DMT5_CRYNH
ID DMT5_CRYNH Reviewed; 2377 AA.
AC J9VI03;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 2.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=DNA (cytosine-5-)-methyltransferase DMT5 {ECO:0000303|PubMed:31955845};
DE EC=3.6.4.- {ECO:0000269|PubMed:31955845, ECO:0000269|PubMed:32437639};
GN Name=DMT5 {ECO:0000303|PubMed:31955845};
GN Synonyms=DNMT5 {ECO:0000303|PubMed:24630728};
GN ORFNames=CNAG_07552 {ECO:0000312|EMBL:AFR94062.2};
OS Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 /
OS CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=235443 {ECO:0000312|Proteomes:UP000010091};
RN [1] {ECO:0000312|Proteomes:UP000010091}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487
RC {ECO:0000312|Proteomes:UP000010091};
RX PubMed=24743168; DOI=10.1371/journal.pgen.1004261;
RA Janbon G., Ormerod K.L., Paulet D., Byrnes E.J. III, Yadav V.,
RA Chatterjee G., Mullapudi N., Hon C.-C., Billmyre R.B., Brunel F.,
RA Bahn Y.-S., Chen W., Chen Y., Chow E.W.L., Coppee J.-Y., Floyd-Averette A.,
RA Gaillardin C., Gerik K.J., Goldberg J., Gonzalez-Hilarion S., Gujja S.,
RA Hamlin J.L., Hsueh Y.-P., Ianiri G., Jones S., Kodira C.D., Kozubowski L.,
RA Lam W., Marra M., Mesner L.D., Mieczkowski P.A., Moyrand F., Nielsen K.,
RA Proux C., Rossignol T., Schein J.E., Sun S., Wollschlaeger C., Wood I.A.,
RA Zeng Q., Neuveglise C., Newlon C.S., Perfect J.R., Lodge J.K., Idnurm A.,
RA Stajich J.E., Kronstad J.W., Sanyal K., Heitman J., Fraser J.A.,
RA Cuomo C.A., Dietrich F.S.;
RT "Analysis of the genome and transcriptome of Cryptococcus neoformans var.
RT grubii reveals complex RNA expression and microevolution leading to
RT virulence attenuation.";
RL PLoS Genet. 10:E1004261-E1004261(2014).
RN [2] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24630728; DOI=10.1016/j.cell.2014.01.029;
RA Huff J.T., Zilberman D.;
RT "Dnmt1-independent CG methylation contributes to nucleosome positioning in
RT diverse eukaryotes.";
RL Cell 156:1286-1297(2014).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SWI6, SUBCELLULAR LOCATION,
RP DOMAIN, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 87-TRP--TYR-90; CYS-440
RP AND LYS-1469.
RX PubMed=31955845; DOI=10.1016/j.cell.2019.12.012;
RA Catania S., Dumesic P.A., Pimentel H., Nasif A., Stoddard C.I., Burke J.E.,
RA Diedrich J.K., Cook S., Shea T., Geinger E., Lintner R., Yates J.R. III,
RA Hajkova P., Narlikar G.J., Cuomo C.A., Pritchard J.K., Madhani H.D.;
RT "Evolutionary Persistence of DNA Methylation for Millions of Years after
RT Ancient Loss of a De Novo Methyltransferase.";
RL Cell 180:263.277.e20-263.277.e20(2020).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, AND MUTAGENESIS OF LYS-1469.
RX PubMed=32437639; DOI=10.1016/j.molcel.2020.04.029;
RA Dumesic P.A., Stoddard C.I., Catania S., Narlikar G.J., Madhani H.D.;
RT "ATP Hydrolysis by the SNF2 Domain of Dnmt5 Is Coupled to Both Specific
RT Recognition and Modification of Hemimethylated DNA.";
RL Mol. Cell 79:127.139.e4-127.139.e4(2020).
