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Database: UniProt
Entry: Q8IZD2
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ID   KMT2E_HUMAN             Reviewed;        1858 AA.
AC   Q8IZD2; B6ZDE4; B6ZDM3; M4K8J3; Q6P5Y2; Q6PKG4; Q6T316; Q86TI3;
AC   Q86W12; Q86WG0; Q86WL2; Q8IV78; Q8IWR5; Q8NFF8; Q9NWE7;
DT   10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   10-APR-2019, entry version 138.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Green E.D., 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
RP   NKP44L), SUBCELLULAR LOCATION (ISOFORM NKP44L), AND TISSUE
RP   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
RT   receptor 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
RP   [MRNA] OF 624-1858 (ISOFORM 4), NUCLEOTIDE SEQUENCE [MRNA] OF
RP   1149-1251 (ISOFORMS 1/2/4/6/7), NUCLEOTIDE SEQUENCE [MRNA] OF
RP   1190-1355 (ISOFORM 7), AND NUCLEOTIDE SEQUENCE [MRNA] OF 1415-1858
RP   (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.,
RA   Fazekas G., 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.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   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.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RP   SEQUENCE [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
RT   project: 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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
RT   cell 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
RT   cycle 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
RP   SCALE 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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [13]
RP   CAUTION, AND RETRACTION.
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-
RT   acid-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
RT   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),
RP   SUBCELLULAR 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
RT   progression and E2F1-responsive gene expression via association with
RT   host cell factor-1 (HCF-1).";
RL   J. Biol. Chem. 288:17532-17543(2013).
RN   [16]
RP   IDENTIFICATION IN A COMPLEX WITH OGT AND USP7, INTERACTION WITH OGT
RP   AND USP7, SUBCELLULAR LOCATION, GLYCOSYLATION AT SER-435 AND THR-440,
RP   AND 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.,
RA   Zhang Y.;
RT   "Mixed lineage leukemia 5 (MLL5) protein stability is cooperatively
RT   regulated by O-GlcNac transferase (OGT) and ubiquitin specific
RT   protease 7 (USP7).";
RL   PLoS ONE 10:E0145023-E0145023(2015).
RN   [17]
RP   STRUCTURE BY NMR OF 109-188 IN COMPLEX WITH ZINC, FUNCTION, AND
RP   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
RP   ZINC, FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF
RP   PHE-125; 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.,
RA   Parkhurst S.M., 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
RP   CATALYTIC ACTIVITY.
RX   PubMed=27812132; DOI=10.1371/journal.pone.0165139;
RA   Mas-Y-Mas S., Barbon M., Teyssier C., Demene H., Carvalho J.E.,
RA   Bird L.E., Lebedev A., Fattori J., Schubert M., Dumas C., Bourguet W.,
RA   le Maire A.;
RT   "The human mixed lineage leukemia 5 (MLL5), a sequentially and
RT   structurally divergent SET domain-containing protein with no intrinsic
RT   catalytic activity.";
RL   PLoS ONE 11:E0165139-E0165139(2016).
CC   -!- FUNCTION: Associates with chromatin regions downstream of
CC       transcriptional start sites of active genes and thus regulates
CC       gene transcription (PubMed:23629655, PubMed:24130829,
CC       PubMed:23798402). Chromatin interaction is mediated via the
CC       binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3)
CC       (PubMed:24130829, PubMed:23798402). Key regulator of hematopoiesis
CC       involved in terminal myeloid differentiation and in the regulation
CC       of hematopoietic stem cell (HSCs) self-renewal by a mechanism that
CC       involves DNA methylation (By similarity). Also acts as an
CC       important cell cycle regulator, participating in cell cycle
CC       regulatory network machinery at multiple cell cycle stages
CC       including G1/S transition, S phase progression and mitotic entry
CC       (PubMed:14718661, PubMed:18573682, PubMed:19264965,
CC       PubMed:23629655). Recruited to E2F1 responsive promoters by HCFC1
CC       where it stimulates tri-methylation of histone H3 at 'Lys-4' and
CC       transcriptional activation and thereby facilitates G1 to S phase
CC       transition (PubMed:23629655). During myoblast differentiation,
CC       required to suppress inappropriate expression of S-phase-promoting
CC       genes and maintain expression of determination genes in quiescent
CC       cells (By similarity). {ECO:0000250|UniProtKB:Q3UG20,
CC       ECO:0000269|PubMed:14718661, ECO:0000269|PubMed:18573682,
CC       ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:23798402,
CC       ECO:0000269|PubMed:24130829}.
