ID TRX_DROME Reviewed; 3726 AA. AC P20659; A4V2V9; A4V2W0; Q27255; Q27327; Q8INF9; Q960R2; Q9VFL1; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 02-MAR-2010, sequence version 4. DT 04-NOV-2026, entry version 236. DE RecName: Full=Histone-lysine N-methyltransferase trithorax; DE EC=2.1.1.355 {ECO:0000269|PubMed:12408863}; DE AltName: Full=Cysteine methyltransferase KMT2A {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:24235145}; DE AltName: Full=Lysine N-methyltransferase 2A; GN Name=trx {ECO:0000303|PubMed:2107543}; Synonyms=KMT2A; GN ORFNames=CG8651; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida; OC Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota; OC Aparaglossata; Panorpida; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND FUNCTION. RX PubMed=2107543; DOI=10.1073/pnas.87.6.2112; RA Mazo A.M., Huang D.-H., Mozer B.A., Dawid I.B.; RT "The trithorax gene, a trans-acting regulator of the bithorax complex in RT Drosophila, encodes a protein with zinc-binding domains."; RL Proc. Natl. Acad. Sci. U.S.A. 87:2112-2116(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, FUNCTION, RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RX PubMed=7924996; DOI=10.1242/dev.120.7.1907; RA Sedkov Y., Tillib S., Mizrokhi L., Mazo A.; RT "The bithorax complex is regulated by trithorax earlier during Drosophila RT embryogenesis than is the Antennapedia complex, correlating with a RT bithorax-like expression pattern of distinct early trithorax transcripts."; RL Development 120:1907-1917(1994). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING. RC STRAIN=Oregon-R; TISSUE=Embryo; RX PubMed=8555104; DOI=10.1016/0925-4773(95)00429-7; RA Tillib S., Sedkov Y., Mizrokhi L., Mazo A.; RT "Conservation of structure and expression of the trithorax gene between RT Drosophila virilis and Drosophila melanogaster."; RL Mech. Dev. 53:113-122(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C., RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., RA Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [5] RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic RT review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2970-3726 (ISOFORMS A/B). RC STRAIN=Berkeley; TISSUE=Embryo; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., RA Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [7] RP INTERACTION WITH ASH1. RX PubMed=10454589; DOI=10.1128/mcb.19.9.6441; RA Rozovskaia T., Tillib S., Smith S., Sedkov Y., Rozenblatt-Rosen O., RA Petruk S., Yano T., Nakamura T., Ben-Simchon L., Gildea J., Croce C.M., RA Shearn A., Canaani E., Mazo A.; RT "Trithorax and ASH1 interact directly and associate with the trithorax RT group-responsive bxd region of the Ultrabithorax promoter."; RL Mol. Cell. Biol. 19:6441-6447(1999). RN [8] RP INTERACTION WITH ASH1. RX PubMed=10656681; DOI=10.1038/sj.onc.1203307; RA Rozovskaia T., Rozenblatt-Rosen O., Sedkov Y., Burakov D., Yano T., RA Nakamura T., Petruck S., Ben-Simchon L., Croce C.M., Mazo A., Canaani E.; RT "Self-association of the SET domains of human ALL-1 and of Drosophila RT TRITHORAX and ASH1 proteins."; RL Oncogene 19:351-357(2000). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=7958911; DOI=10.1101/gad.8.20.2478; RA Kuzin B., Tillib S., Sedkov Y., Mizrokhi L., Mazo A.; RT "The Drosophila trithorax gene encodes a chromosomal protein and directly RT regulates the region-specific homeotic gene fork head."; RL Genes Dev. 8:2478-2490(1994). RN [10] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=12408863; DOI=10.1016/s0092-8674(02)00975-3; RA Czermin B., Melfi R., McCabe D., Seitz V., Imhof A., Pirrotta V.; RT "Drosophila Enhancer of zeste/ESC complexes have a histone H3 RT methyltransferase activity that marks chromosomal Polycomb sites."; RL Cell 111:185-196(2002). RN [11] RP FUNCTION, INTERACTION WITH NUP98, AND DISRUPTION PHENOTYPE. RX PubMed=25310983; DOI=10.1016/j.celrep.2014.09.002; RA Pascual-Garcia P., Jeong J., Capelson M.; RT "Nucleoporin Nup98 associates with Trx/MLL and NSL histone-modifying RT complexes and regulates Hox gene expression."; RL Cell Rep. 9:433-442(2014). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, METHYLATION AT CYS-3641, AND MUTAGENESIS OF RP CYS-3641. RX PubMed=24235145; DOI=10.1074/jbc.m113.501064; RA Patel A., Vought V.E., Swatkoski S., Viggiano S., Howard B., RA Dharmarajan V., Monteith K.E., Kupakuwana G., Namitz K.E., Shinsky S.A., RA Cotter R.J., Cosgrove M.S.; RT "Automethylation activities within the mixed lineage leukemia-1 (MLL1) core RT complex reveal evidence supporting a 'two-active site' model for multiple RT histone H3 lysine 4 methylation."; RL J. Biol. Chem. 289:868-884(2014). CC -!- FUNCTION: Histone methyltransferase that methylates 'Lys-4' of histone CC H3 (H3K4me) (PubMed:12408863). H3K4me represents a specific tag for CC epigenetic transcriptional activation (PubMed:12408863). Functions in CC segment determination through interaction with genes of bithorax (BX-C) CC and antennapedia (ANT-C) complexes (PubMed:2107543, PubMed:7958911). CC Acts as an activator of BX-C (PubMed:7924996). Involved in the very CC early regulation of homeotic genes expressed only in the posterior CC region of the embryo (PubMed:25310983, PubMed:7924996). Also has auto- CC methylation activity on Cys-3641 (PubMed:24235145). CC {ECO:0000269|PubMed:12408863, ECO:0000269|PubMed:2107543, CC ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:25310983, CC ECO:0000269|PubMed:7924996, ECO:0000269|PubMed:7958911}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = CC N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L- CC homocysteine + 3 H(+); Xref=Rhea:RHEA:60276, Rhea:RHEA-COMP:15538, CC Rhea:RHEA-COMP:15546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; CC EC=2.1.1.355; Evidence={ECO:0000269|PubMed:12408863}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60277; CC Evidence={ECO:0000269|PubMed:12408863}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-cysteinyl-[protein] + S-adenosyl-L-methionine = S-methyl-L- CC cysteinyl-[protein] + S-adenosyl-L-homocysteine + H(+); CC Xref=Rhea:RHEA:66544, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:82612; CC Evidence={ECO:0000269|PubMed:24235145}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66545; CC Evidence={ECO:0000269|PubMed:24235145}; CC -!- SUBUNIT: Interacts (via SET domain) with ash1 (via SET domain) CC (PubMed:10454589, PubMed:10656681). Interacts with Nup98 CC (PubMed:25310983). {ECO:0000269|PubMed:10454589, CC ECO:0000269|PubMed:10656681, ECO:0000269|PubMed:25310983}. CC -!- INTERACTION: CC P20659; Q9V3G3: cyp33; NbExp=2; IntAct=EBI-591327, EBI-128445; CC P20659; P20659: trx; NbExp=7; IntAct=EBI-591327, EBI-591327; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407, CC ECO:0000269|PubMed:7958911}. Chromosome {ECO:0000269|PubMed:7958911}. CC Note=Binds to 16 discrete sites on larval salivary gland polytene CC chromosomes. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; Synonyms=D; CC IsoId=P20659-1; Sequence=Displayed; CC Name=B; Synonyms=C, E; CC IsoId=P20659-2; Sequence=VSP_006665; CC -!- TISSUE SPECIFICITY: Maternal isoforms are expressed in syncytial CC blastoderm, confined to the ventral region fated to become mesoderm. An CC additional broad domain of expression arises during cellularization and CC is quickly resolved into four pair-rule-like stripes in the posterior CC half of the embryo. {ECO:0000269|PubMed:7924996}. CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. CC {ECO:0000269|PubMed:7924996}. CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knock-down in the larva results in CC decreased expression of Hox genes such as Ubx and Antp. CC {ECO:0000269|PubMed:25310983}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. Histone-lysine methyltransferase family. TRX/MLL CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}. CC -!- SEQUENCE CAUTION: CC Sequence=AAK93328.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; M31617; AAA29025.1; -; mRNA. DR EMBL; Z50152; CAA90514.1; -; Genomic_DNA. DR EMBL; Z50152; CAA90513.1; -; Genomic_DNA. DR EMBL; Z31725; CAA83516.1; -; Genomic_DNA. DR EMBL; Z31725; CAA83515.1; -; Genomic_DNA. DR EMBL; AE014297; AAF55041.2; -; Genomic_DNA. DR EMBL; AE014297; AAN13599.1; -; Genomic_DNA. DR EMBL; AE014297; AAN13600.1; -; Genomic_DNA. DR EMBL; AE014297; AAN13601.1; -; Genomic_DNA. DR EMBL; AE014297; AAX52951.1; -; Genomic_DNA. DR EMBL; AY051904; AAK93328.1; ALT_INIT; mRNA. DR PIR; A35085; A35085. DR RefSeq; NP_001014621.1; NM_001014621.2. [P20659-2] DR RefSeq; NP_476769.1; NM_057421.3. [P20659-1] DR RefSeq; NP_476770.1; NM_057422.3. [P20659-2] DR RefSeq; NP_599108.1; NM_134281.2. [P20659-2] DR RefSeq; NP_599109.1; NM_134282.2. [P20659-1] DR SMR; P20659; -. DR BioGRID; 66813; 50. DR ComplexPortal; CPX-2245; Trithorax acetylation complex 1. DR ComplexPortal; CPX-2287; Histone-lysine N-methyltransferase TRX complex. DR ELM; P20659; -. DR FunCoup; P20659; 1462. DR IntAct; P20659; 14. DR STRING; 7227.FBpp0082406; -. DR GlyCosmos; P20659; 4 sites, No reported glycans. DR GlyGen; P20659; 6 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P20659; -. DR PaxDb; 7227-FBpp0082406; -. DR PeptideAtlas; P20659; -. DR DNASU; 41737; -. DR EnsemblMetazoa; FBtr0082947; FBpp0082406; FBgn0003862. DR EnsemblMetazoa; FBtr0082950; FBpp0082409; FBgn0003862. DR GeneID; 41737; -. DR KEGG; dme:Dmel_CG8651; -. DR UCSC; CG8651-RC; d. melanogaster. DR UCSC; CG8651-RD; d. melanogaster. DR AGR; FB:FBgn0003862; -. DR CTD; 41737; -. DR FlyBase; FBgn0003862; trx. DR VEuPathDB; VectorBase:FBgn0003862; -. DR eggNOG; KOG1084; Eukaryota. DR InParanoid; P20659; -. DR OMA; AAASXAT; -. DR OrthoDB; 308383at2759; -. DR PhylomeDB; P20659; -. DR Reactome; R-DME-201722; Formation of the beta-catenin:TCF transactivating complex. DR Reactome; R-DME-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function. DR Reactome; R-DME-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs. DR Reactome; R-DME-9772755; Formation of WDR5-containing histone-modifying complexes. DR Reactome; R-DME-9909649; Regulation of PD-L1(CD274) transcription. DR SignaLink; P20659; -. DR BioGRID-ORCS; 41737; 0 hits in 3 CRISPR screens. DR GenomeRNAi; 41737; -. DR PRO; PR:P20659; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0003862; Expressed in peripheral glial cell (Drosophila) in insect leg and 313 other cell types or tissues. DR GO; GO:0070775; C:H3 histone acetyltransferase complex; IPI:ComplexPortal. DR GO; GO:0000123; C:histone acetyltransferase complex; IDA:FlyBase. DR GO; GO:0035097; C:histone methyltransferase complex; IDA:FlyBase. DR GO; GO:0044665; C:MLL1/2 complex; IDA:FlyBase. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0005700; C:polytene chromosome; IDA:UniProtKB. DR GO; GO:0005704; C:polytene chromosome band; IDA:FlyBase. DR GO; GO:0008023; C:transcription elongation factor complex; IPI:FlyBase. DR GO; GO:0005667; C:transcription regulator complex; IPI:ComplexPortal. DR GO; GO:0003682; F:chromatin binding; IDA:FlyBase. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro. DR GO; GO:0042800; F:histone H3K4 methyltransferase activity; IDA:FlyBase. DR GO; GO:0140949; F:histone H3K9 trimethyltransferase activity; EXP:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0008157; F:protein phosphatase 1 binding; IPI:FlyBase. DR GO; GO:0106363; F:protein-cysteine methyltransferase activity; IDA:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase. DR GO; GO:0006325; P:chromatin organization; IC:FlyBase. DR GO; GO:0001654; P:eye development; IMP:UniProtKB. DR GO; GO:0007482; P:haltere development; IGI:UniProtKB. DR GO; GO:0007507; P:heart development; IMP:FlyBase. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; IDA:FlyBase. DR GO; GO:0008354; P:primordial germ cell migration; IMP:FlyBase. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:ComplexPortal. DR CDD; cd15664; ePHD_KMT2A_like; 1. DR CDD; cd15506; PHD1_KMT2A_like; 1. DR CDD; cd15508; PHD3_KMT2A_like; 1. DR CDD; cd15489; PHD_SF; 1. DR CDD; cd19170; SET_KMT2A_2B; 1. DR FunFam; 2.170.270.10:FF:000004; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.160.360:FF:000010; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.40.10:FF:000002; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.40.10:FF:000471; Histone-lysine N-methyltransferase trithorax; 1. DR Gene3D; 3.30.160.360; -; 2. DR Gene3D; 1.20.920.10; Bromodomain-like; 1. DR Gene3D; 2.170.270.10; SET domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 3. DR InterPro; IPR001487; Bromodomain. DR InterPro; IPR036427; Bromodomain-like_sf. DR InterPro; IPR034732; EPHD. DR InterPro; IPR003889; FYrich_C. DR InterPro; IPR003888; FYrich_N. DR InterPro; IPR047219; KMT2A_2B_SET. DR InterPro; IPR016569; MeTrfase_trithorax. DR InterPro; IPR003616; Post-SET_dom. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR019787; Znf_PHD-finger. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR45838:SF4; HISTONE-LYSINE N-METHYLTRANSFERASE TRITHORAX; 1. DR PANTHER; PTHR45838; HISTONE-LYSINE-N-METHYLTRANSFERASE 2 KMT2 FAMILY MEMBER; 1. DR Pfam; PF05965; FYRC; 1. DR Pfam; PF05964; FYRN; 1. DR Pfam; PF00628; PHD; 1. DR Pfam; PF00856; SET; 1. DR Pfam; PF13771; zf-HC5HC2H; 1. DR PIRSF; PIRSF010354; Methyltransferase_trithorax; 1. DR SMART; SM00542; FYRC; 1. DR SMART; SM00541; FYRN; 1. DR SMART; SM00249; PHD; 4. DR SMART; SM00508; PostSET; 2. DR SMART; SM00184; RING; 4. DR SMART; SM00317; SET; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 2. DR SUPFAM; SSF82199; SET domain; 1. DR PROSITE; PS50014; BROMODOMAIN_2; 1. DR PROSITE; PS51805; EPHD; 1. DR PROSITE; PS51543; FYRC; 1. DR PROSITE; PS51542; FYRN; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR PROSITE; PS50868; POST_SET; 1. DR PROSITE; PS50280; SET; 1. DR PROSITE; PS01359; ZF_PHD_1; 4. DR PROSITE; PS50016; ZF_PHD_2; 3. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Bromodomain; Chromatin regulator; KW Chromosome; Developmental protein; DNA-binding; Metal-binding; Methylation; KW Methyltransferase; Nucleus; Reference proteome; Repeat; KW S-adenosyl-L-methionine; Transcription; Transcription regulation; KW Transferase; Zinc; Zinc-finger. FT CHAIN 1..3726 FT /note="Histone-lysine N-methyltransferase trithorax" FT /id="PRO_0000124874" FT DOMAIN 1496..1663 FT /note="Bromo" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035" FT DOMAIN 1884..1941 FT /note="FYR N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00875" FT DOMAIN 3386..3470 FT /note="FYR C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00876" FT DOMAIN 3588..3704 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT DOMAIN 3710..3726 FT /note="Post-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155" FT DNA_BIND 759..884 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 1266..1347 FT /note="PHD-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1348..1393 FT /note="PHD-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1421..1482 FT /note="PHD-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1734..1774 FT /note="C2HC pre-PHD-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT ZN_FING 1795..1842 FT /note="PHD-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT REGION 1..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 321..352 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 371..429 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 509..624 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 915..937 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 981..1049 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1115..1184 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1208..1231 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1573..1592 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1991..2019 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2068..2110 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2283..2302 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2649..2669 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2866..2894 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3029..3096 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3347..3381 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 31..53 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 71..101 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 102..115 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 126..143 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 147..205 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 206..215 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 222..247 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 384..402 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 509..525 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 553..586 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 587..610 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 918..937 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 986..1000 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1031..1041 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1123..1132 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1173..1183 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1211..1223 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2074..2087 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2283..2302 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3032..3043 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3044..3057 