DNM3L_MOUSE
ID DNM3L_MOUSE Reviewed; 421 AA.
AC Q9CWR8;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=DNA (cytosine-5)-methyltransferase 3-like;
GN Name=Dnmt3l;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11306809; DOI=10.1159/000056881;
RA Aapola U., Lyle R., Krohn K., Antonarakis S.E., Peterson P.;
RT "Isolation and initial characterization of the mouse Dnmt3l gene.";
RL Cytogenet. Cell Genet. 92:122-126(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shaoping X., Hata K., Li E.;
RT "Full-length cDNA of a murine Dnmt3-like gene.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11719692; DOI=10.1126/science.1065848;
RA Bourc'his D., Xu G.L., Lin C.S., Bollman B., Bestor T.H.;
RT "Dnmt3L and the establishment of maternal genomic imprints.";
RL Science 294:2536-2539(2001).
RN [6]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=15318244; DOI=10.1038/nature02886;
RA Bourc'his D., Bestor T.H.;
RT "Meiotic catastrophe and retrotransposon reactivation in male germ cells
RT lacking Dnmt3L.";
RL Nature 431:96-99(2004).
RN [7]
RP FUNCTION.
RX PubMed=15671018; DOI=10.1074/jbc.m413412200;
RA Gowher H., Liebert K., Hermann A., Xu G., Jeltsch A.;
RT "Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-
RT (cytosine-C5)-methyltransferases by Dnmt3L.";
RL J. Biol. Chem. 280:13341-13348(2005).
RN [8]
RP FUNCTION, AND INTERACTION WITH EZH2.
RX PubMed=24074865; DOI=10.1016/j.cell.2013.08.056;
RA Neri F., Krepelova A., Incarnato D., Maldotti M., Parlato C., Galvagni F.,
RA Matarese F., Stunnenberg H.G., Oliviero S.;
RT "Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA
RT methylation at gene bodies in ESCs.";
RL Cell 155:121-134(2013).
RN [9]
RP MUTAGENESIS OF PHE-297.
RX PubMed=18945701; DOI=10.1093/nar/gkn747;
RA Jurkowska R.Z., Anspach N., Urbanke C., Jia D., Reinhardt R., Nellen W.,
RA Cheng X., Jeltsch A.;
RT "Formation of nucleoprotein filaments by mammalian DNA methyltransferase
RT Dnmt3a in complex with regulator Dnmt3L.";
RL Nucleic Acids Res. 36:6656-6663(2008).
RN [10]
RP INTERACTION WITH SPOCD1.
RX PubMed=32674113; DOI=10.1038/s41586-020-2557-5;
RA Zoch A., Auchynnikava T., Berrens R.V., Kabayama Y., Schoepp T., Heep M.,
RA Vasiliauskaite L., Perez-Rico Y.A., Cook A.G., Shkumatava A.,
RA Rappsilber J., Allshire R.C., O'Carroll D.;
RT "SPOCD1 is an essential executor of piRNA-directed de novo DNA
RT methylation.";
RL Nature 584:635-639(2020).
CC -!- FUNCTION: Catalytically inactive regulatory factor of DNA
CC methyltransferases that can either promote or inhibit DNA methylation
CC depending on the context (PubMed:11719692, PubMed:15318244,
CC PubMed:15671018, PubMed:24074865). Essential for the function of DNMT3A
CC and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic
CC domain (PubMed:15671018). Acts by accelerating the binding of DNA and
CC S-adenosyl-L-methionine (AdoMet) to the methyltransferases and
CC dissociates from the complex after DNA binding to the
CC methyltransferases (PubMed:15671018). Recognizes unmethylated histone
CC H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by
CC recruitment or activation of DNMT3 (By similarity). Plays a key role in
CC embryonic stem cells and germ cells (PubMed:11719692, PubMed:15318244,
CC PubMed:24074865). In germ cells, required for the methylation of
CC imprinted loci together with DNMT3A (PubMed:11719692). In male germ
CC cells, specifically required to methylate retrotransposons, preventing
CC their mobilization (PubMed:15318244). Plays a key role in embryonic
CC stem cells (ESCs) by acting both as an positive and negative regulator
CC of DNA methylation (PubMed:24074865). While it promotes DNA methylation
CC of housekeeping genes together with DNMT3A and DNMT3B, it also acts as
CC an inhibitor of DNA methylation at the promoter of bivalent genes
CC (PubMed:24074865). Interacts with the EZH2 component of the PRC2/EED-
CC EZH2 complex, preventing interaction of DNMT3A and DNMT3B with the
CC PRC2/EED-EZH2 complex, leading to maintain low methylation levels at
CC the promoters of bivalent genes (PubMed:24074865). Promotes
CC differentiation of ESCs into primordial germ cells by inhibiting DNA
CC methylation at the promoter of RHOX5, thereby activating its expression
CC (PubMed:24074865). {ECO:0000250|UniProtKB:Q9UJW3,
CC ECO:0000269|PubMed:11719692, ECO:0000269|PubMed:15318244,
CC ECO:0000269|PubMed:15671018, ECO:0000269|PubMed:24074865}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterotetramer composed of 1 DNMT3A
CC homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) (By
CC similarity). Interacts with histone H3 (via N-terminus); interaction is
CC strongly inhibited by methylation at lysine 4 (H3K4me) (By similarity).
