NMAD1_CAEEL
ID NMAD1_CAEEL Reviewed; 291 AA.
AC Q8MNT9; Q8MNT8;
DT 22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=DNA N6-methyl adenine demethylase {ECO:0000305};
DE EC=1.14.11.51 {ECO:0000305|PubMed:25936839};
DE AltName: Full=N6-methyl adenine demethylase 1 {ECO:0000303|PubMed:25936839};
GN Name=nmad-1 {ECO:0000303|PubMed:25936839, ECO:0000312|WormBase:F09F7.7a};
GN ORFNames=F09F7.7 {ECO:0000312|WormBase:F09F7.7a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-186.
RX PubMed=25936839; DOI=10.1016/j.cell.2015.04.005;
RA Greer E.L., Blanco M.A., Gu L., Sendinc E., Liu J.,
RA Aristizabal-Corrales D., Hsu C.H., Aravind L., He C., Shi Y.;
RT "DNA Methylation on N(6)-Adenine in C. elegans.";
RL Cell 161:868-878(2015).
RN [3]
RP FUNCTION, INTERACTION WITH TOP-2; MTSS-1; HIS-24; ULE-3; C18B2.3; PGL-1;
RP CEH-93; MCM-4 AND F37C4.5, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-186.
RX PubMed=31283754; DOI=10.1371/journal.pgen.1008252;
RA Wang S.Y., Mao H., Shibuya H., Uzawa S., O'Brown Z.K., Wesenberg S.,
RA Shin N., Saito T.T., Gao J., Meyer B.J., Colaiacovo M.P., Greer E.L.;
RT "The demethylase NMAD-1 regulates DNA replication and repair in the
RT Caenorhabditis elegans germline.";
RL PLoS Genet. 15:E1008252-E1008252(2019).
CC -!- FUNCTION: Dioxygenase that specifically demethylates DNA methylated on
CC the 6th position of adenine (N(6)-methyladenosine) DNA
CC (PubMed:25936839). N(6)-methyladenosine (m6A) DNA is involved in
CC epigenetic transgenerational inheritance (PubMed:25936839). Plays an
CC essential role in DNA replication and repair in the germline during
CC meiosis (PubMed:31283754). Binds to components of the DNA replication
CC machinery such as top-2, and directs their localization to DNA to
CC control DNA replication (PubMed:31283754).
CC {ECO:0000269|PubMed:25936839, ECO:0000269|PubMed:31283754}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + an N(6)-methyl-2'-deoxyadenosine in DNA + O2
CC = a 2'-deoxyadenosine in DNA + CO2 + formaldehyde + succinate;
CC Xref=Rhea:RHEA:49524, Rhea:RHEA-COMP:12418, Rhea:RHEA-COMP:12419,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:90615,
CC ChEBI:CHEBI:90616; EC=1.14.11.51;
CC Evidence={ECO:0000305|PubMed:25936839};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q96BT7};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q96BT7};
CC -!- SUBUNIT: Interacts with top-2; the interaction is required for
CC localization of top-2 to DNA (PubMed:31283754). Also interacts with
CC mtss-1, his-24, ule-3, C18B2.3, pgl-1, ceh-93, mcm-4 and F37C4.5
CC (PubMed:31283754). {ECO:0000269|PubMed:31283754}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:31283754}. Note=May
CC co-localize with top-2 on DNA. {ECO:0000305|PubMed:31283754}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:F09F7.7a};
CC IsoId=Q8MNT9-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F09F7.7b};
CC IsoId=Q8MNT9-2; Sequence=VSP_057825, VSP_057826;
CC -!- DISRUPTION PHENOTYPE: Mutants lay fewer eggs.
CC {ECO:0000269|PubMed:25936839}.
CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
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DR EMBL; BX284603; CCD68390.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD68391.1; -; Genomic_DNA.
DR RefSeq; NP_741141.1; NM_171124.4. [Q8MNT9-1]
DR RefSeq; NP_741142.1; NM_171125.3. [Q8MNT9-2]
DR AlphaFoldDB; Q8MNT9; -.
DR SMR; Q8MNT9; -.
DR DIP; DIP-26791N; -.
DR STRING; 6239.F09F7.7a; -.
