KMT2E_HUMAN
ID KMT2E_HUMAN Reviewed; 1858 AA.
AC Q8IZD2; B6ZDE4; B6ZDM3; M4K8J3; Q6P5Y2; Q6PKG4; Q6T316; Q86TI3; Q86W12;
AC Q86WG0; Q86WL2; Q8IV78; Q8IWR5; Q8NFF8; Q9NWE7;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Inactive histone-lysine N-methyltransferase 2E {ECO:0000305};
DE Short=Inactive lysine N-methyltransferase 2E {ECO:0000305};
DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia protein 5;
GN Name=KMT2E; Synonyms=MLL5;
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] {ECO:0000305, ECO:0000312|EMBL:AAM74947.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=12101424; DOI=10.1038/sj.onc.1205615;
RA Emerling B.M., Bonifas J., Kratz C.P., Donovan S., Taylor B.R., Green E.D.,
RA Le Beau M.M., Shannon K.M.;
RT "MLL5, a homolog of Drosophila trithorax located within a segment of
RT chromosome band 7q22 implicated in myeloid leukemia.";
RL Oncogene 21:4849-4854(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM NKP44L), FUNCTION (ISOFORM NKP44L),
RP SUBCELLULAR LOCATION (ISOFORM NKP44L), AND TISSUE SPECIFICITY.
RX PubMed=23958951; DOI=10.1182/blood-2013-03-489054;
RA Baychelier F., Sennepin A., Ermonval M., Dorgham K., Debre P.,
RA Vieillard V.;
RT "Identification of a cellular ligand for the natural cytotoxicity receptor
RT NKp44.";
RL Blood 122:2935-2942(2013).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAN17675.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), NUCLEOTIDE SEQUENCE [MRNA]
RP OF 624-1858 (ISOFORM 4), NUCLEOTIDE SEQUENCE [MRNA] OF 1149-1251 (ISOFORMS
RP 1/2/4/6/7), NUCLEOTIDE SEQUENCE [MRNA] OF 1190-1355 (ISOFORM 7), AND
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1415-1858 (ISOFORMS 5 AND 6).
RC TISSUE=Brain {ECO:0000312|EMBL:AAO47010.1}, and
RC Peripheral blood leukocyte {ECO:0000312|EMBL:AAO89072.1};
RA Dohner K., Obermiller R.T., Lipka D.B., Hofmann K., Habdank M., Fazekas G.,
RA Frohling S., Lichter P., Scherer S.W., Dohner H.;
RT "Identification and characterization of a novel gene located in the
RT commonly deleted region 7q22-q31.1 in myeloid leukemias.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5] {ECO:0000305, ECO:0000312|EMBL:AAN17675.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAH62583.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-491.
RC TISSUE=Choriocarcinoma {ECO:0000312|EMBL:AAH01296.1},
RC Liver {ECO:0000312|EMBL:AAH40004.1}, and
RC Uterus {ECO:0000312|EMBL:AAH53906.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-594.
RC TISSUE=Embryo;
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 [8] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14718661; DOI=10.1073/pnas.2036345100;
RA Deng L.-W., Chiu I., Strominger J.L.;
RT "MLL 5 protein forms intranuclear foci, and overexpression inhibits cell
RT cycle progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:757-762(2004).
RN [9]
RP FUNCTION.
RX PubMed=18573682; DOI=10.1016/j.biocel.2008.04.012;
RA Cheng F., Liu J., Zhou S.H., Wang X.N., Chew J.F., Deng L.-W.;
RT "RNA interference against mixed lineage leukemia 5 resulted in cell cycle
RT arrest.";
RL Int. J. Biochem. Cell Biol. 40:2472-2481(2008).
RN [10]
RP CAUTION.
RX PubMed=19377461; DOI=10.1038/nature07954;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced
RT granulopoiesis.";
RL Nature 459:455-459(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-623; SER-837; SER-1070;
RP SER-1273 AND SER-1359, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [12]
RP 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 [13]
RP CAUTION, AND RETRACTION NOTICE OF PUBMED:24275569.
RX PubMed=24336203; DOI=10.1038/nature12896;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "Retraction: GlcNAcylation of a histone methyltransferase in retinoic-acid-
RT induced granulopoiesis.";
RL Nature 505:574-574(2014).
RN [14]
RP LACK OF CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-411.
RX PubMed=19264965; DOI=10.1073/pnas.0807136106;
RA Sebastian S., Sreenivas P., Sambasivan R., Cheedipudi S., Kandalla P.,
RA Pavlath G.K., Dhawan J.;
RT "MLL5, a trithorax homolog, indirectly regulates H3K4 methylation,
RT represses cyclin A2 expression, and promotes myogenic differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:4719-4724(2009).
RN [15]
RP FUNCTION, INTERACTION WITH HCFC1; E2F1 AND OGT (ISOFORM 3), SUBCELLULAR
RP LOCATION, MOTIF, AND MUTAGENESIS OF 62-ASP--TYR-66.