CC -!- FUNCTION: ATP-dependent cytosine methylase that maintains DNA
CC methylation by acting at hemimethylated palindromic 5'-CG-3' sites to
CC produce symmetrically methylated DNA strands (PubMed:24630728,
CC PubMed:31955845, PubMed:32437639). DNA methylation may play a role in
CC transcriptional silencing, particularly at transposable elements
CC (PubMed:24630728). {ECO:0000269|PubMed:24630728,
CC ECO:0000269|PubMed:31955845, ECO:0000269|PubMed:32437639,
CC ECO:0000303|PubMed:24630728}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxycytidine in DNA + ATP + H2O + S-adenosyl-L-
CC methionine = a 5-methyl-2'-deoxycytidine in DNA + ADP + 2 H(+) +
CC phosphate + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:68984,
CC Rhea:RHEA-COMP:11369, Rhea:RHEA-COMP:11370, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:85452,
CC ChEBI:CHEBI:85454, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:31955845, ECO:0000269|PubMed:32437639};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68985;
CC Evidence={ECO:0000269|PubMed:31955845, ECO:0000269|PubMed:32437639};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:32437639};
CC -!- ACTIVITY REGULATION: Hemimethylated DNA substrates stimulate ATP
CC hydrolysis and this is a prerequisite for methyltransferase activity.
CC {ECO:0000269|PubMed:32437639}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.9 uM for ATP (in the presence of unmethylated DNA and at 23
CC degrees Celsius) {ECO:0000269|PubMed:32437639};
CC KM=6.2 uM for ATP (in the presence of hemimethylated DNA and at 23
CC degrees Celsius) {ECO:0000269|PubMed:32437639};
CC Note=kcat is 5.0 min(-1) for ATP (in the presence of unmethylated DNA
CC and at 23 degrees Celsius) (PubMed:32437639). kcat is 11.1 min(-1)
CC for ATP (in the presence of hemimethylated DNA and at 23 degrees
CC Celsius) (PubMed:32437639). {ECO:0000269|PubMed:32437639};
CC -!- SUBUNIT: Interacts with SWI6. {ECO:0000269|PubMed:31955845}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31955845}. Chromosome
CC {ECO:0000269|PubMed:31955845}. Note=Localizes to heterochromatin
CC characterized by trimethylation of histone H3 'Lys-9'.
CC {ECO:0000269|PubMed:31955845}.
CC -!- DOMAIN: The chromo domain is involved in binding heterochromatin at
CC histone H3 tails methylated on 'Lys-9'. {ECO:0000269|PubMed:31955845}.
CC -!- DOMAIN: The helicase ATP-binding domain contributes to identifying
CC hemi-methylated CG DNA motifs. {ECO:0000269|PubMed:32437639}.
CC -!- DOMAIN: The SAM-dependent MTase C5-type domain is involved in
CC hemimethylated DNA binding. {ECO:0000269|PubMed:32437639}.
CC -!- DISRUPTION PHENOTYPE: Abolishes localization of DMT5 to DNA and
CC abolishes methylation of the fifth carbon of cytosine (5mC) in DNA
CC (PubMed:31955845, PubMed:24630728). Abnormal distribution of histone H3
CC 'Lys-9' methylation (PubMed:31955845). Sensitive to thiabendazole
CC (PubMed:31955845). {ECO:0000269|PubMed:24630728,
CC ECO:0000269|PubMed:31955845}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like SAM-
CC binding methyltransferase superfamily. C5-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01016}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the SNF2/RAD54
CC helicase family. {ECO:0000305}.
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DR EMBL; CP003822; AFR94062.2; -; Genomic_DNA.
DR RefSeq; XP_012047964.1; XM_012192574.1.
DR PDB; 7R76; EM; 3.20 A; A=58-2377.
DR PDB; 7R77; EM; 3.00 A; A=58-2377.
DR PDB; 7R78; EM; 3.50 A; A=58-2377.
DR PDB; 7T02; EM; 3.80 A; A=58-2377.
DR PDBsum; 7R76; -.
DR PDBsum; 7R77; -.
DR PDBsum; 7R78; -.
DR PDBsum; 7T02; -.
DR SMR; J9VI03; -.
DR EnsemblFungi; AFR94062; AFR94062; CNAG_07552.
DR GeneID; 23890389; -.
DR VEuPathDB; FungiDB:CNAG_07552; -.
DR HOGENOM; CLU_000796_0_0_1; -.
DR Proteomes; UP000010091; Chromosome 3.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IC:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB.
