TET1_NAEGR
ID TET1_NAEGR Reviewed; 321 AA.
AC D2W6T1;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Tet-like dioxygenase 1 {ECO:0000303|PubMed:26323320};
DE EC=1.14.11.n2 {ECO:0000269|PubMed:24390346, ECO:0000269|PubMed:26323320};
DE AltName: Full=NgTet1 {ECO:0000303|PubMed:26323320};
GN Name=TET1 {ECO:0000303|PubMed:26323320};
GN ORFNames=NAEGRDRAFT_55029 {ECO:0000312|EMBL:EFC35221.1};
OS Naegleria gruberi (Amoeba).
OC Eukaryota; Discoba; Heterolobosea; Tetramitia; Eutetramitia;
OC Vahlkampfiidae; Naegleria.
OX NCBI_TaxID=5762 {ECO:0000312|Proteomes:UP000006671};
RN [1] {ECO:0000312|EMBL:EFC35221.1, ECO:0000312|Proteomes:UP000006671}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 30224 / NEG-M;
RX PubMed=20211133; DOI=10.1016/j.cell.2010.01.032;
RA Fritz-Laylin L.K., Prochnik S.E., Ginger M.L., Dacks J.B., Carpenter M.L.,
RA Field M.C., Kuo A., Paredez A., Chapman J., Pham J., Shu S., Neupane R.,
RA Cipriano M., Mancuso J., Tu H., Salamov A., Lindquist E., Shapiro H.,
RA Lucas S., Grigoriev I.V., Cande W.Z., Fulton C., Rokhsar D.S., Dawson S.C.;
RT "The genome of Naegleria gruberi illuminates early eukaryotic
RT versatility.";
RL Cell 140:631-642(2010).
RN [2] {ECO:0007744|PDB:4LT5}
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) IN COMPLEX WITH MANGANESE; SUBSTRATE
RP ANALOG N-OXALYLGLYCINE AND 5-METHYLCYTOSINE DNA, FUNCTION, CATALYTIC
RP ACTIVITY, COFACTOR, AND MUTAGENESIS OF ASN-147; ASP-234; HIS-297 AND
RP GLN-310.
RX PubMed=24390346; DOI=10.1038/nature12905;
RA Hashimoto H., Pais J.E., Zhang X., Saleh L., Fu Z.Q., Dai N., Correa I.R.,
RA Zheng Y., Cheng X.;
RT "Structure of a Naegleria Tet-like dioxygenase in complex with 5-
RT methylcytosine DNA.";
RL Nature 506:391-395(2014).
RN [3] {ECO:0007744|PDB:5CG8, ECO:0007744|PDB:5CG9}
RP X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS) OF 57-321 IN COMPLEX WITH MANGANESE;
RP 2-OXOGLUTARATE AND 5-METHYLCYTOSINE DNA, CATALYTIC ACTIVITY, FUNCTION,
RP COFACTOR, AND MUTAGENESIS OF ALA-212.
RX PubMed=26323320; DOI=10.1093/nar/gkv870;
RA Hashimoto H., Pais J.E., Dai N., Correa I.R., Zhang X., Zheng Y., Cheng X.;
RT "Structure of Naegleria Tet-like dioxygenase (NgTet1) in complexes with a
RT reaction intermediate 5-hydroxymethylcytosine DNA.";
RL Nucleic Acids Res. 43:10713-10721(2015).
CC -!- FUNCTION: Dioxygenase that catalyzes the conversion of the modified
CC genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine
CC (5hmC), and thereby plays a role in active DNA demethylation. Also
CC mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and
CC conversion of 5fC to 5-carboxylcytosine (5caC).
