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Protein

Lethal(3)malignant brain tumor-like protein 1

Gene

L3mbtl1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei429 – 4291Mediates recognition of monomethylated and dimethylated peptidesBy similarity
Sitei432 – 4321Positioned at the entrance of MBT 2 and is required for recognition of monomethylated and dimethylated peptidesBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri626 – 65227C2HC-typeAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-6804760. Regulation of TP53 Activity through Methylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Lethal(3)malignant brain tumor-like protein 1
Short name:
H-l(3)mbt
Short name:
H-l(3)mbt protein
Short name:
L(3)mbt-like
Alternative name(s):
L(3)mbt protein homolog
Gene namesi
Name:L3mbtl1
Synonyms:Kiaa0681, L3mbt, L3mbtl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2676663. L3mbtl1.

Subcellular locationi

  • Nucleus By similarity

  • Note: Excluded from the nucleolus. Does not colocalizes with the PcG protein BMI1, suggesting that these two proteins do not belong to the same complex (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice develop and reproduc normally. Mice were followed for more than 2 years, without any alteration in normal lifespan or survival with or without sublethal irradiation.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 826826Lethal(3)malignant brain tumor-like protein 1PRO_0000405831Add
BLAST

Post-translational modificationi

Ubiquitinated in a VCP/p97-dependent way following DNA damage, leading to its removal from DNA damage sites, promoting accessibility of H4K20me2 mark for DNA repair protein TP53BP1, which is then recruited to DNA damage sites.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiA2A5N8.
PRIDEiA2A5N8.

PTM databases

iPTMnetiA2A5N8.
PhosphoSiteiA2A5N8.

Expressioni

Tissue specificityi

Highly expressed in brain, testis, eyes, and ES cells.1 Publication

Gene expression databases

BgeeiA2A5N8.
ExpressionAtlasiA2A5N8. baseline.

Interactioni

Subunit structurei

Homodimer. Interacts with RB1/RB (when monomethylated at 'Lys-860'). Interacts with p53/TP53 (when monomethylated at 'Lys-382'). Interacts with CBX3, ETV6, KMT5A and VCP/p97 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000044038.

Structurei

3D structure databases

ProteinModelPortaliA2A5N8.
SMRiA2A5N8. Positions 280-592, 627-655, 755-811.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati280 – 380101MBT 1Add
BLAST
Repeati388 – 487100MBT 2Add
BLAST
Repeati496 – 59196MBT 3Add
BLAST
Domaini757 – 82165SAMPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni453 – 4608Interaction with monomethylated and dimethylated peptidesBy similarity

Domaini

The MBT repeat 2 specifically recognizes and binds monomethylated and dimethylated proteins. In contrast, it does not bind trimethylated proteins. The MBT repeat 1 does not bind methylated peptides but inserts a proline ring in a Pro-Ser-Ser/Thr sequence context (By similarity).By similarity

Sequence similaritiesi

Contains 1 C2HC-type zinc finger.Curated
Contains 3 MBT repeats.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri626 – 65227C2HC-typeAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG3766. Eukaryota.
ENOG410Y4AQ. LUCA.
GeneTreeiENSGT00760000119024.
HOGENOMiHOG000231019.
HOVERGENiHBG071375.
InParanoidiA2A5N8.
OMAiCTSASEL.
OrthoDBiEOG7FR7FT.
PhylomeDBiA2A5N8.
TreeFamiTF316498.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
InterProiIPR004092. Mbt.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR002515. Znf_C2HC.
[Graphical view]
PfamiPF02820. MBT. 3 hits.
PF00536. SAM_1. 1 hit.
PF01530. zf-C2HC. 1 hit.
[Graphical view]
SMARTiSM00561. MBT. 3 hits.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
PROSITEiPS51079. MBT. 3 hits.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A2A5N8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGHTDMEIL RTVKGSSTGE VNVHLVARDS AGPHPQLPTT AFIIPTNAAT
60 70 80 90 100
LGLPSTALDV PYPREPVHVG ALERVAGSEP VTATILPQLS TGTGTNSTVR
110 120 130 140 150
LLDWTGVSAP LPGSGMRFRI NEYAPLNMIG VERPRSPEQR HEGGMARRDA
160 170 180 190 200
GIQHPDVHQD RQDITSLEPP VDASSCKCQA CGPQQSSGLD VGSSGDRCSQ
210 220 230 240 250
PFQKRSVIVE NSGCTIASEL LKPMKKRKHK EYQSPSEESE PEAVKQGEGK
260 270 280 290 300
DAEREPTPST PENEEWSRSQ LVSSEKKDGW SWESYLEEQK AVTAPVSLFQ
310 320 330 340 350
DSQAVTHNKN GFKLGMKLEG IDPQHPSMYF ILTVAEVCGY RLRLHFDGYS
360 370 380 390 400
ECHDFWVNAN SPDIHPAGWF EKTGHKLQLP KGYKEEEFSW SQYLRSTKAQ
410 420 430 440 450
AAPKHLFVSQ SHSTPPVGFQ VGMKLEAVDR MNPSLVCVAS VTDVVDSRFL
460 470 480 490 500
VHFDDWGDTY DYWCDPSSPY IHPVGWCQKQ GKPLTPPQDY PDPDSFCWEK
510 520 530 540 550
YLEETGTSAV PNWAFKVRPP HSFLVNMKLE AVDRRNPALI RVASVEDVED
560 570 580 590 600
HRIKLHFDGW SHNYDFWIDA DHPDIHPAGW CSKTGHPLEP PLRPRESSSV
610 620 630 640 650
SPGGCPPLSH RSPPHTKTSK YNFHHRKCPT PGCDGSGHVT GKFTAHHCLS
660 670 680 690 700
GCPLAEKNQS RLKAELSDSE TAARKKNPSN LSPRKKPRHQ GRIGRPPKYR
710 720 730 740 750
KIPEEDLQAL PPSVVHQSLF MSTLPTHADR PLSVCWEQHC KLLPGVAGIS
760 770 780 790 800
ASTVSKWTIE EVFGFVQTLT GSEDQARLFK DEMIDGEAFL LLTQADIVKI
810 820
MSVKLGPALK IYNAILMFKN TDDAFK
Length:826
Mass (Da):91,781
Last modified:February 20, 2007 - v1
Checksum:iF27CE3D490434A44
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti824 – 8241A → V in BAD90413 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK220350 mRNA. Translation: BAD90413.1.
AL606473, AL591584 Genomic DNA. Translation: CAM20950.1.
AL591584, AL606473 Genomic DNA. Translation: CAM21343.1.
CH466551 Genomic DNA. Translation: EDL06309.1.
CCDSiCCDS38314.1.
RefSeqiNP_001074807.1. NM_001081338.1.
XP_011237848.1. XM_011239546.1.
UniGeneiMm.187086.

