DNM3C_MOUSE
ID DNM3C_MOUSE Reviewed; 740 AA.
AC P0DOY1; A0A286YDX7;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2018, sequence version 2.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=DNA (cytosine-5)-methyltransferase 3C {ECO:0000305};
DE Short=Dnmt3c {ECO:0000303|PubMed:27856912};
DE EC=2.1.1.37 {ECO:0000255|PROSITE-ProRule:PRU10018, ECO:0000305|PubMed:27856912};
GN Name=Dnmt3c {ECO:0000303|PubMed:27856912, ECO:0000312|MGI:MGI:3649996};
GN Synonyms=Gm14490 {ECO:0000312|MGI:MGI:3649996};
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 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 [2]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP ACTIVE SITE, AND MUTAGENESIS OF CYS-538.
RX PubMed=27856912; DOI=10.1126/science.aah5143;
RA Barau J., Teissandier A., Zamudio N., Roy S., Nalesso V., Herault Y.,
RA Guillou F., Bourc'his D.;
RT "The DNA methyltransferase DNMT3C protects male germ cells from transposon
RT activity.";
RL Science 354:909-912(2016).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF GLU-693.
RX PubMed=28854222; DOI=10.1371/journal.pgen.1006964;
RA Jain D., Meydan C., Lange J., Claeys Bouuaert C., Lailler N., Mason C.E.,
RA Anderson K.V., Keeney S.;
RT "rahu is a mutant allele of Dnmt3c, encoding a DNA methyltransferase
RT homolog required for meiosis and transposon repression in the mouse male
RT germline.";
RL PLoS Genet. 13:E1006964-E1006964(2017).
RN [4]
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: DNA methyltransferase that specifically methylates the
CC promoters of evolutionarily young retrotransposons in the male germline
CC (PubMed:27856912, PubMed:28854222). De novo methylation and subsequent
CC repression of transposable elements prevents their mobilization, which
CC is essential for germline integrity (PubMed:27856912, PubMed:28854222).
CC {ECO:0000269|PubMed:27856912, ECO:0000269|PubMed:28854222}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-
CC methyl-2'-deoxycytidine in DNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:13681, Rhea:RHEA-COMP:11369, Rhea:RHEA-COMP:11370,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:85452, ChEBI:CHEBI:85454; EC=2.1.1.37;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10018,
CC ECO:0000305|PubMed:27856912};
CC -!- SUBUNIT: Interacts with SPOCD1. {ECO:0000269|PubMed:32674113}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in testis.
CC {ECO:0000269|PubMed:27856912}.
CC -!- DEVELOPMENTAL STAGE: Expression peaks around 16.5 dpc, when de novo
CC methylation takes place in male germline.
CC {ECO:0000269|PubMed:27856912}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and healthy but show male
CC sterility due to defects in spermatogenesis (PubMed:27856912). Male
CC mice show hypogonadism and azoospermia with interruption of
CC spermatogenesis at the pachytene stage of meiosis I (PubMed:27856912).
CC Retrotransposons are derepressed due to DNA demethylation
CC (PubMed:27856912). {ECO:0000269|PubMed:27856912}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. C5-methyltransferase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01016}.
CC -!- CAUTION: Evolved via a duplication of Dnmt3B and was initially
CC annotated as a pseudogene. {ECO:0000269|PubMed:27856912}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Best left unsaid - Issue 207
CC of September 2018;
CC URL="https://web.expasy.org/spotlight/back_issues/207/";
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DR EMBL; AL929021; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL833803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DOY1; -.
DR SMR; P0DOY1; -.
DR jPOST; P0DOY1; -.
DR PRIDE; P0DOY1; -.
DR Ensembl; ENSMUST00000119996; ENSMUSP00000153622; ENSMUSG00000082079.
DR MGI; MGI:3649996; Dnmt3c.
DR VEuPathDB; HostDB:ENSMUSG00000082079; -.
DR GeneTree; ENSGT00940000156928; -.
DR OMA; CNEDETS; -.
DR PRO; PR:P0DOY1; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P0DOY1; protein.