CC {ECO:0000269|PubMed:24390346, ECO:0000269|PubMed:26323320}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5-methyl-2'-deoxycytidine in DNA + O2 = a
CC 5-hydroxymethyl-2'-deoxycytidine in DNA + CO2 + succinate;
CC Xref=Rhea:RHEA:52636, Rhea:RHEA-COMP:11370, Rhea:RHEA-COMP:13315,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:85454, ChEBI:CHEBI:136731;
CC EC=1.14.11.n2; Evidence={ECO:0000269|PubMed:24390346,
CC ECO:0000269|PubMed:26323320};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5-hydroxymethyl-2'-deoxycytidine in DNA +
CC O2 = a 5-formyl-2'-deoxycytidine in DNA + CO2 + H2O + succinate;
CC Xref=Rhea:RHEA:53828, Rhea:RHEA-COMP:13315, Rhea:RHEA-COMP:13656,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:136731,
CC ChEBI:CHEBI:137731; Evidence={ECO:0000269|PubMed:24390346,
CC ECO:0000269|PubMed:26323320};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5-formyl-2'-deoxycytidine in DNA + O2 = a
CC 5-carboxyl-2'-deoxycytidine in DNA + CO2 + H(+) + succinate;
CC Xref=Rhea:RHEA:53832, Rhea:RHEA-COMP:13656, Rhea:RHEA-COMP:13657,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:137731,
CC ChEBI:CHEBI:137732; Evidence={ECO:0000269|PubMed:24390346,
CC ECO:0000269|PubMed:26323320};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805,
CC ECO:0000269|PubMed:24390346, ECO:0000269|PubMed:26323320};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805, ECO:0000269|PubMed:24390346,
CC ECO:0000269|PubMed:26323320};
CC -!- DOMAIN: Has good structural similarity to 2-oxoglutarate-dependent
CC dioxygenases of the TET and the alkB families, in spite of very low
CC overall sequence similarity. {ECO:0000305|PubMed:24390346}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; GG739552; EFC35221.1; -; Genomic_DNA.
DR PDB; 4LT5; X-ray; 2.89 A; A=2-321.
DR PDB; 5CG8; X-ray; 2.70 A; A=57-321.
DR PDB; 5CG9; X-ray; 2.69 A; A/D=57-321.
DR PDBsum; 4LT5; -.
DR PDBsum; 5CG8; -.
DR PDBsum; 5CG9; -.
DR AlphaFoldDB; D2W6T1; -.
DR SMR; D2W6T1; -.
DR EnsemblProtists; EFC35221; EFC35221; NAEGRDRAFT_55029.
DR VEuPathDB; AmoebaDB:NAEGRDRAFT_55029; -.
DR Proteomes; UP000006671; Unassembled WGS sequence.
DR GO; GO:0010385; F:double-stranded methylated DNA binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0070579; F:methylcytosine dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0035511; P:oxidative DNA demethylation; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; DNA-binding; Iron; Metal-binding;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..321
FT /note="Tet-like dioxygenase 1"
FT /id="PRO_0000444157"
FT DOMAIN 198..298
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 214
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:24390346,
FT ECO:0000269|PubMed:26323320, ECO:0007744|PDB:4LT5,
FT ECO:0007744|PDB:5CG8, ECO:0007744|PDB:5CG9"
FT BINDING 224
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:24390346,
FT ECO:0000269|PubMed:26323320, ECO:0007744|PDB:4LT5,
FT ECO:0007744|PDB:5CG8, ECO:0007744|PDB:5CG9"
FT BINDING 229
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805,
FT ECO:0000305|PubMed:24390346, ECO:0000305|PubMed:26323320"
FT BINDING 231
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805,
FT ECO:0000305|PubMed:24390346, ECO:0000305|PubMed:26323320"
FT BINDING 242
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:24390346,
FT ECO:0000269|PubMed:26323320, ECO:0007744|PDB:4LT5,
FT ECO:0007744|PDB:5CG8, ECO:0007744|PDB:5CG9"
FT BINDING 279
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805,
FT ECO:0000305|PubMed:24390346, ECO:0000305|PubMed:26323320"
FT BINDING 289
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805,
FT ECO:0000269|PubMed:24390346, ECO:0000269|PubMed:26323320,
FT ECO:0007744|PDB:4LT5, ECO:0007744|PDB:5CG8,
FT ECO:0007744|PDB:5CG9"
FT BINDING 310
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24390346,
FT ECO:0000269|PubMed:26323320"
FT SITE 148
FT /note="Interaction with DNA"
FT /evidence="ECO:0000269|PubMed:24390346,
FT ECO:0000269|PubMed:26323320"
FT MUTAGEN 147
FT /note="N->D: Reduced enzyme activity with DNA containing 5-
FT methylcytosine."