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 3598 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 3600 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 3642 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 3665..3666 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:Q03164" FT BINDING 3668 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q03164" FT BINDING 3714 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q03164" FT BINDING 3716 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q03164" FT BINDING 3721 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q03164" FT MOD_RES 3641 FT /note="S-methylcysteine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:24235145" FT VAR_SEQ 1..368 FT /note="Missing (in isoform B)" FT /evidence="ECO:0000305" FT /id="VSP_006665" FT MUTAGEN 3641 FT /note="C->S: Abolished auto-methylation." FT /evidence="ECO:0000269|PubMed:24235145" FT CONFLICT 239..249 FT /note="GTTSEATTSGL -> LEQLVKQQPLV (in Ref. 1; AAA29025, 2; FT CAA90513 and 3; CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 303 FT /note="N -> K (in Ref. 1; AAA29025, 2; CAA90513 and 3; FT CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 337 FT /note="A -> L (in Ref. 1; AAA29025, 2; CAA90513 and 3; FT CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 521 FT /note="G -> R (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 578 FT /note="E -> Q (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 587 FT /note="V -> A (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 700 FT /note="N -> I (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 720 FT /note="T -> A (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 1073 FT /note="K -> P (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 1529..1530 FT /note="KL -> NV (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 1594 FT /note="S -> P (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 1627 FT /note="A -> E (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 1690 FT /note="T -> A (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 2010 FT /note="E -> Q (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 2025 FT /note="P -> PWLTSPLKFLGLSTHGGLLLWLLLGVVVRLKQGG (in Ref. 1; FT AAA29025)" FT /evidence="ECO:0000305" FT CONFLICT 2341 FT /note="S -> R (in Ref. 2; CAA90513/CAA90514 and 3; FT CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 2365 FT /note="S -> N (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 2392 FT /note="S -> G (in Ref. 2; CAA90513/CAA90514 and 3; FT CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 3157 FT /note="E -> Q (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 3234 FT /note="A -> R (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" FT CONFLICT 3690 FT /note="L -> V (in Ref. 1; AAA29025, 2; CAA90513/CAA90514 FT and 3; CAA83515/CAA83516)" FT /evidence="ECO:0000305" SQ SEQUENCE 3726 AA; 400098 MW; E3DDB8F062BD7796 CRC64; MGRSKFPGKP SKSINRKRIS VLQLEDDAAN PAEPQQPAPE SQQPSGSGSG SSAAREKGNN CDNDEDDNAP GGASISGNTA SSSAGSGNSG NGSSSGSSTG SGSSGSGSTN GGSVNGGTHH KSAANLDKEA VTKDQNGDGD KTRGNVSSAP SGKLSAAASG KALSKSSRTF SASTSVTSSG RSSGSSPDGN SGASSDGASS GISCGKSTAK STEASSGKLA KTTGAGTCSS AKSSKASSGT TSEATTSGLS GACLKALFVA TPATSTGLAC ALVSPGGSSQ GGTFPISAAL LRARKNSNKK FKNLNLARGE VMLPSTSKLK QLNSPVVDNP SPSPPIASGS TPSVEGGIGV GGVVSPGEDA ALKRVLTEMP NEVARDPSPS SCTAAANGAA SGKGSASNGP PAMASSGDGS SPKSGADTGP STSSTTAKQK KTVTFRNVLE TSDDKSVVKR FYNPDIRIPI VSIMKKDSLN RPLNYSRGGE CIVRPSILSK ILNKNSNIDK LNSLKFRSAG ASSSSSNQES GSSSNVFGLS RAFGAPMDED