GenomeNet

Database: UniProt
Entry: P55200
LinkDB: P55200
Original site: P55200 
ID   KMT2A_MOUSE             Reviewed;        3966 AA.
AC   P55200; E9QNE7; Q3UEU1; Q3USE7;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 3.
DT   10-APR-2019, entry version 175.
DE   RecName: Full=Histone-lysine N-methyltransferase 2A;
DE            Short=Lysine N-methyltransferase 2A;
DE            EC=2.1.1.43 {ECO:0000250|UniProtKB:Q03164};
DE   AltName: Full=ALL-1;
DE   AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia;
DE   AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia protein 1;
DE   AltName: Full=Zinc finger protein HRX;
DE   Contains:
DE     RecName: Full=MLL cleavage product N320;
DE     AltName: Full=N-terminal cleavage product of 320 kDa;
DE              Short=p320;
DE   Contains:
DE     RecName: Full=MLL cleavage product C180;
DE     AltName: Full=C-terminal cleavage product of 180 kDa;
DE              Short=p180;
GN   Name=Kmt2a; Synonyms=All1, Hrx, Mll, Mll1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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.,
RA   She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA   Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA   Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA   Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA   Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of
RT   the mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 101-3966 (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6 X CBA, and C57BL/6J; TISSUE=Lung, and Spleen;
RX   PubMed=8327517; DOI=10.1073/pnas.90.13.6350;
RA   Ma Q., Alder H., Nelson K.K., Chatterjee D., Gu Y., Nakamura T.,
RA   Canaani E., Croce C.M., Siracusa L.D., Buchberg A.M.;
RT   "Analysis of the murine All-1 gene reveals conserved domains with
RT   human ALL-1 and identifies a motif shared with DNA
RT   methyltransferases.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:6350-6354(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 372-1517 (ISOFORM 1).
RC   STRAIN=C57BL/6J; TISSUE=Medulla oblongata, and Retina;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-1053; SER-1839;
RP   THR-1847; SER-2100 AND SER-2560, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Kidney, Liver, Lung, 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
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH CLOCK AND ARNTL.
RX   PubMed=21113167; DOI=10.1038/nsmb.1961;
RA   Katada S., Sassone-Corsi P.;
RT   "The histone methyltransferase MLL1 permits the oscillation of
RT   circadian gene expression.";
RL   Nat. Struct. Mol. Biol. 17:1414-1421(2010).
RN   [6]
RP   IDENTIFICATION IN MLL COMPLEX, AND INTERACTION WITH ASH2L; DPY30;
RP   KMT2D; RRBP5 AND WDR5.
RX   PubMed=21335234; DOI=10.1016/j.cell.2011.01.020;
RA   Jiang H., Shukla A., Wang X., Chen W.Y., Bernstein B.E., Roeder R.G.;
RT   "Role for Dpy-30 in ES cell-fate specification by regulation of H3K4
RT   methylation within bivalent domains.";
RL   Cell 144:513-525(2011).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-237; LYS-371; LYS-2954 AND
RP   LYS-3459, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z.,
RA   Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: Histone methyltransferase that plays an essential role
CC       in early development and hematopoiesis. Catalytic subunit of the
CC       MLL1/MLL complex, a multiprotein complex that mediates both
CC       methylation of 'Lys-4' of histone H3 (H3K4me) complex and
CC       acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL
CC       complex, it specifically mediates H3K4me, a specific tag for
CC       epigenetic transcriptional activation. Has weak methyltransferase
CC       activity by itself, and requires other component of the MLL1/MLL
CC       complex to obtain full methyltransferase activity. Has no activity
CC       toward histone H3 phosphorylated on 'Thr-3', less activity toward
CC       H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher
CC       activity toward H3 acetylated on 'Lys-9'. Binds to unmethylated
CC       CpG elements in the promoter of target genes and helps maintain
CC       them in the nonmethylated state. Required for transcriptional
CC       activation of HOXA9 (By similarity). Promotes PPP1R15A-induced
CC       apoptosis. Plays a critical role in the control of circadian gene
CC       expression and is essential for the transcriptional activation
CC       mediated by the CLOCK-ARNTL/BMAL1 heterodimer. Establishes a
CC       permissive chromatin state for circadian transcription by
CC       mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me)
CC       and this histone modification directs the circadian acetylation at
CC       H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to
CC       chromatin (PubMed:21113167). {ECO:0000250|UniProtKB:Q03164,
CC       ECO:0000269|PubMed:21113167}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC         Evidence={ECO:0000250|UniProtKB:Q03164};
CC   -!- SUBUNIT: MLL cleavage product N320 heterodimerizes with MLL
CC       cleavage product C180 (via SET and FYRC domains). Component of
CC       some MLL1/MLL complex, at least composed of the core components
CC       KMT2A/MLL1, ASH2L, HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as
CC       well as the facultative components BAP18, CHD8, E2F6, HSP70,
CC       INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, PELP1,
CC       PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1,
CC       TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with WDR5; the
CC       interaction is direct (PubMed:21335234). Interaction with WDR5 is
CC       required for stable interaction with ASH2L and RBBP5, and thereby
CC       also for optimal histone methyltransferase activity. Interacts
CC       with KAT8/MOF; the interaction is direct. Interacts with SBF1 and
CC       PPP1R15A. Interacts with ZNF335 (By similarity). Interacts with
CC       CLOCK and ARNTL/BMAL1 in a circadian manner (PubMed:21113167).