CC   -!- FUNCTION: Isoform NKp44L: Cellular ligand for NCR2/NKp44, may play
CC       a role as a danger signal in cytotoxicity and NK-cell-mediated
CC       innate immunity. {ECO:0000269|PubMed:23958951}.
CC   -!- SUBUNIT: Component of a complex composed of KMT2E (isoform 3), OGT
CC       and USP7; the complex stabilizes KMT2E, preventing KMT2E
CC       ubiquitination and proteosomal-mediated degradation
CC       (PubMed:26678539). Isoform 3 interacts (via N-terminus) with OGT
CC       (via TRP repeats) (PubMed:26678539, PubMed:23629655). Isoform 3
CC       interacts with deubiquitinating enzyme USP7 (via MATH domain)
CC       (PubMed:26678539). Isoform 3 interacts (via HBM motif) with HCFC1
CC       (via Kelch domain) (PubMed:23629655). Isoform 3 interacts with
CC       E2F1; the interaction is probably indirect and is mediated via
CC       HCFC1 (PubMed:23629655). {ECO:0000269|PubMed:23629655,
CC       ECO:0000269|PubMed:26678539}.
CC   -!- INTERACTION:
CC       O95944:NCR2; NbExp=4; IntAct=EBI-15014150, EBI-14058375;
CC       P04637:TP53; NbExp=4; IntAct=EBI-2689959, EBI-366083;
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
CC       to centrosomes during mitosis (PubMed:23798402). Dissociation from
CC       mitotic chromosome is likely due to histone H3 phosphorylation on
CC       'Thr-3' and 'Thr-6' (PubMed:23798402).
CC       {ECO:0000269|PubMed:14718661, ECO:0000269|PubMed:23798402}.
CC   -!- SUBCELLULAR LOCATION: Isoform 3: Nucleus, nucleoplasm
CC       {ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26678539}.
CC       Nucleus speckle {ECO:0000269|PubMed:23798402}. Note=Absent from
CC       the nucleolus (PubMed:23629655). Localizes to chromosome during
CC       interphase and to nucleus speckle during mitosis
CC       (PubMed:23798402). Dissociation from mitotic chromosome is likely
CC       due to histone H3 phosphorylation on 'Thr-3' and 'Thr-6'
CC       (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         Note=No experimental confirmation available. {ECO:0000305};
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         Note=No experimental confirmation available. {ECO:0000305};
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         Note=No experimental confirmation available. {ECO:0000305};
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
CC       tissues (PubMed:12101424, PubMed:23958951). Highest levels of
CC       expression observed in fetal thymus and kidney and in adult
CC       hematopoietic tissues, jejunum and cerebellum (PubMed:12101424,
CC       PubMed:23958951). Isoform NKp44L: Not detected on circulating
CC       cells from healthy individuals, but is expressed on a large panel
CC       of tumor and transformed cells (PubMed:23958951).
CC       {ECO:0000269|PubMed:12101424, 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
CC       chromatin. {ECO:0000269|PubMed:23798402,
CC       ECO:0000269|PubMed:24130829}.
CC   -!- DOMAIN: The SET domain does not bind the methyl group donor S-
CC       adenosyl-L-methionine and histone 3 H3K4 peptide as a large loop
CC       prevents the docking of the 'Lys-4' side chain.
CC       {ECO:0000269|PubMed:27812132}.
CC   -!- DOMAIN: The C-terminus domain is responsible for the localization
CC       to 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
CC       OGT which probably prevents KMT2E proteasomal-mediated
CC       degradation. {ECO:0000269|PubMed:26678539}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. TRX/MLL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC   -!- CAUTION: Isoform 3 was originally thought to display histone
CC       methyltransferase activity only following O-glycosylation at Thr-
CC       440 (PubMed:19377461). However, the corresponding article has been
CC       retracted (PubMed:24336203). Does not exhibit histone
CC       methyltransferase towards histone H3 in vitro (PubMed:19264965,
CC       PubMed:27812132). The isolated catalytic SET domain lacks binding
CC       activity towards cofactor S-adenosyl-L-methionine; instead of the
CC       highly conserved XGXG, Y and NH motifs, KMT2E displays NKKI (Asn-
CC       339-Ile-342), F (Phe-381) and RR (Arg-408-Arg-409) motifs
CC       (PubMed:27812132). Also lacks binding activity towards histone H3
CC       due to a poor conservation of the key residues involved in the
CC       binding and the presence of large loop which prevents the docking
CC       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};
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   UniGene; Hs.592262; -.
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   ProteinModelPortal; Q8IZD2; -.
