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}, Kmt3a GN {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, RC Pancreas, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR Genevisible; E9Q5F9; MM. 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 //