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Histone-lysine N-methyltransferase 2C (Lysine N-methyltransferase 2C) (EC 2.1.1.43) (Homologous to ALR protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 3)

 KMT2C_HUMAN             Reviewed;        4911 AA.
Q8NEZ4; Q8NC02; Q8NDF6; Q9H9P4; Q9NR13; Q9P222; Q9UDR7;
10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
20-JAN-2009, sequence version 3.
18-SEP-2019, entry version 178.
RecName: Full=Histone-lysine N-methyltransferase 2C;
Short=Lysine N-methyltransferase 2C;
EC=2.1.1.43;
AltName: Full=Homologous to ALR protein;
AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia protein 3;
Name=KMT2C; Synonyms=HALR, KIAA1506, MLL3;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-526.
TISSUE=Fetal thymus;
PubMed=11891048; DOI=10.1016/s0378-1119(02)00392-x;
Ruault M., Brun M.-E., Ventura M., Roizes G., De Sario A.;
"MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a
chromosome region frequently deleted in myeloid leukaemia.";
Gene 284:73-81(2002).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Cervix carcinoma;
PubMed=11718452;
Tan Y.C., Chow V.T.;
"Novel human HALR (MLL3) gene encodes a protein homologous to ALR and
to ALL-1 involved in leukemia, and maps to chromosome 7q36 associated
with leukemia and developmental defects.";
Cancer Detect. Prev. 25:454-469(2001).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12853948; DOI=10.1038/nature01782;
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 556-3865 (ISOFORM 1).
TISSUE=Brain;
PubMed=10819331; DOI=10.1093/dnares/7.2.143;
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
"Prediction of the coding sequences of unidentified human genes. XVII.
The complete sequences of 100 new cDNA clones from brain which code
for large proteins in vitro.";
DNA Res. 7:143-150(2000).
[5]
SEQUENCE REVISION.
PubMed=12168954; DOI=10.1093/dnares/9.3.99;
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
"Construction of expression-ready cDNA clones for KIAA genes: manual
curation of 330 KIAA cDNA clones.";
DNA Res. 9:99-106(2002).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3193-3865 AND 4460-4911.
TISSUE=Placenta;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[7]
PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
TISSUE=Testis;
PubMed=17974005; DOI=10.1186/1471-2164-8-399;
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
"The full-ORF clone resource of the German cDNA consortium.";
BMC Genomics 8:399-399(2007).
[8]
INTERACTION WITH MLL2/3 COMPLEX (ISOFORM 2).
TISSUE=Cervix carcinoma;
PubMed=12482968; DOI=10.1128/mcb.23.1.140-149.2003;
Goo Y.-H., Sohn Y.C., Kim D.-H., Kim S.-W., Kang M.-J., Jung D.-J.,
Kwak E., Barlev N.A., Berger S.L., Chow V.T., Roeder R.G.,
Azorsa D.O., Meltzer P.S., Suh P.-G., Song E.J., Lee K.-J., Lee Y.C.,
Lee J.W.;
"Activating signal cointegrator 2 belongs to a novel steady-state
complex that contains a subset of trithorax group proteins.";
Mol. Cell. Biol. 23:140-149(2003).
[9]
IDENTIFICATION IN THE MLL2/3 (ASCOM) COMPLEX.
PubMed=17021013; DOI=10.1073/pnas.0607313103;
Lee S., Lee D.K., Dou Y., Lee J., Lee B., Kwak E., Kong Y.Y.,
Lee S.K., Roeder R.G., Lee J.W.;
"Coactivator as a target gene specificity determinant for histone H3
lysine 4 methyltransferases.";
Proc. Natl. Acad. Sci. U.S.A. 103:15392-15397(2006).
[10]
FUNCTION, ENZYME ACTIVITY, IDENTIFICATION BY MASS SPECTROMETRY, AND
IDENTIFICATION IN THE MLL2/3 COMPLEX.
PubMed=17500065; DOI=10.1074/jbc.m701574200;
Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T.,
Dressler G.R., Copeland T.D., Kalkum M., Ge K.;
"PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4
methyltransferase complex.";
J. Biol. Chem. 282:20395-20406(2007).
[11]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[12]
ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-758; LYS-1508; LYS-1772;
LYS-2009; LYS-2802; LYS-2809; LYS-2832 AND LYS-3714, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19608861; DOI=10.1126/science.1175371;
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
Walther T.C., Olsen J.V., Mann M.;
"Lysine acetylation targets protein complexes and co-regulates major
cellular functions.";
Science 325:834-840(2009).