DR   SMR; Q8IZD2; -.
DR   BioGrid; 120990; 38.
DR   CORUM; Q8IZD2; -.
DR   IntAct; Q8IZD2; 11.
DR   STRING; 9606.ENSP00000312379; -.
DR   iPTMnet; Q8IZD2; -.
DR   PhosphoSitePlus; Q8IZD2; -.
DR   BioMuta; KMT2E; -.
DR   DMDM; 74723669; -.
DR   EPD; Q8IZD2; -.
DR   jPOST; Q8IZD2; -.
DR   MaxQB; Q8IZD2; -.
DR   PaxDb; Q8IZD2; -.
DR   PeptideAtlas; Q8IZD2; -.
DR   PRIDE; Q8IZD2; -.
DR   ProteomicsDB; 71322; -.
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   DNASU; 55904; -.
DR   Ensembl; ENST00000257745; ENSP00000257745; ENSG00000005483. [Q8IZD2-1]
DR   Ensembl; ENST00000311117; ENSP00000312379; ENSG00000005483. [Q8IZD2-1]
DR   Ensembl; ENST00000334884; ENSP00000335398; ENSG00000005483. [Q8IZD2-4]
DR   Ensembl; ENST00000476671; ENSP00000417888; ENSG00000005483. [Q8IZD2-3]
DR   GeneID; 55904; -.
DR   KEGG; hsa:55904; -.
DR   UCSC; uc003vcl.5; human. [Q8IZD2-1]
DR   CTD; 55904; -.
DR   DisGeNET; 55904; -.
DR   EuPathDB; HostDB:ENSG00000005483.19; -.
DR   GeneCards; KMT2E; -.
DR   HGNC; HGNC:18541; KMT2E.
DR   HPA; HPA022812; -.
DR   HPA; HPA056125; -.
DR   MIM; 608444; gene.
DR   neXtProt; NX_Q8IZD2; -.
DR   OpenTargets; ENSG00000005483; -.
DR   PharmGKB; PA38568; -.
DR   eggNOG; KOG1844; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000157862; -.
DR   HOVERGEN; HBG105683; -.
DR   InParanoid; Q8IZD2; -.
DR   KO; K09189; -.
DR   OMA; TIYSSWV; -.
DR   PhylomeDB; Q8IZD2; -.
DR   TreeFam; TF106417; -.
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   ChiTaRS; KMT2E; human.
DR   GenomeRNAi; 55904; -.
DR   PRO; PR:Q8IZD2; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000005483; Expressed in 213 organ(s), highest expression level in visceral pleura.
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:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR   GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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:0035327; C:transcriptionally active chromatin; IDA:UniProtKB.
DR   GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; TAS:Reactome.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR   GO; GO:0007050; P:cell cycle arrest; 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:0045652; P:regulation of megakaryocyte differentiation; TAS:Reactome.
DR   Gene3D; 3.30.40.10; -; 1.
DR   InterPro; IPR037955; KMT2E.
DR   InterPro; IPR001214; SET_dom.
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; PTHR44512:SF1; PTHR44512:SF1; 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   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; Complete proteome;
KW   Cytoplasm; Cytoskeleton; Glycoprotein; Growth arrest; Membrane;
KW   Metal-binding; Nucleus; Phosphoprotein; Polymorphism;
KW   Reference proteome; Transcription; Transcription regulation;
KW   Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN         1   1858       Inactive histone-lysine N-
FT                                methyltransferase 2E.
FT                                /FTId=PRO_0000341419.
FT   DOMAIN      330    447       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   ZN_FING     118    166       PHD-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   COILED      559    615       {ECO:0000255}.
FT   MOTIF        63     66       HCFC1-binding motif (HBM).
FT                                {ECO:0000269|PubMed:23629655}.
FT   COMPBIAS   1433   1846       Pro-rich. {ECO:0000255}.
FT   METAL       121    121       Zinc 1. {ECO:0000244|PDB:2LV9,
FT                                ECO:0000244|PDB:4L58,
FT                                ECO:0000269|PubMed:23798402,
FT                                ECO:0000269|PubMed:24130829}.
FT   METAL       123    123       Zinc 1. {ECO:0000244|PDB:2LV9,
FT                                ECO:0000244|PDB:4L58,
FT                                ECO:0000269|PubMed:23798402,
FT                                ECO:0000269|PubMed:24130829}.
FT   METAL       135    135       Zinc 2. {ECO:0000244|PDB:2LV9,
FT                                ECO:0000244|PDB:4L58,
FT                                ECO:0000269|PubMed:23798402,
FT                                ECO:0000269|PubMed:24130829}.
