ID   LMBL3_MOUSE             Reviewed;         883 AA.
AC   Q8BLB7; Q0VGT0; Q641L7; Q6ZPI2; Q8C0G4;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 143.
DE   RecName: Full=Lethal(3)malignant brain tumor-like protein 3 {ECO:0000305};
DE            Short=L(3)mbt-like protein 3;
DE   AltName: Full=MBT-1;
GN   Name=L3mbtl3 {ECO:0000312|MGI:MGI:2143628}; Synonyms=Mbt1;
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] (ISOFORMS 1 AND 3).
RC   STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, and Fetal testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J; TISSUE=Brain, and Eye;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 123-883.
RC   TISSUE=Embryonic tail;
RX   PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA   Saga Y., Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT   The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT   identified by screening of terminal sequences of cDNA clones randomly
RT   sampled from size-fractionated libraries.";
RL   DNA Res. 10:167-180(2003).
RN   [4]
RP   DISRUPTION PHENOTYPE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=15889154; DOI=10.1038/sj.emboj.7600654;
RA   Arai S., Miyazaki T.;
RT   "Impaired maturation of myeloid progenitors in mice lacking novel Polycomb
RT   group protein MBT-1.";
RL   EMBO J. 24:1863-1873(2005).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Lung;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   INTERACTION WITH RBPJ.
RX   PubMed=29030483; DOI=10.15252/embj.201796525;
RA   Xu T., Park S.S., Giaimo B.D., Hall D., Ferrante F., Ho D.M., Hori K.,
RA   Anhezini L., Ertl I., Bartkuhn M., Zhang H., Milon E., Ha K., Conlon K.P.,
RA   Kuick R., Govindarajoo B., Zhang Y., Sun Y., Dou Y., Basrur V.,
RA   Elenitoba-Johnson K.S., Nesvizhskii A.I., Ceron J., Lee C.Y., Borggrefe T.,
RA   Kovall R.A., Rual J.F.;
RT   "RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch
RT   signaling via histone demethylase KDM1A/LSD1.";
RL   EMBO J. 36:3232-3249(2017).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH DCAF5; SOX2 AND SFMBT1.
RX   PubMed=30442713; DOI=10.1074/jbc.ra118.005336;
RA   Zhang C., Leng F., Saxena L., Hoang N., Yu J., Alejo S., Lee L., Qi D.,
RA   Lu F., Sun H., Zhang H.;
RT   "Proteolysis of methylated SOX2 protein is regulated by L3MBTL3 and CRL4-
RT   DCAF5 ubiquitin ligase.";
RL   J. Biol. Chem. 294:476-489(2019).
RN   [8]
RP   INTERACTION WITH SAMD1, AND SUBCELLULAR LOCATION.
RX   PubMed=33980486; DOI=10.1126/sciadv.abf2229;
RA   Stielow B., Zhou Y., Cao Y., Simon C., Pogoda H.M., Jiang J., Ren Y.,
RA   Phanor S.K., Rohner I., Nist A., Stiewe T., Hammerschmidt M., Shi Y.,
RA   Bulyk M.L., Wang Z., Liefke R.;
RT   "The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin
RT   regulator at unmethylated CpG islands.";
RL   Sci. Adv. 7:0-0(2021).
CC   -!- FUNCTION: Is a negative regulator of Notch target genes expression,
CC       required for RBPJ-mediated transcriptional repression. It recruits
CC       KDM1A to Notch-responsive elements and promotes KDM1A-mediated H3K4me
CC       demethylation (By similarity). Involved in the regulation of ubiquitin-
CC       dependent degradation of a set of methylated non-histone proteins,
CC       including SOX2. It acts as an adapter recruiting the CRL4-DCAF5 E3
CC       ubiquitin ligase complex to methylated target proteins
CC       (PubMed:30442713). Also involved in the regulation of ubiquitin-
CC       dependent degradation of methylated DNMT1 and E2F1 (By similarity).