[13]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=20068231; DOI=10.1126/scisignal.2000475;
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
Mann M.;
"Quantitative phosphoproteomics reveals widespread full
phosphorylation site occupancy during mitosis.";
Sci. Signal. 3:RA3-RA3(2010).
[14]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-89 AND SER-1301, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21406692; DOI=10.1126/scisignal.2001570;
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
Blagoev B.;
"System-wide temporal characterization of the proteome and
phosphoproteome of human embryonic stem cell differentiation.";
Sci. Signal. 4:RS3-RS3(2011).
[15]
INVOLVEMENT IN KLEFS2, AND VARIANT KLEFS2 1481-ARG--ASN-4911 DEL.
PubMed=22726846; DOI=10.1016/j.ajhg.2012.05.003;
Kleefstra T., Kramer J.M., Neveling K., Willemsen M.H., Koemans T.S.,
Vissers L.E., Wissink-Lindhout W., Fenckova M., van den Akker W.M.,
Kasri N.N., Nillesen W.M., Prescott T., Clark R.D., Devriendt K.,
van Reeuwijk J., de Brouwer A.P., Gilissen C., Zhou H., Brunner H.G.,
Veltman J.A., Schenck A., van Bokhoven H.;
"Disruption of an EHMT1-associated chromatin-modification module
causes intellectual disability.";
Am. J. Hum. Genet. 91:73-82(2012).
[16]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-113; SER-854;
SER-1987; SER-2828 AND SER-4267, AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[17]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200; SER-3758; SER-4034
AND SER-4267, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[18]
INVOLVEMENT IN KLEFS2, AND VARIANTS KLEFS2 564-LYS--ASN-4911 DEL AND
2517-SER--ASN-4911 DEL.
PubMed=29069077; DOI=10.1371/journal.pgen.1006864;
Koemans T.S., Kleefstra T., Chubak M.C., Stone M.H., Reijnders M.R.F.,
de Munnik S., Willemsen M.H., Fenckova M., Stumpel C.T.R.M., Bok L.A.,
Sifuentes Saenz M., Byerly K.A., Baughn L.B., Stegmann A.P.A.,
Pfundt R., Zhou H., van Bokhoven H., Schenck A., Kramer J.M.;
"Functional convergence of histone methyltransferases EHMT1 and KMT2C
involved in intellectual disability and autism spectrum disorder.";
PLoS Genet. 13:E1006864-E1006864(2017).
[19]
STRUCTURE BY NMR OF 342-439.
RIKEN structural genomics initiative (RSGI);
"Solution structure of the first and second PHD domain from
myeloid/lymphoid or mixed-lineage leukemia protein 3 homolog.";
Submitted (OCT-2007) to the PDB data bank.
[20]
STRUCTURE BY NMR OF 1624-1713.
RIKEN structural genomics initiative (RSGI);
"Solution structure of the HMG box of human myeloid/lymphoid or mixed-
lineage leukemia protein 3 homolog.";
Submitted (APR-2008) to the PDB data bank.
[21]
VARIANTS [LARGE SCALE ANALYSIS] GLY-347; ASN-400; TRP-478 AND
SER-3698.
PubMed=16959974; DOI=10.1126/science.1133427;
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal
cancers.";
Science 314:268-274(2006).
-!- FUNCTION: Histone methyltransferase. Methylates 'Lys-4' of histone
H3. H3 'Lys-4' methylation represents a specific tag for
epigenetic transcriptional activation. Central component of the
MLL2/3 complex, a coactivator complex of nuclear receptors,
involved in transcriptional coactivation. KMT2C/MLL3 may be a
catalytic subunit of this complex. May be involved in
leukemogenesis and developmental disorder.
{ECO:0000269|PubMed:17500065}.
-!- CATALYTIC ACTIVITY:
Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
Evidence={ECO:0000269|PubMed:17500065};
-!- SUBUNIT: Component of the MLL2/3 complex (also named ASCOM
complex), at least composed of KMT2D/MLL2 or KMT2C/MLL3, ASH2L,
RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and
alpha- and beta-tubulin. Interacts with histone H3.