CC       Interacts with PPIE; this results in decreased histone H3
CC       methyltransferase activity. Interacts with CREBBP (By similarity).
CC       {ECO:0000250|UniProtKB:Q03164, ECO:0000269|PubMed:21113167,
CC       ECO:0000269|PubMed:21335234}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q03164}.
CC   -!- SUBCELLULAR LOCATION: MLL cleavage product N320: Nucleus
CC       {ECO:0000250|UniProtKB:Q03164}.
CC   -!- SUBCELLULAR LOCATION: MLL cleavage product C180: Nucleus
CC       {ECO:0000250|UniProtKB:Q03164}. Note=Localizes to a diffuse
CC       nuclear pattern when not associated with MLL cleavage product
CC       N320. {ECO:0000250|UniProtKB:Q03164}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P55200-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P55200-2; Sequence=VSP_006667;
CC   -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a
CC       large number of yeast and animal transcription factors.
CC       {ECO:0000250|UniProtKB:Q03164}.
CC   -!- DOMAIN: The SET domain structure is atypical and is not in an
CC       optimal position to have methyltransferase activity. It requires
CC       other components of the MLL1/MLL complex, such as ASH2L or RBBP5,
CC       to order the active site and obtain optimal histone
CC       methyltransferase activity. {ECO:0000250|UniProtKB:Q03164}.
CC   -!- DOMAIN: The CXXC-type zinc finger binds to DNA sequence elements
CC       containing nonmethylated CpG dinucleotides.
CC       {ECO:0000250|UniProtKB:Q03164}.
CC   -!- DOMAIN: The third PHD-type zinc-finger binds both trimethylated
CC       histone H3K4me3 and PPIE; histone and PPIE bind to distinct
CC       surfaces. Nevertheless, PPIE binding and histone binding are
CC       mutually inhibitory. Isomerization of a peptidylproline bond in
CC       the linker between the third PHD-type zinc-finger and the bromo
CC       domain disrupts the interaction between the bromo domain and the
CC       third PHD-type zinc-finger, and thereby facilitates interaction
CC       with PPIE. {ECO:0000250|UniProtKB:Q03164}.
CC   -!- PTM: Proteolytic cleavage by TASP1 generates MLL cleavage product
CC       N320 and MLL cleavage product C180, which reassemble through a
CC       non-covalent association. 2 cleavage sites exist, cleavage site 1
CC       (CS1) and cleavage site 2 (CS2), to generate MLL cleavage products
CC       N320 and C180. CS2 is the major site.
CC       {ECO:0000250|UniProtKB:Q03164}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. TRX/MLL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAE24386.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
DR   EMBL; AC061963; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC142113; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; L17069; AAA62593.1; -; mRNA.
DR   EMBL; AK140439; BAE24386.1; ALT_INIT; mRNA.
DR   EMBL; AK149341; BAE28820.1; -; mRNA.
DR   RefSeq; NP_001074518.1; NM_001081049.1.
DR   UniGene; Mm.2389; -.
DR   ProteinModelPortal; P55200; -.
DR   SMR; P55200; -.
DR   BioGrid; 229502; 6.
DR   DIP; DIP-58597N; -.
