MTHR2_YEAST
ID MTHR2_YEAST Reviewed; 600 AA.
AC P53128; D6VU23; O94090; Q92318;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Methylenetetrahydrofolate reductase 2;
DE EC=1.5.1.20;
DE AltName: Full=YmL45;
GN Name=MET13; Synonyms=MET11, MRPL45; OrderedLocusNames=YGL125W;
GN ORFNames=G2882;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8896269;
RX DOI=10.1002/(sici)1097-0061(199609)12:10b<1047::aid-yea991>3.0.co;2-n;
RA Tizon B., Rodriguez-Torres A.M., Rodriguez-Belmonte E., Cadahia J.L.,
RA Cerdan E.;
RT "Identification of a putative methylenetetrahydrofolate reductase by
RT sequence analysis of a 6.8 kb DNA fragment of yeast chromosome VII.";
RL Yeast 12:1047-1051(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP PROTEIN SEQUENCE OF 39-49.
RX PubMed=9151978; DOI=10.1111/j.1432-1033.1997.t01-2-00449.x;
RA Kitakawa M., Graack H.-R., Grohmann L., Goldschmidt-Reisin S., Herfurth E.,
RA Wittmann-Liebold B., Nishimura T., Isono K.;
RT "Identification and characterization of the genes for mitochondrial
RT ribosomal proteins of Saccharomyces cerevisiae.";
RL Eur. J. Biochem. 245:449-456(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 120-286.
RC STRAIN=ATCC 28383 / FL100 / VTT C-80102;
RA Housen I., Lafontaine D., Belot N., Vandenhaute J.;
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION.
RX PubMed=10600168; DOI=10.1006/abbi.1999.1498;
RA Raymond R.K., Kastanos E.K., Appling D.R.;
RT "Saccharomyces cerevisiae expresses two genes encoding isozymes of
RT methylenetetrahydrofolate reductase.";
RL Arch. Biochem. Biophys. 372:300-308(1999).
RN [7]
RP FUNCTION.
RX PubMed=11729203; DOI=10.1074/jbc.m110651200;
RA Roje S., Chan S.Y., Kaplan F., Raymond R.K., Horne D.W., Appling D.R.,
RA Hanson A.D.;
RT "Metabolic engineering in yeast demonstrates that S-adenosylmethionine
RT controls flux through the methylenetetrahydrofolate reductase reaction in
RT vivo.";
RL J. Biol. Chem. 277:4056-4061(2002).
RN [8]
RP ERRATUM OF PUBMED:11729203, AND SEQUENCE REVISION TO 176-181; 197-198 AND
RP 230.
RA Roje S., Chan S.Y., Kaplan F., Raymond R.K., Horne D.W., Appling D.R.,
RA Hanson A.D.;
RL J. Biol. Chem. 277:36904-36904(2002).
RN [9]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-
CC methylene-5,6,7,8-tetrahydrofolate + H(+) + NADPH;
CC Xref=Rhea:RHEA:19817, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.20;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NAD(+) = (6R)-5,10-
CC methylene-5,6,7,8-tetrahydrofolate + H(+) + NADH;
CC Xref=Rhea:RHEA:19821, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.5.1.20;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC -!- INTERACTION:
CC P53128; P46151: MET12; NbExp=2; IntAct=EBI-11572, EBI-11567;
CC -!- MISCELLANEOUS: Present with 8600 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a mitochondrial ribosomal
CC protein. {ECO:0000305|PubMed:9151978}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA63833.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305};
CC Sequence=CAA96833.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305};
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DR EMBL; Z72647; CAA96833.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X94106; CAA63833.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U24271; AAC99805.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA07984.1; -; Genomic_DNA.
DR PIR; S64136; S64136.
DR RefSeq; NP_011390.2; NM_001180990.1.
DR AlphaFoldDB; P53128; -.
DR SMR; P53128; -.
DR BioGRID; 33126; 92.
DR DIP; DIP-5188N; -.
DR IntAct; P53128; 3.
DR MINT; P53128; -.
DR STRING; 4932.YGL125W; -.
DR CarbonylDB; P53128; -.
DR iPTMnet; P53128; -.
DR MaxQB; P53128; -.
DR PaxDb; P53128; -.
DR PRIDE; P53128; -.