RX PubMed=23629655; DOI=10.1074/jbc.m112.439729;
RA Zhou P., Wang Z., Yuan X., Zhou C., Liu L., Wan X., Zhang F., Ding X.,
RA Wang C., Xiong S., Wang Z., Yuan J., Li Q., Zhang Y.;
RT "Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle progression
RT and E2F1-responsive gene expression via association with host cell factor-1
RT (HCF-1).";
RL J. Biol. Chem. 288:17532-17543(2013).
RN [16]
RP IDENTIFICATION IN A COMPLEX WITH OGT AND USP7, INTERACTION WITH OGT AND
RP USP7, SUBCELLULAR LOCATION, GLYCOSYLATION AT SER-435 AND THR-440, AND
RP UBIQUITINATION.
RX PubMed=26678539; DOI=10.1371/journal.pone.0145023;
RA Ding X., Jiang W., Zhou P., Liu L., Wan X., Yuan X., Wang X., Chen M.,
RA Chen J., Yang J., Kong C., Li B., Peng C., Wong C.C., Hou F., Zhang Y.;
RT "Mixed lineage leukemia 5 (MLL5) protein stability is cooperatively
RT regulated by O-GlcNac transferase (OGT) and ubiquitin specific protease 7
RT (USP7).";
RL PLoS ONE 10:E0145023-E0145023(2015).
RN [17]
RP STRUCTURE BY NMR OF 109-188 IN COMPLEX WITH ZINC, FUNCTION, AND DOMAIN.
RX PubMed=24130829; DOI=10.1371/journal.pone.0077020;
RA Lemak A., Yee A., Wu H., Yap D., Zeng H., Dombrovski L., Houliston S.,
RA Aparicio S., Arrowsmith C.H.;
RT "Solution NMR structure and histone binding of the PHD domain of human
RT MLL5.";
RL PLoS ONE 8:E77020-E77020(2013).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 117-181 IN COMPLEX WITH ZINC,
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF PHE-125;
RP ASP-128; TYR-131 AND TRP-141.
RX PubMed=23798402; DOI=10.1073/pnas.1310156110;
RA Ali M., Rincon-Arano H., Zhao W., Rothbart S.B., Tong Q., Parkhurst S.M.,
RA Strahl B.D., Deng L.W., Groudine M., Kutateladze T.G.;
RT "Molecular basis for chromatin binding and regulation of MLL5.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:11296-11301(2013).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 323-458, AND LACK OF CATALYTIC
RP ACTIVITY.
RX PubMed=27812132; DOI=10.1371/journal.pone.0165139;
RA Mas-Y-Mas S., Barbon M., Teyssier C., Demene H., Carvalho J.E., Bird L.E.,
RA Lebedev A., Fattori J., Schubert M., Dumas C., Bourguet W., le Maire A.;
RT "The human mixed lineage leukemia 5 (MLL5), a sequentially and structurally
RT divergent SET domain-containing protein with no intrinsic catalytic
RT activity.";
RL PLoS ONE 11:E0165139-E0165139(2016).
RN [20]
RP INVOLVEMENT IN ODLURO, VARIANTS ODLURO ILE-140; 151-ARG--HIS-1858 DEL;
RP HIS-284; 754-SER--HIS-1858 DEL; 818-ARG--HIS-1858 DEL; 874-ARG--HIS-1858
RP DEL; VAL-907; 1024-GLN--HIS-1858 DEL; 1185-SER--HIS-1858 DEL;
RP 1224-TYR--HIS-1858 DEL AND SER-1376, AND VARIANT LEU-1376D.
RX PubMed=31079897; DOI=10.1016/j.ajhg.2019.03.021;
RG Deciphering Developmental Disorders (DDD) Study;
RA O'Donnell-Luria A.H., Pais L.S., Faundes V., Wood J.C., Sveden A.,
RA Luria V., Abou Jamra R., Accogli A., Amburgey K., Anderlid B.M.,
RA Azzarello-Burri S., Basinger A.A., Bianchini C., Bird L.M., Buchert R.,
RA Carre W., Ceulemans S., Charles P., Cox H., Culliton L., Curro A.,
RA Demurger F., Dowling J.J., Duban-Bedu B., Dubourg C., Eiset S.E.,
RA Escobar L.F., Ferrarini A., Haack T.B., Hashim M., Heide S., Helbig K.L.,
RA Helbig I., Heredia R., Heron D., Isidor B., Jonasson A.R., Joset P.,
RA Keren B., Kok F., Kroes H.Y., Lavillaureix A., Lu X., Maas S.M.,
RA Maegawa G.H.B., Marcelis C.L.M., Mark P.R., Masruha M.R., McLaughlin H.M.,
RA McWalter K., Melchinger E.U., Mercimek-Andrews S., Nava C., Pendziwiat M.,
RA Person R., Ramelli G.P., Ramos L.L.P., Rauch A., Reavey C., Renieri A.,
RA Riess A., Sanchez-Valle A., Sattar S., Saunders C., Schwarz N., Smol T.,
RA Srour M., Steindl K., Syrbe S., Taylor J.C., Telegrafi A., Thiffault I.,
RA Trauner D.A., van der Linden H. Jr., van Koningsbruggen S., Villard L.,
RA Vogel I., Vogt J., Weber Y.G., Wentzensen I.M., Widjaja E., Zak J.,
RA Baxter S., Banka S., Rodan L.H.;
RT "Heterozygous variants in KMT2E cause a spectrum of neurodevelopmental
RT disorders and epilepsy.";
RL Am. J. Hum. Genet. 104:1210-1222(2019).