DR   IntAct; P55200; 3.
DR   STRING; 10090.ENSMUSP00000110337; -.
DR   iPTMnet; P55200; -.
DR   PhosphoSitePlus; P55200; -.
DR   jPOST; P55200; -.
DR   MaxQB; P55200; -.
DR   PaxDb; P55200; -.
DR   PeptideAtlas; P55200; -.
DR   PRIDE; P55200; -.
DR   Ensembl; ENSMUST00000002095; ENSMUSP00000002095; ENSMUSG00000002028. [P55200-2]
DR   Ensembl; ENSMUST00000114689; ENSMUSP00000110337; ENSMUSG00000002028. [P55200-1]
DR   GeneID; 214162; -.
DR   UCSC; uc009pep.1; mouse. [P55200-2]
DR   UCSC; uc009peq.1; mouse. [P55200-1]
DR   CTD; 4297; -.
DR   MGI; MGI:96995; Kmt2a.
DR   eggNOG; KOG1084; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000160099; -.
DR   HOGENOM; HOG000112954; -.
DR   HOVERGEN; HBG051927; -.
DR   InParanoid; P55200; -.
DR   OrthoDB; 738155at2759; -.
DR   TreeFam; TF319820; -.
DR   Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR   Reactome; R-MMU-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR   Reactome; R-MMU-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR   ChiTaRS; Kmt2a; mouse.
DR   PRO; PR:P55200; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   Bgee; ENSMUSG00000002028; Expressed in 287 organ(s), highest expression level in retina.
DR   ExpressionAtlas; P55200; baseline and differential.
DR   Genevisible; P55200; MM.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0035097; C:histone methyltransferase complex; ISS:UniProtKB.
DR   GO; GO:0071339; C:MLL1 complex; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0070577; F:lysine-acetylated histone binding; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:0044212; F:transcription regulatory region DNA binding; ISO:MGI.
DR   GO; GO:0045322; F:unmethylated CpG binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR   GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0050890; P:cognition; IMP:MGI.
DR   GO; GO:0060216; P:definitive hemopoiesis; IMP:CACAO.
DR   GO; GO:0006306; P:DNA methylation; IMP:MGI.
DR   GO; GO:0035162; P:embryonic hemopoiesis; IMP:MGI.
DR   GO; GO:0035640; P:exploration behavior; IMP:MGI.
DR   GO; GO:0044648; P:histone H3-K4 dimethylation; IMP:MGI.
DR   GO; GO:0051568; P:histone H3-K4 methylation; ISS:UniProtKB.
DR   GO; GO:0080182; P:histone H3-K4 trimethylation; IMP:MGI.
DR   GO; GO:0043984; P:histone H4-K16 acetylation; ISS:UniProtKB.
DR   GO; GO:0048873; P:homeostasis of number of cells within a tissue; IGI:MGI.
DR   GO; GO:0051899; P:membrane depolarization; IEA:Ensembl.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR   GO; GO:1905642; P:negative regulation of DNA methylation; ISO:MGI.
DR   GO; GO:0018026; P:peptidyl-lysine monomethylation; IMP:MGI.
DR   GO; GO:2001040; P:positive regulation of cellular response to drug; ISO:MGI.
DR   GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0032411; P:positive regulation of transporter activity; ISO:MGI.
DR   GO; GO:0009791; P:post-embryonic development; IGI:MGI.
DR   GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR   GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR   GO; GO:0071440; P:regulation of histone H3-K14 acetylation; IMP:UniProtKB.
DR   GO; GO:1901674; P:regulation of histone H3-K27 acetylation; IMP:MGI.
DR   GO; GO:0051569; P:regulation of histone H3-K4 methylation; IMP:MGI.
DR   GO; GO:2000615; P:regulation of histone H3-K9 acetylation; IMP:UniProtKB.
DR   GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IMP:MGI.
DR   GO; GO:0009416; P:response to light stimulus; IMP:MGI.
DR   GO; GO:0035864; P:response to potassium ion; IEA:Ensembl.
DR   GO; GO:0048536; P:spleen development; IGI:MGI.
DR   GO; GO:0008542; P:visual learning; IMP:MGI.
DR   Gene3D; 3.30.40.10; -; 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; IPR037927; KMT2A.
DR   InterPro; IPR016569; MeTrfase_trithorax.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR002857; Znf_CXXC.