DR EnsemblFungi; YGL125W_mRNA; YGL125W; YGL125W.
DR GeneID; 852752; -.
DR KEGG; sce:YGL125W; -.
DR SGD; S000003093; MET13.
DR VEuPathDB; FungiDB:YGL125W; -.
DR eggNOG; KOG0564; Eukaryota.
DR HOGENOM; CLU_025841_2_2_1; -.
DR InParanoid; P53128; -.
DR OMA; HPVHGWG; -.
DR BioCyc; YEAST:YGL125W-MON; -.
DR BRENDA; 1.5.1.20; 984.
DR BRENDA; 1.5.1.53; 984.
DR Reactome; R-SCE-196757; Metabolism of folate and pterines.
DR SABIO-RK; P53128; -.
DR UniPathway; UPA00193; -.
DR PRO; PR:P53128; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P53128; protein.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0004489; F:methylenetetrahydrofolate reductase (NAD(P)H) activity; IDA:SGD.
DR GO; GO:0106312; F:methylenetetrahydrofolate reductase NADH activity; IEA:RHEA.
DR GO; GO:0106313; F:methylenetetrahydrofolate reductase NADPH activity; IEA:RHEA.
DR GO; GO:0009086; P:methionine biosynthetic process; IMP:SGD.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR CDD; cd00537; MTHFR; 1.
DR InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR InterPro; IPR004621; Fadh2_euk.
DR InterPro; IPR003171; Mehydrof_redctse-like.
DR Pfam; PF02219; MTHFR; 1.
DR SUPFAM; SSF51730; SSF51730; 1.
DR TIGRFAMs; TIGR00677; fadh2_euk; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; FAD; Flavoprotein; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..600
FT /note="Methylenetetrahydrofolate reductase 2"
FT /id="PRO_0000190256"
FT ACT_SITE 22
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 22..27
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 54..55
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 54..55
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 84
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 114..116
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 116
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 133..134
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 156
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 282
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 41..42
FT /note="RM -> LA (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="P -> A (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="A -> R (in Ref. 1; CAA63833)"
FT /evidence="ECO:0000305"
FT CONFLICT 152..154
FT /note="GVA -> RC (in Ref. 5; AAC99805)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="Missing (in Ref. 5; AAC99805)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="V -> L (in Ref. 5; AAC99805)"
FT /evidence="ECO:0000305"
FT CONFLICT 233..243
FT /note="GQISIPQHFSS -> ANLHPSTFLV (in Ref. 5; AAC99805)"
FT /evidence="ECO:0000305"
FT CONFLICT 266..276
FT /note="MCQKLLDSGYV -> CVKIARQWLR (in Ref. 5; AAC99805)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 600 AA; 68560 MW; 470B0EFE4E2D1D75 CRC64;
MKITEKLEQH RQTSGKPTYS FEYFVPKTTQ GVQNLYDRMD RMYEASLPQF IDITWNAGGG
RLSHLSTDLV ATAQSVLGLE TCMHLTCTNM PISMIDDALE NAYHSGCQNI LALRGDPPRD
AENWTPVEGG FQYAKDLIKY IKSKYGDHFA IGVAGYPECH PELPNKDVKL DLEYLKQKID
AGGDFIITQM FYDVDNFINW CSQVRAAGMD VPIIPGIMPI TTYAAFLRRA QWGQISIPQH
FSSRLDPIKD DDELVRDIGT NLIVEMCQKL LDSGYVSHLH IYTMNLEKAP LMILERLNIL
PTESEFNAHP LAVLPWRKSL NPKRKNEEVR PIFWKRRPYS YVARTSQWAV DEFPNGRFGD
SSSPAFGDLD LCGSDLIRQS ANKCLELWST PTSINDVAFL VINYLNGNLK CLPWSDIPIN
DEINPIKAHL IELNQHSIIT INSQPQVNGI RSNDKIHGWG PKDGYVYQKQ YLEFMLPKTK
LPKLIDTLKN NEFLTYFAID SQGDLLSNHP DNSKSNAVTW GIFPGREILQ PTIVEKISFL
AWKEEFYHIL NEWKLNMNKY DKPHSAQFIQ SLIDDYCLVN IVDNDYISPD DQIHSILLSL