{ECO:0000269|PubMed:17021013, ECO:0000269|PubMed:17500065}.
-!- INTERACTION:
Q9UBL3-3:ASH2L; NbExp=5; IntAct=EBI-1042997, EBI-16130425;
Q14686:NCOA6; NbExp=7; IntAct=EBI-1042997, EBI-78670;
P61964:WDR5; NbExp=4; IntAct=EBI-1042997, EBI-540834;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=Q8NEZ4-1; Sequence=Displayed;
Name=2;
IsoId=Q8NEZ4-2; Sequence=VSP_008561, VSP_008562, VSP_036223;
Note=No experimental confirmation available.;
Name=3;
IsoId=Q8NEZ4-3; Sequence=VSP_008562;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Highly expressed in testis and ovary, followed
by brain and liver. Also expressed in placenta, peripherical
blood, fetal thymus, heart, lung and kidney. Within brain,
expression was highest in hippocampus, caudate nucleus, and
substantia nigra. Not detected in skeletal muscle and fetal liver.
-!- DOMAIN: The SET domain interacts with histone H3 but not H2A, H2B
and H4, and may have a H3 lysine specific methylation activity.
-!- DISEASE: Kleefstra syndrome 2 (KLEFS2) [MIM:617768]: A form of
Kleefstra syndrome, an autosomal dominant disease characterized by
variable mental retardation, psychomotor developmental delay,
seizures, behavioral abnormalities, and facial dysmorphisms.
{ECO:0000269|PubMed:22726846, ECO:0000269|PubMed:29069077}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- MISCELLANEOUS: Found in a critical region of chromosome 7, which
is commonly deleted in malignant myeloid disorders. Partial
duplication of the KMT2C gene are found in the juxtacentromeric
region of chromosomes 1, 2, 13 and 21. Juxtacentromeric
reshuffling of the KMT2C gene has generated the BAGE genes.
-!- SIMILARITY: Belongs to the class V-like SAM-binding
methyltransferase superfamily. Histone-lysine methyltransferase
family. TRX/MLL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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EMBL; AY024361; AAK00583.1; -; mRNA.
EMBL; AF264750; AAF74766.2; -; mRNA.
EMBL; AC006017; AAD45822.1; -; Genomic_DNA.
EMBL; AC104692; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC005631; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AB040939; BAA96030.2; -; mRNA.
EMBL; AK022687; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AK075113; BAC11409.1; -; mRNA.
EMBL; AL833924; CAD38780.1; -; mRNA.
CCDS; CCDS5931.1; -. [Q8NEZ4-1]
RefSeq; NP_733751.2; NM_170606.2. [Q8NEZ4-1]
PDB; 2YSM; NMR; -; A=342-439.
PDB; 2YUK; NMR; -; A=1631-1713.
PDB; 3UVL; X-ray; 2.20 A; B=4707-4717.
PDB; 4ERY; X-ray; 1.30 A; D=4703-4716.
PDB; 5F59; X-ray; 2.80 A; A=4757-4910.
PDB; 5F6K; X-ray; 2.41 A; C/E=4757-4911.
PDB; 6MLC; X-ray; 1.80 A; A/B/C/D=1055-1144.
PDBsum; 2YSM; -.
PDBsum; 2YUK; -.
PDBsum; 3UVL; -.
PDBsum; 4ERY; -.
PDBsum; 5F59; -.
PDBsum; 5F6K; -.
PDBsum; 6MLC; -.
SMR; Q8NEZ4; -.
BioGrid; 121835; 34.
CORUM; Q8NEZ4; -.
DIP; DIP-48649N; -.
IntAct; Q8NEZ4; 24.
MINT; Q8NEZ4; -.
STRING; 9606.ENSP00000262189; -.
BindingDB; Q8NEZ4; -.
ChEMBL; CHEMBL2189113; -.
iPTMnet; Q8NEZ4; -.
PhosphoSitePlus; Q8NEZ4; -.
BioMuta; KMT2C; -.
DMDM; 221222521; -.
EPD; Q8NEZ4; -.
jPOST; Q8NEZ4; -.
MassIVE; Q8NEZ4; -.
MaxQB; Q8NEZ4; -.
PaxDb; Q8NEZ4; -.
