CMD1_CHLRE
ID CMD1_CHLRE Reviewed; 532 AA.
AC A0A2K3D5Z7;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=5-methylcytosine-modifying enzyme 1 {ECO:0000305};
DE Short=5mC-modifying enzyme 1 {ECO:0000303|PubMed:31043749};
DE EC=1.14.99.- {ECO:0000269|PubMed:31043749, ECO:0000269|PubMed:33531488};
DE AltName: Full=Ten-eleven translocation 1 gene protein homolog {ECO:0000305};
DE Short=CrTET1 {ECO:0000303|PubMed:31043749};
GN Name=CMD1 {ECO:0000303|PubMed:31043749};
GN ORFNames=CHLRE_12g553400v5 {ECO:0000312|EMBL:PNW75956.1};
OS Chlamydomonas reinhardtii (Chlamydomonas smithii).
OC Eukaryota; Viridiplantae; Chlorophyta; core chlorophytes; Chlorophyceae;
OC CS clade; Chlamydomonadales; Chlamydomonadaceae; Chlamydomonas.
OX NCBI_TaxID=3055;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CC-503;
RX PubMed=17932292; DOI=10.1126/science.1143609;
RA Merchant S.S., Prochnik S.E., Vallon O., Harris E.H., Karpowicz S.J.,
RA Witman G.B., Terry A., Salamov A., Fritz-Laylin L.K., Marechal-Drouard L.,
RA Marshall W.F., Qu L.H., Nelson D.R., Sanderfoot A.A., Spalding M.H.,
RA Kapitonov V.V., Ren Q., Ferris P., Lindquist E., Shapiro H., Lucas S.M.,
RA Grimwood J., Schmutz J., Cardol P., Cerutti H., Chanfreau G., Chen C.L.,
RA Cognat V., Croft M.T., Dent R., Dutcher S., Fernandez E., Fukuzawa H.,
RA Gonzalez-Ballester D., Gonzalez-Halphen D., Hallmann A., Hanikenne M.,
RA Hippler M., Inwood W., Jabbari K., Kalanon M., Kuras R., Lefebvre P.A.,
RA Lemaire S.D., Lobanov A.V., Lohr M., Manuell A., Meier I., Mets L.,
RA Mittag M., Mittelmeier T., Moroney J.V., Moseley J., Napoli C.,
RA Nedelcu A.M., Niyogi K., Novoselov S.V., Paulsen I.T., Pazour G.J.,
RA Purton S., Ral J.P., Riano-Pachon D.M., Riekhof W., Rymarquis L.,
RA Schroda M., Stern D., Umen J., Willows R., Wilson N., Zimmer S.L.,
RA Allmer J., Balk J., Bisova K., Chen C.J., Elias M., Gendler K., Hauser C.,
RA Lamb M.R., Ledford H., Long J.C., Minagawa J., Page M.D., Pan J.,
RA Pootakham W., Roje S., Rose A., Stahlberg E., Terauchi A.M., Yang P.,
RA Ball S., Bowler C., Dieckmann C.L., Gladyshev V.N., Green P., Jorgensen R.,
RA Mayfield S., Mueller-Roeber B., Rajamani S., Sayre R.T., Brokstein P.,
RA Dubchak I., Goodstein D., Hornick L., Huang Y.W., Jhaveri J., Luo Y.,
RA Martinez D., Ngau W.C., Otillar B., Poliakov A., Porter A., Szajkowski L.,
RA Werner G., Zhou K., Grigoriev I.V., Rokhsar D.S., Grossman A.R.;
RT "The Chlamydomonas genome reveals the evolution of key animal and plant
RT functions.";
RL Science 318:245-250(2007).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF ALA-330; HIS-345; ASP-347 AND ASP-350.
