KMT2A_MOUSE
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 03-AUG-2022, entry version 192.
DE RecName: Full=Histone-lysine N-methyltransferase 2A;
DE Short=Lysine N-methyltransferase 2A;
DE EC=2.1.1.364 {ECO:0000250|UniProtKB:Q03164};
DE AltName: Full=ALL-1;
DE AltName: Full=Cysteine methyltransferase KMT2A {ECO:0000305};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q03164};
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; 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 [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 human
RT ALL-1 and identifies a motif shared with DNA 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., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., 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., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., 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 SPECTROMETRY
RP [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 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 circadian
RT gene expression.";
RL Nat. Struct. Mol. Biol. 17:1414-1421(2010).
RN [6]
RP IDENTIFICATION IN MLL COMPLEX, AND INTERACTION WITH ASH2L; DPY30; KMT2D;
RP 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 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., Zhang Y.,
RA 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 in
CC early development and hematopoiesis (By similarity). Catalytic subunit
CC of the MLL1/MLL complex, a multiprotein complex that mediates both
CC methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation
CC of 'Lys-16' of histone H4 (H4K16ac) (By similarity). Catalyzes methyl
CC group transfer from S-adenosyl-L-methionine to the epsilon-amino group
CC of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of
CC chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2
CC methylation marks at active chromatin sites where transcription and DNA
CC repair take place (By similarity). Has weak methyltransferase activity
CC by itself, and requires other component of the MLL1/MLL complex to
CC obtain full methyltransferase activity (By similarity). Has no activity
CC toward histone H3 phosphorylated on 'Thr-3', less activity toward H3
CC dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward
CC H3 acetylated on 'Lys-9' (By similarity). Binds to unmethylated CpG
CC elements in the promoter of target genes and helps maintain them in the
CC nonmethylated state (By similarity). Required for transcriptional
CC activation of HOXA9 (By similarity). Promotes PPP1R15A-induced
CC apoptosis (By similarity). Plays a critical role in the control of
CC circadian gene expression and is essential for the transcriptional
CC activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer
CC (PubMed:21113167). Establishes a permissive chromatin state for
CC circadian transcription by mediating a rhythmic methylation of 'Lys-4'
CC of histone H3 (H3K4me) and this histone modification directs the
CC circadian acetylation at H3K9 and H3K14 allowing the recruitment of
CC CLOCK-ARNTL/BMAL1 to chromatin (PubMed:21113167). Also has auto-
CC methylation activity on Cys-3879 in absence of histone H3 substrate (By
CC similarity). {ECO:0000250|UniProtKB:Q03164,
CC ECO:0000269|PubMed:21113167}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60264, Rhea:RHEA-COMP:15543, Rhea:RHEA-COMP:15547,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.364;
CC Evidence={ECO:0000250|UniProtKB:Q03164};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60265;
CC Evidence={ECO:0000250|UniProtKB:Q03164};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60268, Rhea:RHEA-COMP:15540, Rhea:RHEA-
CC COMP:15543, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000250|UniProtKB:Q03164};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60269;
CC Evidence={ECO:0000250|UniProtKB:Q03164};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-cysteinyl-[protein] + S-adenosyl-L-methionine = H(+) + S-
CC adenosyl-L-homocysteine + S-methyl-L-cysteinyl-[protein];
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:0000250|UniProtKB:Q03164};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66545;
CC Evidence={ECO:0000250|UniProtKB:Q03164};
CC -!- SUBUNIT: MLL cleavage product N320 heterodimerizes with MLL cleavage
CC product C180 (via SET and FYRC domains). Component of some MLL1/MLL
CC complex, at least composed of the core components KMT2A/MLL1, ASH2L,
CC HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative
CC components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1,
CC MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A,
CC RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts
CC (via WIN motif) with WDR5; the interaction is direct. Interaction with
CC WDR5 is required for stable interaction with ASH2L and RBBP5, and
CC thereby 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 CLOCK
CC and ARNTL/BMAL1 in a circadian manner (PubMed:21113167). Interacts with
CC PPIE; this results in decreased histone H3 methyltransferase activity.
CC Interacts with CREBBP (By similarity). Interacts with the WRAD complex
CC composed of WDR5, RBBP5, ASH2L and DPY30 (By similarity). Interacts
CC (via MBM motif) with MEN1 (By similarity). Interacts (via IBM motifs)
CC with PSIP1 (via IBD domain) with moderate affinity whereas the KMT2A-
CC MEN1 complex interacts with a greater affinity; MEN1 enhances
CC interaction of KMT2A with PSIP1 (By similarity). Phosphorylation
CC increases its affinity for PSIP1 (By similarity). Forms a complex with
CC CREBBP and CREB1 (By similarity). {ECO:0000250|UniProtKB:Q03164,
CC ECO:0000269|PubMed:21113167, 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 nuclear
CC pattern when not associated with MLL cleavage product N320.