PeptideAtlas; Q8NEZ4; -.
PRIDE; Q8NEZ4; -.
ProteomicsDB; 73252; -. [Q8NEZ4-1]
ProteomicsDB; 73253; -. [Q8NEZ4-2]
ProteomicsDB; 73254; -. [Q8NEZ4-3]
Ensembl; ENST00000262189; ENSP00000262189; ENSG00000055609. [Q8NEZ4-1]
Ensembl; ENST00000355193; ENSP00000347325; ENSG00000055609. [Q8NEZ4-1]
GeneID; 58508; -.
KEGG; hsa:58508; -.
UCSC; uc003wla.3; human. [Q8NEZ4-1]
CTD; 58508; -.
DisGeNET; 58508; -.
GeneCards; KMT2C; -.
HGNC; HGNC:13726; KMT2C.
HPA; HPA074736; -.
MalaCards; KMT2C; -.
MIM; 606833; gene.
MIM; 617768; phenotype.
neXtProt; NX_Q8NEZ4; -.
OpenTargets; ENSG00000055609; -.
Orphanet; 261652; Kleefstra syndrome due to a point mutation.
PharmGKB; PA30847; -.
eggNOG; KOG4443; Eukaryota.
eggNOG; COG2940; LUCA.
GeneTree; ENSGT00940000155281; -.
InParanoid; Q8NEZ4; -.
KO; K09188; -.
OMA; VNPGFIQ; -.
OrthoDB; 61027at2759; -.
PhylomeDB; Q8NEZ4; -.
TreeFam; TF354317; -.
Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
ChiTaRS; KMT2C; human.
EvolutionaryTrace; Q8NEZ4; -.
GeneWiki; MLL3; -.
GenomeRNAi; 58508; -.
Pharos; Q8NEZ4; -.
PRO; PR:Q8NEZ4; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000055609; Expressed in 216 organ(s), highest expression level in placenta.
ExpressionAtlas; Q8NEZ4; baseline and differential.
Genevisible; Q8NEZ4; HS.
GO; GO:0035097; C:histone methyltransferase complex; IDA:MGI.
GO; GO:0044666; C:MLL3/4 complex; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
GO; GO:0042393; F:histone binding; IBA:GO_Central.
GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:MGI.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
GO; GO:0016746; F:transferase activity, transferring acyl groups; IEA:UniProtKB-KW.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
GO; GO:0045652; P:regulation of megakaryocyte differentiation; TAS:Reactome.
CDD; cd15696; ePHD1_KMT2C; 1.
CDD; cd15697; ePHD2_KMT2C; 1.
Gene3D; 1.10.30.10; -; 1.
Gene3D; 3.30.40.10; -; 7.
InterPro; IPR034732; EPHD.
InterPro; IPR003889; FYrich_C.
InterPro; IPR003888; FYrich_N.
InterPro; IPR009071; HMG_box_dom.
InterPro; IPR036910; HMG_box_dom_sf.
InterPro; IPR000637; HMGI/Y_DNA-bd_CS.
InterPro; IPR037877; KMT2C.
InterPro; IPR041967; KMT2C_ePHD1.
InterPro; IPR041968; KMT2C_ePHD2.
InterPro; IPR003616; Post-SET_dom.
InterPro; IPR001214; SET_dom.
InterPro; IPR011011; Znf_FYVE_PHD.
InterPro; IPR001965; Znf_PHD.
InterPro; IPR019787; Znf_PHD-finger.
InterPro; IPR001841; Znf_RING.
InterPro; IPR013083; Znf_RING/FYVE/PHD.
PANTHER; PTHR45888:SF1; PTHR45888:SF1; 2.
Pfam; PF05965; FYRC; 1.
Pfam; PF05964; FYRN; 1.
Pfam; PF00628; PHD; 2.
Pfam; PF00856; SET; 1.
SMART; SM00542; FYRC; 1.
SMART; SM00541; FYRN; 1.
SMART; SM00398; HMG; 1.
SMART; SM00249; PHD; 8.
SMART; SM00508; PostSET; 1.
SMART; SM00184; RING; 4.
SMART; SM00317; SET; 1.
SUPFAM; SSF47095; SSF47095; 1.
SUPFAM; SSF57903; SSF57903; 6.
PROSITE; PS50216; DHHC; 1.
