KMT2C_HUMAN
ID KMT2C_HUMAN Reviewed; 4911 AA.
AC Q8NEZ4; Q8NC02; Q8NDF6; Q9H9P4; Q9NR13; Q9P222; Q9UDR7;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2009, sequence version 3.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Histone-lysine N-methyltransferase 2C;
DE Short=Lysine N-methyltransferase 2C;
DE EC=2.1.1.364 {ECO:0000269|PubMed:25561738};
DE AltName: Full=Homologous to ALR protein;
DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia protein 3;
GN Name=KMT2C; Synonyms=HALR, KIAA1506, MLL3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-526.
RC TISSUE=Fetal thymus;
RX PubMed=11891048; DOI=10.1016/s0378-1119(02)00392-x;
RA Ruault M., Brun M.-E., Ventura M., Roizes G., De Sario A.;
RT "MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a
RT chromosome region frequently deleted in myeloid leukaemia.";
RL Gene 284:73-81(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 556-3865 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 845-4911 (ISOFORM 2).
RC TISSUE=Cervix carcinoma;
RX PubMed=11718452;
RA Tan Y.C., Chow V.T.;
RT "Novel human HALR (MLL3) gene encodes a protein homologous to ALR and to
RT ALL-1 involved in leukemia, and maps to chromosome 7q36 associated with
RT leukemia and developmental defects.";
RL Cancer Detect. Prev. 25:454-469(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3193-3865 AND 4460-4911.
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP INTERACTION WITH MLL2/3 COMPLEX.
RC TISSUE=Cervix carcinoma;
RX PubMed=12482968; DOI=10.1128/mcb.23.1.140-149.2003;
RA Goo Y.-H., Sohn Y.C., Kim D.-H., Kim S.-W., Kang M.-J., Jung D.-J.,
RA Kwak E., Barlev N.A., Berger S.L., Chow V.T., Roeder R.G., Azorsa D.O.,
RA Meltzer P.S., Suh P.-G., Song E.J., Lee K.-J., Lee Y.C., Lee J.W.;
RT "Activating signal cointegrator 2 belongs to a novel steady-state complex
RT that contains a subset of trithorax group proteins.";
RL Mol. Cell. Biol. 23:140-149(2003).
RN [9]
RP IDENTIFICATION IN THE MLL2/3 COMPLEX.
RX PubMed=17021013; DOI=10.1073/pnas.0607313103;
RA Lee S., Lee D.K., Dou Y., Lee J., Lee B., Kwak E., Kong Y.Y., Lee S.K.,
RA Roeder R.G., Lee J.W.;
RT "Coactivator as a target gene specificity determinant for histone H3 lysine
RT 4 methyltransferases.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15392-15397(2006).
RN [10]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE
RP MLL2/3 COMPLEX.
RX PubMed=17500065; DOI=10.1074/jbc.m701574200;
RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T.,
RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.;
RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4
RT methyltransferase complex.";
RL J. Biol. Chem. 282:20395-20406(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-758; LYS-1508; LYS-1772;
RP LYS-2009; LYS-2802; LYS-2809; LYS-2832 AND LYS-3714, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-89 AND SER-1301, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP INVOLVEMENT IN KLEFS2, AND VARIANT KLEFS2 1481-ARG--ASN-4911 DEL.
RX PubMed=22726846; DOI=10.1016/j.ajhg.2012.05.003;
RA Kleefstra T., Kramer J.M., Neveling K., Willemsen M.H., Koemans T.S.,
RA Vissers L.E., Wissink-Lindhout W., Fenckova M., van den Akker W.M.,
RA Kasri N.N., Nillesen W.M., Prescott T., Clark R.D., Devriendt K.,
RA van Reeuwijk J., de Brouwer A.P., Gilissen C., Zhou H., Brunner H.G.,
RA Veltman J.A., Schenck A., van Bokhoven H.;
RT "Disruption of an EHMT1-associated chromatin-modification module causes
RT intellectual disability.";
RL Am. J. Hum. Genet. 91:73-82(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-113; SER-854;
RP SER-1987; SER-2828 AND SER-4267, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP IDENTIFICATION IN MLL3 COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=23508102; DOI=10.1128/mcb.01742-12;
RA van Nuland R., Smits A.H., Pallaki P., Jansen P.W., Vermeulen M.,
RA Timmers H.T.;
RT "Quantitative dissection and stoichiometry determination of the human
RT SET1/MLL histone methyltransferase complexes.";
RL Mol. Cell. Biol. 33:2067-2077(2013).
RN [18]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24081332; DOI=10.1128/mcb.01181-13;
RA Hu D., Gao X., Morgan M.A., Herz H.M., Smith E.R., Shilatifard A.;
RT "The MLL3/MLL4 branches of the COMPASS family function as major histone
RT H3K4 monomethylases at enhancers.";
RL Mol. Cell. Biol. 33:4745-4754(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200; SER-3758; SER-4034 AND
RP SER-4267, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ARG-4779;
RP TYR-4786; ASN-4848; GLN-4877 AND HIS-4900.
RX PubMed=25561738; DOI=10.1074/jbc.m114.627646;
RA Shinsky S.A., Monteith K.E., Viggiano S., Cosgrove M.S.;
RT "Biochemical reconstitution and phylogenetic comparison of human SET1
RT family core complexes involved in histone methylation.";
RL J. Biol. Chem. 290:6361-6375(2015).