CC {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 large
CC 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 optimal
CC position to have methyltransferase activity. It requires other
CC components of the MLL1/MLL complex, such as ASH2L or RBBP5, to order
CC the active site and obtain optimal histone methyltransferase activity.
CC {ECO:0000250|UniProtKB:Q03164}.
CC -!- DOMAIN: The CXXC-type zinc finger binds to DNA sequence elements
CC containing unmethylated CpG dinucleotides.
CC {ECO:0000250|UniProtKB:Q03164}.
CC -!- DOMAIN: The third PHD-type zinc-finger binds both trimethylated histone
CC H3K4me3 and PPIE; histone and PPIE bind to distinct surfaces.
CC Nevertheless, PPIE binding and histone binding are mutually inhibitory.
CC Isomerization of a peptidylproline bond in the linker between the third
CC PHD-type zinc-finger and the bromo domain disrupts the interaction
CC between the bromo domain and the third PHD-type zinc-finger, and
CC thereby facilitates interaction with PPIE.
CC {ECO:0000250|UniProtKB:Q03164}.
CC -!- PTM: Proteolytic cleavage by TASP1 generates MLL cleavage 3product N320
CC and MLL cleavage product C180, which reassemble through a non-covalent
CC association. 2 cleavage sites exist, cleavage site 1 (CS1) and cleavage
CC site 2 (CS2), to generate MLL cleavage products N320 and C180. CS2 is
CC the major site. {ECO:0000250|UniProtKB:Q03164}.
CC -!- PTM: Phosphorylation increases its interaction with PSIP1.
CC {ECO:0000250|UniProtKB:Q03164}.
CC -!- PTM: Auto-methylated at Cys-3879: auto-methylation is inhibited by the
CC WRAD complex and unmodified histone H3. {ECO:0000250|UniProtKB:Q03164}.
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=BAE24386.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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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 BMRB; P55200; -.
DR SMR; P55200; -.
DR BioGRID; 229502; 28.
DR DIP; DIP-58597N; -.
DR IntAct; P55200; 3.
DR STRING; 10090.ENSMUSP00000110337; -.
DR iPTMnet; P55200; -.
DR PhosphoSitePlus; P55200; -.
DR EPD; P55200; -.
DR jPOST; P55200; -.
DR MaxQB; P55200; -.
DR PaxDb; P55200; -.
DR PeptideAtlas; P55200; -.
DR PRIDE; P55200; -.
DR ProteomicsDB; 263666; -. [P55200-1]
DR ProteomicsDB; 263667; -. [P55200-2]
DR Ensembl; ENSMUST00000002095; ENSMUSP00000002095; ENSMUSG00000002028. [P55200-2]
DR Ensembl; ENSMUST00000114689; ENSMUSP00000110337; ENSMUSG00000002028. [P55200-1]
DR UCSC; uc009pep.1; mouse. [P55200-2]
DR UCSC; uc009peq.1; mouse. [P55200-1]
DR MGI; MGI:96995; Kmt2a.
DR VEuPathDB; HostDB:ENSMUSG00000002028; -.
DR eggNOG; KOG1084; Eukaryota.
DR GeneTree; ENSGT00940000160099; -.
DR HOGENOM; CLU_000208_2_0_1; -.
DR InParanoid; P55200; -.
DR OMA; FPWFTSS; -.
DR OrthoDB; 738155at2759; -.
DR PhylomeDB; P55200; -.
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 BioGRID-ORCS; 214162; 14 hits in 75 CRISPR screens.
DR ChiTaRS; Kmt2a; mouse.
DR PRO; PR:P55200; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P55200; protein.
DR Bgee; ENSMUSG00000002028; Expressed in embryonic post-anal tail and 249 other tissues.
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); IDA:CACAO.
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:0106363; F:protein-cysteine methyltransferase activity; ISS:UniProtKB.
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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
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:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0044648; P:histone H3-K4 dimethylation; IMP:MGI.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:CACAO.
DR GO; GO:0097692; P:histone H3-K4 monomethylation; ISO:MGI.
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:1905642; P:negative regulation of DNA methylation; ISO:MGI.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; IMP: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; IMP:CACAO.
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 CDD; cd15693; ePHD_KMT2A; 1.
DR CDD; cd15588; PHD1_KMT2A; 1.
DR CDD; cd15590; PHD2_KMT2A; 1.
DR CDD; cd15592; PHD3_KMT2A; 1.
DR Gene3D; 1.20.920.10; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
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; IPR041958; KMT2A_ePHD.
DR InterPro; IPR042023; KMT2A_PHD1.
DR InterPro; IPR042025; KMT2A_PHD2.