DEGGVTFRRN DSPEDQNNAE DDEMDDDDDD EEAEEDDENE DDNDEAVSEK SAETEKSAGA DERDPDEKQL VMDSHFVLPK RSTRSSRIIK PNKRLLEEGA ISTKKPLSLG DSKGKNVFGT SSSSAGSTAS TFSASTNLKL GKETFFNFGT LKPNSSAAGN FVLRQPRLQF QADNQQATFT APKACPTSPS AIPKPANSLA TSSFGSLAST NSSTVTPTPS ACSICSAVVS SKEVTQARKY GVVACDVCRK FFSKMTKKSI SANSSTANTS SGSQQYLQCK GNEGSPCSIH SAKSQLKNFK KFYKDRCTAC WLKKCMISFQ LPAAHRSRLS AILPPGMRGE AAAREEKSAE LLSPTGSLRF TSTASSSSPS VVASTSVKWK SSGDSTSALT SIKPNPLAEN NVTFGSTPLL RPAILENPLF LKISNAADQK LAAAEAISPS LTKKNSKQEK EKVKESEQSE KLLSPTQAGT KKSGAAEAQV EEVQPQKEEA PQTSTTTQPS ASNGASHGVP QAELAGETNA TGDTLKRQRI DLKGPRVKHV CRSASIVLGQ PLATFGEDQQ PEDAADMQQE IAAPVPSAIM EPSPEKPTHI VTDENDNCAS CKTSPVGDES KPSKSSGSAQ AEVKKATALG KEGTASAAGG SSAKVTTRNA AVASNLIVAA SKKQRNGDIA TSSSVTQSSN QTQGRKTKEH RQQRTLISID FWENYDPAEV CQTGFGLIVT ETVAQRALCF LCGSTGLDPL IFCACCCEPY HQYCVQDEYN LKHGSFEDTT LMGSLLETTV NASTGPSSSL NQLTQRLNWL CPRCTVCYTC NMSSGSKVKC QKCQKNYHST CLGTSKRLLG ADRPLICVNC LKCKSCSTTK VSKFVGNLPM CTGCFKLRKK GNFCPICQRC YDDNDFDLKM MECGDCGQWV HSKCEGLSDE QYNLLSTLPE SIEFICKKCA RRNESSKIKA EEWRQAVMEE FKASLYSVLK LLSKSRQACA LLKLSPRKKL RCTCGASSNQ GKLQPKALQF SSGSDNGLGS DGESQNSDDV YEFKDQQQQQ QQRNANMNKP RVKSLPCSCQ QHISHSQSFS LVDIKQKIAG NSYVSLAEFN YDMSQVIQQS NCDELDIAYK ELLSEQFPWF QNETKACTDA LEEDMFESCS GGNYEDLQDT GGVSASVYNE HSTSQAESRS GVLDIPLEEV DDFGSCGIKM RLDTRMCLFC RKSGEGLSGE EARLLYCGHD CWVHTNCAMW SAEVFEEIDG SLQNVHSAVA RGRMIKCTVC GNRGATVGCN VRSCGEHYHY PCARSIDCAF LTDKSMYCPA HAKNGNALKA NGSPSVTYES NFEVSRPVYV ELDRKRKKLI EPARVQFHIG SLEVRQLGAI VPRFSDSYEA VVPINFLCSR LYWSSKEPWK IVEYTVRTTI QNSSSTLTAL DVGRNYTVDH TNPNSKEVQL GMAQIARWHT SLARSEFLEN GGTDWSGEFP NPNSCVPPDE NTEEEPQQQA DLLPPELKDA IFEDLPHELL DGISMLDIFL YDDKTDLFAI SEQSKDGTQA MTSNQAQNQN QQAGGANSVS ICDEDTRNSN TSLGNGWPAS NPVEDAMLSA ARNSSQVQML KTLAWPKLDG NSAMATAIKR RKLSKNLAEG VFLTLSSQQR NKKEMATVAG VSRRQSISET SVEGVATTSG SVRSKSFTWS AAKRYFEKSE GREEAAKMRI MQMDGVDDSI TEFRIISGDG NLSTAQFSGQ VKCDRCQCTY RNYDAFQRHL PSCSPTMSSN ETESDVSGQG MTNNATQISA ESLNELQKQL LANAGGLNYL QSATSFPQVQ SLGSLGQFGL QGLQQLQLQP QSLGSGFFLS QPNPATQANT DDLQIYANSL QSLAANLGGG FTLAQPTVTA PAQPQLIAVS TNPDGTQQFI QIPQTMQATT TPTATYQTLQ ATNTDKKIML PLTAAGKPLK TVATKAAQQA AVKQRQLKSG HQVKPIQAKL QPHPQQHQQQ QQTQVQQPIT VMGQNLLQPQ LLFQSSTQTQ APQIILPQAQ PQNIISFVTG DGSQGQPLQY ISIPTAGEYK PQPQPTATPT FLTTAPGAGA TYLQTDASGN LVLTTTPSNS GLQMLTAQSL QAQPQVIGTL IQPQTIQLGG GADGNQPGSN QQPLILGGTG GGSSGLEFAT TSPQVILATQ PMYYGLETIV QNTVMSSQQF VSTAMPGMLS QNASFSATTT QVFQASKIEP IVDLPAGYVV LNNTGDASSA GTFLNAASVL QQQTQDDTTT QILQNANFQF QSVPTSSGAS TSMDYTSPVM VTAKIPPVTQ IKRTNAQAKA AGISGVGKVP PQPQVVNKVL PTSIVTQQSQ VQVKNSNLKQ SQVKGKAASG TGTTCGAPPS IASKPLQKKT NMIRPIHKLE VKPKVMKPTP KVQNQNHSLL QQQQQQQPQL QQQIPAVVVN QVPKVTISQQ RIPAQTQQQQ LQQAQMIHIP QQQQPLQQQQ VQVQPSMPII TLAEAPVVQS QFVMEPQALE QQELANRVQH FSTSSSSSSS NCSLPTNVVN PMQQQAPSTT SSSTTRPTNR VLPMQQRQEP APLSNECPVV SSPTPPKPVE QPIIHQMTSA SVSKCYAQKS TLPSPVYEAE LKVSSVLESI VPDVTMDAIL EEQPVTESIY TEGLYEKNSP GESKTEQLLL QQQQREQLNQ QLVNNGYLLD KHTFQVEPMD TDVYREEDLE EEEDEDDDFS LKMATSACND HEMSDSEEPA VKDKISKILD NLTNDDCADS IATATTMEVD ASAGYQQMVE DVLATTAAQS APTEEFEGAL ETAAVEAAAT YINEMADAHV LDLKQLQNGV ELELRRRKEE QRTVSQEQEQ SKAAIVPTAA APEPPQPIQE PKKMTGPHLL YEIQSEDGFT YKSSSITEIW EKVFEAVQVA RRAHGLTPLP EGPLADMGGI QMIGLKTNAL KYLIEQLPGV EKCSKYTPKY HKRNGNVSTA ANGAHGGNLG GSSASAALSV SGGDSHGLLD YGSDQDELEE NAYDCARCEP YSNRSEYDMF SWLASRHRKQ PIQVFVQPSD NELVPRRGTG SNLPMAMKYR TLKETYKDYV GVFRSHIHGR GLYCTKDIEA GEMVIEYAGE LIRSTLTDKR ERYYDSRGIG CYMFKIDDNL VVDATMRGNA ARFINHCCEP NCYSKVVDIL GHKHIIIFAL RRIVQGEELT YDYKFPFEDE KIPCSCGSKR CRKYLN //