CC -!- FUNCTION: Associates with chromatin regions downstream of
CC transcriptional start sites of active genes and thus regulates gene
CC transcription (PubMed:23629655, PubMed:24130829, PubMed:23798402).
CC Chromatin interaction is mediated via the binding to tri-methylated
CC histone H3 at 'Lys-4' (H3K4me3) (PubMed:24130829, PubMed:23798402). Key
CC regulator of hematopoiesis involved in terminal myeloid differentiation
CC and in the regulation of hematopoietic stem cell (HSCs) self-renewal by
CC a mechanism that involves DNA methylation (By similarity). Also acts as
CC an important cell cycle regulator, participating in cell cycle
CC regulatory network machinery at multiple cell cycle stages including
CC G1/S transition, S phase progression and mitotic entry
CC (PubMed:14718661, PubMed:18573682, PubMed:19264965, PubMed:23629655).
CC Recruited to E2F1 responsive promoters by HCFC1 where it stimulates
CC tri-methylation of histone H3 at 'Lys-4' and transcriptional activation
CC and thereby facilitates G1 to S phase transition (PubMed:23629655).
CC During myoblast differentiation, required to suppress inappropriate
CC expression of S-phase-promoting genes and maintain expression of
CC determination genes in quiescent cells (By similarity).
CC {ECO:0000250|UniProtKB:Q3UG20, ECO:0000269|PubMed:14718661,
CC ECO:0000269|PubMed:18573682, ECO:0000269|PubMed:23629655,
CC ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829}.
CC -!- FUNCTION: [Isoform NKp44L]: Cellular ligand for NCR2/NKp44, may play a
CC role as a danger signal in cytotoxicity and NK-cell-mediated innate
CC immunity. {ECO:0000269|PubMed:23958951}.
CC -!- SUBUNIT: Component of a complex composed of KMT2E (isoform 3), OGT and
CC USP7; the complex stabilizes KMT2E, preventing KMT2E ubiquitination and
CC proteosomal-mediated degradation (PubMed:26678539). Isoform 3 interacts
CC (via N-terminus) with OGT (via TRP repeats) (PubMed:26678539,
CC PubMed:23629655). Isoform 3 interacts with deubiquitinating enzyme USP7
CC (via MATH domain) (PubMed:26678539). Isoform 3 interacts (via HBM
CC motif) with HCFC1 (via Kelch domain) (PubMed:23629655). Isoform 3
CC interacts with E2F1; the interaction is probably indirect and is
CC mediated via HCFC1 (PubMed:23629655). {ECO:0000269|PubMed:23629655,
CC ECO:0000269|PubMed:26678539}.
CC -!- INTERACTION:
CC Q8IZD2; P04637: TP53; NbExp=4; IntAct=EBI-2689959, EBI-366083;
CC Q8IZD2-3; Q9HD20-3: ATP13A1; NbExp=3; IntAct=EBI-12900093, EBI-12069500;
CC Q8IZD2-8; O95944: NCR2; NbExp=4; IntAct=EBI-15014150, EBI-14058375;
CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:23798402}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:23798402}. Nucleus speckle
CC {ECO:0000269|PubMed:14718661}. Note=Absent from the nucleolus
CC (PubMed:14718661). Localizes to chromosome during interphase and to
CC centrosomes during mitosis (PubMed:23798402). Dissociation from mitotic
CC chromosome is likely due to histone H3 phosphorylation on 'Thr-3' and
CC 'Thr-6' (PubMed:23798402). {ECO:0000269|PubMed:14718661,
CC ECO:0000269|PubMed:23798402}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26678539}. Nucleus
CC speckle {ECO:0000269|PubMed:23798402}. Note=Absent from the nucleolus
CC (PubMed:23629655). Localizes to chromosome during interphase and to
CC nucleus speckle during mitosis (PubMed:23798402). Dissociation from
CC mitotic chromosome is likely due to histone H3 phosphorylation on 'Thr-
CC 3' and 'Thr-6' (PubMed:23798402). {ECO:0000269|PubMed:23629655,
CC ECO:0000269|PubMed:23798402}.