DR Bgee; ENSMUSG00000082079; Expressed in morula and 9 other tissues.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003886; F:DNA (cytosine-5-)-methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0051718; F:DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0090116; P:C-5 methylation of cytosine; IDA:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
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:0007129; P:homologous chromosome pairing at meiosis; IMP:MGI.
DR GO; GO:0007141; P:male meiosis I; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0010529; P:negative regulation of transposition; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 2.
DR InterPro; IPR025766; ADD.
DR InterPro; IPR018117; C5_DNA_meth_AS.
DR InterPro; IPR001525; C5_MeTfrase.
DR InterPro; IPR040552; DNMT3_ADD.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR Pfam; PF17980; ADD_DNMT3; 1.
DR Pfam; PF00145; DNA_methylase; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51533; ADD; 1.
DR PROSITE; PS00094; C5_MTASE_1; 1.
DR PROSITE; PS51679; SAM_MT_C5; 1.
PE 1: Evidence at protein level;
KW Differentiation; DNA-binding; Metal-binding; Methyltransferase; Nucleus;
KW Reference proteome; Repressor; S-adenosyl-L-methionine; Spermatogenesis;
KW Transferase; Zinc; Zinc-finger.
FT CHAIN 1..740
FT /note="DNA (cytosine-5)-methyltransferase 3C"
FT /id="PRO_0000439036"
FT DOMAIN 309..441
FT /note="ADD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT DOMAIN 462..740
FT /note="SAM-dependent MTase C5-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT ZN_FING 320..350
FT /note="GATA-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT ZN_FING 361..417
FT /note="PHD-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT REGION 75..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 248..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..273
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 289..307
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 538
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016,
FT ECO:0000255|PROSITE-ProRule:PRU10018,
FT ECO:0000269|PubMed:27856912"
FT BINDING 469..473
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K1"
FT BINDING 492
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K1"
FT BINDING 514..516
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K1"
FT BINDING 719..721
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K1"
FT MUTAGEN 538
FT /note="C->A: Loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:27856912"
FT MUTAGEN 693
FT /note="E->G: In rahu mutant; male sterility due to defects
FT in spermatogenesis, probably caused by transposon
FT derepression due to impaired DNA demethylation."
FT /evidence="ECO:0000269|PubMed:28854222"
SQ SEQUENCE 740 AA; 82921 MW; 82744B38622FA144 CRC64;
MRGGSRHLSN EEDVSGCEDC IIISGTCSDQ SSDPKTVPLT QVLEAVCTVE NRGCRTSSQP
SKRKASSLIS YVQDLTGDGD EDRDGEVGGS SGSGTPVMPQ LFCETRIPSK TPAPLSWQAN
TSASTPWLSP ASPYPIIDLT DEDVIPQSIS TPSVDWSQDS HQEGMDTTQV DAESRDGGNI
EYQVSADKLL LSQSCILAAF YKLVPYRESI YRTLEKARVR AGKACPSSPG ESLEDQLKPM
LEWAHGGFKP TGIEGLKPNK KQPENKSRRR TTNDPAASES SPPKRLKTNS YGGKDRGEDE
ESREQMASDV TNNKGNLEDH CLSCGRKDPV SFHPLFEGGL CQSCRDRFLE LFYMYDEDGY
QSYCTVCCEG RELLLCSNTS CCRCFCVECL EVLVGAGTAE DVKLQEPWSC YMCLPQRCHG
VLRRRKDWNM RLQDFFTTDP DLEEFEPPKL YPAIPAAKRR PIRVLSLFDG IATGYLVLKE
LGIKVEKYIA SEVCAESIAV GTVKHEGQIK YVDDIRNITK EHIDEWGPFD LVIGGSPCND
LSCVNPVRKG LFEGTGRLFF EFYRLLNYSC PEEEDDRPFF WMFENVVAME VGDKRDISRF
LECNPVMIDA IKVSAAHRAR YFWGNLPGMN RPVMASKNDK LELQDCLEFS RTAKLKKVQT
ITTKSNSIRQ GKNQLFPVVM NGKDDVLWCT ELERIFGFPE HYTDVSNMGR GARQKLLGRS
WSVPVIRHLF APLKDHFACE