FT   METAL       138    138       Zinc 2. {ECO:0000244|PDB:2LV9,
FT                                ECO:0000244|PDB:4L58,
FT                                ECO:0000269|PubMed:23798402,
FT                                ECO:0000269|PubMed:24130829}.
FT   METAL       143    143       Zinc 1; via pros nitrogen.
FT                                {ECO:0000244|PDB:2LV9,
FT                                ECO:0000244|PDB:4L58,
FT                                ECO:0000269|PubMed:23798402,
FT                                ECO:0000269|PubMed:24130829}.
FT   METAL       146    146       Zinc 1. {ECO:0000244|PDB:2LV9,
FT                                ECO:0000244|PDB:4L58,
FT                                ECO:0000269|PubMed:23798402,
FT                                ECO:0000269|PubMed:24130829}.
FT   METAL       160    160       Zinc 2. {ECO:0000244|PDB:2LV9,
FT                                ECO:0000244|PDB:4L58,
FT                                ECO:0000269|PubMed:23798402,
FT                                ECO:0000269|PubMed:24130829}.
FT   METAL       163    163       Zinc 2. {ECO:0000244|PDB:2LV9,
FT                                ECO:0000244|PDB:4L58,
FT                                ECO:0000269|PubMed:23798402,
FT                                ECO:0000269|PubMed:24130829}.
FT   MOD_RES     623    623       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     837    837       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     845    845       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q3UG20}.
FT   MOD_RES    1070   1070       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1273   1273       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1359   1359       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   CARBOHYD    435    435       O-linked (GlcNAc) serine.
FT                                {ECO:0000269|PubMed:26678539}.
FT   CARBOHYD    440    440       O-linked (GlcNAc) threonine.
FT                                {ECO:0000269|PubMed:26678539}.
FT   VAR_SEQ     494    573       Missing (in isoform 2).
FT                                {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_052803.
FT   VAR_SEQ     575    609       TREERKMEAILQAFARLEKREKRREQALERISTAK -> VS
FT                                WEASSLGLVTAALHMVIVAAFTWAFTLFFEVSE (in
FT                                isoform 3).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_052804.
FT   VAR_SEQ     610   1858       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_052805.
FT   VAR_SEQ     850    865       GENKSPLLLNDSCSLP -> EYFFPRKFSRNKETHL (in
FT                                isoform 4). {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_052806.
FT   VAR_SEQ     866   1858       Missing (in isoform 4).
FT                                {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_052807.
FT   VAR_SEQ    1157   1168       VSLLEYRKRQRE -> SPVGNFVGSNVV (in isoform
FT                                NKp44L). {ECO:0000303|PubMed:23958951}.
FT                                /FTId=VSP_053834.
FT   VAR_SEQ    1169   1858       Missing (in isoform NKp44L).
FT                                {ECO:0000303|PubMed:23958951}.
FT                                /FTId=VSP_053835.
FT   VAR_SEQ    1282   1323       Missing (in isoform 7).
FT                                {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_052808.
FT   VAR_SEQ    1443   1621       PSPHLENPPKSSTPHTPVQHGYLSPKPPSQQLGSPYRPHHS
FT                                QSPQVGTPQREPQRNFYPAAQNLPANTQQATSGTLFTQTPS
FT                                GQSSATYSQFNQQSLNSTAPPPPPPPPPSSSYYQNQQPSAN
FT                                FQNYNQLKGSLSQQTVFTSGPNQALPGTTSQQTVPGHHVTP
FT                                GHFLPSQNPTIHHQT -> SSPSTTPSIHRTPRSTSTTPAC
FT                                CKFSTPTTPSAATFQCFGFWASYHISSSLTPPTSSRTSTFS
FT                                FECSSNCTTVSLTSYTSYHFGTGTPAPAFWNRATLSITCHR
FT                                SSSPAPRTKQYSNTYCFRVLSSSWLCGPATWGSRTSAGISS
FT                                AWTDSNSQSTGATNISKQLPWVRVALKWTPKTFF (in
FT                                isoform 6). {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_052809.
