EGT1_NEUCR
ID EGT1_NEUCR Reviewed; 876 AA.
AC Q7RX33;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 3.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Ergothioneine biosynthesis protein 1 {ECO:0000303|PubMed:22209968};
DE Includes:
DE RecName: Full=L-histidine N(alpha)-methyltransferase {ECO:0000305|PubMed:5484456};
DE EC=2.1.1.44 {ECO:0000305|PubMed:5484456};
DE Includes:
DE RecName: Full=Hercynylcysteine S-oxide synthase {ECO:0000305|PubMed:4276459};
DE EC=1.14.99.51 {ECO:0000269|PubMed:25275953, ECO:0000305|PubMed:4276459};
GN Name=egt-1 {ECO:0000303|PubMed:22209968}; ORFNames=NCU04343;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(2003).
RN [2]
RP CATALYTIC ACTIVITY.
RX PubMed=5484456; DOI=10.1016/s0021-9258(18)62649-3;
RA Ishikawa Y., Melville D.B.;
RT "The enzymatic alpha-N-methylation of histidine.";
RL J. Biol. Chem. 245:5967-5973(1970).
RN [3]
RP CATALYTIC ACTIVITY.
RX PubMed=4276459; DOI=10.1016/s0021-9258(19)42435-6;
RA Ishikawa Y., Israel S.E., Melville D.B.;
RT "Participation of an intermediate sulfoxide in the enzymatic thiolation of
RT the imidazole ring of hercynine to form ergothioneine.";
RL J. Biol. Chem. 249:4420-4427(1974).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22209968; DOI=10.1016/j.fgb.2011.12.007;
RA Bello M.H., Barrera-Perez V., Morin D., Epstein L.;
RT "The Neurospora crassa mutant NcDeltaEgt-1 identifies an ergothioneine
RT biosynthetic gene and demonstrates that ergothioneine enhances conidial
RT survival and protects against peroxide toxicity during conidial
RT germination.";
RL Fungal Genet. Biol. 49:160-172(2012).
RN [5]
RP FUNCTION.
RX PubMed=25446508; DOI=10.1016/j.fgb.2014.10.007;
RA Bello M.H., Mogannam J.C., Morin D., Epstein L.;
RT "Endogenous ergothioneine is required for wild type levels of
RT conidiogenesis and conidial survival but does not protect against 254 nm
RT UV-induced mutagenesis or kill.";
RL Fungal Genet. Biol. 73:120-127(2014).
RN [6]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX PubMed=25275953; DOI=10.1021/ol502596z;
RA Hu W., Song H., Sae Her A., Bak D.W., Naowarojna N., Elliott S.J., Qin L.,
RA Chen X., Liu P.;
RT "Bioinformatic and biochemical characterizations of C-S bond formation and
RT cleavage enzymes in the fungus Neurospora crassa ergothioneine biosynthetic
RT pathway.";
RL Org. Lett. 16:5382-5385(2014).
CC -!- FUNCTION: Catalyzes the SAM-dependent triple methylation of the alpha-
CC amino group of histidine to form hercynine and subsequent conjugation
CC with cysteine and oxygen to form hercynylcysteine sulfoxide, the first
CC two steps in the biosynthesis pathway of ergothioneine
CC (PubMed:22209968). Ergothioneine is an antioxidant against peroxide in
CC conidia and contributes to conidial longevity (PubMed:22209968,
CC PubMed:25446508). {ECO:0000269|PubMed:22209968,
CC ECO:0000269|PubMed:25446508}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-histidine + 3 S-adenosyl-L-methionine = 3 H(+) + hercynine +
CC 3 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:38471, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15781, ChEBI:CHEBI:57595, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789; EC=2.1.1.44;
CC Evidence={ECO:0000305|PubMed:5484456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hercynine + L-cysteine + O2 = H2O + S-(hercyn-2-yl)-L-cysteine
CC S-oxide; Xref=Rhea:RHEA:42704, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15781, ChEBI:CHEBI:35235, ChEBI:CHEBI:82706;
CC EC=1.14.99.51; Evidence={ECO:0000269|PubMed:25275953,
CC ECO:0000305|PubMed:4276459};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:25275953};
CC Note=Binds 1 Fe(2+) ion per monomer. {ECO:0000269|PubMed:25275953};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=436 uM for hercynine {ECO:0000269|PubMed:25275953};
CC KM=603 uM for cysteine {ECO:0000269|PubMed:25275953};
CC -!- PATHWAY: Amino-acid biosynthesis; ergothioneine biosynthesis.
CC {ECO:0000269|PubMed:22209968}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O94632}. Nucleus
CC {ECO:0000250|UniProtKB:O94632}.