DR   InterPro; IPR011011; Znf_FYVE_PHD.
DR   InterPro; IPR001965; Znf_PHD.
DR   InterPro; IPR019787; Znf_PHD-finger.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR22884:SF387; PTHR22884:SF387; 1.
DR   Pfam; PF05965; FYRC; 1.
DR   Pfam; PF05964; FYRN; 1.
DR   Pfam; PF00628; PHD; 2.
DR   Pfam; PF00856; SET; 1.
DR   Pfam; PF02008; zf-CXXC; 1.
DR   PIRSF; PIRSF010354; Methyltransferase_trithorax; 1.
DR   SMART; SM00297; BROMO; 1.
DR   SMART; SM00542; FYRC; 1.
DR   SMART; SM00541; FYRN; 1.
DR   SMART; SM00249; PHD; 4.
DR   SMART; SM00508; PostSET; 1.
DR   SMART; SM00317; SET; 1.
DR   SUPFAM; SSF47370; SSF47370; 1.
DR   SUPFAM; SSF57903; SSF57903; 2.
DR   PROSITE; PS50014; BROMODOMAIN_2; 1.
DR   PROSITE; PS51805; EPHD; 1.
DR   PROSITE; PS51543; FYRC; 1.
DR   PROSITE; PS51542; FYRN; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50280; SET; 1.
DR   PROSITE; PS51058; ZF_CXXC; 1.
DR   PROSITE; PS01359; ZF_PHD_1; 3.
DR   PROSITE; PS50016; ZF_PHD_2; 3.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Biological rhythms; Bromodomain;
KW   Chromatin regulator; Complete proteome; DNA-binding; Isopeptide bond;
KW   Metal-binding; Methyltransferase; Nucleus; Phosphoprotein;
KW   Polymorphism; Reference proteome; Repeat; S-adenosyl-L-methionine;
KW   Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW   Zinc; Zinc-finger.
FT   CHAIN         1   3966       Histone-lysine N-methyltransferase 2A.
FT                                /FTId=PRO_0000124877.
FT   CHAIN         1   2714       MLL cleavage product N320. {ECO:0000250}.
FT                                /FTId=PRO_0000390951.
FT   CHAIN      2715   3966       MLL cleavage product C180. {ECO:0000250}.
FT                                /FTId=PRO_0000390952.
FT   DOMAIN     1705   1750       Bromo; divergent. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00035}.
FT   DOMAIN     2020   2076       FYR N-terminal. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00875}.
FT   DOMAIN     3663   3744       FYR C-terminal. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00876}.
FT   DOMAIN     3826   3942       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN     3950   3966       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   DNA_BIND    167    178       A.T hook 1.
FT   DNA_BIND    215    225       A.T hook 2.
FT   DNA_BIND    299    307       A.T hook 3.
FT   ZN_FING    1144   1192       CXXC-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00509}.
FT   ZN_FING    1430   1481       PHD-type 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    1478   1532       PHD-type 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    1565   1629       PHD-type 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    1872   1912       C2HC pre-PHD-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01146}.
FT   ZN_FING    1933   1980       PHD-type 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01146}.
FT   REGION     1583   1599       Interaction with histone H3K4me3.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   REGION     3761   3768       Interaction with WDR5.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   REGION     3903   3904       S-adenosyl-L-methionine binding.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOTIF      2843   2851       9aaTAD. {ECO:0000250|UniProtKB:Q03164}.
FT   COMPBIAS     14    150       Gly-rich.
FT   COMPBIAS     17    100       Ala/Gly/Ser-rich.
FT   COMPBIAS     80     99       Ser-rich.
FT   COMPBIAS    135    141       Poly-Gly.
FT   COMPBIAS    199    287       Lys-rich.
FT   COMPBIAS    443    491       Ser-rich.
FT   COMPBIAS    559    601       Pro-rich.
FT   COMPBIAS    559    562       Poly-Pro.
FT   COMPBIAS    566    569       Poly-Pro.
FT   COMPBIAS    703    807       Ser-rich.
FT   COMPBIAS   1234   1366       Pro-rich.
FT   COMPBIAS   1819   1867       Pro-rich.
FT   COMPBIAS   2185   2320       Ser-rich.
FT   METAL      3906   3906       Zinc. {ECO:0000250|UniProtKB:Q03164}.