CC       Required for normal maturation of myeloid progenitor cells.
CC       {ECO:0000250|UniProtKB:Q96JM7, ECO:0000269|PubMed:15889154,
CC       ECO:0000269|PubMed:30442713}.
CC   -!- SUBUNIT: Interacts with RNF2. Interacts (via SAM domain) with SAMD1
CC       (via SAM domain); the interaction mediates L3MBTL3 binding to chromatin
CC       (PubMed:33980486). Interacts with RBPJ; the interaction is required for
CC       L3MBTL3 localization to chromatin and is impaired the Notch-derived
CC       peptides containing the intracellular domain (NICD) (PubMed:29030483).
CC       Interacts (via SAM domain) with KDM1A (By similarity). Interacts with
CC       DCAF5 (PubMed:30442713). Interacts with DNMT1 (By similarity).
CC       Interacts with E2F1 (By similarity). Interacts with SOX2
CC       (PubMed:30442713). Interacts with SFMBT1 (PubMed:30442713).
CC       {ECO:0000250|UniProtKB:Q96JM7, ECO:0000269|PubMed:15889154,
CC       ECO:0000269|PubMed:29030483, ECO:0000269|PubMed:30442713,
CC       ECO:0000269|PubMed:33980486}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15889154,
CC       ECO:0000269|PubMed:33980486}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q8BLB7-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8BLB7-2; Sequence=VSP_013509;
CC       Name=3;
CC         IsoId=Q8BLB7-3; Sequence=VSP_013510, VSP_013511;
CC   -!- TISSUE SPECIFICITY: Detected in hematopoietic progenitor cells in fetal
CC       liver. Detected in adult bone marrow, heart, brain, spleen, lung,
CC       liver, kidney and testis. {ECO:0000269|PubMed:15889154}.
CC   -!- DISRUPTION PHENOTYPE: Death at a late embryonic stage due defective
CC       erythropoiesis, defects in the maturation of other types of myeloid
CC       lineage cells and anemia. {ECO:0000269|PubMed:15889154}.
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DR   EMBL; AK031398; BAC27386.1; -; mRNA.
DR   EMBL; AK045667; BAC32449.1; -; mRNA.
DR   EMBL; BC082309; AAH82309.1; -; mRNA.
DR   EMBL; BC085192; AAH85192.1; -; mRNA.
DR   EMBL; AK129443; BAC98253.1; -; mRNA.
DR   CCDS; CCDS23756.1; -. [Q8BLB7-1]
DR   CCDS; CCDS83689.1; -. [Q8BLB7-2]
DR   RefSeq; NP_001334396.1; NM_001347467.1. [Q8BLB7-2]
DR   RefSeq; NP_766375.1; NM_172787.3. [Q8BLB7-1]
DR   RefSeq; XP_006512794.1; XM_006512731.3.
DR   RefSeq; XP_006512795.1; XM_006512732.3.
DR   RefSeq; XP_006512796.1; XM_006512733.3. [Q8BLB7-1]
DR   RefSeq; XP_006512798.1; XM_006512735.3.
DR   AlphaFoldDB; Q8BLB7; -.
DR   SMR; Q8BLB7; -.
DR   BioGRID; 231865; 8.
DR   STRING; 10090.ENSMUSP00000037619; -.
DR   iPTMnet; Q8BLB7; -.
DR   PhosphoSitePlus; Q8BLB7; -.
DR   EPD; Q8BLB7; -.
DR   jPOST; Q8BLB7; -.
DR   MaxQB; Q8BLB7; -.
DR   PaxDb; 10090-ENSMUSP00000037619; -.
DR   PeptideAtlas; Q8BLB7; -.
DR   ProteomicsDB; 286214; -. [Q8BLB7-1]
DR   ProteomicsDB; 286215; -. [Q8BLB7-2]
DR   ProteomicsDB; 286216; -. [Q8BLB7-3]
DR   Pumba; Q8BLB7; -.