CC -!- SUBCELLULAR LOCATION: [Isoform NKp44L]: Cytoplasm
CC {ECO:0000269|PubMed:23958951}. Cell membrane
CC {ECO:0000269|PubMed:23958951}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23958951}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1 {ECO:0000269|PubMed:12101424, ECO:0000269|Ref.3};
CC IsoId=Q8IZD2-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|Ref.3};
CC IsoId=Q8IZD2-2; Sequence=VSP_052803;
CC Name=3 {ECO:0000269|PubMed:15489334};
CC IsoId=Q8IZD2-3; Sequence=VSP_052804, VSP_052805;
CC Name=4 {ECO:0000269|Ref.3};
CC IsoId=Q8IZD2-4; Sequence=VSP_052806, VSP_052807;
CC Name=5 {ECO:0000269|Ref.3};
CC IsoId=Q8IZD2-5; Sequence=VSP_052810, VSP_052812;
CC Name=6 {ECO:0000269|Ref.3};
CC IsoId=Q8IZD2-6; Sequence=VSP_052809, VSP_052811;
CC Name=7 {ECO:0000269|Ref.3};
CC IsoId=Q8IZD2-7; Sequence=VSP_052808;
CC Name=NKp44L {ECO:0000303|PubMed:23958951};
CC IsoId=Q8IZD2-8; Sequence=VSP_053834, VSP_053835;
CC -!- TISSUE SPECIFICITY: Widely expressed in both adult and fetal tissues
CC (PubMed:12101424, PubMed:23958951). Highest levels of expression
CC observed in fetal thymus and kidney and in adult hematopoietic tissues,
CC jejunum and cerebellum (PubMed:12101424, PubMed:23958951). Isoform
CC NKp44L: Not detected on circulating cells from healthy individuals, but
CC is expressed on a large panel of tumor and transformed cells
CC (PubMed:23958951). {ECO:0000269|PubMed:12101424,
CC ECO:0000269|PubMed:23958951}.
CC -!- DOMAIN: The PHD-type domain binds specifically histone H3 tri-
CC methylated at 'Lys-4' (H3K4me3), thus promoting binding to chromatin.
CC {ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829}.
CC -!- DOMAIN: The SET domain does not bind the methyl group donor S-adenosyl-
CC L-methionine and histone 3 H3K4 peptide as a large loop prevents the
CC docking of the 'Lys-4' side chain. {ECO:0000269|PubMed:27812132}.
CC -!- DOMAIN: The C-terminus domain is responsible for the localization to
CC the centrosome during mitosis. {ECO:0000269|PubMed:23798402}.
CC -!- PTM: Ubiquitinated. Deubiquitinated by USP7.
CC {ECO:0000269|PubMed:26678539}.
CC -!- PTM: O-glycosylated at Ser-435 and Thr-440 in the SET domain by OGT
CC which probably prevents KMT2E proteasomal-mediated degradation.
CC {ECO:0000269|PubMed:26678539}.
CC -!- DISEASE: O'Donnell-Luria-Rodan syndrome (ODLURO) [MIM:618512]: A
CC neurodevelopmental disorder characterized by global developmental
CC delay, speech delay, intellectual disability and a subtle facial
CC gestalt. Additional common features include autism, seizures, hypotonia
CC and functional gastrointestinal abnormalities.
CC {ECO:0000269|PubMed:31079897}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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 -!- CAUTION: Isoform 3 was originally thought to display histone
CC methyltransferase activity only following O-glycosylation at Thr-440
CC (PubMed:19377461). However, the corresponding article has been
CC retracted (PubMed:24336203). Does not exhibit histone methyltransferase
CC towards histone H3 in vitro (PubMed:19264965, PubMed:27812132). The
CC isolated catalytic SET domain lacks binding activity towards cofactor
CC S-adenosyl-L-methionine; instead of the highly conserved XGXG, Y and NH
CC motifs, KMT2E displays NKKI (Asn-339-Ile-342), F (Phe-381) and RR (Arg-
CC 408-Arg-409) motifs (PubMed:27812132). Also lacks binding activity
CC towards histone H3 due to a poor conservation of the key residues
CC involved in the binding and the presence of large loop which prevents
CC the docking of the H3 'Lys-4' side chain (PubMed:27812132).
CC {ECO:0000269|PubMed:19264965, ECO:0000269|PubMed:19377461,
CC ECO:0000269|PubMed:24336203, ECO:0000269|PubMed:27812132}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH01296.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 492.; Evidence={ECO:0000305};
CC Sequence=AAH40004.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 227.; Evidence={ECO:0000305};
CC Sequence=AAH53906.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 227.; Evidence={ECO:0000305};
CC Sequence=AAI42988.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 492.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF519459; AAM74947.1; -; mRNA.
DR EMBL; JQ809698; AGE34449.1; -; mRNA.
DR EMBL; AY147037; AAN17675.1; -; mRNA.
DR EMBL; AY157990; AAN76325.1; -; mRNA.
DR EMBL; AY195568; AAO47009.1; -; mRNA.
DR EMBL; AY195569; AAO47010.1; -; mRNA.
DR EMBL; AY222296; AAO64395.1; -; mRNA.
DR EMBL; AY234382; AAO89072.1; -; mRNA.
DR EMBL; AY438698; AAR13893.1; -; mRNA.
DR EMBL; AC005065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005070; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471070; EAW83356.1; -; Genomic_DNA.