RN [21]
RP INVOLVEMENT IN KLEFS2, AND VARIANTS KLEFS2 564-LYS--ASN-4911 DEL AND
RP 2517-SER--ASN-4911 DEL.
RX PubMed=29069077; DOI=10.1371/journal.pgen.1006864;
RA Koemans T.S., Kleefstra T., Chubak M.C., Stone M.H., Reijnders M.R.F.,
RA de Munnik S., Willemsen M.H., Fenckova M., Stumpel C.T.R.M., Bok L.A.,
RA Sifuentes Saenz M., Byerly K.A., Baughn L.B., Stegmann A.P.A., Pfundt R.,
RA Zhou H., van Bokhoven H., Schenck A., Kramer J.M.;
RT "Functional convergence of histone methyltransferases EHMT1 and KMT2C
RT involved in intellectual disability and autism spectrum disorder.";
RL PLoS Genet. 13:E1006864-E1006864(2017).
RN [22]
RP STRUCTURE BY NMR OF 342-439.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first and second PHD domain from
RT myeloid/lymphoid or mixed-lineage leukemia protein 3 homolog.";
RL Submitted (OCT-2007) to the PDB data bank.
RN [23]
RP STRUCTURE BY NMR OF 1624-1713.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the HMG box of human myeloid/lymphoid or mixed-
RT lineage leukemia protein 3 homolog.";
RL Submitted (APR-2008) to the PDB data bank.
RN [24] {ECO:0007744|PDB:4ERY}
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 4703-4716 IN COMPLEX WITH WDR5,
RP INTERACTION WITH WDR5, AND MOTIF WIN.
RX PubMed=22665483; DOI=10.1074/jbc.m112.364125;
RA Dharmarajan V., Lee J.H., Patel A., Skalnik D.G., Cosgrove M.S.;
RT "Structural basis for WDR5 interaction (Win) motif recognition in human
RT SET1 family histone methyltransferases.";
RL J. Biol. Chem. 287:27275-27289(2012).
RN [25] {ECO:0007744|PDB:3UVL}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 4707-4717 IN COMPLEX WITH WDR5,
RP INTERACTION WITH WDR5, MOTIF WIN, AND FUNCTION.
RX PubMed=22266653; DOI=10.1093/nar/gkr1235;
RA Zhang P., Lee H., Brunzelle J.S., Couture J.F.;
RT "The plasticity of WDR5 peptide-binding cleft enables the binding of the
RT SET1 family of histone methyltransferases.";
RL Nucleic Acids Res. 40:4237-4246(2012).
RN [26]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-347; ASN-400; TRP-478 AND SER-3698.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Histone methyltransferase that catalyzes methyl group
CC transfer from S-adenosyl-L-methionine to the epsilon-amino group of
CC 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin
CC remodeling machinery predominantly forms H3K4me1 methylation marks at
CC active chromatin sites where transcription and DNA repair take place
CC (PubMed:25561738, PubMed:24081332, PubMed:22266653). Likely plays a
CC redundant role with KMT2D in enriching H3K4me1 mark on primed and
CC active enhancer elements (PubMed:24081332).
CC {ECO:0000269|PubMed:22266653, ECO:0000269|PubMed:24081332,
CC ECO:0000269|PubMed:25561738}.
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:0000269|PubMed:25561738};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60265;
CC Evidence={ECO:0000305|PubMed:24081332, ECO:0000305|PubMed:25561738};
CC -!- SUBUNIT: Component of the MLL3 complex (also named ASCOM complex), at
CC least composed of catalytic subunit KMT2C/MLL3, ASH2L, RBBP5, WDR5,
CC NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin
CC (PubMed:17021013, PubMed:17500065, PubMed:23508102). Forms a core
CC complex with the evolutionary conserved subcomplex WRAD composed of
CC WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially
CC stimulates the methyltransferase activity (PubMed:25561738). Interacts
CC (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653).
CC {ECO:0000269|PubMed:17021013, ECO:0000269|PubMed:17500065,
CC ECO:0000269|PubMed:22266653, ECO:0000269|PubMed:22665483,
CC ECO:0000269|PubMed:23508102, ECO:0000269|PubMed:25561738}.
CC -!- INTERACTION:
CC Q8NEZ4; Q9UBL3-3: ASH2L; NbExp=5; IntAct=EBI-1042997, EBI-16130425;
CC Q8NEZ4; Q14686: NCOA6; NbExp=7; IntAct=EBI-1042997, EBI-78670;
CC Q8NEZ4; P61964: WDR5; NbExp=5; IntAct=EBI-1042997, EBI-540834;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23508102}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NEZ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NEZ4-2; Sequence=VSP_008562, VSP_036223;
CC Name=3;
CC IsoId=Q8NEZ4-3; Sequence=VSP_008562;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and ovary, followed by
CC brain and liver. Also expressed in placenta, peripherical blood, fetal
CC thymus, heart, lung and kidney. Within brain, expression was highest in
CC hippocampus, caudate nucleus, and substantia nigra. Not detected in
CC skeletal muscle and fetal liver.