DR GO; GO:0140658; F:ATP-dependent chromatin remodeler activity; IEA:InterPro.
DR GO; GO:0120328; F:ATP-dependent DNA (cytosine-5-)-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003886; F:DNA (cytosine-5-)-methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0090116; P:C-5 methylation of cytosine; IDA:UniProtKB.
DR GO; GO:0010424; P:DNA methylation on cytosine within a CG sequence; IDA:UniProtKB.
DR Gene3D; 3.40.50.10810; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR001525; C5_MeTfrase.
DR InterPro; IPR016197; Chromo-like_dom_sf.
DR InterPro; IPR000953; Chromo/chromo_shadow_dom.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR038718; SNF2-like_sf.
DR InterPro; IPR000330; SNF2_N.
DR Pfam; PF00385; Chromo; 1.
DR Pfam; PF00145; DNA_methylase; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF00176; SNF2-rel_dom; 1.
DR SMART; SM00298; CHROMO; 1.
DR SMART; SM00487; DEXDc; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF54160; SSF54160; 1.
DR PROSITE; PS50013; CHROMO_2; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Chromosome; DNA-binding; Hydrolase; Methylation;
KW Methyltransferase; Nucleotide-binding; Nucleus; Repeat; Transferase.
FT CHAIN 1..2377
FT /note="DNA (cytosine-5-)-methyltransferase DMT5"
FT /id="PRO_0000454226"
FT DOMAIN 62..126
FT /note="Chromo; shadow subtype"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT DOMAIN 347..753
FT /note="SAM-dependent MTase C5-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT DOMAIN 1450..1771
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 2152..2315
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 24..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1642..1680
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2313..2334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2347..2377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 150..197
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..259
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1642..1666
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2315..2334
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2362..2377
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 440
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT BINDING 1463..1470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MUTAGEN 87..90
FT /note="WAGY->AAGA: Severely decreases binding to histone H3
FT trimethylated on 'Lys-9'."
FT /evidence="ECO:0000269|PubMed:31955845"
FT MUTAGEN 440
FT /note="C->A: Abolishes methylation of the fifth carbon of
FT cytosine (5mC) in DNA."
FT /evidence="ECO:0000269|PubMed:31955845"
FT MUTAGEN 1469
FT /note="K->A: Abolishes methylation of the fifth carbon of
FT cytosine (5mC) in DNA. Abolishes methyltransferase activity
