T1M1_ECOLX
ID T1M1_ECOLX Reviewed; 520 AA.
AC P10484;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Type I restriction enzyme EcoR124II methylase subunit;
DE Short=M protein;
DE EC=2.1.1.72 {ECO:0000269|PubMed:32483229, ECO:0000303|PubMed:12654995};
DE AltName: Full=Type I methyltransferase M.EcoR124II {ECO:0000303|PubMed:12654995};
DE Short=M.EcoR124II {ECO:0000303|PubMed:12654995};
DE AltName: Full=Type I restriction enzyme EcoR124/3 methylase subunit {ECO:0000303|PubMed:2784505};
GN Name=hsdM; Synonyms=hsm;
OS Escherichia coli.
OG Plasmid IncFIV R124/3.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2784505; DOI=10.1016/0022-2836(89)90369-0;
RA Price C., Lingner J., Bickle J., Firman T.A., Glover S.W.;
RT "Basis for changes in DNA recognition by the EcoR124 and EcoR124/3 type I
RT DNA restriction and modification enzymes.";
RL J. Mol. Biol. 205:115-125(1989).
RN [2]
RP NOMENCLATURE, AND SUBTYPE.
RX PubMed=12654995; DOI=10.1093/nar/gkg274;
RA Roberts R.J., Belfort M., Bestor T., Bhagwat A.S., Bickle T.A.,
RA Bitinaite J., Blumenthal R.M., Degtyarev S.K., Dryden D.T., Dybvig K.,
RA Firman K., Gromova E.S., Gumport R.I., Halford S.E., Hattman S.,
RA Heitman J., Hornby D.P., Janulaitis A., Jeltsch A., Josephsen J., Kiss A.,
RA Klaenhammer T.R., Kobayashi I., Kong H., Krueger D.H., Lacks S.,
RA Marinus M.G., Miyahara M., Morgan R.D., Murray N.E., Nagaraja V.,
RA Piekarowicz A., Pingoud A., Raleigh E., Rao D.N., Reich N., Repin V.E.,
RA Selker E.U., Shaw P.C., Stein D.C., Stoddard B.L., Szybalski W.,
RA Trautner T.A., Van Etten J.L., Vitor J.M., Wilson G.G., Xu S.Y.;
RT "A nomenclature for restriction enzymes, DNA methyltransferases, homing
RT endonucleases and their genes.";
RL Nucleic Acids Res. 31:1805-1812(2003).
RN [3] {ECO:0007744|PDB:7BST, ECO:0007744|PDB:7BTO, ECO:0007744|PDB:7BTP, ECO:0007744|PDB:7BTQ, ECO:0007744|PDB:7BTR}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.97 ANGSTROMS) IN COMPLEX WITH R AND S
RP SUBUNITS AND WITH ESCHERICHIA PHAGE T7 PROTEIN OCR, STRUCTURE BY ELECTRON
RP MICROSCOPY (6.33 ANGSTROMS) IN COMPLEX WITH S SUBUNIT AND DNA, FUNCTION,
RP CATALYTIC ACTIVITY, INTERACTION WITH ESCHERICHIA PHAGE T7 PROTEIN OCR
RP (MICROBIAL INFECTION), DOMAIN, DNA-BINDING, AND MUTAGENESIS OF
RP 135-ASP--THR-146 AND 476-ALA--VAL-510.
RX PubMed=32483229; DOI=10.1038/s41564-020-0731-z;
RA Gao Y., Cao D., Zhu J., Feng H., Luo X., Liu S., Yan X.X., Zhang X.,
RA Gao P.;
RT "Structural insights into assembly, operation and inhibition of a type I
RT restriction-modification system.";
RL Nat. Microbiol. 5:1107-1118(2020).
CC -!- FUNCTION: The subtype gamma methyltransferase (M) subunit of a type I
CC restriction enzyme. The M and S subunits together form a
CC methyltransferase (MTase) that methylates A-3 on the top and bottom
CC strand of the sequence 5'-GAAN(7)RTCG-3'. In the presence of the R
CC subunit the complex can also act as an endonuclease, binding to the
CC same target sequence but cutting the DNA some distance from this site.
CC Whether the DNA is cut or modified depends on the methylation state of
CC the target sequence. When the target site is unmodified, the DNA is
CC cut. When the target site is hemimethylated, the complex acts as a
CC maintenance MTase modifying the DNA so that both strands become
CC methylated (PubMed:12654995, PubMed:32483229). After locating a non-
CC methylated recognition site, the enzyme complex serves as a molecular
CC motor that translocates DNA in an ATP-dependent manner until a
CC collision occurs that triggers cleavage (Probable).
CC {ECO:0000269|PubMed:32483229, ECO:0000303|PubMed:12654995,
CC ECO:0000305|PubMed:32483229}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyadenosine in DNA + S-adenosyl-L-methionine = an
CC N(6)-methyl-2'-deoxyadenosine in DNA + H(+) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:15197, Rhea:RHEA-COMP:12418, Rhea:RHEA-
CC COMP:12419, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:90615, ChEBI:CHEBI:90616; EC=2.1.1.72;
CC Evidence={ECO:0000269|PubMed:32483229};
CC -!- SUBUNIT: The type I restriction/modification system is composed of
CC three polypeptides R, M and S; the restriction enzyme has stoichiometry
CC R(2)M(2)S(1) while the methyltransferase is M(2)S(1). There is an
CC equilibrium between R(2)M(2)S(1) and R(1)M(2)S(1); the latter is
CC methylation and translocation proficient but restriction deficient.
CC {ECO:0000269|PubMed:32483229}.