DR EMBL; BC001296; AAH01296.1; ALT_SEQ; mRNA.
DR EMBL; BC040004; AAH40004.1; ALT_SEQ; mRNA.
DR EMBL; BC053906; AAH53906.1; ALT_SEQ; mRNA.
DR EMBL; BC062583; AAH62583.1; -; mRNA.
DR EMBL; BC142987; AAI42988.1; ALT_SEQ; mRNA.
DR EMBL; AK000940; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS34723.1; -. [Q8IZD2-1]
DR RefSeq; NP_061152.3; NM_018682.3. [Q8IZD2-1]
DR RefSeq; NP_891847.1; NM_182931.2. [Q8IZD2-1]
DR RefSeq; XP_005250550.1; XM_005250493.1. [Q8IZD2-1]
DR RefSeq; XP_011514702.1; XM_011516400.1. [Q8IZD2-1]
DR PDB; 2LV9; NMR; -; A=109-188.
DR PDB; 4L58; X-ray; 1.48 A; A=117-181.
DR PDB; 5HT6; X-ray; 2.09 A; A/B=323-458.
DR PDBsum; 2LV9; -.
DR PDBsum; 4L58; -.
DR PDBsum; 5HT6; -.
DR AlphaFoldDB; Q8IZD2; -.
DR BMRB; Q8IZD2; -.
DR SMR; Q8IZD2; -.
DR BioGRID; 120990; 44.
DR CORUM; Q8IZD2; -.
DR IntAct; Q8IZD2; 13.
DR STRING; 9606.ENSP00000312379; -.
DR ChEMBL; CHEMBL4523393; -.
DR GlyGen; Q8IZD2; 12 sites, 1 O-linked glycan (12 sites).
DR iPTMnet; Q8IZD2; -.
DR PhosphoSitePlus; Q8IZD2; -.
DR BioMuta; KMT2E; -.
DR DMDM; 74723669; -.
DR EPD; Q8IZD2; -.
DR jPOST; Q8IZD2; -.
DR MassIVE; Q8IZD2; -.
DR MaxQB; Q8IZD2; -.
DR PaxDb; Q8IZD2; -.
DR PeptideAtlas; Q8IZD2; -.
DR PRIDE; Q8IZD2; -.
DR ProteomicsDB; 71322; -. [Q8IZD2-1]
DR ProteomicsDB; 71323; -. [Q8IZD2-2]
DR ProteomicsDB; 71324; -. [Q8IZD2-3]
DR ProteomicsDB; 71325; -. [Q8IZD2-4]
DR ProteomicsDB; 71326; -. [Q8IZD2-5]
DR ProteomicsDB; 71327; -. [Q8IZD2-6]
DR ProteomicsDB; 71328; -. [Q8IZD2-7]
DR Antibodypedia; 31243; 203 antibodies from 32 providers.
DR DNASU; 55904; -.
DR Ensembl; ENST00000311117.8; ENSP00000312379.3; ENSG00000005483.22. [Q8IZD2-1]
DR Ensembl; ENST00000334884.9; ENSP00000335398.5; ENSG00000005483.22. [Q8IZD2-4]
DR Ensembl; ENST00000476671.5; ENSP00000417888.1; ENSG00000005483.22. [Q8IZD2-3]
DR GeneID; 55904; -.
DR KEGG; hsa:55904; -.
DR MANE-Select; ENST00000311117.8; ENSP00000312379.3; NM_182931.3; NP_891847.1.
DR UCSC; uc003vcl.5; human. [Q8IZD2-1]
DR CTD; 55904; -.
DR DisGeNET; 55904; -.
DR GeneCards; KMT2E; -.
DR HGNC; HGNC:18541; KMT2E.
DR HPA; ENSG00000005483; Low tissue specificity.
DR MalaCards; KMT2E; -.
DR MIM; 608444; gene.
DR MIM; 618512; phenotype.
DR neXtProt; NX_Q8IZD2; -.
DR OpenTargets; ENSG00000005483; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA38568; -.
DR VEuPathDB; HostDB:ENSG00000005483; -.
DR eggNOG; KOG1844; Eukaryota.
DR GeneTree; ENSGT00940000157862; -.
DR HOGENOM; CLU_002373_2_1_1; -.
DR InParanoid; Q8IZD2; -.
DR OMA; SGWIKSP; -.
DR OrthoDB; 86638at2759; -.
DR PhylomeDB; Q8IZD2; -.
DR TreeFam; TF106417; -.
DR BioCyc; MetaCyc:HS00145-MON; -.
DR PathwayCommons; Q8IZD2; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR SignaLink; Q8IZD2; -.
DR SIGNOR; Q8IZD2; -.
DR BioGRID-ORCS; 55904; 25 hits in 1059 CRISPR screens.
DR ChiTaRS; KMT2E; human.
DR GenomeRNAi; 55904; -.
DR Pharos; Q8IZD2; Tbio.
DR PRO; PR:Q8IZD2; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q8IZD2; protein.