CC -!- DOMAIN: The SET domain interacts with histone H3 but not H2A, H2B and
CC H4, and may have a H3 lysine specific methylation activity.
CC -!- DISEASE: Kleefstra syndrome 2 (KLEFS2) [MIM:617768]: A form of
CC Kleefstra syndrome, an autosomal dominant disease characterized by
CC variable intellectual disability, psychomotor developmental delay,
CC seizures, behavioral abnormalities, and facial dysmorphisms.
CC {ECO:0000269|PubMed:22726846, ECO:0000269|PubMed:29069077}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Found in a critical region of chromosome 7, which is
CC commonly deleted in malignant myeloid disorders. Partial duplication of
CC the KMT2C gene are found in the juxtacentromeric region of chromosomes
CC 1, 2, 13 and 21. Juxtacentromeric reshuffling of the KMT2C gene has
CC generated the BAGE genes.
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=AAF74766.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AY024361; AAK00583.1; -; mRNA.
DR EMBL; AC006017; AAD45822.1; -; Genomic_DNA.
DR EMBL; AC104692; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005631; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB040939; BAA96030.2; -; mRNA.
DR EMBL; AF264750; AAF74766.2; ALT_SEQ; mRNA.
DR EMBL; AK022687; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK075113; BAC11409.1; -; mRNA.
DR EMBL; AL833924; CAD38780.1; -; mRNA.
DR CCDS; CCDS5931.1; -. [Q8NEZ4-1]
DR RefSeq; NP_733751.2; NM_170606.2. [Q8NEZ4-1]
DR PDB; 2YSM; NMR; -; A=342-439.
DR PDB; 2YUK; NMR; -; A=1631-1713.
DR PDB; 3UVL; X-ray; 2.20 A; B=4707-4717.
DR PDB; 4ERY; X-ray; 1.30 A; D=4703-4716.
DR PDB; 5F59; X-ray; 2.80 A; A=4757-4910.
DR PDB; 5F6K; X-ray; 2.41 A; C/E=4757-4911.
DR PDB; 6KIW; EM; 4.00 A; K=4707-4911.
DR PDB; 6MLC; X-ray; 1.80 A; A/B/C/D=1055-1144.
DR PDBsum; 2YSM; -.
DR PDBsum; 2YUK; -.
DR PDBsum; 3UVL; -.
DR PDBsum; 4ERY; -.
DR PDBsum; 5F59; -.
DR PDBsum; 5F6K; -.
DR PDBsum; 6KIW; -.
DR PDBsum; 6MLC; -.
DR SMR; Q8NEZ4; -.
DR BioGRID; 121835; 108.
DR ComplexPortal; CPX-7091; Histone-lysine N-methyltransferase complex, KMT2C variant.
DR CORUM; Q8NEZ4; -.
DR DIP; DIP-48649N; -.
DR IntAct; Q8NEZ4; 71.
DR MINT; Q8NEZ4; -.
DR STRING; 9606.ENSP00000262189; -.
DR BindingDB; Q8NEZ4; -.
DR ChEMBL; CHEMBL2189113; -.
DR GlyGen; Q8NEZ4; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q8NEZ4; -.
DR PhosphoSitePlus; Q8NEZ4; -.
DR BioMuta; KMT2C; -.
DR DMDM; 221222521; -.
DR EPD; Q8NEZ4; -.
DR jPOST; Q8NEZ4; -.
DR MassIVE; Q8NEZ4; -.
DR MaxQB; Q8NEZ4; -.
DR PaxDb; Q8NEZ4; -.
DR PeptideAtlas; Q8NEZ4; -.
DR PRIDE; Q8NEZ4; -.
DR ProteomicsDB; 73252; -. [Q8NEZ4-1]
DR ProteomicsDB; 73253; -. [Q8NEZ4-2]
DR ProteomicsDB; 73254; -. [Q8NEZ4-3]
DR Antibodypedia; 33048; 90 antibodies from 23 providers.
DR DNASU; 58508; -.
DR Ensembl; ENST00000262189.11; ENSP00000262189.6; ENSG00000055609.21. [Q8NEZ4-1]
DR Ensembl; ENST00000682283.1; ENSP00000507485.1; ENSG00000055609.21. [Q8NEZ4-3]
DR GeneID; 58508; -.
DR KEGG; hsa:58508; -.
DR MANE-Select; ENST00000262189.11; ENSP00000262189.6; NM_170606.3; NP_733751.2.
DR UCSC; uc003wla.3; human. [Q8NEZ4-1]
DR CTD; 58508; -.
DR DisGeNET; 58508; -.
DR GeneCards; KMT2C; -.
DR HGNC; HGNC:13726; KMT2C.
DR HPA; ENSG00000055609; Low tissue specificity.
DR MalaCards; KMT2C; -.
DR MIM; 606833; gene.
DR MIM; 617768; phenotype.
DR neXtProt; NX_Q8NEZ4; -.
DR OpenTargets; ENSG00000055609; -.
DR Orphanet; 261652; Kleefstra syndrome due to a point mutation.
DR PharmGKB; PA30847; -.
DR VEuPathDB; HostDB:ENSG00000055609; -.
DR eggNOG; KOG4443; Eukaryota.
DR GeneTree; ENSGT00940000155281; -.
DR HOGENOM; CLU_000065_3_0_1; -.
