LMBL1_HUMAN
ID LMBL1_HUMAN Reviewed; 840 AA.
AC Q9Y468; B4DRC9; E1P5W7; Q5H8Y8; Q5H8Y9; Q8IUV7; Q9H1E6; Q9H1G5; Q9UG06;
AC Q9UJB9; Q9Y4C9;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 4.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Lethal(3)malignant brain tumor-like protein 1;
DE Short=H-l(3)mbt;
DE Short=H-l(3)mbt protein;
DE Short=L(3)mbt-like;
DE AltName: Full=L(3)mbt protein homolog;
DE AltName: Full=L3MBTL1;
GN Name=L3MBTL1; Synonyms=KIAA0681, L3MBT, L3MBTL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10445843; DOI=10.1038/sj.onc.1202732;
RA Koga H., Matsui S., Hirota T., Takebayashi S., Okumura K., Saya H.;
RT "A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt)
RT protein associates with condensed mitotic chromosomes.";
RL Oncogene 18:3799-3809(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-117.
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 283-840 (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [7]
RP INTERACTION WITH ETV6.
RX PubMed=12588862; DOI=10.1074/jbc.m300592200;
RA Boccuni P., MacGrogan D., Scandura J.M., Nimer S.D.;
RT "The human L(3)MBT Polycomb group protein is a transcriptional repressor
RT and interacts physically and functionally with TEL (ETV6).";
RL J. Biol. Chem. 278:15412-15420(2003).
RN [8]
RP IMPRINTING.
RX PubMed=15123827; DOI=10.1073/pnas.0308195101;
RA Li J., Bench A.J., Vassiliou G.S., Fourouclas N., Ferguson-Smith A.C.,
RA Green A.R.;
RT "Imprinting of the human L3MBTL gene, a polycomb family member located in a
RT region of chromosome 20 deleted in human myeloid malignancies.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7341-7346(2004).
RN [9]
RP FUNCTION, INTERACTION WITH CBX3 AND HISTONES, AND MUTAGENESIS OF ASP-316;
RP PHE-340; ASP-423; PHE-447; ASP-527 AND PHE-551.
RX PubMed=17540172; DOI=10.1016/j.cell.2007.03.048;
RA Trojer P., Li G., Sims R.J. III, Vaquero A., Kalakonda N., Boccuni P.,
RA Lee D., Erdjument-Bromage H., Tempst P., Nimer S.D., Wang Y.H.,
RA Reinberg D.;
RT "L3MBTL1, a histone-methylation-dependent chromatin lock.";
RL Cell 129:915-928(2007).
RN [10]
RP FUNCTION, AND INTERACTION WITH KMT5A.
RX PubMed=18408754; DOI=10.1038/onc.2008.67;
RA Kalakonda N., Fischle W., Boccuni P., Gurvich N., Hoya-Arias R., Zhao X.,
RA Miyata Y., Macgrogan D., Zhang J., Sims J.K., Rice J.C., Nimer S.D.;
RT "Histone H4 lysine 20 monomethylation promotes transcriptional repression
RT by L3MBTL1.";
RL Oncogene 27:4293-4304(2008).
RN [11]
RP FUNCTION, AND INTERACTION WITH RB1.
RX PubMed=20870719; DOI=10.1074/jbc.m110.137612;
RA Saddic L.A., West L.E., Aslanian A., Yates J.R. III, Rubin S.M., Gozani O.,
RA Sage J.;
RT "Methylation of the retinoblastoma tumor suppressor by SMYD2.";
RL J. Biol. Chem. 285:37733-37740(2010).
RN [12]
RP UBIQUITINATION, AND INTERACTION WITH VCP.
RX PubMed=22120668; DOI=10.1038/nsmb.2188;
RA Acs K., Luijsterburg M.S., Ackermann L., Salomons F.A., Hoppe T.,
RA Dantuma N.P.;
RT "The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from
RT DNA double-strand breaks.";
RL Nat. Struct. Mol. Biol. 18:1345-1350(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 265-595.