DR   Antibodypedia; 32840; 192 antibodies from 26 providers.
DR   DNASU; 237339; -.
DR   Ensembl; ENSMUST00000040219.13; ENSMUSP00000037619.7; ENSMUSG00000039089.16. [Q8BLB7-1]
DR   Ensembl; ENSMUST00000105519.10; ENSMUSP00000101158.4; ENSMUSG00000039089.16. [Q8BLB7-2]
DR   Ensembl; ENSMUST00000174766.2; ENSMUSP00000133479.2; ENSMUSG00000039089.16. [Q8BLB7-1]
DR   GeneID; 237339; -.
DR   KEGG; mmu:237339; -.
DR   UCSC; uc007esa.1; mouse. [Q8BLB7-2]
DR   UCSC; uc007esb.1; mouse. [Q8BLB7-1]
DR   UCSC; uc007esd.1; mouse. [Q8BLB7-3]
DR   AGR; MGI:2143628; -.
DR   CTD; 84456; -.
DR   MGI; MGI:2143628; L3mbtl3.
DR   VEuPathDB; HostDB:ENSMUSG00000039089; -.
DR   eggNOG; KOG3766; Eukaryota.
DR   GeneTree; ENSGT00940000159800; -.
DR   HOGENOM; CLU_004064_0_1_1; -.
DR   InParanoid; Q8BLB7; -.
DR   OMA; SADTMYH; -.
DR   OrthoDB; 2905251at2759; -.
DR   PhylomeDB; Q8BLB7; -.
DR   TreeFam; TF316498; -.
DR   BioGRID-ORCS; 237339; 4 hits in 82 CRISPR screens.
DR   ChiTaRS; L3mbtl3; mouse.
DR   PRO; PR:Q8BLB7; -.
DR   Proteomes; UP000000589; Chromosome 10.
DR   RNAct; Q8BLB7; Protein.
DR   Bgee; ENSMUSG00000039089; Expressed in manus and 229 other cell types or tissues.
DR   GO; GO:0005730; C:nucleolus; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR   GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0140034; F:methylation-dependent protein binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR   GO; GO:0043249; P:erythrocyte maturation; IDA:MGI.
DR   GO; GO:0030851; P:granulocyte differentiation; IMP:MGI.
DR   GO; GO:0030225; P:macrophage differentiation; IMP:MGI.
DR   GO; GO:0030099; P:myeloid cell differentiation; IMP:MGI.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI.
DR   GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISO:MGI.
DR   GO; GO:0090308; P:regulation of DNA methylation-dependent heterochromatin formation; ISS:UniProtKB.
DR   GO; GO:2000058; P:regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR   CDD; cd20132; MBT_L3MBTL3_rpt1; 1.
DR   CDD; cd20135; MBT_L3MBTL3_rpt2; 1.
DR   CDD; cd20138; MBT_L3MBTL3_rpt3; 1.
DR   CDD; cd09582; SAM_Scm-like-3MBT3_4; 1.
DR   Gene3D; 2.30.30.140; -; 3.
DR   Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1.
DR   InterPro; IPR004092; Mbt.
DR   InterPro; IPR001660; SAM.
DR   InterPro; IPR013761; SAM/pointed_sf.
DR   InterPro; IPR002515; Znf_C2H2C.
DR   PANTHER; PTHR12247:SF72; LETHAL(3)MALIGNANT BRAIN TUMOR-LIKE PROTEIN 3; 1.
DR   PANTHER; PTHR12247; POLYCOMB GROUP PROTEIN; 1.
DR   Pfam; PF02820; MBT; 3.
DR   Pfam; PF00536; SAM_1; 1.
DR   SMART; SM00561; MBT; 3.
DR   SMART; SM00454; SAM; 1.
DR   SUPFAM; SSF47769; SAM/Pointed domain; 1.
DR   SUPFAM; SSF63748; Tudor/PWWP/MBT; 3.