CC Interacts with EZH2; the interaction is direct (PubMed:24074865).
CC Interacts with SPOCD1 (PubMed:32674113). {ECO:0000250|UniProtKB:Q9UJW3,
CC ECO:0000269|PubMed:24074865, ECO:0000269|PubMed:32674113}.
CC -!- INTERACTION:
CC Q9CWR8; O88508: Dnmt3a; NbExp=6; IntAct=EBI-3043871, EBI-995154;
CC Q9CWR8; O88508-1: Dnmt3a; NbExp=6; IntAct=EBI-3043871, EBI-15650457;
CC Q9CWR8; O88509: Dnmt3b; NbExp=6; IntAct=EBI-3043871, EBI-7987547;
CC Q9CWR8; Q61188: Ezh2; NbExp=10; IntAct=EBI-3043871, EBI-904311;
CC Q9CWR8; Q15910: EZH2; Xeno; NbExp=2; IntAct=EBI-3043871, EBI-530054;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, thymus, ovary, and heart
CC (PubMed:11306809). {ECO:0000269|PubMed:11306809}.
CC -!- DEVELOPMENTAL STAGE: In testis, first observed in non-dividing
CC prospermatogonia after 12.5 dpc and is highest at about the time of
CC birth; expression declines rapidly after birth and is extinguished by 6
CC days post partum, when most prospermatogonia have differentiated into
CC dividing spermatogonial stem cells (PubMed:15318244).
CC {ECO:0000269|PubMed:15318244}.
CC -!- DISRUPTION PHENOTYPE: Oogenesis in female mice takes place normally,
CC but the heterozygous offspring of homozygous mutant females die before
CC mid-gestation due to biallelic expression of imprinted genes normally
CC methylated and silenced on the allele of maternal origin
CC (PubMed:11719692). Male mice are viable but sterile, with a complete
CC absence of germ cells in adult males (PubMed:11719692). Spermatocytes
CC show asynapsis or abnormal synapsis, and do not progress to the full
CC pachytene stage due to demethylation of methylation of both long-
CC terminal-repeat (LTR) and non-LTR retrotransposons (PubMed:15318244).
CC {ECO:0000269|PubMed:11719692, ECO:0000269|PubMed:15318244}.
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DR EMBL; AJ404467; CAB94726.1; -; mRNA.
DR EMBL; AF220524; AAF73868.1; -; mRNA.
DR EMBL; AK010434; BAB26936.1; -; mRNA.
DR EMBL; BC083147; AAH83147.1; -; mRNA.
DR CCDS; CCDS23962.1; -.
DR RefSeq; NP_001075164.1; NM_001081695.2.
DR RefSeq; NP_001271126.1; NM_001284197.1.
DR RefSeq; NP_062321.1; NM_019448.4.
DR AlphaFoldDB; Q9CWR8; -.
DR SMR; Q9CWR8; -.
DR BioGRID; 207659; 6.
DR DIP; DIP-49029N; -.
DR IntAct; Q9CWR8; 8.
DR MINT; Q9CWR8; -.
DR STRING; 10090.ENSMUSP00000121562; -.
DR REBASE; 6168; M.MmuDnmt3L.
DR iPTMnet; Q9CWR8; -.
DR PhosphoSitePlus; Q9CWR8; -.
DR PaxDb; Q9CWR8; -.
DR PRIDE; Q9CWR8; -.
DR DNASU; 54427; -.
DR Ensembl; ENSMUST00000000746; ENSMUSP00000000746; ENSMUSG00000000730.
