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 03-AUG-2022, entry version 84.
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 iPTMnet; E9Q5F9; -.
DR PhosphoSitePlus; E9Q5F9; -.
DR EPD; E9Q5F9; -.
DR jPOST; E9Q5F9; -.
DR MaxQB; E9Q5F9; -.
DR PaxDb; E9Q5F9; -.
DR PeptideAtlas; E9Q5F9; -.
DR PRIDE; E9Q5F9; -.
DR ProteomicsDB; 261169; -. [E9Q5F9-1]
DR ProteomicsDB; 261170; -. [E9Q5F9-2]
DR Antibodypedia; 29842; 352 antibodies from 34 providers.
DR Ensembl; ENSMUST00000153838; ENSMUSP00000116313; ENSMUSG00000044791. [E9Q5F9-1]
DR GeneID; 235626; -.
DR KEGG; mmu:235626; -.
DR UCSC; uc009rug.2; mouse. [E9Q5F9-1]
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; TCMQHSK; -.
DR OrthoDB; 507784at2759; -.
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 116 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 225 other 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 methyltransferase activity (H3-K36 specific); IMP:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; ISS:UniProtKB.
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:0097676; P:histone H3-K36 dimethylation; ISO:MGI.
DR GO; GO:0010452; P:histone H3-K36 methylation; IMP:MGI.
DR GO; GO:0097198; P:histone H3-K36 trimethylation; IMP:UniProtKB.
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:0018026; P:peptidyl-lysine monomethylation; ISS:UniProtKB.
DR GO; GO:0018023; P:peptidyl-lysine trimethylation; IMP:MGI.
DR GO; GO:0060039; P:pericardium development; IMP:MGI.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; ISS:UniProtKB.
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:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
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 from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR CDD; cd19172; SET_SETD2; 1.
DR CDD; cd00201; WW; 1.
DR Gene3D; 1.10.1740.100; -; 1.
DR Gene3D; 1.20.930.10; -; 1.
DR Gene3D; 2.170.270.10; -; 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; PTHR46711; 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; SSF51045; SSF51045; 1.
DR SUPFAM; SSF82199; SSF82199; 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