FT   METAL      3954   3954       Zinc. {ECO:0000250|UniProtKB:Q03164}.
FT   METAL      3956   3956       Zinc. {ECO:0000250|UniProtKB:Q03164}.
FT   METAL      3961   3961       Zinc. {ECO:0000250|UniProtKB:Q03164}.
FT   BINDING    3836   3836       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   BINDING    3838   3838       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   BINDING    3880   3880       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   BINDING    3955   3955       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   SITE       2662   2663       Cleavage; by TASP1, site 1.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   SITE       2714   2715       Cleavage; by TASP1, site 2.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   SITE       3762   3762       Important for WDR5-recognition and
FT                                binding. {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES     151    151       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     195    195       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES     237    237       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:23806337}.
FT   MOD_RES     371    371       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:23806337}.
FT   MOD_RES     516    516       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES     634    634       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES     678    678       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES     837    837       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES     923    923       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    1053   1053       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    1127   1127       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    1232   1232       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    1839   1839       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    1847   1847       Phosphothreonine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    1860   1860       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    2100   2100       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    2148   2148       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    2152   2152       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    2202   2202       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    2560   2560       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    2607   2607       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    2792   2792       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    2951   2951       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    2954   2954       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:23806337}.
FT   MOD_RES    3032   3032       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    3369   3369       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    3459   3459       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:23806337}.
FT   MOD_RES    3510   3510       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   MOD_RES    3523   3523       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   CROSSLNK   2524   2524       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000250|UniProtKB:Q03164}.