RX PubMed=12842041; DOI=10.1016/s0969-2126(03)00127-8;
RA Wang W.K., Tereshko V., Boccuni P., MacGrogan D., Nimer S.D., Patel D.J.;
RT "Malignant brain tumor repeats: a three-leaved propeller architecture with
RT ligand/peptide binding pockets.";
RL Structure 11:775-789(2003).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 274-587 IN COMPLEX WITH
RP MONOMETHYLATED AND DIMETHYLATED PEPTIDES, DOMAIN MBT REPEAT, AND
RP MUTAGENESIS OF ASP-423 AND ASN-426.
RX PubMed=18042461; DOI=10.1016/j.molcel.2007.10.023;
RA Li H., Fischle W., Wang W., Duncan E.M., Liang L., Murakami-Ishibe S.,
RA Allis C.D., Patel D.J.;
RT "Structural basis for lower lysine methylation state-specific readout by
RT MBT repeats of L3MBTL1 and an engineered PHD finger.";
RL Mol. Cell 28:677-691(2007).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 268-598 IN COMPLEX WITH
RP DIMETHYLATED HISTONE H4, AND MUTAGENESIS OF ASP-423 AND CYS-431.
RX PubMed=18026117; DOI=10.1038/nsmb1340;
RA Min J., Allali-Hassani A., Nady N., Qi C., Ouyang H., Liu Y., MacKenzie F.,
RA Vedadi M., Arrowsmith C.H.;
RT "L3MBTL1 recognition of mono- and dimethylated histones.";
RL Nat. Struct. Mol. Biol. 14:1229-1230(2007).
RN [17]
RP ERRATUM OF PUBMED:18026117.
RA Min J., Allali-Hassani A., Nady N., Qi C., Ouyang H., Liu Y., MacKenzie F.,
RA Vedadi M., Arrowsmith C.H.;
RL Nat. Struct. Mol. Biol. 15:114-114(2008).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 259-598 IN COMPLEX WITH
RP MONOMETHYLATED PEPTIDE, FUNCTION, INTERACTION WITH TP53, AND MUTAGENESIS OF
RP ASP-423; ASN-426; PHE-447; TRP-450 AND TYR-454.
RX PubMed=20870725; DOI=10.1074/jbc.m110.139527;
RA West L.E., Roy S., Lachmi-Weiner K., Hayashi R., Shi X., Appella E.,
RA Kutateladze T.G., Gozani O.;
RT "The MBT repeats of L3MBTL1 link SET8-mediated p53 methylation at lysine
RT 382 to target gene repression.";
RL J. Biol. Chem. 285:37725-37732(2010).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 268-590.
RG Structural genomics consortium (SGC);
RT "Small molecule ligands of methyl-lysine binding proteins.";
RL Submitted (NOV-2010) to the PDB data bank.
CC -!- FUNCTION: Polycomb group (PcG) protein that specifically recognizes and
CC binds mono- and dimethyllysine residues on target proteins, therey
CC acting as a 'reader' of a network of post-translational modifications.
CC PcG proteins maintain the transcriptionally repressive state of genes:
CC acts as a chromatin compaction factor by recognizing and binding
CC mono- and dimethylated histone H1b/H1-4 at 'Lys-26' (H1bK26me1 and
CC H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading
CC to condense chromatin and repress transcription. Recognizes and binds
CC p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-
CC target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-
CC 860'. Participates in the ETV6-mediated repression. Probably plays a
CC role in cell proliferation. Overexpression induces multinucleated
CC cells, suggesting that it is required to accomplish normal mitosis.
CC {ECO:0000269|PubMed:17540172, ECO:0000269|PubMed:18408754,
CC ECO:0000269|PubMed:20870719, ECO:0000269|PubMed:20870725}.
CC -!- SUBUNIT: Homodimer. Interacts with RB1/RB (when monomethylated at 'Lys-
CC 860'). Interacts with p53/TP53 (when monomethylated at 'Lys-382').
CC Interacts with CBX3, ETV6, KMT5A and VCP/p97.
