MTHR1_SCHPO
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 03-AUG-2022, entry version 146.
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}.
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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; 4896.SPAC56F8.10.1; -.
DR iPTMnet; Q10258; -.
DR MaxQB; Q10258; -.
DR PaxDb; Q10258; -.
DR PRIDE; Q10258; -.
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; HPVHGWG; -.
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:0005829; C:cytosol; IBA:GO_Central.
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 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 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