DR InParanoid; Q8NEZ4; -.
DR OMA; GGTDTQN; -.
DR OrthoDB; 61027at2759; -.
DR PhylomeDB; Q8NEZ4; -.
DR TreeFam; TF354317; -.
DR BioCyc; MetaCyc:HS00685-MON; -.
DR PathwayCommons; Q8NEZ4; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR SignaLink; Q8NEZ4; -.
DR SIGNOR; Q8NEZ4; -.
DR BioGRID-ORCS; 58508; 34 hits in 1065 CRISPR screens.
DR ChiTaRS; KMT2C; human.
DR EvolutionaryTrace; Q8NEZ4; -.
DR GeneWiki; MLL3; -.
DR GenomeRNAi; 58508; -.
DR Pharos; Q8NEZ4; Tbio.
DR PRO; PR:Q8NEZ4; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q8NEZ4; protein.
DR Bgee; ENSG00000055609; Expressed in oocyte and 195 other tissues.
DR ExpressionAtlas; Q8NEZ4; baseline and differential.
DR Genevisible; Q8NEZ4; HS.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:MGI.
DR GO; GO:0044666; C:MLL3/4 complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0051568; P:histone H3-K4 methylation; IC:ComplexPortal.
DR GO; GO:0097692; P:histone H3-K4 monomethylation; IDA:CACAO.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd15696; ePHD1_KMT2C; 1.
DR CDD; cd15697; ePHD2_KMT2C; 1.
DR Gene3D; 1.10.30.10; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.40.10; -; 7.
DR IDEAL; IID00389; -.
DR InterPro; IPR034732; EPHD.
DR InterPro; IPR003889; FYrich_C.
DR InterPro; IPR003888; FYrich_N.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR000637; HMGI/Y_DNA-bd_CS.
DR InterPro; IPR037877; KMT2C.
DR InterPro; IPR041967; KMT2C_ePHD1.
DR InterPro; IPR041968; KMT2C_ePHD2.
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; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR45888:SF1; PTHR45888:SF1; 2.
DR Pfam; PF05965; FYRC; 1.
DR Pfam; PF05964; FYRN; 1.
DR Pfam; PF00628; PHD; 2.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00542; FYRC; 1.
DR SMART; SM00541; FYRN; 1.
DR SMART; SM00398; HMG; 1.
DR SMART; SM00249; PHD; 8.
DR SMART; SM00508; PostSET; 1.
DR SMART; SM00184; RING; 4.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR SUPFAM; SSF57903; SSF57903; 6.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50216; DHHC; 1.
DR PROSITE; PS51805; EPHD; 2.
DR PROSITE; PS51543; FYRC; 1.
DR PROSITE; PS51542; FYRN; 1.
DR PROSITE; PS00354; HMGI_Y; 1.
DR PROSITE; PS50868; POST_SET; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS01359; ZF_PHD_1; 5.
DR PROSITE; PS50016; ZF_PHD_2; 6.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Acyltransferase;
KW Alternative splicing; Chromatin regulator; Coiled coil; Disease variant;
KW DNA-binding; Intellectual disability; Lipoprotein; Metal-binding;
KW Methylation; Methyltransferase; Nucleus; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..4911
FT /note="Histone-lysine N-methyltransferase 2C"
FT /id="PRO_0000124879"
FT DOMAIN 436..489
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT DOMAIN 4545..4605
FT /note="FYR N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00875"
FT DOMAIN 4606..4691
FT /note="FYR C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00876"
FT DOMAIN 4771..4887
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 4895..4911
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT DNA_BIND 34..46
FT /note="A.T hook"
FT ZN_FING 227..262
FT /note="C2HC pre-PHD-type 1; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT ZN_FING 283..331
FT /note="PHD-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT ZN_FING 341..391
FT /note="PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 344..389
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 388..438
FT /note="PHD-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 464..520
FT /note="PHD-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 957..1010
FT /note="PHD-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1007..1057
FT /note="PHD-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1084..1139
FT /note="PHD-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 4399..4439
FT /note="C2HC pre-PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT ZN_FING 4460..4507
FT /note="PHD-type 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT REGION 1..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 164..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 721..742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 763..798
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 828..864
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 885..912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1215..1324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1406..1431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1458..1485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1604..1630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1709..2448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2589..2694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2793..2887
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2925..2954
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2989..3029
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3205..3241
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3353..3409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3527..3583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3596..3919
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4024..4053
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 92..112
FT /evidence="ECO:0000255"
FT COILED 644..672
FT /evidence="ECO:0000255"
FT COILED 1338..1366
FT /evidence="ECO:0000255"
FT COILED 1754..1787
FT /evidence="ECO:0000255"
FT COILED 3054..3081
FT /evidence="ECO:0000255"
FT COILED 3173..3272
FT /evidence="ECO:0000255"
FT COILED 3391..3433
FT /evidence="ECO:0000255"
FT MOTIF 4707..4712
FT /note="WDR5 interaction motif (WIN)"
FT /evidence="ECO:0000269|PubMed:22266653,
FT ECO:0000269|PubMed:22665483"
FT COMPBIAS 10..26
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..50
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 842..859
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1225..1272
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1406..1422
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1466..1485
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1709..1729
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1730..1757