Genome annotation databases

EnsembliENSMUST00000035751; ENSMUSP00000044038; ENSMUSG00000035576.
GeneIDi241764.
KEGGimmu:241764.
UCSCiuc008nsd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK220350 mRNA. Translation: BAD90413.1.
AL606473, AL591584 Genomic DNA. Translation: CAM20950.1.
AL591584, AL606473 Genomic DNA. Translation: CAM21343.1.
CH466551 Genomic DNA. Translation: EDL06309.1.
CCDSiCCDS38314.1.
RefSeqiNP_001074807.1. NM_001081338.1.
XP_011237848.1. XM_011239546.1.
UniGeneiMm.187086.

3D structure databases

ProteinModelPortaliA2A5N8.
SMRiA2A5N8. Positions 280-592, 627-655, 755-811.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000044038.

PTM databases

iPTMnetiA2A5N8.
PhosphoSiteiA2A5N8.

Proteomic databases

PaxDbiA2A5N8.
PRIDEiA2A5N8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035751; ENSMUSP00000044038; ENSMUSG00000035576.
GeneIDi241764.
KEGGimmu:241764.
UCSCiuc008nsd.1. mouse.

Organism-specific databases

CTDi26013.
MGIiMGI:2676663. L3mbtl1.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG3766. Eukaryota.
ENOG410Y4AQ. LUCA.
GeneTreeiENSGT00760000119024.
HOGENOMiHOG000231019.
HOVERGENiHBG071375.
InParanoidiA2A5N8.
OMAiCTSASEL.
OrthoDBiEOG7FR7FT.
PhylomeDBiA2A5N8.
TreeFamiTF316498.

Enzyme and pathway databases

ReactomeiR-MMU-6804760. Regulation of TP53 Activity through Methylation.

Miscellaneous databases

PROiA2A5N8.
SOURCEiSearch...

Gene expression databases

BgeeiA2A5N8.
ExpressionAtlasiA2A5N8. baseline.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
InterProiIPR004092. Mbt.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR002515. Znf_C2HC.
[Graphical view]
PfamiPF02820. MBT. 3 hits.
PF00536. SAM_1. 1 hit.
PF01530. zf-C2HC. 1 hit.
[Graphical view]
SMARTiSM00561. MBT. 3 hits.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
PROSITEiPS51079. MBT. 3 hits.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Prediction of the coding sequences of mouse homologues of KIAA gene. The complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., Koga H.
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Fetal brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Chromatin protein L3MBTL1 is dispensable for development and tumor suppression in mice."
    Qin J., Van Buren D., Huang H.S., Zhong L., Mostoslavsky R., Akbarian S., Hock H.
    J. Biol. Chem. 285:27767-27775(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiLMBL1_MOUSE
AccessioniPrimary (citable) accession number: A2A5N8
Secondary accession number(s): Q5DU20
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 8, 2011
Last sequence update: February 20, 2007
Last modified: June 8, 2016
This is version 82 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.