DR Ensembl; ENSMUST00000138785; ENSMUSP00000121562; ENSMUSG00000000730.
DR Ensembl; ENSMUST00000151242; ENSMUSP00000116970; ENSMUSG00000000730.
DR GeneID; 54427; -.
DR KEGG; mmu:54427; -.
DR UCSC; uc007fxe.2; mouse.
DR CTD; 29947; -.
DR MGI; MGI:1859287; Dnmt3l.
DR VEuPathDB; HostDB:ENSMUSG00000000730; -.
DR eggNOG; ENOG502SIGQ; Eukaryota.
DR GeneTree; ENSGT00940000162228; -.
DR HOGENOM; CLU_006958_9_0_1; -.
DR InParanoid; Q9CWR8; -.
DR OMA; EDVCICC; -.
DR OrthoDB; 1015783at2759; -.
DR PhylomeDB; Q9CWR8; -.
DR TreeFam; TF329039; -.
DR BioGRID-ORCS; 54427; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Dnmt3l; mouse.
DR PRO; PR:Q9CWR8; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9CWR8; protein.
DR Bgee; ENSMUSG00000000730; Expressed in urinary bladder urothelium and 78 other tissues.
DR ExpressionAtlas; Q9CWR8; baseline and differential.
DR Genevisible; Q9CWR8; MM.
DR GO; GO:1902494; C:catalytic complex; ISO:MGI.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0000792; C:heterochromatin; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0008047; F:enzyme activator activity; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0090116; P:C-5 methylation of cytosine; ISO:MGI.
DR GO; GO:0060718; P:chorionic trophoblast cell differentiation; IMP:MGI.
DR GO; GO:0006306; P:DNA methylation; IMP:MGI.
DR GO; GO:0043046; P:DNA methylation involved in gamete generation; IMP:UniProtKB.
DR GO; GO:0032776; P:DNA methylation on cytosine; IMP:UniProtKB.
DR GO; GO:0071514; P:genomic imprinting; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0007141; P:male meiosis I; IMP:UniProtKB.
DR GO; GO:0032259; P:methylation; IMP:MGI.
DR GO; GO:1905642; P:negative regulation of DNA methylation; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; IMP:MGI.
DR GO; GO:0001890; P:placenta development; IMP:MGI.
DR GO; GO:1905643; P:positive regulation of DNA methylation; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR GO; GO:0048863; P:stem cell differentiation; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR025766; ADD.
DR InterPro; IPR040552; DNMT3_ADD.
DR InterPro; IPR030486; DNMT3L.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR PANTHER; PTHR23068:SF13; PTHR23068:SF13; 1.
DR Pfam; PF17980; ADD_DNMT3; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51533; ADD; 1.
PE 1: Evidence at protein level;
KW Differentiation; Metal-binding; Nucleus; Reference proteome;
KW Spermatogenesis; Zinc; Zinc-finger.
FT CHAIN 1..421
FT /note="DNA (cytosine-5)-methyltransferase 3-like"
FT /id="PRO_0000088048"
FT DOMAIN 75..207
FT /note="ADD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT ZN_FING 86..116
FT /note="GATA-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT ZN_FING 127..183
FT /note="PHD-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 297
FT /note="F->A,E: Loss of binding to DNMT3A."
FT /evidence="ECO:0000269|PubMed:18945701"
SQ SEQUENCE 421 AA; 47993 MW; 6C996D220C6F6D83 CRC64;
MGSRETPSSC SKTLETLDLE TSDSSSPDAD SPLEEQWLKS SPALKEDSVD VVLEDCKEPL
SPSSPPTGRE MIRYEVKVNR RSIEDICLCC GTLQVYTRHP LFEGGLCAPC KDKFLESLFL
YDDDGHQSYC TICCSGGTLF ICESPDCTRC YCFECVDILV GPGTSERINA MACWVCFLCL
PFSRSGLLQR RKRWRHQLKA FHDQEGAGPM EIYKTVSAWK RQPVRVLSLF RNIDKVLKSL
GFLESGSGSG GGTLKYVEDV TNVVRRDVEK WGPFDLVYGS TQPLGSSCDR CPGWYMFQFH
RILQYALPRQ ESQRPFFWIF MDNLLLTEDD QETTTRFLQT EAVTLQDVRG RDYQNAMRVW
SNIPGLKSKH APLTPKEEEY LQAQVRSRSK LDAPKVDLLV KNCLLPLREY FKYFSQNSLP
L