CC {ECO:0000269|PubMed:12588862, ECO:0000269|PubMed:17540172,
CC ECO:0000269|PubMed:18026117, ECO:0000269|PubMed:18042461,
CC ECO:0000269|PubMed:18408754, ECO:0000269|PubMed:20870719,
CC ECO:0000269|PubMed:20870725, ECO:0000269|PubMed:22120668}.
CC -!- INTERACTION:
CC Q9Y468; P10412: H1-4; NbExp=7; IntAct=EBI-1265089, EBI-358163;
CC Q9Y468; P68431: H3C12; NbExp=2; IntAct=EBI-1265089, EBI-79722;
CC Q9Y468; P62805: H4C9; NbExp=4; IntAct=EBI-1265089, EBI-302023;
CC Q9Y468; P49736: MCM2; NbExp=2; IntAct=EBI-1265089, EBI-374819;
CC Q9Y468; P33992: MCM5; NbExp=2; IntAct=EBI-1265089, EBI-359410;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10445843}.
CC Note=Excluded from the nucleolus. Does not colocalizes with the PcG
CC protein BMI1, suggesting that these two proteins do not belong to the
CC same complex.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=5;
CC IsoId=Q9Y468-5; Sequence=Displayed;
CC Name=1; Synonyms=mbt-I;
CC IsoId=Q9Y468-1; Sequence=VSP_059458;
CC Name=2; Synonyms=mbt-II;
CC IsoId=Q9Y468-2; Sequence=VSP_059458, VSP_059459;
CC Name=3;
CC IsoId=Q9Y468-3; Sequence=VSP_003901, VSP_059459;
CC Name=4;
CC IsoId=Q9Y468-4; Sequence=VSP_059458, VSP_059460;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expression is reduced in
CC colorectal cancer cell line SW480 and promyelocytic leukemia cell line
CC HL-60. {ECO:0000269|PubMed:10445843}.
CC -!- DEVELOPMENTAL STAGE: In interphase cells, it is scattered throughout
CC the nucleoplasm. In mitotic cells, it strongly associates with
CC condensed chromosomes from the prophase to telophase.
CC -!- DOMAIN: The MBT repeat 2 specifically recognizes and binds
CC monomethylated and dimethylated proteins. In contrast, it does not bind
CC trimethylated proteins. The MBT repeat 1 does not bind methylated
CC peptides but inserts a proline ring in a Pro-Ser-Ser/Thr sequence
CC context. {ECO:0000269|PubMed:18042461}.
CC -!- PTM: Ubiquitinated in a VCP/p97-dependent way following DNA damage,
CC leading to its removal from DNA damage sites, promoting accessibility
CC of H4K20me2 mark for DNA repair protein TP53BP1, which is then
CC recruited to DNA damage sites. {ECO:0000269|PubMed:22120668}.
CC -!- MISCELLANEOUS: The L3MBTL1 locus is imprinted. Paternal inherited gene
CC is expressed, while the maternal inherited gene is silenced.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAW75958.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAW75961.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAW75962.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U89358; AAC69438.1; -; mRNA.
DR EMBL; AK299199; BAG61241.1; -; mRNA.
DR EMBL; AL110279; CAB53714.1; -; mRNA.
DR EMBL; AL031681; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z98752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75958.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471077; EAW75961.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471077; EAW75962.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC039820; AAH39820.1; -; mRNA.
DR EMBL; AB014581; BAA31656.1; -; mRNA.
DR CCDS; CCDS13319.1; -. [Q9Y468-1]
DR CCDS; CCDS46602.2; -. [Q9Y468-5]
DR PIR; T14794; T14794.
DR RefSeq; NP_056293.4; NM_015478.6. [Q9Y468-1]
DR RefSeq; NP_115479.4; NM_032107.4. [Q9Y468-5]
DR PDB; 1OYX; X-ray; 1.85 A; A/B/C=265-595.
DR PDB; 1OZ2; X-ray; 1.55 A; A=265-595.
DR PDB; 1OZ3; X-ray; 1.85 A; A/B/C=265-595.
DR PDB; 2PQW; X-ray; 2.00 A; A=268-590.