DR InterPro; IPR044133; KMT2A_PHD3.
DR InterPro; IPR016569; MeTrfase_trithorax.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
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; PTHR45838:SF2; PTHR45838:SF2; 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 SUPFAM; SSF82199; SSF82199; 1.
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; DNA-binding; Isopeptide bond; Metal-binding;
KW Methylation; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..3966
FT /note="Histone-lysine N-methyltransferase 2A"
FT /id="PRO_0000124877"
FT CHAIN 1..2714
FT /note="MLL cleavage product N320"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT /id="PRO_0000390951"
FT CHAIN 2715..3966
FT /note="MLL cleavage product C180"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT /id="PRO_0000390952"
FT DOMAIN 1705..1750
FT /note="Bromo; divergent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 2020..2076
FT /note="FYR N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00875"
FT DOMAIN 3663..3744
FT /note="FYR C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00876"
FT DOMAIN 3826..3942
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 3950..3966
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT DNA_BIND 167..178
FT /note="A.T hook 1"
FT DNA_BIND 215..225
FT /note="A.T hook 2"
FT DNA_BIND 299..307
FT /note="A.T hook 3"
FT ZN_FING 1144..1192
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT ZN_FING 1430..1481
FT /note="PHD-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1478..1532
FT /note="PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1565..1629
FT /note="PHD-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1872..1912
FT /note="C2HC pre-PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT ZN_FING 1933..1980
FT /note="PHD-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT REGION 1..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 440..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 711..943
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 963..1003
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1034..1064
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1101..1161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1196..1390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1583..1599
FT /note="Interaction with histone H3K4me3"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT REGION 1665..1714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1807..1870
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2147..2174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2214..2339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2371..2619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2639..2673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2709..2759
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2958..3060
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3164..3239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3462..3640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3782..3805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 6..25
FT /note="Menin-binding motif (MBM)"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOTIF 121..132
FT /note="Integrase domain-binding motif 1 (IBM1)"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOTIF 145..150
FT /note="Integrase domain-binding motif 2 (IBM2)"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOTIF 2843..2851
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOTIF 3759..3764
FT /note="WDR5 interaction motif (WIN)"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT COMPBIAS 79..101
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..201
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..224
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 323..343
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 443..498
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 533..554
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 555..574
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 711..729
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 745..836
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 842..895
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 921..935
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 986..1003
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1043..1058
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1246..1269
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1287..1301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1325..1339
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1370..1390
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1824..1849
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2216..2234
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2246..2288
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2303..2320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2414..2443
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2524..2541
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2563..2590
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2717..2742
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2743..2759
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3007..3060
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3164..3179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3192..3213
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3462..3528
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3537..3568
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3573..3594
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1170
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 3836
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 3838
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 3880
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 3903..3904
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT BINDING 3906
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT BINDING 3954
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT BINDING 3955
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 3956
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT BINDING 3961
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT SITE 2662..2663
FT /note="Cleavage; by TASP1, site 1"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT SITE 2714..2715
FT /note="Cleavage; by TASP1, site 2"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT SITE 3762
FT /note="Important for WDR5-recognition and binding"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 134
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 140
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 237
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 371
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 634
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 837
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 923
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 1053
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1127
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 1232
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 1839
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1847
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1860
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 2100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2148
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 2152
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 2202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 2560
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2607
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 2792
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 2951
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 2954
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 3032
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 3369
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 3459
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 3510
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 3523
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 3879
FT /note="S-methylcysteine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT CROSSLNK 2524
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT VAR_SEQ 1603..1605
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8327517"
FT /id="VSP_006667"
FT VARIANT 1597
FT /note="K -> T"
FT CONFLICT 372
FT /note="Q -> E (in Ref. 3; BAE28820)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="Q -> K (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="L -> F (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 797
FT /note="P -> S (in Ref. 3; BAE28820)"
FT /evidence="ECO:0000305"
FT CONFLICT 806
FT /note="E -> D (in Ref. 2; AAA62593 and 3; BAE28820)"
FT /evidence="ECO:0000305"
FT CONFLICT 821
FT /note="L -> P (in Ref. 2; AAA62593 and 3; BAE28820)"
FT /evidence="ECO:0000305"
FT CONFLICT 1069
FT /note="C -> Y (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 1230
FT /note="A -> S (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 1349
FT /note="R -> L (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 1437
FT /note="A -> S (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 1440
FT /note="G -> E (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 1632
FT /note="A -> P (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 2292
FT /note="S -> L (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 3481
FT /note="N -> I (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 3493
FT /note="R -> S (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 3548
FT /note="G -> V (in Ref. 2; AAA62593)"
FT /evidence="ECO:0000305"
FT CONFLICT 3769
FT /note="Q -> K (in Ref. 2; AAA62593)"
FT /evidence="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