FT   VAR_SEQ    1603   1605       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:8327517}.
FT                                /FTId=VSP_006667.
FT   VARIANT    1597   1597       K -> T.
FT   CONFLICT    372    372       Q -> E (in Ref. 3; BAE28820).
FT                                {ECO:0000305}.
FT   CONFLICT    554    554       Q -> K (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT    564    564       L -> F (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT    797    797       P -> S (in Ref. 3; BAE28820).
FT                                {ECO:0000305}.
FT   CONFLICT    806    806       E -> D (in Ref. 2; AAA62593 and 3;
FT                                BAE28820). {ECO:0000305}.
FT   CONFLICT    821    821       L -> P (in Ref. 2; AAA62593 and 3;
FT                                BAE28820). {ECO:0000305}.
FT   CONFLICT   1069   1069       C -> Y (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   1230   1230       A -> S (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   1349   1349       R -> L (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   1437   1437       A -> S (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   1440   1440       G -> E (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   1632   1632       A -> P (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   2292   2292       S -> L (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   3481   3481       N -> I (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   3493   3493       R -> S (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   3548   3548       G -> V (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
FT   CONFLICT   3769   3769       Q -> K (in Ref. 2; AAA62593).
FT                                {ECO:0000305}.
SQ   SEQUENCE   3966 AA;  429649 MW;  EA9CB2A467AB3545 CRC64;
     MAHSCRWRFP ARPGTTGGGG GGGRRGLGGA PRQRVPALLL PPGPQAGGGG PGAPPSPPAV
     AAAAAGSSGA GVPGGAAAAS AASSSSASSS SSSSSSASSG PALLRVGPGF DAALQVSAAI
     GTNLRRFRAV FGESGGGGGS GEDEQFLGFG SDEEVRVRSP TRSPSVKASP RKPRGRPRSG
     SDRNPAILSD PSVFSPLNKS ETKSADKIKK KDSKSIEKKR GRPPTFPGVK IKITHGKDIA
     ELTQGSKEDS LKKVKRTPSA MFQQATKIKK LRAGKLSPLK SKFKTGKLQI GRKGVQIVRR
     RGRPPSTERI KTPSGLLINS ELEKPQKVRK DKEGTPPLTK EDKTVVRQSP RRIKPVRIIP
     SCKRTDATIA KQLLQRAKKG AQKKIEKEAA QLQGRKVKTQ VKNIRQFIMP VVSAISSRII
     KTPRRFIEDE DYDPPMKIAR LESTPNSRFS ATSCGSSEKS SAASQHSSQM SSDSSRSSSP
     SIDTTSDSQA SEEIQALPEE RSNTPEVHTP LPISQSPENE SNDRRSRRYS MSERSFGSRA
     TKKLPTLQSA PQQQTSSSPP PPLLTPPPPL QPASGISDHT PWLMPPTIPL ASPFLPASAA
     PMQGKRKSIL REPTFRWTSL KHSRSEPQYF SSAKYAKEGL IRKPIFDNFR PPPLTPEDVG
     FASGFSASGT AASARLFSPL HSGTRFDIHK RSPILRAPRF TPSEAHSRIF ESVTLPSNRT
     SSGASSSGVS NRKRKRKVFS PIRSEPRSPS HSMRTRSGRL STSELSPLTP PSSVSSSLSI
     PVSPLAASAL NPTFTFPSHS LTQSGESTEK NQRARKQTSA LAEPFSSNSP ALFPWFTPGS
     QTEKGRKKDT APEELSKDRD ADKSVEKDKS RERDREREKE NKRESRKEKR KKGSDIQSSS
     ALYPVGRVSK EKVAGEDVGT SSSAKKATGR KKSSSLDSGA DVAPVTLGDT TAVKAKILIK
     KGRGNLEKNN LDLGPAAPSL EKERTPCLSA PSSSTVKHST SSIGSMLAQA DKLPMTDKRV
     ASLLKKAKAQ LCKIEKSKSL KQTDQPKAQG QESDSSETSV RGPRIKHVCR RAAVALGRKR
     AVFPDDMPTL SALPWEEREK ILSSMGNDDK SSVAGSEDAE PLAPPIKPIK PVTRNKAPQE
     PPVKKGRRSR RCGQCPGCQV PEDCGICTNC LDKPKFGGRN IKKQCCKMRK CQNLQWMPSK