DR EPD; Q8MNT9; -.
DR PaxDb; Q8MNT9; -.
DR PeptideAtlas; Q8MNT9; -.
DR EnsemblMetazoa; F09F7.7a.1; F09F7.7a.1; WBGene00017304. [Q8MNT9-1]
DR EnsemblMetazoa; F09F7.7b.1; F09F7.7b.1; WBGene00017304. [Q8MNT9-2]
DR GeneID; 175765; -.
DR KEGG; cel:CELE_F09F7.7; -.
DR UCSC; F09F7.7a; c. elegans.
DR CTD; 175765; -.
DR WormBase; F09F7.7a; CE30655; WBGene00017304; nmad-1. [Q8MNT9-1]
DR WormBase; F09F7.7b; CE30656; WBGene00017304; nmad-1. [Q8MNT9-2]
DR eggNOG; KOG3959; Eukaryota.
DR GeneTree; ENSGT00390000006344; -.
DR HOGENOM; CLU_060545_0_0_1; -.
DR InParanoid; Q8MNT9; -.
DR OMA; DDMWIWG; -.
DR OrthoDB; 933314at2759; -.
DR PhylomeDB; Q8MNT9; -.
DR PRO; PR:Q8MNT9; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00017304; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0032451; F:demethylase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035516; F:oxidative DNA demethylase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006260; P:DNA replication; IMP:UniProtKB.
DR GO; GO:0010032; P:meiotic chromosome condensation; IMP:UniProtKB.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
DR GO; GO:0035511; P:oxidative DNA demethylation; IDA:UniProtKB.
DR GO; GO:2001252; P:positive regulation of chromosome organization; IMP:UniProtKB.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; IMP:UniProtKB.
DR GO; GO:1905516; P:positive regulation of fertilization; IMP:UniProtKB.
DR GO; GO:0060903; P:positive regulation of meiosis I; IMP:UniProtKB.
DR GO; GO:1901046; P:positive regulation of oviposition; IMP:UniProtKB.
DR Gene3D; 2.60.120.590; -; 1.
DR InterPro; IPR027450; AlkB-like.
DR InterPro; IPR037151; AlkB-like_sf.
DR InterPro; IPR032857; ALKBH4.
DR PANTHER; PTHR12463; PTHR12463; 1.
DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Dioxygenase; Iron; Metal-binding; Nucleus;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..291
FT /note="DNA N6-methyl adenine demethylase"
FT /id="PRO_0000433612"
FT DOMAIN 85..256
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 171..173
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7"
FT BINDING 184
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7,
FT ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 186
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7,
FT ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 239
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7,
FT ECO:0000255|PROSITE-ProRule:PRU00805"
FT VAR_SEQ 197..208
FT /note="SINLINGSVMTL -> RYEFLFKKVLFN (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057825"
FT VAR_SEQ 209..291
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057826"
FT MUTAGEN 186
FT /note="D->A: Abolishes ability to demethylate m6A DNA in
FT vitro. Reduces fertility and results in a high proportion
FT of male progeny (also known as a Him phenotype). Defective
FT DNA replication and aberrant rad-51 expression in germline
FT nuclei indicative of defective DNA damage repair
FT mechanisms. No change in phosphorylation levels of histone
FT H3 'Ser-10'."
FT /evidence="ECO:0000269|PubMed:25936839,
FT ECO:0000269|PubMed:31283754"
SQ SEQUENCE 291 AA; 33292 MW; E8D064902AD1E44F CRC64;
MGSAEQACGC KGARFCALCE TTERVKKLRV VEDKHVNYKV FIYDHIRQIA IPTTNLNSQS
SLEDIIDEST SCQSVSTDGS IEIDGLTLIH NFLSESEESK ILNMIDTVEW AQSQSGRRKQ
DYGPKVNFKH KKVKTDTFVG MPEYADMLLN KMSEYDVKKL GNYQPFEMCN LEYEEVKKSA
IEMHQDDMWI WGNRLISINL INGSVMTLSN DNKSFLCYVH MPHRSLLCMA DECRYDWKHG
VLAHHIRGRR IALTMREAAK DFAEGGELYE KYGAELIRLG NIRVPLSKTS V