DR Bgee; ENSG00000005483; Expressed in tendon of biceps brachii and 197 other tissues.
DR ExpressionAtlas; Q8IZD2; baseline and differential.
DR Genevisible; Q8IZD2; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000791; C:euchromatin; IDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0070210; C:Rpd3L-Expanded complex; IBA:GO_Central.
DR GO; GO:0034967; C:Set3 complex; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006306; P:DNA methylation; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0042119; P:neutrophil activation; ISS:UniProtKB.
DR GO; GO:0002446; P:neutrophil mediated immunity; ISS:UniProtKB.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:1905437; P:positive regulation of histone H3-K4 trimethylation; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0035065; P:regulation of histone acetylation; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR CDD; cd19182; SET_KMT2E; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00485; -.
DR InterPro; IPR037955; KMT2E.
DR InterPro; IPR044434; KMT2E_SET.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
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; PTHR46462:SF2; PTHR46462:SF2; 1.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00249; PHD; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell membrane;
KW Chromatin regulator; Chromosome; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disease variant; Glycoprotein; Growth arrest; Intellectual disability;
KW Membrane; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..1858
FT /note="Inactive histone-lysine N-methyltransferase 2E"
FT /id="PRO_0000341419"
FT DOMAIN 330..447
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 118..166
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 217..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 475..530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 887..960
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1039..1068
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1164..1561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1581..1835
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 559..615
FT /evidence="ECO:0000255"
FT MOTIF 63..66
FT /note="HCFC1-binding motif (HBM)"
FT /evidence="ECO:0000269|PubMed:23629655"
FT COMPBIAS 226..257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..503
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..518
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 645..667
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 673..687
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 887..906
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..960
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1048..1068
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1176..1212
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1218..1263
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1268..1283
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1286..1310
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1329..1353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1378..1434
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1438..1452
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1453..1540
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1541..1556
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1581..1602
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1624..1640
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1675..1695
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1712..1726
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1744..1758
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1759..1777
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23798402,
FT ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9,
FT ECO:0007744|PDB:4L58"
FT BINDING 123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23798402,
FT ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9,
FT ECO:0007744|PDB:4L58"
FT BINDING 135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23798402,
FT ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9,
FT ECO:0007744|PDB:4L58"
FT BINDING 138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23798402,
FT ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9,
FT ECO:0007744|PDB:4L58"
FT BINDING 143
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23798402,
FT ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9,