DR PDB; 2RHI; X-ray; 1.66 A; A=265-594.
DR PDB; 2RHU; X-ray; 1.90 A; A=274-587.
DR PDB; 2RHX; X-ray; 2.10 A; A=265-594.
DR PDB; 2RHY; X-ray; 1.90 A; A=274-587.
DR PDB; 2RHZ; X-ray; 2.20 A; A=274-587.
DR PDB; 2RI2; X-ray; 2.20 A; A=274-587.
DR PDB; 2RI3; X-ray; 2.00 A; A=274-587.
DR PDB; 2RI5; X-ray; 2.00 A; A=274-587.
DR PDB; 2RJC; X-ray; 2.00 A; A/B/C=268-598.
DR PDB; 2RJD; X-ray; 1.65 A; A=268-598.
DR PDB; 2RJE; X-ray; 1.86 A; A/B/C=268-598.
DR PDB; 2RJF; X-ray; 2.05 A; A/C/E=268-598.
DR PDB; 3OQ5; X-ray; 2.50 A; A/B/C=259-598.
DR PDB; 3P8H; X-ray; 2.55 A; A/B/C=268-590.
DR PDB; 3UWN; X-ray; 2.15 A; A=268-598.
DR PDB; 6BYB; X-ray; 1.74 A; A=200-522.
DR PDBsum; 1OYX; -.
DR PDBsum; 1OZ2; -.
DR PDBsum; 1OZ3; -.
DR PDBsum; 2PQW; -.
DR PDBsum; 2RHI; -.
DR PDBsum; 2RHU; -.
DR PDBsum; 2RHX; -.
DR PDBsum; 2RHY; -.
DR PDBsum; 2RHZ; -.
DR PDBsum; 2RI2; -.
DR PDBsum; 2RI3; -.
DR PDBsum; 2RI5; -.
DR PDBsum; 2RJC; -.
DR PDBsum; 2RJD; -.
DR PDBsum; 2RJE; -.
DR PDBsum; 2RJF; -.
DR PDBsum; 3OQ5; -.
DR PDBsum; 3P8H; -.
DR PDBsum; 3UWN; -.
DR PDBsum; 6BYB; -.
DR AlphaFoldDB; Q9Y468; -.
DR SMR; Q9Y468; -.
DR BioGRID; 117486; 114.
DR ComplexPortal; CPX-469; L3MBTL1 complex.
DR DIP; DIP-29628N; -.
DR IntAct; Q9Y468; 100.
DR MINT; Q9Y468; -.
DR STRING; 9606.ENSP00000398516; -.
DR BindingDB; Q9Y468; -.
DR ChEMBL; CHEMBL1287622; -.
DR DrugBank; DB03814; 2-(N-morpholino)ethanesulfonic acid.
DR DrugCentral; Q9Y468; -.
DR iPTMnet; Q9Y468; -.
DR PhosphoSitePlus; Q9Y468; -.
DR BioMuta; L3MBTL1; -.
DR DMDM; 325511398; -.
DR EPD; Q9Y468; -.
DR jPOST; Q9Y468; -.
DR MassIVE; Q9Y468; -.
DR PaxDb; Q9Y468; -.
DR PeptideAtlas; Q9Y468; -.
DR PRIDE; Q9Y468; -.
DR ProteomicsDB; 86115; -. [Q9Y468-4]
DR ProteomicsDB; 86116; -. [Q9Y468-1]
DR ProteomicsDB; 86117; -. [Q9Y468-2]
DR ProteomicsDB; 86118; -. [Q9Y468-3]
DR ProteomicsDB; 86119; -. [Q9Y468-5]
DR ABCD; Q9Y468; 3 sequenced antibodies.
DR Antibodypedia; 27135; 153 antibodies from 26 providers.
DR DNASU; 26013; -.
DR Ensembl; ENST00000373135.8; ENSP00000362227.3; ENSG00000185513.17. [Q9Y468-1]
DR Ensembl; ENST00000422861.3; ENSP00000410139.2; ENSG00000185513.17. [Q9Y468-4]
DR Ensembl; ENST00000427442.8; ENSP00000402107.4; ENSG00000185513.17. [Q9Y468-5]
DR GeneID; 26013; -.