FT /evidence="ECO:0000269|PubMed:24390346"
FT MUTAGEN 212
FT /note="A->F,I,L: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:26323320"
FT MUTAGEN 212
FT /note="A->G: No effect on enzyme activity."
FT /evidence="ECO:0000269|PubMed:26323320"
FT MUTAGEN 212
FT /note="A->V: Decreases enzyme activity with DNA containing
FT 5-hydroxymethylcytosine."
FT /evidence="ECO:0000269|PubMed:26323320"
FT MUTAGEN 234
FT /note="D->A: Nearly abolishes enzyme activity with DNA
FT containing 5-methylcytosine."
FT /evidence="ECO:0000269|PubMed:24390346"
FT MUTAGEN 234
FT /note="D->N: Strongly reduced enzyme activity with DNA
FT containing 5-methylcytosine."
FT /evidence="ECO:0000269|PubMed:24390346"
FT MUTAGEN 297
FT /note="H->N: Strongly reduced enzyme activity with DNA
FT containing 5-methylcytosine."
FT /evidence="ECO:0000269|PubMed:24390346"
FT MUTAGEN 297
FT /note="H->Q: Reduced enzyme activity with DNA containing 5-
FT methylcytosine."
FT /evidence="ECO:0000269|PubMed:24390346"
FT MUTAGEN 310
FT /note="Q->A: Reduced enzyme activity with DNA containing 5-
FT methylcytosine."
FT /evidence="ECO:0000269|PubMed:24390346"
FT HELIX 59..74
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:5CG9"
FT HELIX 118..133
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 136..145
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:5CG9"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:5CG9"
FT HELIX 161..168
FT /evidence="ECO:0007829|PDB:5CG9"
FT HELIX 170..184
FT /evidence="ECO:0007829|PDB:5CG9"
FT HELIX 187..193
FT /evidence="ECO:0007829|PDB:5CG9"
FT HELIX 198..204
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 206..216
FT /evidence="ECO:0007829|PDB:5CG9"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 238..245
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:5CG9"
FT TURN 256..259
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:5CG9"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 285..295
FT /evidence="ECO:0007829|PDB:5CG9"
FT HELIX 298..302
FT /evidence="ECO:0007829|PDB:5CG9"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:5CG8"
FT HELIX 310..320
FT /evidence="ECO:0007829|PDB:5CG9"
SQ SEQUENCE 321 AA; 36498 MW; 3FEE0C3BBB3064FB CRC64;
MTTFKQQTIK EKETKRKYCI KGTTANLTQT HPNGPVCVNR GEEVANTTTL LDSGGGINKK
SLLQNLLSKC KTTFQQSFTN ANITLKDEKW LKNVRTAYFV CDHDGSVELA YLPNVLPKEL
VEEFTEKFES IQTGRKKDTG YSGILDNSMP FNYVTADLSQ ELGQYLSEIV NPQINYYISK
LLTCVSSRTI NYLVSLNDSY YALNNCLYPS TAFNSLKPSN DGHRIRKPHK DNLDITPSSL
FYFGNFQNTE GYLELTDKNC KVFVQPGDVL FFKGNEYKHV VANITSGWRI GLVYFAHKGS
KTKPYYEDTQ KNSLKIHKET K