FT ECO:0007744|PDB:4L58"
FT BINDING 146
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23798402,
FT ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9,
FT ECO:0007744|PDB:4L58"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23798402,
FT ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9,
FT ECO:0007744|PDB:4L58"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23798402,
FT ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9,
FT ECO:0007744|PDB:4L58"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 837
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 845
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UG20"
FT MOD_RES 1070
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1273
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1359
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 435
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:26678539"
FT CARBOHYD 440
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000269|PubMed:26678539"
FT VAR_SEQ 494..573
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_052803"
FT VAR_SEQ 575..609
FT /note="TREERKMEAILQAFARLEKREKRREQALERISTAK -> VSWEASSLGLVTA
FT ALHMVIVAAFTWAFTLFFEVSE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052804"
FT VAR_SEQ 610..1858
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052805"
FT VAR_SEQ 850..865
FT /note="GENKSPLLLNDSCSLP -> EYFFPRKFSRNKETHL (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_052806"
FT VAR_SEQ 866..1858
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_052807"
FT VAR_SEQ 1157..1168
FT /note="VSLLEYRKRQRE -> SPVGNFVGSNVV (in isoform NKp44L)"
FT /evidence="ECO:0000303|PubMed:23958951"
FT /id="VSP_053834"
FT VAR_SEQ 1169..1858
FT /note="Missing (in isoform NKp44L)"
FT /evidence="ECO:0000303|PubMed:23958951"
FT /id="VSP_053835"
FT VAR_SEQ 1282..1323
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_052808"
FT VAR_SEQ 1443..1621
FT /note="PSPHLENPPKSSTPHTPVQHGYLSPKPPSQQLGSPYRPHHSQSPQVGTPQRE
FT PQRNFYPAAQNLPANTQQATSGTLFTQTPSGQSSATYSQFNQQSLNSTAPPPPPPPPPS
FT SSYYQNQQPSANFQNYNQLKGSLSQQTVFTSGPNQALPGTTSQQTVPGHHVTPGHFLPS
FT QNPTIHHQT -> SSPSTTPSIHRTPRSTSTTPACCKFSTPTTPSAATFQCFGFWASYH
FT ISSSLTPPTSSRTSTFSFECSSNCTTVSLTSYTSYHFGTGTPAPAFWNRATLSITCHRS
FT SSPAPRTKQYSNTYCFRVLSSSWLCGPATWGSRTSAGISSAWTDSNSQSTGATNISKQL
FT PWVRVALKWTPKTFF (in isoform 6)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_052809"
FT VAR_SEQ 1508..1653
FT /note="ANTQQATSGTLFTQTPSGQSSATYSQFNQQSLNSTAPPPPPPPPPSSSYYQN
FT QQPSANFQNYNQLKGSLSQQTVFTSGPNQALPGTTSQQTVPGHHVTPGHFLPSQNPTIH
FT HQTAAAVVPPPPPPPPAPGPHLVQQPNSHQQHSVA -> VFWLLGIIPHQLKPYTTHLI
FT KDLHFFLRVLIQLYHRIPHKLHIIPLWDRDPSTSLLEQGHIVHYLSQVLISSPKDQTVF
FT QHLLLQGSVLILALWPCHMGFKDLSRHLQCLDRFQFTEHRCHQHFKTITMGQGGIKMDS
FT KNIFLNVL (in isoform 5)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_052810"
FT VAR_SEQ 1622..1858
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_052811"
FT VAR_SEQ 1654..1858
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_052812"
FT VARIANT 140
FT /note="V -> I (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083126"
FT VARIANT 151..1858
FT /note="Missing (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083127"
FT VARIANT 284
FT /note="Y -> H (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083128"
FT VARIANT 754..1858
FT /note="Missing (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083129"
FT VARIANT 818..1858
FT /note="Missing (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083130"
FT VARIANT 874..1858
FT /note="Missing (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083131"
FT VARIANT 907
FT /note="D -> V (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083132"
FT VARIANT 1024..1858
FT /note="Missing (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083133"
FT VARIANT 1185..1858
FT /note="Missing (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083134"
FT VARIANT 1224..1858
FT /note="Missing (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083135"
FT VARIANT 1376
FT /note="P -> L"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083136"
FT VARIANT 1376
FT /note="P -> S (in ODLURO)"
FT /evidence="ECO:0000269|PubMed:31079897"
FT /id="VAR_083137"
FT VARIANT 1424
FT /note="S -> P (in dbSNP:rs35605511)"
FT /id="VAR_052656"
FT MUTAGEN 63..66
FT /note="DHNY->AAAA: Abolishes interaction with HCFC1."
FT /evidence="ECO:0000269|PubMed:23629655"
FT MUTAGEN 125
FT /note="F->A: No effect on binding to tri-methylated 'Lys-4'
FT of histone H3 (H3K4me3)."