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1758..1847
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1863..1893
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1918..1964
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2035..2053
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2111..2130
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2139..2160
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2170..2199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2205..2224
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2230..2253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2262..2276
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2277..2291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2302..2323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2331..2378
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2388..2402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2431..2447
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2628..2648
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2661..2684
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2793..2809
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2810..2833
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2834..2848
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2849..2863
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2864..2883
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3218..3236
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3364..3378
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3391..3409
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3527..3552
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3567..3583
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3622..3705
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3709..3740
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3799..3813
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3843..3878
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3879..3897
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3898..3912
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 4825
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 4848..4849
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 4851
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 4899
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 4901
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 4906
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 758
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 854
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1508
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1772
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1987
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2009
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 2454
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8BRH4"
FT MOD_RES 2571
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8BRH4"
FT MOD_RES 2802
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 2809
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 2828
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2832
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 2867
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BRH4"
FT MOD_RES 3714
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 3758
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 4034
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 4139
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8BRH4"
FT MOD_RES 4267
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 3890
FT /note="Q -> QVRQLSLLPLMEPIIGVNFAHFLPYGSGQFNSGNRLLGTFGSATLEG
FT VSDYYSQLIYK (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11718452"
FT /id="VSP_008562"
FT VAR_SEQ 4721..4724
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11718452"
FT /id="VSP_036223"
FT VARIANT 291
FT /note="L -> F (in dbSNP:rs56850341)"
FT /id="VAR_061911"
FT VARIANT 316
FT /note="T -> S (in dbSNP:rs10454320)"
FT /id="VAR_061912"
FT VARIANT 347
FT /note="C -> G (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036311"
FT VARIANT 400
FT /note="D -> N (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036312"
FT VARIANT 478
FT /note="L -> W (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036313"
FT VARIANT 526
FT /note="R -> P (in dbSNP:rs3735156)"
FT /evidence="ECO:0000269|PubMed:11891048"
FT /id="VAR_057360"
FT VARIANT 564..4911
FT /note="Missing (in KLEFS2)"
FT /evidence="ECO:0000269|PubMed:29069077"
FT /id="VAR_080246"
FT VARIANT 823
FT /note="I -> N (in dbSNP:rs2838171)"
FT /id="VAR_017118"
FT VARIANT 823
FT /note="I -> T (in dbSNP:rs2838171)"
FT /id="VAR_017117"
FT VARIANT 1481..4911
FT /note="Missing (in KLEFS2)"
FT /evidence="ECO:0000269|PubMed:22726846"
FT /id="VAR_080247"
FT VARIANT 1836
FT /note="S -> N (in dbSNP:rs11771635)"
FT /id="VAR_057361"
FT VARIANT 2008
FT /note="T -> A (in dbSNP:rs6951159)"
FT /id="VAR_057362"
FT VARIANT 2412
FT /note="P -> T (in dbSNP:rs13231116)"
FT /id="VAR_057363"
FT VARIANT 2517..4911
FT /note="Missing (in KLEFS2)"
FT /evidence="ECO:0000269|PubMed:29069077"
FT /id="VAR_080248"
FT VARIANT 2600
FT /note="P -> A (in dbSNP:rs2270234)"
FT /id="VAR_057364"
FT VARIANT 3698
FT /note="T -> S (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036314"
FT MUTAGEN 4779
FT /note="R->P: Confers a WRAD-dependent gain-of-function
FT histone H3 dimethylation activity. Converts H3K4me1 into
FT H3K4me2."
FT /evidence="ECO:0000269|PubMed:25561738"
FT MUTAGEN 4786
FT /note="Y->F: Confers a WRAD-dependent gain-of-function
FT histone H3 dimethylation activity. Converts H3K4me1 into
FT H3K4me2."
FT /evidence="ECO:0000269|PubMed:25561738"
FT MUTAGEN 4848
FT /note="N->A: Abolishes interaction with S-adenosyl-L-
FT methionine."
FT /evidence="ECO:0000269|PubMed:25561738"
FT MUTAGEN 4877
FT /note="Q->Y: Confers a WRAD-dependent gain-of-function
FT histone H3 dimethylation activity. Converts H3K4me1 into
FT H3K4me2."
FT /evidence="ECO:0000269|PubMed:25561738"
FT MUTAGEN 4900
FT /note="H->N: Confers a WRAD-dependent gain-of-function
FT histone H3 dimethylation activity. Converts H3K4me1 into
FT H3K4me2."
