                   /note="Interaction with POLR2A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   COILED          2090..2119
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        1..17
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        91..107
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        156..170
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        185..212
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        270..298
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        299..328
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        341..412
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        425..479
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        510..530
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        609..627
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        829..844
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        845..860
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        870..894
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        947..974
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1040..1073
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1139..1153
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1154..1168
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1303..1320
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1321..1346
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1806..1841
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1926..1945
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1993..2021
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2028..2053
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2063..2103
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2422..2438
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         1473
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1475
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1490
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1490
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1494
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1503
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1507
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1513
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1534..1536
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1577..1579
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1602..1603
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1605
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1650
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         1652
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1653
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         1654
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   BINDING         1659
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         132
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         242
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         322
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         324
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         345
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         423
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         532
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         614
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         624
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         626
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         633
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         697
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         707
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         743
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         753
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         1077
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         1201
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         1387
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319"
FT   MOD_RES         1389
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319"
FT   MOD_RES         1391
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319"
FT   MOD_RES         1670
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         1818
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         1819
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         1827
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         1846
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         1862
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         1926
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         1954
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         1962
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         1969
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         2053
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   MOD_RES         2055
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   CROSSLNK        360
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   CROSSLNK        637
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   CROSSLNK        775
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BYW2"
FT   VAR_SEQ         2011
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_047946"
SQ   SEQUENCE   2537 AA;  285663 MW;  4ED47D778291DA9D CRC64;
     MKPLPSQQPP PKMGDFYDPE HPTPEEEENE AKIENVQKTG FIKGPVFKGV ASSRFLPKGT
     KTKVNLEEQG RQKVSFSFSF TKKTLQNRFL TALSNEKQSD SPNSPAPPLQ VDSNPKVKMD
     AGDTFPATEE SSPPKSRVEL GRIHFKKHLL HVTSRPQLAA STTAASPLPP TTQLPAVLAE
     SMIDSPPSSP PPPPPPPQAS SPSPPAQISE PVALPQPPAT ALMTSPPGPL PGDVAVRAQK
     ESPVKSGPEV LEVDTKQDIV SNSLEEHTVQ TLKEQADHLL QKEDSHIGKE EEVSDGSKIS
     LSSKKASSKK KSSQFEGTFL GSESDEDSVR TSSSQRSHDL KSSTSIDKER DFKKSSAPSK
     SEDLGKSSRS KTERDDRYCS YSKLERDTRY VSSRCRSERD RRRSRSRSRS DRASRTSLSY
     SRSERSHYYD SERRYHRSSP YRERTRYSRP YTDNRARESS DSEDEYKKTY PRRTSAHSYR
     DLRTSSSYSK FDRDCKTETS YLEMERRGKY TSKLERESKR TSEHETIKRC CSPPNELGFR
     RGSSYSKHDN STSRYKSALS KSISKNDKFK NSFCCTELNE ENKQSHSFSL QTPCSKGSEL
     RTINKISERE KTGSPTPSNQ LNDSPTFKKL DESPVLKPEF IGHDGRESIK ELELSKVKND
     QLRNFCSIEL NVNGSPETEA DVATFCTSKT DAISMTSDDS VTGSEVSPLI KACMLSSNGF
     QNVGRCRERD SDDTCRQHNT SKSPFREMEP LLSPHHDKLM SLPVKTIDYP KTLIKEPVDK
     RHSCCKTKDS DIYCSPNENP EAENAEPSAM TISSHSFVNV HLESKTVICD NREPTDRHSE
     NTCDEYKQSI GSTSSASHNH FDGLYEPIGS SGISSLQSPP SGIRCEENTS PTLDAVESKK
     GIDFLKYARK ETDVGSALPD SGKGFSWENR HNNVLSGQSL QEAQEEGNSI LHERRGRPEI
     PLDEEQRGHT HISDDSEVVF PYDLNLTMED SDGITYTLKC DSSGNAPEIV STVHEDYSGS
     SASSSDESDS EDTESDDSSI PRNRLQSVVV VPKNSTLPME ETSPCSSRSS QSYKHYSDRW
     EDGLETRRHA YEEEYESKGC SQTEKYFLHK GTERSAESCY SQFGRKADNH LPDIAHAQSD
     GVDSTSQTDS RSDHLGHLNP EDTLRAKTSR PQELPVYSDD FEDLPNKSRQ QMIFSNRPDS
     SRLGKTELSF SSSCDISRMD GLHSSEELRN LGWDFSQQER PTTTYQQPDS SYGTCGTHKY
     QQSTEHYGGT HNYWQGNGYW DPRSAGRPPG TGLAYDRIQG QVPDSLTDDR EEEEHWDQRS
     GSHFSSPSNK FFFHQKDKGS VQAPEISSNS IKDALVMNER KDFSKNFEKN DIKERGPPKK
     RRQELESDSE SDGELQARKK VRVEMEQGES SVPQHSELMG PSCAMDDFRD PQRWKEFAKL
     GKMPCYFDLI EENVYLTERK KNKSHRDIKR MQCECTPLSK DERAQGEVAC GEDCLNRLLM
     IECSSRCPNG DYCSNRRFQR KQHADVEVIL TEKKGWGLRA AKDLPSNTFV LEYCGEVLDH
     KEFKARVKEY ARNKNIHYYF MALKNDEIID ATQKGNCSRF MNHSCEPNCE TQKWTVNGQL
     RVGFFTTKLV PSGSELTFDY QFQRYGKEAQ KCFCGSANCR GYLGGENRVS IRAAGGKMKK
     ERSRKKDSVD GELEALMENG EGLSDKNQVL SLSRLMVRIE TLEQKLTCLK LIQNTHSQSC
     LKSFLERHGL SLLWIWMAEL GDGRESNQKL QEEIIKTLEH LPIPTKNMLE ESKVLPIIQR
     WSQTKTAVPQ LSEGDGYSSE NTSRAHTPLN TPDPSAKPST EMDTDTPKKL IFRRLKIISE
     NSMDSAVSDV TSELECKDGK EDLDQLETVT VEEDEELQSQ QLLPQQLCES KVESEATIEV
     SKLPTSEPEA DTETEPKDSN GTKLEETIAE ETPSQDEEEG VSDVESERSQ EPPDKTVDIS
     DLATKLLDSW KDLKEVYRIP KKSQTEKEST VAERGRDAAA FRDQTAPKTP NRSRERDPDK
     QSQNKEKRKR RGSLSPPSSA YERGTKRPDD RYDTPTSKKK VRIKDRNKLS TEERRKLFEQ
     EVAQREAQKQ QQQMQNLGMT SPLPFDSLGY NASHHPFAGY PPGYPMQAYV DPSNPNAGKV
     LLPTPSMDPV CSPAPYDHAQ PLVGHSTESL AAPPSVPVVP HVAASVEVSS SQYVAQNESV
     VHQDSNVPVM PVQAPGPVQG QNYNVWESNQ QSVSVQQQYS PAQSQTTIYY QGQTCSTVYS
     VTSPYSQTTP PIVQSYAQPS LQYIQGQQIF TAHPQGVVVQ PTAAVTSIVA PGQPQSLQPP
     EMVVTNNLLD LPPPSPPKPK TIVLPPNWKT ARDPEGKIYY YHVITRQTQW DPPTWESPGD
     DASLEHEAEM DLGTPTYDEN PMKTSKKPKT AEADTSSELA KKSKEVFRKE MSQFIVQCLN
     PYRKPDCKVG RITTTEDFKH LARKLTHGVM NKELKYCKNP EDLECNENVK HKTKEYIKKY
     MQKFGAVYKP KEDTELE
//
DBGET integrated database retrieval system