RX PubMed=31043749; DOI=10.1038/s41586-019-1160-0;
RA Xue J.H., Chen G.D., Hao F., Chen H., Fang Z., Chen F.F., Pang B.,
RA Yang Q.L., Wei X., Fan Q.Q., Xin C., Zhao J., Deng X., Wang B.A.,
RA Zhang X.J., Chu Y., Tang H., Yin H., Ma W., Chen L., Ding J., Weinhold E.,
RA Kohli R.M., Liu W., Zhu Z.J., Huang K., Tang H., Xu G.L.;
RT "A vitamin-C-derived DNA modification catalysed by an algal TET
RT homologue.";
RL Nature 569:581-585(2019).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH L-ASCORBATE AND IRON
RP ION, FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=33531488; DOI=10.1038/s41467-021-21061-2;
RA Li W., Zhang T., Sun M., Shi Y., Zhang X.J., Xu G.L., Ding J.;
RT "Molecular mechanism for vitamin C-derived C5-glyceryl-methylcytosine DNA
RT modification catalyzed by algal TET homologue CMD1.";
RL Nat. Commun. 12:744-744(2021).
CC -!- FUNCTION: Dioxygenase that catalyzes DNA modification by mediating the
CC conversion of the modified genomic base 5-methylcytosine (5mC) into 5-
CC glyceryl-methylcytosine (5gmC) (PubMed:31043749, PubMed:33531488).
CC Catalyzes the conjugation of a glyceryl moiety from L-ascorbate
CC (vitamin C) to the methyl group of 5mC through a carbon-carbon bond
CC (PubMed:31043749, PubMed:33531488). 5gmC DNA modification may be
CC required during photosynthesis as an epigenetic mark that couteracts
CC DNA methylation (PubMed:31043749). {ECO:0000269|PubMed:31043749,
CC ECO:0000269|PubMed:33531488}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5-methyl-2'-deoxycytidine in DNA + L-ascorbate + O2 = a
CC (8S,9S)-5-glyceryl-2'-deoxycytidine in DNA + CO2 + glyoxylate;
CC Xref=Rhea:RHEA:60132, Rhea:RHEA-COMP:11370, Rhea:RHEA-COMP:15515,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:36655,
CC ChEBI:CHEBI:38290, ChEBI:CHEBI:85454, ChEBI:CHEBI:143613;
CC Evidence={ECO:0000269|PubMed:31043749, ECO:0000269|PubMed:33531488};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60133;
CC Evidence={ECO:0000269|PubMed:31043749, ECO:0000269|PubMed:33531488};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5-methyl-2'-deoxycytidine in DNA + L-ascorbate + O2 = a
CC (8S,9R)-5-glyceryl-2'-deoxycytidine in DNA + CO2 + glyoxylate;
CC Xref=Rhea:RHEA:60136, Rhea:RHEA-COMP:11370, Rhea:RHEA-COMP:15516,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:36655,
CC ChEBI:CHEBI:38290, ChEBI:CHEBI:85454, ChEBI:CHEBI:143614;
CC Evidence={ECO:0000269|PubMed:31043749, ECO:0000269|PubMed:33531488};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60137;
CC Evidence={ECO:0000269|PubMed:31043749, ECO:0000269|PubMed:33531488};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:31043749, ECO:0000269|PubMed:33531488};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:33531488};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Decreased 5-glyceryl-methylcytosines (5gmC) DNA
CC modification in the genome (PubMed:31043749). Reduced fitness of cells
CC during exposure to high light levels (PubMed:31043749). Defects may be
CC caused by hypermethylation and down-regulation of LHCSR3, a protein-
CC coding gene required for the protection of C.reinhardtii cells from
CC photo-oxidative damage under high light conditions, causing a reduced
CC capacity for photoprotective non-photochemical quenching
CC (PubMed:31043749). {ECO:0000269|PubMed:31043749}.
CC -!- SIMILARITY: Belongs to the TET family. {ECO:0000305}.
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DR EMBL; CM008973; PNW75956.1; -; Genomic_DNA.
DR PDB; 7CY4; X-ray; 2.20 A; A=1-532.
DR PDB; 7CY5; X-ray; 2.20 A; A=1-532.
DR PDB; 7CY6; X-ray; 2.10 A; A=1-532.
DR PDB; 7CY7; X-ray; 2.15 A; A=1-532.
DR PDB; 7CY8; X-ray; 2.40 A; A=1-532.
DR PDBsum; 7CY4; -.
DR PDBsum; 7CY5; -.
DR PDBsum; 7CY6; -.
DR PDBsum; 7CY7; -.
DR PDBsum; 7CY8; -.
DR AlphaFoldDB; A0A2K3D5Z7; -.
DR SMR; A0A2K3D5Z7; -.
DR EnsemblPlants; PNW75956; PNW75956; CHLRE_12g553400v5.