FT /evidence="ECO:0000269|PubMed:25561738"
FT CONFLICT 579
FT /note="A -> T (in Ref. 1; AAK00583)"
FT /evidence="ECO:0000305"
FT CONFLICT 1286
FT /note="M -> V (in Ref. 1; AAK00583)"
FT /evidence="ECO:0000305"
FT CONFLICT 2360
FT /note="P -> S (in Ref. 1; AAK00583)"
FT /evidence="ECO:0000305"
FT CONFLICT 2797
FT /note="K -> R (in Ref. 1; AAK00583)"
FT /evidence="ECO:0000305"
FT CONFLICT 2882
FT /note="T -> A (in Ref. 1; AAK00583)"
FT /evidence="ECO:0000305"
FT CONFLICT 3289
FT /note="P -> S (in Ref. 6; BAC11409)"
FT /evidence="ECO:0000305"
FT CONFLICT 3428
FT /note="R -> W (in Ref. 6; BAC11409)"
FT /evidence="ECO:0000305"
FT CONFLICT 4613
FT /note="I -> V (in Ref. 6; AK022687)"
FT /evidence="ECO:0000305"
FT CONFLICT 4866
FT /note="H -> P (in Ref. 6; AK022687)"
FT /evidence="ECO:0000305"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:2YSM"
FT TURN 353..355
FT /evidence="ECO:0007829|PDB:2YSM"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:2YSM"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:2YSM"
FT TURN 368..372
FT /evidence="ECO:0007829|PDB:2YSM"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:2YSM"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:2YSM"
FT TURN 392..394
FT /evidence="ECO:0007829|PDB:2YSM"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:2YSM"
FT STRAND 407..409
FT /evidence="ECO:0007829|PDB:2YSM"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:2YSM"
FT HELIX 415..417
FT /evidence="ECO:0007829|PDB:2YSM"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:2YSM"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:2YSM"
FT TURN 1058..1060
FT /evidence="ECO:0007829|PDB:6MLC"
FT STRAND 1062..1064
FT /evidence="ECO:0007829|PDB:6MLC"
FT STRAND 1071..1073
FT /evidence="ECO:0007829|PDB:6MLC"
FT HELIX 1079..1082
FT /evidence="ECO:0007829|PDB:6MLC"
FT TURN 1083..1085
FT /evidence="ECO:0007829|PDB:6MLC"
FT TURN 1088..1090
FT /evidence="ECO:0007829|PDB:6MLC"
FT STRAND 1099..1102
FT /evidence="ECO:0007829|PDB:6MLC"
FT TURN 1104..1106
FT /evidence="ECO:0007829|PDB:6MLC"
FT STRAND 1109..1112
FT /evidence="ECO:0007829|PDB:6MLC"
FT HELIX 1113..1115
FT /evidence="ECO:0007829|PDB:6MLC"
FT HELIX 1120..1129
FT /evidence="ECO:0007829|PDB:6MLC"
FT TURN 1134..1136
FT /evidence="ECO:0007829|PDB:6MLC"
FT HELIX 1636..1645
FT /evidence="ECO:0007829|PDB:2YUK"
FT HELIX 1646..1648
FT /evidence="ECO:0007829|PDB:2YUK"
FT STRAND 1650..1652
FT /evidence="ECO:0007829|PDB:2YUK"
FT HELIX 1653..1660
FT /evidence="ECO:0007829|PDB:2YUK"
FT HELIX 1664..1667
FT /evidence="ECO:0007829|PDB:2YUK"
FT HELIX 1671..1684
FT /evidence="ECO:0007829|PDB:2YUK"
FT HELIX 1687..1706
FT /evidence="ECO:0007829|PDB:2YUK"
FT STRAND 4707..4709
FT /evidence="ECO:0007829|PDB:4ERY"
FT HELIX 4758..4768
FT /evidence="ECO:0007829|PDB:5F6K"
FT HELIX 4769..4771
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4773..4777
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4779..4789
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4796..4800