PROSITE; PS51805; EPHD; 2.
PROSITE; PS51543; FYRC; 1.
PROSITE; PS51542; FYRN; 1.
PROSITE; PS00354; HMGI_Y; 1.
PROSITE; PS50868; POST_SET; 1.
PROSITE; PS50280; SET; 1.
PROSITE; PS01359; ZF_PHD_1; 5.
PROSITE; PS50016; ZF_PHD_2; 6.
PROSITE; PS50089; ZF_RING_2; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Activator; Acyltransferase;
Alternative splicing; Chromatin regulator; Coiled coil;
Complete proteome; Disease mutation; DNA-binding; Lipoprotein;
Mental retardation; Metal-binding; Methylation; Methyltransferase;
Nucleus; Palmitate; Phosphoprotein; Polymorphism; Reference proteome;
Repeat; S-adenosyl-L-methionine; Transcription;
Transcription regulation; Transferase; Zinc; Zinc-finger.
CHAIN 1 4911 Histone-lysine N-methyltransferase 2C.
/FTId=PRO_0000124879.
DOMAIN 436 489 DHHC. {ECO:0000255|PROSITE-
ProRule:PRU00067}.
DOMAIN 4545 4605 FYR N-terminal. {ECO:0000255|PROSITE-
ProRule:PRU00875}.
DOMAIN 4606 4691 FYR C-terminal. {ECO:0000255|PROSITE-
ProRule:PRU00876}.
DOMAIN 4771 4887 SET. {ECO:0000255|PROSITE-
ProRule:PRU00190}.
DOMAIN 4895 4911 Post-SET. {ECO:0000255|PROSITE-
ProRule:PRU00155}.
DNA_BIND 34 46 A.T hook.
ZN_FING 227 262 C2HC pre-PHD-type 1; degenerate.
{ECO:0000255|PROSITE-ProRule:PRU01146}.
ZN_FING 283 331 PHD-type 1. {ECO:0000255|PROSITE-
ProRule:PRU01146}.
ZN_FING 341 391 PHD-type 2. {ECO:0000255|PROSITE-
ProRule:PRU00146}.
ZN_FING 344 389 RING-type. {ECO:0000255|PROSITE-
ProRule:PRU00175}.
ZN_FING 388 438 PHD-type 3. {ECO:0000255|PROSITE-
ProRule:PRU00146}.
ZN_FING 464 520 PHD-type 4. {ECO:0000255|PROSITE-
ProRule:PRU00146}.
ZN_FING 957 1010 PHD-type 5. {ECO:0000255|PROSITE-
ProRule:PRU00146}.
ZN_FING 1007 1057 PHD-type 6. {ECO:0000255|PROSITE-
ProRule:PRU00146}.
ZN_FING 1084 1139 PHD-type 7. {ECO:0000255|PROSITE-
ProRule:PRU00146}.
ZN_FING 4399 4439 C2HC pre-PHD-type 2.
{ECO:0000255|PROSITE-ProRule:PRU01146}.
ZN_FING 4460 4507 PHD-type 8. {ECO:0000255|PROSITE-
ProRule:PRU01146}.
REGION 4848 4849 S-adenosyl-L-methionine binding.
{ECO:0000250}.
COILED 92 112 {ECO:0000255}.
COILED 644 672 {ECO:0000255}.
COILED 1338 1366 {ECO:0000255}.
COILED 1754 1787 {ECO:0000255}.
COILED 3054 3081 {ECO:0000255}.
COILED 3173 3272 {ECO:0000255}.
COILED 3391 3433 {ECO:0000255}.
COMPBIAS 1719 1796 Gln-rich.
COMPBIAS 1834 2281 Pro-rich.
COMPBIAS 2412 2630 Pro-rich.
COMPBIAS 2690 2786 Asp-rich.
COMPBIAS 3012 3509 Gln-rich.
COMPBIAS 3277 3381 Pro-rich.
METAL 4851 4851 Zinc. {ECO:0000250}.
METAL 4899 4899 Zinc. {ECO:0000250}.
METAL 4901 4901 Zinc. {ECO:0000250}.
METAL 4906 4906 Zinc. {ECO:0000250}.
BINDING 4825 4825 S-adenosyl-L-methionine.
{ECO:0000255|PROSITE-ProRule:PRU00190}.