DR Gramene; PNW75956; PNW75956; CHLRE_12g553400v5.
DR Proteomes; UP000006906; Chromosome 12.
DR ExpressionAtlas; A0A2K3D5Z7; baseline.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0120204; F:methylcytosine to 5-glyceryl-methylcytosine dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0006211; P:5-methylcytosine catabolic process; IDA:UniProtKB.
DR GO; GO:0010109; P:regulation of photosynthesis; IMP:UniProtKB.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..532
FT /note="5-methylcytosine-modifying enzyme 1"
FT /id="PRO_0000447622"
FT BINDING 335..337
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000269|PubMed:33531488,
FT ECO:0007744|PDB:7CY5, ECO:0007744|PDB:7CY8"
FT BINDING 345
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:33531488,
FT ECO:0000305|PubMed:31043749"
FT BINDING 347
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:33531488,
FT ECO:0000305|PubMed:31043749"
FT BINDING 397..399
FT /ligand="L-ascorbate"
FT /ligand_id="ChEBI:CHEBI:38290"
FT /evidence="ECO:0000269|PubMed:33531488,
FT ECO:0007744|PDB:7CY5, ECO:0007744|PDB:7CY8"
FT BINDING 397
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:33531488"
FT MUTAGEN 330
FT /note="A->V: Abolished dioxygenase activity."
FT /evidence="ECO:0000269|PubMed:31043749"
FT MUTAGEN 345
FT /note="H->A: Abolished dioxygenase activity."
FT /evidence="ECO:0000269|PubMed:31043749"
FT MUTAGEN 347
FT /note="D->A: Abolished dioxygenase activity."
FT /evidence="ECO:0000269|PubMed:31043749"
FT MUTAGEN 350
FT /note="D->A: Abolished dioxygenase activity."
FT /evidence="ECO:0000269|PubMed:31043749"
FT HELIX 1..13
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 23..47
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 61..69
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 100..110
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 126..142
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 149..156
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 166..173
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 206..216
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 221..235
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 240..244
FT /evidence="ECO:0007829|PDB:7CY6"
FT TURN 245..248
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 249..256
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 271..279
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 286..305
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 308..316
FT /evidence="ECO:0007829|PDB:7CY6"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 325..330
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 333..339
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:7CY4"
FT STRAND 352..362
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 364..368
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:7CY6"
FT TURN 374..377
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 384..390
FT /evidence="ECO:0007829|PDB:7CY6"
FT TURN 392..394
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 402..407
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 409..416
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 419..432
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:7CY5"
FT HELIX 437..454
FT /evidence="ECO:0007829|PDB:7CY6"
FT HELIX 457..480
FT /evidence="ECO:0007829|PDB:7CY6"
FT TURN 490..492
FT /evidence="ECO:0007829|PDB:7CY6"
FT STRAND 502..504
FT /evidence="ECO:0007829|PDB:7CY6"
SQ SEQUENCE 532 AA; 56994 MW; 0F3EC0A73B698B1B CRC64;
MSVALASEYQ LVQNAQLPQR WSQSARKSLA ILEATARKEA TAQMEAAGGS FCGQFPVDPA
FKVLSLEYSA PNPDIARAIR RVDSVPNPPL PSHVVAIQST AVDADLSLAM GVSLTPGRHT
SYLVDARALQ QSNSAAVAAR KADGDKWGPA CDEMFRGCRC VTGQEVVFYT AVKEPAGEVE
GGEGSLFKPS FDGPAFRPSW GELSGKATGV VACVLQVPIG KETDIICAEY DNLVSKGQFA
TVDRFGGDHT VNMTGNALIQ NDGKAISKGY AVAHRARVTS NVYGKANDVS LQRLAETVWS
VVEKRLSFMP AYRDLVITEQ GKPFMLGATA TNIISLTENQ GVMLHLDTDD GVWTIILWFH
RHSGIIAGGE FVLPSLGISF QPLDFTIVVF AANTIVHGTR PLQTTGKIIR WGSSHFLRFK
DVNALAQLGA AYGVDELDAK QRDQLEEVDA ANSKDGVGAA RRVASCMAAE RKAAIEAQKA
ACVRGVVMNP CTGRMPSLLF WQVWRKPPAL AVRANAVAGK KRAAADVDFC GA