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4802..4806
FT /evidence="ECO:0007829|PDB:5F6K"
FT HELIX 4807..4817
FT /evidence="ECO:0007829|PDB:5F6K"
FT TURN 4818..4821
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4826..4828
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4830..4841
FT /evidence="ECO:0007829|PDB:5F6K"
FT HELIX 4843..4846
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4854..4862
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4865..4874
FT /evidence="ECO:0007829|PDB:5F6K"
FT STRAND 4908..4910
FT /evidence="ECO:0007829|PDB:5F59"
SQ SEQUENCE 4911 AA; 541370 MW; 898CEE324772BD75 CRC64;
MSSEEDKSVE QPQPPPPPPE EPGAPAPSPA AADKRPRGRP RKDGASPFQR ARKKPRSRGK
TAVEDEDSMD GLETTETETI VETEIKEQSA EEDAEAEVDN SKQLIPTLQR SVSEESANSL
VSVGVEAKIS EQLCAFCYCG EKSSLGQGDL KQFRITPGFI LPWRNQPSNK KDIDDNSNGT
YEKMQNSAPR KQRGQRKERS PQQNIVSCVS VSTQTASDDQ AGKLWDELSL VGLPDAIDIQ
ALFDSTGTCW AHHRCVEWSL GVCQMEEPLL VNVDKAVVSG STERCAFCKH LGATIKCCEE
KCTQMYHYPC AAGAGTFQDF SHIFLLCPEH IDQAPERSKE DANCAVCDSP GDLLDQFFCT
TCGQHYHGMC LDIAVTPLKR AGWQCPECKV CQNCKQSGED SKMLVCDTCD KGYHTFCLQP
VMKSVPTNGW KCKNCRICIE CGTRSSSQWH HNCLICDNCY QQQDNLCPFC GKCYHPELQK
DMLHCNMCKR WVHLECDKPT DHELDTQLKE EYICMYCKHL GAEMDRLQPG EEVEIAELTT
DYNNEMEVEG PEDQMVFSEQ AANKDVNGQE STPGIVPDAV QVHTEEQQKS HPSESLDTDS
LLIAVSSQHT VNTELEKQIS NEVDSEDLKM SSEVKHICGE DQIEDKMEVT ENIEVVTHQI
TVQQEQLQLL EEPETVVSRE ESRPPKLVME SVTLPLETLV SPHEESISLC PEEQLVIERL
QGEKEQKENS ELSTGLMDSE MTPTIEGCVK DVSYQGGKSI KLSSETESSF SSSADISKAD
VSSSPTPSSD LPSHDMLHNY PSALSSSAGN IMPTTYISVT PKIGMGKPAI TKRKFSPGRP
RSKQGAWSTH NTVSPPSWSP DISEGREIFK PRQLPGSAIW SIKVGRGSGF PGKRRPRGAG
LSGRGGRGRS KLKSGIGAVV LPGVSTADIS SNKDDEENSM HNTVVLFSSS DKFTLNQDMC
VVCGSFGQGA EGRLLACSQC GQCYHPYCVS IKITKVVLSK GWRCLECTVC EACGKATDPG
RLLLCDDCDI SYHTYCLDPP LQTVPKGGWK CKWCVWCRHC GATSAGLRCE WQNNYTQCAP
CASLSSCPVC YRNYREEDLI LQCRQCDRWM HAVCQNLNTE EEVENVADIG FDCSMCRPYM
PASNVPSSDC CESSLVAQIV TKVKELDPPK TYTQDGVCLT ESGMTQLQSL TVTVPRRKRS
KPKLKLKIIN QNSVAVLQTP PDIQSEHSRD GEMDDSREGE LMDCDGKSES SPEREAVDDE
TKGVEGTDGV KKRKRKPYRP GIGGFMVRQR SRTGQGKTKR SVIRKDSSGS ISEQLPCRDD
GWSEQLPDTL VDESVSVTES TEKIKKRYRK RKNKLEETFP AYLQEAFFGK DLLDTSRQSK
ISLDNLSEDG AQLLYKTNMN TGFLDPSLDP LLSSSSAPTK SGTHGPADDP LADISEVLNT
DDDILGIISD DLAKSVDHSD IGPVTDDPSS LPQPNVNQSS RPLSEEQLDG ILSPELDKMV
TDGAILGKLY KIPELGGKDV EDLFTAVLSP ANTQPTPLPQ PPPPTQLLPI HNQDAFSRMP
LMNGLIGSSP HLPHNSLPPG SGLGTFSAIA QSSYPDARDK NSAFNPMASD PNNSWTSSAP
TVEGENDTMS NAQRSTLKWE KEEALGEMAT VAPVLYTNIN FPNLKEEFPD WTTRVKQIAK
LWRKASSQER APYVQKARDN RAALRINKVQ MSNDSMKRQQ QQDSIDPSSR IDSELFKDPL
KQRESEHEQE WKFRQQMRQK SKQQAKIEAT QKLEQVKNEQ QQQQQQQFGS QHLLVQSGSD
TPSSGIQSPL TPQPGNGNMS PAQSFHKELF TKQPPSTPTS TSSDDVFVKP QAPPPPPAPS
RIPIQDSLSQ AQTSQPPSPQ VFSPGSSNSR PPSPMDPYAK MVGTPRPPPV GHSFSRRNSA
APVENCTPLS SVSRPLQMNE TTANRPSPVR DLCSSSTTNN DPYAKPPDTP RPVMTDQFPK
SLGLSRSPVV SEQTAKGPIA AGTSDHFTKP SPRADVFQRQ RIPDSYARPL LTPAPLDSGP
GPFKTPMQPP PSSQDPYGSV SQASRRLSVD PYERPALTPR PIDNFSHNQS NDPYSQPPLT
PHPAVNESFA HPSRAFSQPG TISRPTSQDP YSQPPGTPRP VVDSYSQSSG TARSNTDPYS