MOD_RES 28 28 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 46 46 Phosphoserine.
{ECO:0000244|PubMed:20068231}.
MOD_RES 89 89 Phosphoserine.
{ECO:0000244|PubMed:21406692}.
MOD_RES 113 113 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 200 200 Phosphoserine.
{ECO:0000244|PubMed:24275569}.
MOD_RES 758 758 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 854 854 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 1301 1301 Phosphoserine.
{ECO:0000244|PubMed:21406692}.
MOD_RES 1508 1508 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 1772 1772 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 1987 1987 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 2009 2009 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 2454 2454 Asymmetric dimethylarginine.
{ECO:0000250|UniProtKB:Q8BRH4}.
MOD_RES 2571 2571 Asymmetric dimethylarginine.
{ECO:0000250|UniProtKB:Q8BRH4}.
MOD_RES 2802 2802 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 2809 2809 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 2828 2828 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 2832 2832 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 2867 2867 N6-acetyllysine.
{ECO:0000250|UniProtKB:Q8BRH4}.
MOD_RES 3714 3714 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 3758 3758 Phosphoserine.
{ECO:0000244|PubMed:24275569}.
MOD_RES 4034 4034 Phosphoserine.
{ECO:0000244|PubMed:24275569}.
MOD_RES 4139 4139 Asymmetric dimethylarginine.
{ECO:0000250|UniProtKB:Q8BRH4}.
MOD_RES 4267 4267 Phosphoserine.
{ECO:0000244|PubMed:23186163,
ECO:0000244|PubMed:24275569}.
VAR_SEQ 1 939 Missing (in isoform 2).
{ECO:0000303|PubMed:11718452}.
/FTId=VSP_008561.
VAR_SEQ 3890 3890 Q -> QVRQLSLLPLMEPIIGVNFAHFLPYGSGQFNSGNRL
LGTFGSATLEGVSDYYSQLIYK (in isoform 2 and
isoform 3).
{ECO:0000303|PubMed:11718452}.
/FTId=VSP_008562.
VAR_SEQ 4721 4724 Missing (in isoform 2).
{ECO:0000303|PubMed:11718452}.
/FTId=VSP_036223.
VARIANT 291 291 L -> F (in dbSNP:rs56850341).
/FTId=VAR_061911.
VARIANT 316 316 T -> S (in dbSNP:rs10454320).
/FTId=VAR_061912.
VARIANT 347 347 C -> G (in a colorectal cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036311.
VARIANT 400 400 D -> N (in a colorectal cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036312.
VARIANT 478 478 L -> W (in a colorectal cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036313.
VARIANT 526 526 R -> P (in dbSNP:rs3735156).
{ECO:0000269|PubMed:11891048}.
/FTId=VAR_057360.
VARIANT 564 4911 Missing (in KLEFS2).
{ECO:0000269|PubMed:29069077}.
/FTId=VAR_080246.
VARIANT 823 823 I -> N (in dbSNP:rs2838171).
/FTId=VAR_017118.
VARIANT 823 823 I -> T (in dbSNP:rs2838171).
/FTId=VAR_017117.
VARIANT 1481 4911 Missing (in KLEFS2).
{ECO:0000269|PubMed:22726846}.
/FTId=VAR_080247.
VARIANT 1836 1836 S -> N (in dbSNP:rs11771635).
/FTId=VAR_057361.
VARIANT 2008 2008 T -> A (in dbSNP:rs6951159).
/FTId=VAR_057362.
VARIANT 2412 2412 P -> T (in dbSNP:rs13231116).
/FTId=VAR_057363.
VARIANT 2517 4911 Missing (in KLEFS2).
{ECO:0000269|PubMed:29069077}.
/FTId=VAR_080248.
VARIANT 2600 2600 P -> A (in dbSNP:rs2270234).
/FTId=VAR_057364.
VARIANT 3698 3698 T -> S (in a colorectal cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036314.
CONFLICT 579 579 A -> T (in Ref. 1; AAK00583).
{ECO:0000305}.
CONFLICT 1286 1286 M -> V (in Ref. 1; AAK00583).
{ECO:0000305}.
CONFLICT 2360 2360 P -> S (in Ref. 1; AAK00583).
{ECO:0000305}.