     ASLQKQTKAV KKKEKKSKTT EKKESKESTA VKSPLEPAQK AAPPPREEPA PKKSSSEPPP
     RKPVEEKSEE GGAPAPAPAP EPKQVSAPAS RKSSKQVSQP AAVVPPQPPS TAPQKKEAPK
     AVPSEPKKKQ PPPPEPGPEQ SKQKKVAPRP SIPVKQKPKD KEKPPPVSKQ ENAGTLNILN
     PLSNGISSKQ KIPADGVHRI RVDFKEDCEA ENVWEMGGLG ILTSVPITPR VVCFLCASSG
     HVEFVYCQVC CEPFHKFCLE ENERPLEDQL ENWCCRRCKF CHVCGRQHQA TKQLLECNKC
     RNSYHPECLG PNYPTKPTKK KKVWICTKCV RCKSCGSTTP GKGWDAQWSH DFSLCHDCAK
     LFAKGNFCPL CDKCYDDDDY ESKMMQCGKC DRWVHSKCES LSGTEDEMYE ILSNLPESVA
     YTCVNCTERH PAEWRLALEK ELQASLKQVL TALLNSRTTS HLLRYRQAAK PPDLNPETEE
     SIPSRSSPEG PDPPVLTEVS KQDEQQPLDL EGVKKRMDQG SYVSVLEFSD DIVKIIQAAI
     NSDGGQPEIK KANSMVKSFF IRQMERVFPW FSVKKSRFWE PNKVSNNSGM LPNAVLPPSL
     DHNYAQWQER EESSHTEQPP LMKKIIPAPK PKGPGEPDSP TPLHPPTPPI LSTDRSREDS
     PELNPPPGID DNRQCALCLM YGDDSANDAG RLLYIGQNEW THVNCALWSA EVFEDDDGSL
     KNVHMAVIRG KQLRCEFCQK PGATVGCCLT SCTSNYHFMC SRAKNCVFLD DKKVYCQRHR
     DLIKGEVVPE NGFEVFRRVF VDFEGISLRR KFLNGLEPEN IHMMIGSMTI DCLGILNDLS
     DCEDKLFPIG YQCSRVYWST TDARKRCVYT CKIMECRPPV VEPDINSTVE HDDNRTIAHS
     PSSFIDASCK DSQSTAAILS PPSPDRPHSQ TSGSCYYHVI SKVPRIRTPS YSPTQRSPGC
     RPLPSAGSPT PTTHEIVTVG DPLLSSGLRS IGSRRHSTSS LSPLRSKLRI MSPVRTGSAY
     SRSSVSSVPS LGTATDPEAS AKASDRGGLL SSSANLGHSA PPSSSSQRTV GGSKTSHLDG
     SSPSEVKRCS ASDLVPKGSL VKGEKNRTSS SKSTDGSAHS TAYPGIPKLT PQVHNATPGE
     LNISKIGSFA EPSTVPFSSK DTVSYPQLHL RGQRSDRDQH MDPSQSVKPS PNEDGEIKTL
     KLPGMGHRPS ILHEHIGSSS RDRRQKGKKS SKETCKEKHS SKSYLEPGQV TTGEEGNLKP
     EFADEVLTPG FLGQRPCNNV SSEKIGDKVL PLSGVPKGQS TQVEGSSKEL QAPRKCSVKV
     TPLKMEGENQ SKNTQKESGP GSPAHIESVC PAEPVSASRS PGAGPGVQPS PNNTLSQDPQ
     SNNYQNLPEQ DRNLMIPDGP KPQEDGSFKR RYPRRSARAR SNMFFGLTPL YGVRSYGEED
     IPFYSNSTGK KRGKRSAEGQ VDGADDLSTS DEDDLYYYNF TRTVISSGGE ERLASHNLFR
     EEEQCDLPKI SQLDGVDDGT ESDTSVTATS RKSSQIPKRN GKENGTENLK IDRPEDAGEK
     EHVIKSAVGH KNEPKLDNCH SVSRVKAQGQ DSLEAQLSSL ESSRRVHTST PSDKNLLDTY
     NAELLKSDSD NNNSDDCGNI LPSDIMDFVL KNTPSMQALG ESPESSSSEL LTLGEGLGLD
     SNREKDIGLF EVFSQQLPAT EPVDSSVSSS ISAEEQFELP LELPSDLSVL TTRSPTVPSQ
     NPSRLAVISD SGEKRVTITE KSVASSEGDP ALLSPGVDPA PEGHMTPDHF IQGHMDADHI
     SSPPCGSVEQ GHGNSQDLTR NSGTPGLQVP VSPTVPVQNQ KYVPSSTDSP GPSQISNAAV
     QTTPPHLKPA TEKLIVVNQN MQPLYVLQTL PNGVTQKIQL TSPVSSTPSV METNTSVLGP
     MGSGLTLTTG LNPSLPPSPS LFPPASKGLL SVPHHQHLHS FPAAAQSSFP PNISSPPSGL
     LIGVQPPPDP QLLGSEANQR TDLTTTVATP SSGLKKRPIS RLHTRKNKKL APSSAPSNIA
     PSDVVSNMTL INFTPSQLSN HPSLLDLGSL NPSSHRTVPN IIKRSKSGIM YFEQAPLLPP
     QSVGGTAATA AGSSTISQDT SHLTSGPVSA LASGSSVLNV VSMQTTAAPT SSTSVPGHVT
     LANQRLLGTP DIGSISHLLI KASHQSLGIQ DQPVALPPSS GMFPQLGTSQ TPSAAAMTAA
     SSICVLPSSQ TAGMTAASPP GEAEEHYKLQ RGNQLLAGKT GTLTSQRDRD PDSAPGTQPS
     NFTQTAEAPN GVRLEQNKTL PSAKPASSAS PGSSPSSGQQ SGSSSVPGPT KPKPKAKRIQ
     LPLDKGSGKK HKVSHLRTSS EAHIPHRDTD PAPQPSVTRT PRANREQQDA AGVEQPSQKE
     CGQPAGPVAA LPEVQATQNP ANEQENAEPK AMEEEESGFS SPLMLWLQQE QKRKESITER
     KPKKGLVFEI SSDDGFQICA ESIEDAWKSL TDKVQEARSN ARLKQLSFAG VNGLRMLGIL
     HDAVVFLIEQ LAGAKHCRNY KFRFHKPEEA NEPPLNPHGS ARAEVHLRQS AFDMFNFLAS
     KHRQPPEYNP NDEEEEEVQL KSARRATSMD LPMPMRFRHL KKTSKEAVGV YRSPIHGRGL
     FCKRNIDAGE MVIEYAGNVI RSIQTDKREK YYDSKGIGCY MFRIDDSEVV DATMHGNAAR
     FINHSCEPNC YSRVINIDGQ KHIVIFAMRK IYRGEELTYD YKFPIEDASN KLPCNCGAKK
     CRKFLN
//
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