LMBL1_MOUSE
ID LMBL1_MOUSE Reviewed; 826 AA.
AC A2A5N8; Q5DU20;
DT 08-MAR-2011, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 117.
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;
GN Name=L3mbtl1; Synonyms=Kiaa0681, L3mbt, L3mbtl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=20592034; DOI=10.1074/jbc.m110.115410;
RA Qin J., Van Buren D., Huang H.S., Zhong L., Mostoslavsky R., Akbarian S.,
RA Hock H.;
RT "Chromatin protein L3MBTL1 is dispensable for development and tumor
RT suppression in mice.";
RL J. Biol. Chem. 285:27767-27775(2010).
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 (By
CC similarity). {ECO:0000250}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Excluded from the
CC nucleolus. Does not colocalizes with the PcG protein BMI1, suggesting
CC that these two proteins do not belong to the same complex (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, testis, eyes, and ES
CC cells. {ECO:0000269|PubMed:20592034}.
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 (By similarity). {ECO:0000250}.
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:0000250}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice develop and reproduc
CC normally. Mice were followed for more than 2 years, without any
CC alteration in normal lifespan or survival with or without sublethal
CC irradiation. {ECO:0000269|PubMed:20592034}.
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DR EMBL; AK220350; BAD90413.1; -; mRNA.
DR EMBL; AL591584; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL606473; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06309.1; -; Genomic_DNA.
DR CCDS; CCDS38314.1; -.
DR RefSeq; NP_001074807.1; NM_001081338.1.
DR RefSeq; XP_011237848.1; XM_011239546.2.
DR AlphaFoldDB; A2A5N8; -.
DR SMR; A2A5N8; -.
DR BioGRID; 232346; 1.
DR ComplexPortal; CPX-470; L3MBTL1 complex.
DR STRING; 10090.ENSMUSP00000044038; -.
DR iPTMnet; A2A5N8; -.
DR PhosphoSitePlus; A2A5N8; -.
DR PaxDb; A2A5N8; -.
DR PRIDE; A2A5N8; -.
DR ProteomicsDB; 292342; -.
DR Ensembl; ENSMUST00000035751; ENSMUSP00000044038; ENSMUSG00000035576.
DR GeneID; 241764; -.
DR KEGG; mmu:241764; -.
DR UCSC; uc008nsd.1; mouse.
DR CTD; 26013; -.
DR MGI; MGI:2676663; L3mbtl1.
DR VEuPathDB; HostDB:ENSMUSG00000035576; -.
DR eggNOG; KOG3766; Eukaryota.
DR GeneTree; ENSGT00940000159708; -.
DR HOGENOM; CLU_004064_0_0_1; -.
DR InParanoid; A2A5N8; -.
DR OMA; QVASQHK; -.
DR OrthoDB; 63195at2759; -.
DR PhylomeDB; A2A5N8; -.
DR TreeFam; TF316498; -.
DR Reactome; R-MMU-6804760; Regulation of TP53 Activity through Methylation.
DR BioGRID-ORCS; 241764; 1 hit in 75 CRISPR screens.
DR PRO; PR:A2A5N8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2A5N8; protein.
DR Bgee; ENSMUSG00000035576; Expressed in hypothalamus and 64 other tissues.
DR ExpressionAtlas; A2A5N8; baseline and differential.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0061793; C:chromatin lock complex; ISO:MGI.
DR GO; GO:0000793; C:condensed chromosome; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0031491; F:nucleosome binding; ISS:UniProtKB.
DR GO; GO:0032093; F:SAM domain binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006325; P:chromatin organization; ISS:UniProtKB.
DR GO; GO:0030097; P:hemopoiesis; ISS:UniProtKB.
DR GO; GO:0031507; P:heterochromatin assembly; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; NAS:UniProtKB.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; ISS:UniProtKB.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; ISS:UniProtKB.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR004092; Mbt.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR002515; Znf_C2H2C.
DR InterPro; IPR036060; Znf_C2H2C_sf.
DR Pfam; PF02820; MBT; 3.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF01530; zf-C2HC; 1.
DR SMART; SM00561; MBT; 3.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF103637; SSF103637; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS51079; MBT; 3.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS51802; ZF_CCHHC; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..826
FT /note="Lethal(3)malignant brain tumor-like protein 1"
FT /id="PRO_0000405831"
FT REPEAT 280..380
FT /note="MBT 1"
FT REPEAT 388..487
FT /note="MBT 2"
FT REPEAT 496..591
FT /note="MBT 3"
FT DOMAIN 757..821
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT ZN_FING 619..662
FT /note="CCHHC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT REGION 167..197
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 220..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 453..460
FT /note="Interaction with monomethylated and dimethylated
FT peptides"
FT /evidence="ECO:0000250"
FT REGION 586..621
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 663..699
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..197
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..261
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 679..696
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 628
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT BINDING 633
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 BINDING 652
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT SITE 429
FT /note="Mediates recognition of monomethylated and
FT dimethylated peptides"
FT /evidence="ECO:0000250"
FT SITE 432
FT /note="Positioned at the entrance of MBT 2 and is required
FT for recognition of monomethylated and dimethylated
FT peptides"
FT /evidence="ECO:0000250"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y468"
FT CONFLICT 824
FT /note="A -> V (in Ref. 1; BAD90413)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 826 AA; 91781 MW; F27CE3D490434A44 CRC64;
MEGHTDMEIL RTVKGSSTGE VNVHLVARDS AGPHPQLPTT AFIIPTNAAT LGLPSTALDV
PYPREPVHVG ALERVAGSEP VTATILPQLS TGTGTNSTVR LLDWTGVSAP LPGSGMRFRI
NEYAPLNMIG VERPRSPEQR HEGGMARRDA GIQHPDVHQD RQDITSLEPP VDASSCKCQA
CGPQQSSGLD VGSSGDRCSQ PFQKRSVIVE NSGCTIASEL LKPMKKRKHK EYQSPSEESE
PEAVKQGEGK DAEREPTPST PENEEWSRSQ LVSSEKKDGW SWESYLEEQK AVTAPVSLFQ
DSQAVTHNKN GFKLGMKLEG IDPQHPSMYF ILTVAEVCGY RLRLHFDGYS ECHDFWVNAN
SPDIHPAGWF EKTGHKLQLP KGYKEEEFSW SQYLRSTKAQ AAPKHLFVSQ SHSTPPVGFQ
VGMKLEAVDR MNPSLVCVAS VTDVVDSRFL VHFDDWGDTY DYWCDPSSPY IHPVGWCQKQ
GKPLTPPQDY PDPDSFCWEK YLEETGTSAV PNWAFKVRPP HSFLVNMKLE AVDRRNPALI
RVASVEDVED HRIKLHFDGW SHNYDFWIDA DHPDIHPAGW CSKTGHPLEP PLRPRESSSV
SPGGCPPLSH RSPPHTKTSK YNFHHRKCPT PGCDGSGHVT GKFTAHHCLS GCPLAEKNQS
RLKAELSDSE TAARKKNPSN LSPRKKPRHQ GRIGRPPKYR KIPEEDLQAL PPSVVHQSLF
MSTLPTHADR PLSVCWEQHC KLLPGVAGIS ASTVSKWTIE EVFGFVQTLT GSEDQARLFK
DEMIDGEAFL LLTQADIVKI MSVKLGPALK IYNAILMFKN TDDAFK