DR   PROSITE; PS51079; MBT; 3.
DR   PROSITE; PS50105; SAM_DOMAIN; 1.
DR   PROSITE; PS51802; ZF_CCHHC; 1.
DR   Genevisible; Q8BLB7; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chromatin regulator; Isopeptide bond; Metal-binding;
KW   Nucleus; Reference proteome; Repeat; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..883
FT                   /note="Lethal(3)malignant brain tumor-like protein 3"
FT                   /id="PRO_0000084451"
FT   REPEAT          232..332
FT                   /note="MBT 1"
FT   REPEAT          340..439
FT                   /note="MBT 2"
FT   REPEAT          448..543
FT                   /note="MBT 3"
FT   DOMAIN          811..875
FT                   /note="SAM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT   ZN_FING         549..593
FT                   /note="CCHHC-type; degenerate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01143"
FT   REGION          1..64
FT                   /note="Interaction with RBPJ. Required for transcription
FT                   repressor activity on Notch target genes"
FT                   /evidence="ECO:0000250|UniProtKB:Q96JM7"
FT   REGION          146..223
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          595..768
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        146..205
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        615..657
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        662..768
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CROSSLNK        638
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q96JM7"
FT   VAR_SEQ         72..96
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_013509"
FT   VAR_SEQ         290..302
FT                   /note="CGYRIKLHFDGYS -> SSALYLFGKRDDG (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_013510"
FT   VAR_SEQ         303..883
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_013511"
FT   CONFLICT        146
FT                   /note="H -> Y (in Ref. 3; BAC98253)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        275
FT                   /note="P -> H (in Ref. 1; BAC27386)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   883 AA;  99137 MW;  7A6417202A0E5532 CRC64;
     MTESASSTSG QEFDVFSVMD WKDGVGTLPG SDLKFRVNEF GALEVITDES EMESVKKATA
     TTTWMVPTAQ DAPTSPPSSR PVFPPAYWTS PPGCPTVFSE KTGVPFRLKE QSKADGLQFC
     ENCCQYGNGD ECLSGGKYCS QNCARHAKDK DQKDERDGGE DNDEEDPKCS RKKKPKLSLK
     ADSKDDGEER DDEMENKQDG RILRGSQRAR RKRRGDSAVL KQGLPPKGKK TWCWASYLEE
     EKAVAVPTKL FKEHQSFPYN KNGFKVGMKL EGVDPDHQAM YCVLTVAEVC GYRIKLHFDG
     YSDCYDFWVN ADALDIHPVG WCEKTGHKLR PPKGYKEEEF NWQSYLKTCK AQAAPKSLFE
     NQNITVIPSG FRVGMKLEAA DKKSPSVICV ATVTDMVDNR FLVHFDNWDE SYDYWCESNS
     PHIHPVGWCK EHRRTLITPP GYSHVKHFSW DKYLEETNSL PAPARAFKVK PPHGFQKKMK
     LEAVDKRNPL FIRVATVADT DDHRIKVHFD GWSSCYDYWI DADSPDIHPV GWCSKTGHPL
     QAPLSPAELM EPSETGGCPT LGCRGVGHFK KSRYLGTQSG ANCPYSEINL SKERIFPDRL
     SGDTSPPTTP SFPRSKRMDT RESSSSPETR EKHANNFKED SEKKKENEVK TSAEAKVVRE
     EPTPSVQQSQ PPQQVQQVQH AQPPQQAQKA PQAQQAQQAQ QAQQAPQAPQ TPQPQQAPQV
     QQAQQAPQAQ QAQQPQQAQQ PQQAPPVQQP QQVQQAQPTQ QQAQTQQQAQ RRSAVFLSFK
     PPIPCLPLRW EQQSKLLPTV AGIPASRVSK WSTDEVSEFI QSLPGCEEHG KVFKDEQIDG
     EAFLLMTQTD IVKIMSIKLG PALKIFNSIL MFKAAEKNSH NEL
//