ID   MTHR1_SCHPO             Reviewed;         603 AA.
AC   Q10258;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 153.
DE   RecName: Full=Methylenetetrahydrofolate reductase 1;
DE            EC=1.5.1.20;
GN   Name=met9; ORFNames=SPAC56F8.10;
OS   Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC   Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC   Schizosaccharomyces.
OX   NCBI_TaxID=284812;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   DISRUPTION PHENOTYPE.
RX   PubMed=12112238; DOI=10.1002/yea.877;
RA   Naula N., Walther C., Baumann D., Schweingruber M.E.;
RT   "Two non-complementing genes encoding enzymatically active
RT   methylenetetrahydrofolate reductases control methionine requirement in
RT   fission yeast Schizosaccharomyces pombe.";
RL   Yeast 19:841-848(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=972 / ATCC 24843;
RX   PubMed=11859360; DOI=10.1038/nature724;
RA   Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA   Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA   Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA   Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA   Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA   Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA   Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA   Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA   O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA   Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA   Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA   Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA   Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA   Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA   Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA   Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA   Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA   Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA   Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA   Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA   del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA   Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA   Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA   Nurse P.;
RT   "The genome sequence of Schizosaccharomyces pombe.";
RL   Nature 415:871-880(2002).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-355, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RX   PubMed=18257517; DOI=10.1021/pr7006335;
RA   Wilson-Grady J.T., Villen J., Gygi S.P.;
RT   "Phosphoproteome analysis of fission yeast.";
RL   J. Proteome Res. 7:1088-1097(2008).
CC   -!- FUNCTION: Major methylenetetrahydrofolate reductase required to
CC       generate the methyl groups necessary for methionine synthetase to
CC       convert homocysteine to methionine. Performs 80 to 85 percent of the
CC       total methylenetetrahydrofolate reductase activity of the cells.
CC       {ECO:0000269|PubMed:12112238}.
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         Evidence={ECO:0000269|PubMed:12112238};
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         Evidence={ECO:0000269|PubMed:12112238};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC   -!- DISRUPTION PHENOTYPE: Leads to strict auxotrophy for methionine.
CC       {ECO:0000269|PubMed:12112238}.
CC   -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC       {ECO:0000305}.
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; CU329670; CAA93581.1; -; Genomic_DNA.
DR   PIR; T38920; T38920.
DR   RefSeq; NP_593224.1; NM_001018621.2.
DR   AlphaFoldDB; Q10258; -.
DR   SMR; Q10258; -.
DR   BioGRID; 279431; 1.
DR   STRING; 284812.Q10258; -.
DR   iPTMnet; Q10258; -.
DR   MaxQB; Q10258; -.
DR   PaxDb; 4896-SPAC56F8-10-1; -.
DR   EnsemblFungi; SPAC56F8.10.1; SPAC56F8.10.1:pep; SPAC56F8.10.
DR   GeneID; 2542993; -.
DR   KEGG; spo:SPAC56F8.10; -.
DR   PomBase; SPAC56F8.10; met9.
DR   VEuPathDB; FungiDB:SPAC56F8.10; -.
DR   eggNOG; KOG0564; Eukaryota.
DR   HOGENOM; CLU_025841_2_1_1; -.
DR   InParanoid; Q10258; -.
DR   OMA; VARTSQW; -.
DR   PhylomeDB; Q10258; -.
DR   BRENDA; 1.5.1.20; 5613.
DR   Reactome; R-SPO-196757; Metabolism of folate and pterines.
DR   UniPathway; UPA00193; -.
DR   PRO; PR:Q10258; -.
DR   Proteomes; UP000002485; Chromosome I.
DR   GO; GO:0005739; C:mitochondrion; ISS:PomBase.
DR   GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR   GO; GO:0004489; F:methylenetetrahydrofolate reductase (NAD(P)H) activity; IMP:PomBase.
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:PomBase.
DR   GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR   CDD; cd00537; MTHFR; 1.
DR   Gene3D; 3.20.20.220; -; 1.
DR   InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR   InterPro; IPR004621; Fadh2_euk.
DR   InterPro; IPR003171; Mehydrof_redctse-like.
DR   NCBIfam; TIGR00677; fadh2_euk; 1.
DR   PANTHER; PTHR45754; METHYLENETETRAHYDROFOLATE REDUCTASE; 1.
DR   PANTHER; PTHR45754:SF3; METHYLENETETRAHYDROFOLATE REDUCTASE; 1.
DR   Pfam; PF02219; MTHFR; 1.
DR   SUPFAM; SSF51730; FAD-linked oxidoreductase; 1.
PE   1: Evidence at protein level;
KW   FAD; Flavoprotein; NADP; Oxidoreductase; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..603
FT                   /note="Methylenetetrahydrofolate reductase 1"
FT                   /id="PRO_0000190253"
FT   ACT_SITE        21
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         21..26
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         53..54
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         53..54
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         82
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         112..114
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         114
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         130..131
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         153
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         173
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         184
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         276
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         355
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18257517"
SQ   SEQUENCE   603 AA;  69012 MW;  38519FEE783D331F CRC64;
     MKISDKLLHP DWKEKVTYSY EFFPPKTSTG VQNLYNRIDR MKTWGRPMFV DVTWGAGGTS
     SELTPGIVNV IQTDFEVDTC MHLTCTNMST EMIDAALKRA HETGCRNILA LRGDPVKDTD
     WTEGESGFRY ASDLVRYIRT HYNDEFCIGV AGYPEGYSPD DDIDESIKHL KLKVDEGADF
     IVTQMFYDVD NFIAWVDKVR AAGINIPIFP GIMPIQAWDS FIRRAKWSGV KIPQHFMDTL
     VPVKDDDEGV RERGVELIVE MCRKLIASGI TRLHFYTMNL EKAVKMIIER LGLLDENLAP
     IVDTNNVELT NASSQDRRIN EGVRPIFWRT RNESYVSRTD QWDELPHGRW GDSRSPAFGE
     FDAIRYGLRM SPKEITTSWG SPKSYSEIGD LFARYCEKKI SSLPWSDLPI SDEADLIRDQ
     LLSMNRNAFL TINSQPALNG EKSSHPVFGW GPPNGYVFQK PYVEFFVHPS LLNELKETVK
     KLNSVSYFVT NKNGDLDTNS QYEIPNAVTW GVFPNREIIQ PTIVESTSFL AWKDEAYSLG
     MEWANAYSPD SISRKLLVSM MKEWFLCVIV DNDFQNGQSL FDVFNKMRSL KDIHPELYYA
     NAS
//