DR KEGG; hsa:26013; -.
DR UCSC; uc002xkl.4; human. [Q9Y468-5]
DR CTD; 26013; -.
DR DisGeNET; 26013; -.
DR GeneCards; L3MBTL1; -.
DR HGNC; HGNC:15905; L3MBTL1.
DR HPA; ENSG00000185513; Low tissue specificity.
DR MIM; 608802; gene.
DR neXtProt; NX_Q9Y468; -.
DR OpenTargets; ENSG00000185513; -.
DR PharmGKB; PA30260; -.
DR VEuPathDB; HostDB:ENSG00000185513; -.
DR eggNOG; KOG3766; Eukaryota.
DR GeneTree; ENSGT00940000159708; -.
DR HOGENOM; CLU_004064_0_0_1; -.
DR InParanoid; Q9Y468; -.
DR OMA; KECHSER; -.
DR OrthoDB; 63195at2759; -.
DR PhylomeDB; Q9Y468; -.
DR TreeFam; TF316498; -.
DR PathwayCommons; Q9Y468; -.
DR Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation.
DR SignaLink; Q9Y468; -.
DR SIGNOR; Q9Y468; -.
DR BioGRID-ORCS; 26013; 11 hits in 1108 CRISPR screens.
DR ChiTaRS; L3MBTL1; human.
DR EvolutionaryTrace; Q9Y468; -.
DR GeneWiki; L3MBTL; -.
DR GenomeRNAi; 26013; -.
DR Pharos; Q9Y468; Tchem.
DR PRO; PR:Q9Y468; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9Y468; protein.
DR Bgee; ENSG00000185513; Expressed in right hemisphere of cerebellum and 159 other tissues.
DR ExpressionAtlas; Q9Y468; baseline and differential.
DR Genevisible; Q9Y468; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0061793; C:chromatin lock complex; IPI:ComplexPortal.
DR GO; GO:0000793; C:condensed chromosome; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0031491; F:nucleosome binding; IDA:UniProtKB.
DR GO; GO:0032093; F:SAM domain binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006325; P:chromatin organization; IDA:UniProtKB.
DR GO; GO:0030097; P:hemopoiesis; IEP:UniProtKB.
DR GO; GO:0031507; P:heterochromatin assembly; IDA:ComplexPortal.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; NAS:UniProtKB.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; IDA:UniProtKB.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; IMP:UniProtKB.
DR IDEAL; IID00335; -.
DR InterPro; IPR004092; Mbt.
DR InterPro; IPR002515; Znf_C2H2C.
DR InterPro; IPR036060; Znf_C2H2C_sf.
DR Pfam; PF02820; MBT; 3.
DR Pfam; PF01530; zf-C2HC; 1.
DR SMART; SM00561; MBT; 3.
DR SUPFAM; SSF103637; SSF103637; 1.