CC -!- DISRUPTION PHENOTYPE: Does not produce ergothioneine in either conidia
CC nor mycelia. {ECO:0000269|PubMed:22209968}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the methyltransferase
CC superfamily. EgtD family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the EgtB family.
CC {ECO:0000305}.
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DR EMBL; CM002239; EAA27088.3; -; Genomic_DNA.
DR RefSeq; XP_956324.3; XM_951231.3.
DR AlphaFoldDB; Q7RX33; -.
DR SMR; Q7RX33; -.
DR STRING; 5141.EFNCRP00000005253; -.
DR EnsemblFungi; EAA27088; EAA27088; NCU04343.
DR GeneID; 3872471; -.
DR KEGG; ncr:NCU04343; -.
DR VEuPathDB; FungiDB:NCU04343; -.
DR HOGENOM; CLU_006921_0_1_1; -.
DR InParanoid; Q7RX33; -.
DR BioCyc; MetaCyc:MON-18845; -.
DR BRENDA; 1.14.99.51; 3627.
DR SABIO-RK; Q7RX33; -.
DR UniPathway; UPA01014; -.
DR Proteomes; UP000001805; Chromosome 4, Linkage Group IV.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030745; F:dimethylhistidine N-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0061686; F:hercynylcysteine sulfoxide synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.90.1580.10; -; 1.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR019257; MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR017805; SAM_MeTrfase_EasF-type_put.
DR InterPro; IPR005532; SUMF_dom.
DR InterPro; IPR042095; SUMF_sf.
DR Pfam; PF03781; FGE-sulfatase; 2.
DR Pfam; PF10017; Methyltransf_33; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR TIGRFAMs; TIGR03439; methyl_EasF; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Iron; Metal-binding; Methyltransferase; Nucleus; Oxidoreductase;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..876
FT /note="Ergothioneine biosynthesis protein 1"
FT /id="PRO_0000434987"
FT REGION 36..350
FT /note="L-histidine N(alpha)-methyltransferase"
FT /evidence="ECO:0000305"
FT REGION 378..874
FT /note="Hercynylcysteine S-oxide synthase"
FT /evidence="ECO:0000305"
FT REGION 631..650
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..761
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 88
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 119
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 125
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 146
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 202
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 242
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 315..317
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 413
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:G7CFI3"
FT BINDING 506
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:G7CFI3"
FT BINDING 510
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:G7CFI3"
SQ SEQUENCE 876 AA; 99025 MW; 694FEB44522B96BD CRC64;
MPSAESMTPS SALGQLKATG QHVLSKLQQQ TSNADIIDIR RVAVEINLKT EITSMFRPKD
GPRQLPTLLL YNERGLQLFE RITYLEEYYL TNDEIKILTK HATEMASFIP SGAMIIELGS
GNLRKVNLLL EALDNAGKAI DYYALDLSRE ELERTLAQVP SYKHVKCHGL LGTYDDGRDW
LKAPENINKQ KCILHLGSSI GNFNRSDAAT FLKGFTDVLG PNDKMLIGVD ACNDPARVYH
AYNDKVGITH EFILNGLRNA NEIIGETAFI EGDWRVIGEY VYDEEGGRHQ AFYAPTRDTM
VMGELIRSHD RIQIEQSLKY SKEESERLWS TAGLEQVSEW TYGNEYGLHL LAKSRMSFSL
IPSVYARSAL PTLDDWEALW ATWDVVTRQM LPQEELLEKP IKLRNACIFY LGHIPTFLDI
QLTKTTKQAP SEPAHFCKIF ERGIDPDVDN PELCHAHSEI PDEWPPVEEI LTYQETVRSR
LRGLYAHGIA NIPRNVGRAI WVGFEHELMH IETLLYMMLQ SDKTLIPTHI PRPDFDKLAR
KAESERVPNQ WFKIPAQEIT IGLDDPEDGS DINKHYGWDN EKPPRRVQVA AFQAQGRPIT
NEEYAQYLLE KNIDKLPASW ARLDNENISN GTTNSVSGHH SNRTSKQQLP SSFLEKTAVR
TVYGLVPLKH ALDWPVFASY DELAGCAAYM GGRIPTFEET RSIYAYADAL KKKKEAERQL
GRTVPAVNAH LTNNGVEITP PSSPSSETPA ESSSPSDSNT TLITTEDLFS DLDGANVGFH
NWHPMPITSK GNTLVGQGEL GGVWEWTSSV LRKWEGFEPM ELYPGYTADF FDEKHNIVLG
GSWATHPRIA GRKSFVNWYQ RNYPYAWVGA RVVRDL