FT and severely impairs ATPase activity."
FT /evidence="ECO:0000269|PubMed:31955845,
FT ECO:0000269|PubMed:32437639"
SQ SEQUENCE 2377 AA; 266127 MW; B6683106DE9C1C4A CRC64;
MTTALTFGGG LFKDNTKFDI DMRGTADGAV NGGNIPNSQS QKRKRASPSP EIESEEDGDD
WYEIDYIADS RVIRRKGRQI LQYLIHWAGY AVHERTWEDE DGIGGEDCAL VQEFYRKNPG
KPRLSPSSVR KEVKLARMVE VVITTRRIDG KSRAASSTDQ PSPHRLGITS PQANNIGGED
PNPSLTRRPV RSTVSEIAKR PTSKKVHPNK KCKASSDDES DFVFEEGEWD EDEDDDNDVD
FRSSEDDEDD EQERSAEEPE SDEEIIKPAK KTKSSLPKAK LRPKPANLGG FVTGVRPLNQ
GLDIKAAVRN MSDDLPPISD IEAMFDHLVS RIPDIVELVR QLNGRKLRVA TMCSGTESPL
LALNMIAKAI KAQHGLTLAF EHVFSCEIEP FKQAYIERNF TPPILFRDVT ELGKKRAHTA
YGSMVDVPGD VDILIAGTSC VDYSNLNNVQ QDIDANGESG RTFRGMLQWV KKHQPPIVIL
ENVCNAPWDK VVEYFGQIDY DAQYTRLDTK EFYIPHTRTR VYLFATPSSS ESDDLPEKWA
QTVKDLRRPW SSPFEAFLLH TDDPNIHRAR LELASARAQT DGTSRKTTDW NRCESRHQRA
RQDEALGLLR PLTSWQEAGV CKGLDWTWND WLLAQTERVV DLLEISTLRM AKDGIDSGFK
ACIWNVSQNV DRQTGSSKTA LAPCLTPNMI PWVTIRGGPV TGREALALQG IPVRELLLTS
ENEDQLADLA GNAMTTTVVG SAMIAALKVA CHKITEGANP EKEAALILEK EAVDDEQVAN
RIIGEDYLEH HDLDLAKVTK SNLSEILDLA CRSSRHCQCE GQSGTAPNIL ECQECSYRAC
KSCGGRPEHV YAPCANQRVE PAEFEKRFKG LLPMRVRIAG LTDQCLNAVR KAAEKSNKGS
VNDNDWQLWS TALLEGIHDA EFRFRYLKRQ STWTAVYEAR RAMLSLVLRN QIPEWRLTIK
APASEPNNSQ LRALLLHPVA RLQIDIAGQD VLCGPWELCI PSMKTIDIEI TGKGELLPSW
QASLGLQGPF ANTTRWSEVE ISLQAEDENT LDRKLSGTYQ LLPRCGQAMS SLHKKRPDLS
DDGLPQLYFF LDPTRCGESR EDRYVFSTST ERLDYGTERP VIARLDSHWR EGNEKQRKVK
LDVSGAWVKC PEAHLTAIGG DDIAVVANDA AANEIHRDRA TFAIPSSASA ISASLTTEGC
SHAMALLSCR VPLDPTHSES MWRRGAWAEI DLSHQGNTTF ANLAWITERL PPLDGLKNWA
HIADDVSEHV CERCAPRPPK IHWIKREGKA NKKGNKTKST IIAFEDKLEA GQYEHALKHR
PSPFVVQLRL DQDIGSFRIG LNIVSLAHRA LSRLPPTTSE HKISLSWRLT PGHVTESPQP
RRVFILPSNK QDPENSQPEA FKLPLRKEQL RSLWWMLEQE KATGKTHTFV EEEISESLLP
AVGWRAEGKA ERPVMVRGGV IADQVGYGKT VISIALVAQT LSLPAPEPAT PGLIDLKATL
IVVPGHLSKQ WPNEIARFTG SMFKVIVIQG MKDLQEKTIA ELGKADIIVM ASEIFESDVY
WSRLEYLSAQ PREWLHDTQG GRFFCDRLDA AMESLVSQTK ILKEKGSEAA MRAMEDKKKS
LVDNVGSKKE VHTAVNFGKR MKGQAYRDKH DSDSKAKPIT KEELERWEAS EDEDDDENSK
TYIPIPKFHS FTGSESIFSA SVKKDYKLLP NPVLHMFRFR RVIADEFTYL QKKSLAAVLR
LSSSYRWILS GTPPVSDFAA IRSIATFMGI HLGVEDDGEG DVQYQKARAK DQTQAEKFHA
FREVHSRAWH NRRDELAQEF LNVFVRQNIA EIEDIPTVEH IHTFKLPASE GAVYLELEHH
LQALEMQARK ETKFKNVSQG DRNARLEEAL SDSKTAEEAL LKRCCHFTLD LSDKTQDAKS
AQEACDHITS ARARQLLACQ EDLSRSVNQA IALHGWIKKK GGFSKNDDER QPFAEWIAFS
SNISKHQGDI EAARILLKVI EKCGVKDGNI PPSPSDKQSP SIASGAKMDD VKWQLREQTH
LLRKLVKELV ARVRSLRFFE VVRKIQKGKS DAQIVLESSE CGHKPSTNPD IEMAILSCCG
HVACHKCMRK AAASQRCVKS GECQAAVRPT NIVKVSSLGV EGELSSGRYG AKLEHLVNLI
HSIPKNERVL VFLQWEDLAG KVSEALSAGR IPHVTLSGSA KSRANTLDRF QSTNADSARV
LLLKMNDASA AGSNLTTANH AVFLGPLFTN SLFNYRAVET QAIGRVRRYG QQKKVHIHRL
LALDTIDMTI FNARRTELKE KTDWEEIPQE EYKGRGSSIS MTNEKRTPTL TVKSNPFKRS
SSWALASSFR SKKRSMEARD AEGVSDDDEN SELSDII