DR PROSITE; PS51079; MBT; 3.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS51802; ZF_CCHHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..840
FT /note="Lethal(3)malignant brain tumor-like protein 1"
FT /id="PRO_0000084452"
FT REPEAT 274..374
FT /note="MBT 1"
FT REPEAT 382..481
FT /note="MBT 2"
FT REPEAT 490..585
FT /note="MBT 3"
FT DOMAIN 751..824
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT ZN_FING 613..656
FT /note="CCHHC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT REGION 127..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 447..454
FT /note="Interaction with monomethylated and dimethylated
FT peptides"
FT REGION 580..605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 657..697
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 187..211
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..246
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..269
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 673..691
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 622
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT BINDING 627
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT BINDING 640
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT BINDING 646
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT SITE 423
FT /note="Mediates recognition of monomethylated and
FT dimethylated peptides"
FT SITE 426
FT /note="Positioned at the entrance of MBT 2 and is required
FT for recognition of monomethylated and dimethylated
FT peptides"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..416
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_003901"
FT VAR_SEQ 1..98
FT /note="MHLVAGDSPGSGPHLPATAFIIPASSATLGLPSSALDVSCFPREPIHVGAPE
FT QVAGCEPVSATVLPQLSAGPASSSTSTVRLLEWTEAAAPPPGGGLR -> MRRREGHGT
FT DSEMGQGPVRESQSSDPPALQ (in isoform 1, isoform 2 and isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:10445843,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9734811"
FT /id="VSP_059458"
FT VAR_SEQ 777..840
FT /note="ARIVRVTHVSGKTLVWTVAQLGDLVCSDHLQEGKGILETGVHSLLCSLPTHL
FT LAKLSFASDSQY -> VRCKCRVGDRAGVTVLKTAGSRCPPQRHFC (in isoform
FT 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10445843,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_059459"
FT VAR_SEQ 777..840
FT /note="ARIVRVTHVSGKTLVWTVAQLGDLVCSDHLQEGKGILETGVHSLLCSLPTHL
FT LAKLSFASDSQY -> MIDGEAFLLLTQADIVKIMSVKLGPALKIYNAILMFKNADDTL
FT K (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9734811"
FT /id="VSP_059460"
FT VARIANT 117
FT /note="S -> T (in dbSNP:rs17857202)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_051097"
FT VARIANT 547
FT /note="I -> M (in dbSNP:rs6017104)"
FT /id="VAR_051098"
FT MUTAGEN 316
FT /note="D->N: Does not affect binding to monomethylated and
FT dimethylated peptides."
FT /evidence="ECO:0000269|PubMed:17540172"
FT MUTAGEN 340
FT /note="F->A: Does not affect binding to monomethylated and
FT dimethylated peptides."
FT /evidence="ECO:0000269|PubMed:17540172"
FT MUTAGEN 423
FT /note="D->A: Abolishes binding to monomethylated and
FT dimethylated peptides."
FT /evidence="ECO:0000269|PubMed:17540172,
FT ECO:0000269|PubMed:18026117, ECO:0000269|PubMed:18042461,
FT ECO:0000269|PubMed:20870725"
FT MUTAGEN 423
FT /note="D->N: Strongly impairs binding to monomethylated and
FT dimethylated peptides. Abolishes binding to p53/TP53
FT monomethylated at 'Lys-382'."
FT /evidence="ECO:0000269|PubMed:17540172,
FT ECO:0000269|PubMed:18026117, ECO:0000269|PubMed:18042461,
FT ECO:0000269|PubMed:20870725"
FT MUTAGEN 426
FT /note="N->A: Abolishes binding to monomethylated and
FT dimethylated peptides."
FT /evidence="ECO:0000269|PubMed:18042461,
FT ECO:0000269|PubMed:20870725"
FT MUTAGEN 426
FT /note="N->Q: Strongly impairs binding to monomethylated and
FT dimethylated peptides. Abolishes binding to p53/TP53
FT monomethylated at 'Lys-382'."
FT /evidence="ECO:0000269|PubMed:18042461,
FT ECO:0000269|PubMed:20870725"
FT MUTAGEN 431
FT /note="C->F,R: Strongly impairs binding to monomethylated
FT and dimethylated peptides."
FT /evidence="ECO:0000269|PubMed:18026117"
FT MUTAGEN 447
FT /note="F->A: Abolishes binding to monomethylated and
FT dimethylated peptides. Abolishes binding to p53/TP53
FT monomethylated at 'Lys-382'."
FT /evidence="ECO:0000269|PubMed:17540172,
FT ECO:0000269|PubMed:20870725"
FT MUTAGEN 450
FT /note="W->L: Abolishes binding to p53/TP53 monomethylated
FT at 'Lys-382'."
FT /evidence="ECO:0000269|PubMed:20870725"
FT MUTAGEN 454
FT /note="Y->L: Abolishes binding to p53/TP53 monomethylated
FT at 'Lys-382'."
FT /evidence="ECO:0000269|PubMed:20870725"
FT MUTAGEN 527
FT /note="D->N: Does not affect binding to monomethylated and
FT dimethylated peptides."