CC -!- SUBUNIT: (Microbial infection) Holoenenzyme interacts with Escherichia
CC phage T7 protein Ocr; this interaction leads to the inhibition of the
CC restriction activity, but may still allow methylation and
CC translocation. {ECO:0000269|PubMed:32483229}.
CC -!- DOMAIN: The C-terminus is required for assembly of the restriction
CC enzyme complex. The individual domains assume different positions in
CC the enzyme, allowing the holoenzyme to regulate the methylase,
CC endonuclease and translocation states. {ECO:0000269|PubMed:32483229}.
CC -!- MISCELLANEOUS: Type I restriction and modification enzymes are complex,
CC multifunctional systems which require ATP, S-adenosyl methionine and
CC Mg(2+) as cofactors and, in addition to their endonucleolytic and
CC methylase activities, are potent DNA-dependent ATPases.
CC {ECO:0000269|PubMed:32483229}.
CC -!- SIMILARITY: Belongs to the N(4)/N(6)-methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; X13145; CAA31541.1; -; Genomic_DNA.
DR PIR; S02166; S02166.
DR PDB; 7BST; EM; 4.37 A; D/E=1-520.
DR PDB; 7BTO; EM; 3.97 A; A/B=1-520.
DR PDB; 7BTP; EM; 4.01 A; B/C=1-520.
DR PDB; 7BTQ; EM; 4.54 A; A/D=1-520.
DR PDB; 7BTR; EM; 4.54 A; A/D=1-520.
DR PDBsum; 7BST; -.
DR PDBsum; 7BTO; -.
DR PDBsum; 7BTP; -.
DR PDBsum; 7BTQ; -.
DR PDBsum; 7BTR; -.
DR AlphaFoldDB; P10484; -.
DR SMR; P10484; -.
DR DIP; DIP-17004N; -.
DR REBASE; 162028; M.Wso11848ORF763P.
DR REBASE; 190419; M.Bce021ORF873P.
DR REBASE; 191863; M.Apa1447ORF2453P.
DR REBASE; 191880; M.Apa1468ORF2954P.
DR REBASE; 203796; M.Ppe892ORF47P.
DR REBASE; 203828; M.Bli141ORF4598P.
DR REBASE; 203831; M.Bli27ORF807P.
DR REBASE; 204921; M.Ppe194ORF1864P.
DR REBASE; 233048; M.SpaF3KORF1139P.
DR REBASE; 3391; M.EcoR124II.
DR REBASE; 3392; M.EcoR124I.
DR BRENDA; 2.1.1.72; 2026.
DR PRO; PR:P10484; -.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008170; F:N-methyltransferase activity; IEA:InterPro.
DR GO; GO:0009007; F:site-specific DNA-methyltransferase (adenine-specific) activity; IEA:UniProtKB-EC.
DR GO; GO:0009307; P:DNA restriction-modification system; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1260.30; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR022749; D12N6_MeTrfase_N.
DR InterPro; IPR003356; DNA_methylase_A-5.
DR InterPro; IPR002052; DNA_methylase_N6_adenine_CS.
DR InterPro; IPR004546; Restrct_endonuc_T1M.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR038333; T1MK-like_N_sf.
DR Pfam; PF12161; HsdM_N; 1.
DR Pfam; PF02384; N6_Mtase; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR00497; hsdM; 1.
DR PROSITE; PS00092; N6_MTASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Methyltransferase; Plasmid; Restriction system;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..520
FT /note="Type I restriction enzyme EcoR124II methylase
FT subunit"
FT /id="PRO_0000088023"
FT REGION 10..190
FT /note="N-terminal domain"
FT /evidence="ECO:0000305|PubMed:32483229"
FT REGION 198..473
FT /note="Catalytic domain"
FT /evidence="ECO:0000305|PubMed:32483229"
FT REGION 481..510
FT /note="C-terminal tail"
FT /evidence="ECO:0000305|PubMed:32483229"
FT BINDING 198..203
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q89Z59"
FT BINDING 230..232
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q89Z59"
FT BINDING 254
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q89Z59"
FT MUTAGEN 135..146
FT /note="Missing: Little change in holoenzyme assembly, no
FT DNA restriction."
FT /evidence="ECO:0000269|PubMed:32483229"
FT MUTAGEN 476..510
FT /note="Missing: Almost complete loss of holoenzyme
FT assembly, no DNA restriction."
FT /evidence="ECO:0000269|PubMed:32483229"
SQ SEQUENCE 520 AA; 58013 MW; 8D82E715F41D94C3 CRC64;
MKMTSIQQRA ELHRQIWQIA NDVRGSVDGW DFKQYVLGAL FYRFISENFS SYIEAGDDSI
CYAKLDDSVI TDDIKDDAIK TKGYFIYPSQ LFCNVAAKAN TNDRLNADLN SIFVAIESSA
YGYPSEADIK GLFADFDTTS NRLGNTVKDK NARLAAVLKG VEGLKLGDFN EHQIDLFGDA
YEFLISNYAA NAGKSGGEFF TPQHVSKLIA QLAMHGQTHV NKIYDPAAGS GSLLLQAKKQ
FDNHIIEEGF FGQEINHTTY NLARMNMFLH NINYDKFDIK LGNTLTEPHF RDEKPFDAIV
SNPPYSVKWI GSDDPTLIND ERFAPAGVLA PKSKADFAFV LHALNYLSAK GRAAIVCFPG
IFYRGGAEQK IRQYLVDNNY VETVISLAPN LFFGTTIAVN ILVLSKHKTD TNVQFIDASE
LFKKETNNNI LTDAHIEQIM QVFASKEDVA HLAKSVAFET VVANDYNLSV SSYVEAKDNR
EIIDIAELNA ELKTTVSKID QLRKDIDAIV AEIEGCEVQK