CONFLICT 2797 2797 K -> R (in Ref. 1; AAK00583).
{ECO:0000305}.
CONFLICT 2882 2882 T -> A (in Ref. 1; AAK00583).
{ECO:0000305}.
CONFLICT 3289 3289 P -> S (in Ref. 6; BAC11409).
{ECO:0000305}.
CONFLICT 3428 3428 R -> W (in Ref. 6; BAC11409).
{ECO:0000305}.
CONFLICT 4613 4613 I -> V (in Ref. 6; AK022687).
{ECO:0000305}.
CONFLICT 4866 4866 H -> P (in Ref. 6; AK022687).
{ECO:0000305}.
TURN 345 347 {ECO:0000244|PDB:2YSM}.
TURN 353 355 {ECO:0000244|PDB:2YSM}.
STRAND 356 358 {ECO:0000244|PDB:2YSM}.
STRAND 360 362 {ECO:0000244|PDB:2YSM}.
TURN 368 372 {ECO:0000244|PDB:2YSM}.
TURN 377 379 {ECO:0000244|PDB:2YSM}.
TURN 386 388 {ECO:0000244|PDB:2YSM}.
TURN 392 394 {ECO:0000244|PDB:2YSM}.
STRAND 403 405 {ECO:0000244|PDB:2YSM}.
STRAND 407 409 {ECO:0000244|PDB:2YSM}.
STRAND 412 414 {ECO:0000244|PDB:2YSM}.
HELIX 415 417 {ECO:0000244|PDB:2YSM}.
STRAND 418 420 {ECO:0000244|PDB:2YSM}.
HELIX 433 436 {ECO:0000244|PDB:2YSM}.
TURN 1058 1060 {ECO:0000244|PDB:6MLC}.
STRAND 1062 1064 {ECO:0000244|PDB:6MLC}.
STRAND 1071 1073 {ECO:0000244|PDB:6MLC}.
HELIX 1079 1082 {ECO:0000244|PDB:6MLC}.
TURN 1083 1085 {ECO:0000244|PDB:6MLC}.
TURN 1088 1090 {ECO:0000244|PDB:6MLC}.
STRAND 1099 1102 {ECO:0000244|PDB:6MLC}.
TURN 1104 1106 {ECO:0000244|PDB:6MLC}.
STRAND 1109 1112 {ECO:0000244|PDB:6MLC}.
HELIX 1113 1115 {ECO:0000244|PDB:6MLC}.
HELIX 1120 1129 {ECO:0000244|PDB:6MLC}.
TURN 1134 1136 {ECO:0000244|PDB:6MLC}.
HELIX 1636 1645 {ECO:0000244|PDB:2YUK}.
HELIX 1646 1648 {ECO:0000244|PDB:2YUK}.
STRAND 1650 1652 {ECO:0000244|PDB:2YUK}.
HELIX 1653 1660 {ECO:0000244|PDB:2YUK}.
HELIX 1664 1667 {ECO:0000244|PDB:2YUK}.
HELIX 1671 1684 {ECO:0000244|PDB:2YUK}.
HELIX 1687 1706 {ECO:0000244|PDB:2YUK}.
STRAND 4707 4709 {ECO:0000244|PDB:4ERY}.
HELIX 4758 4768 {ECO:0000244|PDB:5F6K}.
HELIX 4769 4771 {ECO:0000244|PDB:5F6K}.
STRAND 4773 4777 {ECO:0000244|PDB:5F6K}.
STRAND 4779 4789 {ECO:0000244|PDB:5F6K}.
STRAND 4796 4800 {ECO:0000244|PDB:5F6K}.
STRAND 4802 4806 {ECO:0000244|PDB:5F6K}.
HELIX 4807 4817 {ECO:0000244|PDB:5F6K}.
TURN 4818 4821 {ECO:0000244|PDB:5F6K}.
STRAND 4826 4828 {ECO:0000244|PDB:5F6K}.
STRAND 4830 4841 {ECO:0000244|PDB:5F6K}.
HELIX 4843 4846 {ECO:0000244|PDB:5F6K}.
STRAND 4854 4862 {ECO:0000244|PDB:5F6K}.
STRAND 4865 4874 {ECO:0000244|PDB:5F6K}.
STRAND 4908 4910 {ECO:0000244|PDB:5F59}.
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 DPYAH