FT /evidence="ECO:0000269|PubMed:17540172"
FT MUTAGEN 551
FT /note="F->A: Does not affect binding to monomethylated and
FT dimethylated peptides."
FT /evidence="ECO:0000269|PubMed:17540172"
FT CONFLICT 254
FT /note="T -> A (in Ref. 2; BAG61241)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="P -> L (in Ref. 1; AAC69438)"
FT /evidence="ECO:0000305"
FT CONFLICT 388..389
FT /note="LR -> MC (in Ref. 1; AAC69438)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="L -> M (in Ref. 1; AAC69438)"
FT /evidence="ECO:0000305"
FT CONFLICT 561
FT /note="W -> R (in Ref. 2; BAG61241)"
FT /evidence="ECO:0000305"
FT CONFLICT 663
FT /note="S -> P (in Ref. 1; AAC69438)"
FT /evidence="ECO:0000305"
FT HELIX 276..283
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 295..298
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 311..316
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 319..332
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 335..340
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 356..359
FT /evidence="ECO:0007829|PDB:2RJD"
FT HELIX 363..367
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 384..391
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 418..422
FT /evidence="ECO:0007829|PDB:1OZ2"
FT TURN 424..427
FT /evidence="ECO:0007829|PDB:2RI5"
FT STRAND 430..439
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 442..447
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 452..454
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 470..474
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 487..489
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 492..499
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 522..526
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 528..530
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 534..542
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 544..551
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 556..558
FT /evidence="ECO:0007829|PDB:1OZ2"
FT STRAND 560..563
FT /evidence="ECO:0007829|PDB:1OZ2"
FT HELIX 574..578
FT /evidence="ECO:0007829|PDB:1OZ2"
FT VARIANT Q9Y468-1:759
FT /note="H -> R (in dbSNP:rs6030948)"
FT /evidence="ECO:0000305"
FT /id="VAR_082883"
SQ SEQUENCE 840 AA; 92297 MW; 70004D458897CB24 CRC64;
MHLVAGDSPG SGPHLPATAF IIPASSATLG LPSSALDVSC FPREPIHVGA PEQVAGCEPV
SATVLPQLSA GPASSSTSTV RLLEWTEAAA PPPGGGLRFR ISEYKPLNMA GVEQPPSPEL
RQEGVTEYED GGAPAGDGEA GPQQAEDHPQ NPPEDPNQDP PEDDSTCQCQ ACGPHQAAGP
DLGSSNDGCP QLFQERSVIV ENSSGSTSAS ELLKPMKKRK RREYQSPSEE ESEPEAMEKQ
EEGKDPEGQP TASTPESEEW SSSQPATGEK KECWSWESYL EEQKAITAPV SLFQDSQAVT
HNKNGFKLGM KLEGIDPQHP SMYFILTVAE VCGYRLRLHF DGYSECHDFW VNANSPDIHP
AGWFEKTGHK LQPPKGYKEE EFSWSQYLRS TRAQAAPKHL FVSQSHSPPP LGFQVGMKLE
AVDRMNPSLV CVASVTDVVD SRFLVHFDNW DDTYDYWCDP SSPYIHPVGW CQKQGKPLTP
PQDYPDPDNF CWEKYLEETG ASAVPTWAFK VRPPHSFLVN MKLEAVDRRN PALIRVASVE
DVEDHRIKIH FDGWSHGYDF WIDADHPDIH PAGWCSKTGH PLQPPLGPRE PSSASPGGCP
PLSYRSLPHT RTSKYSFHHR KCPTPGCDGS GHVTGKFTAH HCLSGCPLAE RNQSRLKAEL
SDSEASARKK NLSGFSPRKK PRHHGRIGRP PKYRKIPQED FQTLTPDVVH QSLFMSALSA
HPDRSLSVCW EQHCKLLPGV AGISASTVAK WTIDEVFGFV QTLTGCEDQA RLFKDEARIV
RVTHVSGKTL VWTVAQLGDL VCSDHLQEGK GILETGVHSL LCSLPTHLLA KLSFASDSQY