FT   VAR_SEQ    1508   1653       ANTQQATSGTLFTQTPSGQSSATYSQFNQQSLNSTAPPPPP
FT                                PPPPSSSYYQNQQPSANFQNYNQLKGSLSQQTVFTSGPNQA
FT                                LPGTTSQQTVPGHHVTPGHFLPSQNPTIHHQTAAAVVPPPP
FT                                PPPPAPGPHLVQQPNSHQQHSVA -> VFWLLGIIPHQLKP
FT                                YTTHLIKDLHFFLRVLIQLYHRIPHKLHIIPLWDRDPSTSL
FT                                LEQGHIVHYLSQVLISSPKDQTVFQHLLLQGSVLILALWPC
FT                                HMGFKDLSRHLQCLDRFQFTEHRCHQHFKTITMGQGGIKMD
FT                                SKNIFLNVL (in isoform 5).
FT                                {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_052810.
FT   VAR_SEQ    1622   1858       Missing (in isoform 6).
FT                                {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_052811.
FT   VAR_SEQ    1654   1858       Missing (in isoform 5).
FT                                {ECO:0000303|Ref.3}.
FT                                /FTId=VSP_052812.
FT   VARIANT    1424   1424       S -> P (in dbSNP:rs35605511).
FT                                /FTId=VAR_052656.
FT   MUTAGEN      63     66       DHNY->AAAA: Abolishes interaction with
FT                                HCFC1. {ECO:0000269|PubMed:23629655}.
FT   MUTAGEN     125    125       F->A: No effect on binding to tri-
FT                                methylated 'Lys-4' of histone H3
FT                                (H3K4me3). {ECO:0000269|PubMed:23798402}.
FT   MUTAGEN     128    128       D->K: Severe reduction in the binding to
FT                                tri-methylated 'Lys-4' of histone H3
FT                                (H3K4me3). {ECO:0000269|PubMed:23798402}.
FT   MUTAGEN     131    131       Y->A,K: Severe reduction in the binding
FT                                to tri-methylated 'Lys-4' of histone H3
FT                                (H3K4me3). {ECO:0000269|PubMed:23798402}.
FT   MUTAGEN     141    141       W->A: Loss of binding to tri-methylated
FT                                'Lys-4' of histone H3 (H3K4me3).
FT                                {ECO:0000269|PubMed:23798402}.
FT   MUTAGEN     411    411       C->A: Fails to activate the cell cycle
FT                                regulated element (CCRE) in the cyclin A
FT                                promoter. {ECO:0000269|PubMed:19264965}.
FT   CONFLICT    496    496       K -> E (in Ref. 1; AAM74947, 2; AGE34449
FT                                and 7; AK000940). {ECO:0000305}.
FT   CONFLICT    516    516       T -> A (in Ref. 1; AAM74947, 2; AGE34449
FT                                and 7; AK000940). {ECO:0000305}.
FT   CONFLICT    594    594       R -> K (in Ref. 7; AK000940).
FT                                {ECO:0000305}.
FT   CONFLICT   1020   1020       V -> A (in Ref. 1; AAM74947).
FT                                {ECO:0000305}.
FT   CONFLICT   1073   1073       R -> S (in Ref. 1; AAM74947).
FT                                {ECO:0000305}.
FT   CONFLICT   1090   1090       S -> P (in Ref. 1; AAM74947).
FT                                {ECO:0000305}.
FT   CONFLICT   1099   1099       F -> S (in Ref. 1; AAM74947).
FT                                {ECO:0000305}.
FT   CONFLICT   1168   1168       E -> K (in Ref. 1; AAM74947).
FT                                {ECO:0000305}.
FT   STRAND      132    134       {ECO:0000244|PDB:4L58}.
FT   TURN        136    138       {ECO:0000244|PDB:4L58}.
FT   STRAND      141    143       {ECO:0000244|PDB:4L58}.
FT   HELIX       144    147       {ECO:0000244|PDB:4L58}.
FT   STRAND      156    158       {ECO:0000244|PDB:2LV9}.
FT   TURN        161    165       {ECO:0000244|PDB:4L58}.
FT   HELIX       170    178       {ECO:0000244|PDB:4L58}.
FT   STRAND      344    347       {ECO:0000244|PDB:5HT6}.
FT   STRAND      354    357       {ECO:0000244|PDB:5HT6}.
FT   STRAND      360    364       {ECO:0000244|PDB:5HT6}.
FT   HELIX       365    370       {ECO:0000244|PDB:5HT6}.
FT   STRAND      382    385       {ECO:0000244|PDB:5HT6}.
FT   TURN        387    390       {ECO:0000244|PDB:5HT6}.
FT   STRAND      393    396       {ECO:0000244|PDB:5HT6}.
FT   HELIX       403    406       {ECO:0000244|PDB:5HT6}.
FT   STRAND      414    422       {ECO:0000244|PDB:5HT6}.
FT   STRAND      425    434       {ECO:0000244|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
//
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