FT /evidence="ECO:0000269|PubMed:23798402"
FT MUTAGEN 128
FT /note="D->K: Severe reduction in the binding to tri-
FT methylated 'Lys-4' of histone H3 (H3K4me3)."
FT /evidence="ECO:0000269|PubMed:23798402"
FT MUTAGEN 131
FT /note="Y->A,K: Severe reduction in the binding to tri-
FT methylated 'Lys-4' of histone H3 (H3K4me3)."
FT /evidence="ECO:0000269|PubMed:23798402"
FT MUTAGEN 141
FT /note="W->A: Loss of binding to tri-methylated 'Lys-4' of
FT histone H3 (H3K4me3)."
FT /evidence="ECO:0000269|PubMed:23798402"
FT MUTAGEN 411
FT /note="C->A: Fails to activate the cell cycle regulated
FT element (CCRE) in the cyclin A promoter."
FT /evidence="ECO:0000269|PubMed:19264965"
FT CONFLICT 496
FT /note="K -> E (in Ref. 1; AAM74947, 2; AGE34449 and 7;
FT AK000940)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="T -> A (in Ref. 1; AAM74947, 2; AGE34449 and 7;
FT AK000940)"
FT /evidence="ECO:0000305"
FT CONFLICT 594
FT /note="R -> K (in Ref. 7; AK000940)"
FT /evidence="ECO:0000305"
FT CONFLICT 1020
FT /note="V -> A (in Ref. 1; AAM74947)"
FT /evidence="ECO:0000305"
FT CONFLICT 1073
FT /note="R -> S (in Ref. 1; AAM74947)"
FT /evidence="ECO:0000305"
FT CONFLICT 1090
FT /note="S -> P (in Ref. 1; AAM74947)"
FT /evidence="ECO:0000305"
FT CONFLICT 1099
FT /note="F -> S (in Ref. 1; AAM74947)"
FT /evidence="ECO:0000305"
FT CONFLICT 1168
FT /note="E -> K (in Ref. 1; AAM74947)"
FT /evidence="ECO:0000305"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:4L58"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:4L58"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:4L58"
FT HELIX 144..147
FT /evidence="ECO:0007829|PDB:4L58"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:2LV9"
FT TURN 161..165
FT /evidence="ECO:0007829|PDB:4L58"
FT HELIX 170..178
FT /evidence="ECO:0007829|PDB:4L58"
FT STRAND 344..347
FT /evidence="ECO:0007829|PDB:5HT6"
FT STRAND 354..357
FT /evidence="ECO:0007829|PDB:5HT6"
FT STRAND 360..364
FT /evidence="ECO:0007829|PDB:5HT6"
FT HELIX 365..370
FT /evidence="ECO:0007829|PDB:5HT6"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:5HT6"
FT TURN 387..390
FT /evidence="ECO:0007829|PDB:5HT6"
FT STRAND 393..396
FT /evidence="ECO:0007829|PDB:5HT6"
FT HELIX 403..406
FT /evidence="ECO:0007829|PDB:5HT6"
FT STRAND 414..422
FT /evidence="ECO:0007829|PDB:5HT6"
FT STRAND 425..434
FT /evidence="ECO:0007829|PDB:5HT6"
SQ SEQUENCE 1858 AA; 204965 MW; 8ACCB3CDB5BFCEFA CRC64;
MSIVIPLGVD TAETSYLEMA AGSEPESVEA SPVVVEKSNS YPHQLYTSSS HHSHSYIGLP
YADHNYGARP PPTPPASPPP SVLISKNEVG IFTTPNFDET SSATTISTSE DGSYGTDVTR
CICGFTHDDG YMICCDKCSV WQHIDCMGID RQHIPDTYLC ERCQPRNLDK ERAVLLQRRK
RENMSDGDTS ATESGDEVPV ELYTAFQHTP TSITLTASRV SKVNDKRRKK SGEKEQHISK
CKKAFREGSR KSSRVKGSAP EIDPSSDGSN FGWETKIKAW MDRYEEANNN QYSEGVQREA
QRIALRLGNG NDKKEMNKSD LNTNNLLFKP PVESHIQKNK KILKSAKDLP PDALIIEYRG
KFMLREQFEA NGYFFKRPYP FVLFYSKFHG LEMCVDARTF GNEARFIRRS CTPNAEVRHE
IQDGTIHLYI YSIHSIPKGT EITIAFDFDY GNCKYKVDCA CLKENPECPV LKRSSESMEN
INSGYETRRK KGKKDKDISK EKDTQNQNIT LDCEGTTNKM KSPETKQRKL SPLRLSVSNN
QEPDFIDDIE EKTPISNEVE MESEEQIAER KRKMTREERK MEAILQAFAR LEKREKRREQ
ALERISTAKT EVKTECKDTQ IVSDAEVIQE QAKEENASKP TPAKVNRTKQ RKSFSRSRTH
IGQQRRRHRT VSMCSDIQPS SPDIEVTSQQ NDIENTVLTI EPETETALAE IITETEVPAL
NKCPTKYPKT KKHLVNEWLS EKNEKTGKPS DGLSERPLRI TTDPEVLATQ LNSLPGLTYS
PHVYSTPKHY IRFTSPFLSE KRRRKEPTEN ISGSCKKRWL KQALEEENSA ILHRFNSPCQ
ERSRSPAVNG ENKSPLLLND SCSLPDLTTP LKKRRFYQLL DSVYSETSTP TPSPYATPTH
TDITPMDPSF ATPPRIKSDD ETCRNGYKPI YSPVTPVTPG TPGNTMHFEN ISSPESSPEI
KRRTYSQEGY DRSSTMLTLG PFRNSNLTEL GLQEIKTIGY TSPRSRTEVN RQCPGEKEPV
SDLQLGLDAV EPTALHKTLE TPAHDRAEPN SQLDSTHSGR GTMYSSWVKS PDRTGVNFSV
NSNLRDLTPS HQLEVGGGFR ISESKCLMQD DTRGMFMETT VFCTSEDGLV SGFGRTVNDN
LIDGNCTPQN PPQKKKVSLL EYRKRQREAR KSGSKTENFP LISVSPHASG SLSNNGDGCA
SSNDNGEQVD HTASLPLPTP ATVYNATSEE TSNNCPVKDA TASEKNEPEV QWTASTSVEQ
VRERSYQRAL LLSDHRKDKD SGGESPCVSC SPSHVQSSPS SHSNHIPQLQ AKGPVPSFSE
LMEDPDPENP EPTTTNECPS PDTSQNTCKS PPKMSKPGSP GSVIPAQAHG KIFTKPDPQW
DSTVSASEAE NGVHLKTELQ QKQLSNNNQA LSKNHPPQTH VRNSSEQLSQ KLPSVPTKLH
CPPSPHLENP PKSSTPHTPV QHGYLSPKPP SQQLGSPYRP HHSQSPQVGT PQREPQRNFY
PAAQNLPANT QQATSGTLFT QTPSGQSSAT YSQFNQQSLN STAPPPPPPP PPSSSYYQNQ
QPSANFQNYN QLKGSLSQQT VFTSGPNQAL PGTTSQQTVP GHHVTPGHFL PSQNPTIHHQ
TAAAVVPPPP PPPPAPGPHL VQQPNSHQQH SVAHVVGPVH AVTPGSHIHS QTAGHHLPPP
PPPPGPAPHH HPPPHPSTGL QGLQAQHQHV VNSAPPPPPP PPPSSVLASG HHTTSAQALH
HPPHQGPPLF PSSAHPTVPP YPSQATHHTT LGPGPQHQPS GTGPHCPLPV TGPHLQPQGP
NSIPTPTASG FCPHPGSVAL PHGVQGPQQA SPVPGQIPIH RAQVPPTFQN NYHGSGWH