QPPGTPRPTT VDPYSQQPQT PRPSTQTDLF VTPVTNQRHS DPYAHPPGTP RPGISVPYSQ
PPATPRPRIS EGFTRSSMTR PVLMPNQDPF LQAAQNRGPA LPGPLVRPPD TCSQTPRPPG
PGLSDTFSRV SPSAARDPYD QSPMTPRSQS DSFGTSQTAH DVADQPRPGS EGSFCASSNS
PMHSQGQQFS GVSQLPGPVP TSGVTDTQNT VNMAQADTEK LRQRQKLREI ILQQQQQKKI
AGRQEKGSQD SPAVPHPGPL QHWQPENVNQ AFTRPPPPYP GNIRSPVAPP LGPRYAVFPK
DQRGPYPPDV ASMGMRPHGF RFGFPGGSHG TMPSQERFLV PPQQIQGSGV SPQLRRSVSV
DMPRPLNNSQ MNNPVGLPQH FSPQSLPVQQ HNILGQAYIE LRHRAPDGRQ RLPFSAPPGS
VVEASSNLRH GNFIPRPDFP GPRHTDPMRR PPQGLPNQLP VHPDLEQVPP SQQEQGHSVH
SSSMVMRTLN HPLGGEFSEA PLSTSVPSET TSDNLQITTQ PSDGLEEKLD SDDPSVKELD
VKDLEGVEVK DLDDEDLENL NLDTEDGKVV ELDTLDNLET NDPNLDDLLR SGEFDIIAYT
DPELDMGDKK SMFNEELDLP IDDKLDNQCV SVEPKKKEQE NKTLVLSDKH SPQKKSTVTN
EVKTEVLSPN SKVESKCETE KNDENKDNVD TPCSQASAHS DLNDGEKTSL HPCDPDLFEK
RTNRETAGPS ANVIQASTQL PAQDVINSCG ITGSTPVLSS LLANEKSDNS DIRPSGSPPP
PTLPASPSNH VSSLPPFIAP PGRVLDNAMN SNVTVVSRVN HVFSQGVQVN PGLIPGQSTV
NHSLGTGKPA TQTGPQTSQS GTSSMSGPQQ LMIPQTLAQQ NRERPLLLEE QPLLLQDLLD
QERQEQQQQR QMQAMIRQRS EPFFPNIDFD AITDPIMKAK MVALKGINKV MAQNNLGMPP
MVMSRFPFMG QVVTGTQNSE GQNLGPQAIP QDGSITHQIS RPNPPNFGPG FVNDSQRKQY
EEWLQETQQL LQMQQKYLEE QIGAHRKSKK ALSAKQRTAK KAGREFPEED AEQLKHVTEQ
QSMVQKQLEQ IRKQQKEHAE LIEDYRIKQQ QQCAMAPPTM MPSVQPQPPL IPGATPPTMS
QPTFPMVPQQ LQHQQHTTVI SGHTSPVRMP SLPGWQPNSA PAHLPLNPPR IQPPIAQLPI
KTCTPAPGTV SNANPQSGPP PRVEFDDNNP FSESFQERER KERLREQQER QRIQLMQEVD
RQRALQQRME MEQHGMVGSE ISSSRTSVSQ IPFYSSDLPC DFMQPLGPLQ QSPQHQQQMG
QVLQQQNIQQ GSINSPSTQT FMQTNERRQV GPPSFVPDSP SIPVGSPNFS SVKQGHGNLS
GTSFQQSPVR PSFTPALPAA PPVANSSLPC GQDSTITHGH SYPGSTQSLI QLYSDIIPEE
KGKKKRTRKK KRDDDAESTK APSTPHSDIT APPTPGISET TSTPAVSTPS ELPQQADQES
VEPVGPSTPN MAAGQLCTEL ENKLPNSDFS QATPNQQTYA NSEVDKLSME TPAKTEEIKL
EKAETESCPG QEEPKLEEQN GSKVEGNAVA CPVSSAQSPP HSAGAPAAKG DSGNELLKHL
LKNKKSSSLL NQKPEGSICS EDDCTKDNKL VEKQNPAEGL QTLGAQMQGG FGCGNQLPKT
DGGSETKKQR SKRTQRTGEK AAPRSKKRKK DEEEKQAMYS STDTFTHLKQ QNNLSNPPTP
PASLPPTPPP MACQKMANGF ATTEELAGKA GVLVSHEVTK TLGPKPFQLP FRPQDDLLAR
ALAQGPKTVD VPASLPTPPH NNQEELRIQD HCGDRDTPDS FVPSSSPESV VGVEVSRYPD
LSLVKEEPPE PVPSPIIPIL PSTAGKSSES RRNDIKTEPG TLYFASPFGP SPNGPRSGLI
SVAITLHPTA AENISSVVAA FSDLLHVRIP NSYEVSSAPD VPSMGLVSSH RINPGLEYRQ
HLLLRGPPPG SANPPRLVSS YRLKQPNVPF PPTSNGLSGY KDSSHGIAES AALRPQWCCH
CKVVILGSGV RKSFKDLTLL NKDSRESTKR VEKDIVFCSN NCFILYSSTA QAKNSENKES
IPSLPQSPMR ETPSKAFHQY SNNISTLDVH CLPQLPEKAS PPASPPIAFP PAFEAAQVEA
KPDELKVTVK LKPRLRAVHG GFEDCRPLNK KWRGMKWKKW SIHIVIPKGT FKPPCEDEID
EFLKKLGTSL KPDPVPKDYR KCCFCHEEGD GLTDGPARLL NLDLDLWVHL NCALWSTEVY
ETQAGALINV ELALRRGLQM KCVFCHKTGA TSGCHRFRCT NIYHFTCAIK AQCMFFKDKT
MLCPMHKPKG IHEQELSYFA VFRRVYVQRD EVRQIASIVQ RGERDHTFRV GSLIFHTIGQ
LLPQQMQAFH SPKALFPVGY EASRLYWSTR YANRRCRYLC SIEEKDGRPV FVIRIVEQGH
EDLVLSDISP KGVWDKILEP VACVRKKSEM LQLFPAYLKG EDLFGLTVSA VARIAESLPG
VEACENYTFR YGRNPLMELP LAVNPTGCAR SEPKMSAHVK RFVLRPHTLN STSTSKSFQS
TVTGELNAPY SKQFVHSKSS QYRKMKTEWK SNVYLARSRI QGLGLYAARD IEKHTMVIEY
IGTIIRNEVA NRKEKLYESQ NRGVYMFRMD NDHVIDATLT GGPARYINHS CAPNCVAEVV
TFERGHKIII SSSRRIQKGE ELCYDYKFDF EDDQHKIPCH CGAVNCRKWM N
